sham eating experiments in rats have demonstrated that

Sham Feeding in Rats Translates into Modified Sham Feeding in Women with Bulimia Nervosa and Purging

• First Online: 01 January 2012

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• Diane A. Klein M.D. 2 &
• Gerard P. Smith M.D. 3  

Part of the book series: Neuromethods ((NM,volume 74))

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Bulimia nervosa (BN) is a psychiatric illness characterized by repeated binge eating and purging episodes that can be associated with significant psychosocial impairment and chronicity. Mechanisms maintaining this maladaptive set of behaviors remain poorly understood, but several lines of evidence support the presence of enhanced responsiveness to orosensory cues in people with BN. Sham feeding (SF) in the rat is an animal model of binge eating and purging that has been used extensively for the investigation of the orosensory excitatory controls of eating. We translated SF in the rat into modified sham feeding (MSF) in humans to investigate the orosensory excitatory control of eating in patients with BN and purging. BN women sham fed significantly more sweet and unsweetened solutions than control subjects or women with anorexia nervosa. This result validates the utility of the SF rat as an animal model of BN and purging and establishes MSF as a heuristic technique for the analysis of the orosensory controls of ingestion in women with BN and purging.

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Artificial Sweeteners in Animal Models of Binge Eating

The binge eating-prone/binge eating-resistant animal model: a valuable tool for examining neurobiological underpinnings of binge eating.

Emerging Treatments and Areas for Future Research

Kendler KS et al (1991) The genetic epidemiology of bulimia nervosa. Am J Psychiatry 148:1627–1637

PubMed   CAS   Google Scholar  

Garfinkel PE et al (1995) Bulimia nervosa in a Canadian community sample: prevalence and comparison of subgroups. Am J Psychiatry 152:1052–1058

Shapiro JR et al (2007) Bulimia nervosa treatment: a systematic review of randomized controlled trials. Int J Eat Disord 40:321–326

Article   PubMed   Google Scholar  

Keel PK, Brown TA (2010) Update on course and outcome in eating disorders. Int J Eat Disord 43:195–204

Keel PK, Mitchell JE (1997) Outcome in bulimia nervosa. Am J Psychiatry 154:313–321

Mehler PS (2011) Medical complications of bulimia nervosa and their treatments. Int J Eat Disord 44:95–104

PubMed   Google Scholar  

American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders DSM-IV-TR (Text Revision), 4th edn. American Psychiatric Press, Washington, DC

Google Scholar  

Mitchell JE et al (1990) Bulimia nervosa in overweight individuals. J Neur Trans 178:324–327

CAS   Google Scholar  

Masheb R, White MA (2011) Bulimia nervosa in overweight and normal-weight women. Compr Psychiatry 53(2):181–6

Fairburn CG et al (1998) Risk factors for binge-eating disorder: a community-based case-control study. Arch Gen Psychiatry 56:468–476

Article   Google Scholar  

Fairburn CG et al (1996) Risk factors for bulimia nervosa: a community-based case-control study. Arch Gen Psychiatry 54:509–517

Klump KL, Kaye WH, Strober M (2001) The evolving genetic foundations of eating disorders. Psychiatr Clin North Am 24:215–225

Article   PubMed   CAS   Google Scholar  

Haiman C, Devlin MJ (1999) Binge eating before the onset of dieting: a distinct subgroup of bulimia nervosa? Int J Eat Disord 25:151–157

Walsh BT, Devlin MJ (1998) Eating disorders: progress and problems. Science 280:1387–1390

Staiger P, Dawe S, McCarthy R (2000) Responsivity to food cues in bulimic women and controls. Appetite 35:27–33

Carter FA et al (2006) Cue reactivity in bulimia nervosa: a useful self-report approach. Int J Eat Disord 39:694–699

Walsh BT (2011) The importance of eating behavior in eating disorders. Physiol Behav 104:525–529

Zunker C et al (2011) Ecological momentary assessment of bulimia nervosa: does dietary restriction predict binge eating? Behav Res Ther 49:714–717

Guss JL et al (1994) Binge eating behavior in patients with eating disorders. Obes Res 2:355–363

Hadigan CM, Kissileff HR, Walsh BT (1989) Patterns of food selection during meals in women with bulimia. Am J Clin Nutr 50:759–766

Kissileff HR et al (1986) Laboratory studies of eating behavior in women with bulimia. Physiol Behav 38:563–570

Walsh BT et al (1989) Eating behavior of women with bulimia. Arch Gen Psychiatry 46:54–58

Smith GP (2006) In Shils ME et al (eds) Controls of food intake, in modern nutrition in health and disease, 10th edn. Lippincott Williams & Wilkins, Baltimore, pp 707–719

Devlin MJ et al (1997) Postprandial cholecystokinin release and gastric emptying in patients with bulimia nervosa. Am J Clin Nutr 65:114–120

Geliebter A et al (1992) Gastric capacity, gastric emptying, and test-meal intake in normal and bulimic women. Am J Clin Nutr 56:656–661

Walsh BT et al (2003) A disturbance of gastric function in bulimia nervosa. Biol Psychiatry 54:929–933

Zimmerli EJ et al (2006) Gastric compliance in bulimia nervosa. Physiol Behav 87:441–446

Geracioti TD, Liddle RA (1988) Impaired cholecystokinin secretion in bulimia nervosa. N Engl J Med 319:683–688

Keel PK et al (2007) Clinical features and physiological response to a test meal in purging disorder and bulimia nervosa. Arch Gen Psychiatry 64:1058–1066

Faris PL et al (2006) Evidence for a vagal pathophysiology for bulimia nervosa and the accompanying depressive symptoms. J Affect Disord 92:79–90

Raymond NC et al (1999) A preliminary report on pain thresholds in bulimia nervosa during a bulimic episode. Compr Psychiatry 40:229–233

Faris PL et al (2000) Effect of decreasing afferent vagal activity with ondansetron on symptoms of bulimia nervosa: a randomised, double-blind trial. Lancet 355:792–797

Kissileff HR et al (1996) A direct measure of satiety disturbance in patients with bulimia nervosa. Physiol Behav 60:1077–1085

Sunday SR, Halmi KA (1996) Micro- and macroanalyses of patterns within a meal in anorexia and bulimia nervosa. Appetite 26:21–36

Walsh BT, Kissileff HR, Hadigan CM (1989) Eating behavior in bulimia. Ann NY Acad Sci 575:446–454

Guss JL, Kissileff HR (2000) Microstructural analyses of human ingestive patterns: from description to mechanistic hypotheses. Neurosci Biobehav Rev 24:261–268

Smith GP (1996) The direct and indirect controls of meal size. Neurosci Biobehav Rev 20:41–46

Drewnowski A et al (1987) Taste and eating disorders. Am J Clin Nutr 46:442–450

Drewnowski A et al (1987) Taste and bulimia. Physiol Behav 41:621–626

Kovacs D, Mahon J, Palmer RL (2002) Chewing and spitting out food among eating-disordered patients. Int J Eat Disord 32:112–115

Eckern M, Stevens W, Mitchell JE (1999) The relationship between rumination and eating disorders. Int J Eat Disord 26:414–419

Guarda AS et al (2004) Chewing and spitting in eating disorders and its relationship to binge eating. Eat Behav 5:231–239

Klein DA et al (2006) Artificial sweetener use among individuals with eating disorders. Int J Eat Disord 39:341–345

Gibbs J, Young RC, Smith GP (1973) Cholecystokinin elicits satiety in rats with open gastric fistulas. Nature 245:323–325

Smith GP, Gibbs J, Young RC (1974) Cholecystokinin and intestinal satiety in the rat. Fed Proc 33:1146–1149

Smith GP (2000) The controls of eating: a shift from nutritional homeostasis to behavioral neuroscience. Nutrition 16:814–820

Young RC et al (1974) Absence of satiety during sham feeding in the rat. J Comp Physiol Psychol 87:795–800

Antin J et al (1975) Cholecystokinin elicits the complete behavioral sequence of satiety in rats. J Comp Physiol Psychol 89:784–790

Davis JD, Smith GP (2009) The conditioned satiating effect of orosensory stimuli. Physiol Behav 97:293–303

Davis JD, Smith GP (1990) Learning to sham feed: behavioral adjustments to loss of physiological postingestional stimuli. Am J Physiol 259:R1228–R1235

Kraly FS, Carty WJ, Smith GP (1978) Effect of pregastric food stimuli on meal size and internal intermeal in the rat. Physiol Behav 20:779–784

Snowdon CT (1970) Gastrointestinal sensory and motor control of food intake. J Comp Physiol Psychol 71:68–76

Richardson CT et al (1977) Studies on the role of cephalic-vagal stimulation in the acid secretory response to eating in normal human subjects. J Clin Invest 60:435–441

Katschinski M (2000) Nutritional implications of cephalic phase gastrointestinal responses. Appetite 34:189–196

Teff KL et al (1993) Oral sensory stimulation in men: effects on insulin, C-peptide, and catecholamines. Am J Physiol 265:R1223–R1230

Geary N, Smith GP (2000) Appetite. In: Sadock BJ, Sadock VA (eds) Kaplan and Sadock’s comprehensive textbook of psychiatry, vol 1, 7th edn. Lippincott Williams & Wilkins, Philadelphia, pp 209–218

Van Vort W, Smith GP (1987) Sham feeding experience produces a conditioned increase of meal size. Appetite 9:21–29

Klein DA et al (2006) Intake, sweetness and liking during modified sham feeding of sucrose solutions. Physiol Behav 87:602–606

Klein DA et al (2009) Modified sham feeding of sweet solutions in women with and without bulimia nervosa. Physiol Behav 96:44–50

Klein DA et al (2010) Modified sham feeding of sweet solutions in women with anorexia nervosa. Physiol Behav 101:132–140

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Acknowledgements

This work was supported by grants from the NIH (MH083795 and MH071285 (PI Klein), and MH079397 and MH65024 (PI Walsh)). We would like to acknowledge the critical contributions of Drs. B. Timothy Walsh and Janet Schebendach to the design and execution of the MSF paradigm. GPS thanks his Chairman, Jack Barchas, for his continuing support.

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Diane A. Klein M.D.

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Gerard P. Smith M.D.

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Nicole M. Avena

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Klein, D.A., Smith, G.P. (2013). Sham Feeding in Rats Translates into Modified Sham Feeding in Women with Bulimia Nervosa and Purging. In: Avena, N. (eds) Animal Models of Eating Disorders. Neuromethods, vol 74. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-104-2_10

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DOI : https://doi.org/10.1007/978-1-62703-104-2_10

Published : 24 August 2012

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Nucleus accumbens deep brain stimulation in a rat model of binge eating

W t doucette.

1 Department of Psychiatry, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA

J Y Khokhar

2 Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA

3 The Dartmouth Clinical and Translational Science Institute, Dartmouth College, Lebanon, NH, USA

Binge eating (BE) is a difficult-to-treat behavior with high relapse rates, thus complicating several disorders including obesity. In this study, we tested the effects of high-frequency deep brain stimulation (DBS) in a rodent model of BE. We hypothesized that BE rats receiving high-frequency DBS in the nucleus accumbens (NAc) core would have reduced binge sizes compared with sham stimulation in both a ‘chronic BE' model as well as in a ‘relapse to chronic BE' model. Male Sprague–Dawley rats ( N =18) were implanted with stimulating electrodes in bilateral NAc core, and they received either active stimulation ( N =12) or sham stimulation ( N =6) for the initial chronic BE experiments. After testing in the chronic BE state, rats did not engage in binge sessions for 1 month, and then resumed binge sessions (relapse to chronic BE) with active or sham stimulation ( N =5–7 per group). A significant effect of intervention group was observed on binge size in the chronic BE state, but no significant difference between intervention groups was observed in the relapse to chronic BE experiments. This research, making use of both a chronic BE model as well as a relapse to chronic BE model, provides data supporting the hypothesis that DBS of the NAc core can decrease BE. Further research will be needed to learn how to increase the effect size and decrease deep brain stimulation-treatment outcome variability across the continuum of BE behavior.

Introduction

The syndrome of binge eating (BE) is a component of a number of important disorders, including BE disorder, bulimia nervosa and obesity. With the lifetime incidence of BE increasing with obesity in the general population (affecting 30% of dieting obese individuals), BE contributes to significant morbidity, mortality and associated health-care costs. 1 , 2 As BE is very difficult to manage, the development of new treatments is of great public health importance.

Emerging evidence suggests that BE, like other appetitive disorders (for example, addictions), is associated with dysfunction of the brain reward circuit (BRC). 3 , 4 , 5 , 6 , 7 This knowledge has led to both preclinical and clinical investigations using deep brain stimulation (DBS; inducing direct, focal modulation of the BRC) to treat disorders of appetitive behavior. 8 , 9 , 10 DBS of the nucleus accumbens (NAc), a key element of the BRC, is currently under investigation as a potential therapy for major depression, eating disorders, substance use disorders and obesity. 11 , 12 , 13 As DBS has already been established as a relatively safe and effective treatment for Parkinson's disease and other movement disorders, it would appear to be a potentially viable future treatment option for severe appetitive disorders. 14

In rodents, a significant body of literature has implicated the NAc core and shell subregions in mediating reward cue-driven consumptive behaviors. 15 , 16 , 17 DBS studies targeting the NAc to modify appetitive behaviors have had success within both subregions of the NAc, with some selectivity depending on the rewarding substance or the behavioral context being investigated. 4 , 8 , 9 , 18 One prior study of BE investigated unilateral DBS in the NAc shell and demonstrated a large decrease in binge size in mice . 19 The present study was designed to test the hypothesis that bilateral NAc core stimulation in BE rats would lead to a reduction in binge size when performed during a chronic BE state as well as during relapse to chronic BE. The ultimate goal of this line of research is to move toward efficacious treatment of BE through neuromodulation of the BRC.

Materials and methods

Male Sprague–Dawley rats ( N =24) were purchased from Harlan (South Easton, MA, USA) at 60 days of age and were individually housed on a reverse 12-h light/dark schedule with food and water ad libitum . ‘House chow' contained 28% protein, 58% carbohydrates and 18% fat by calories and 3.1 kcal g −1 (Harlan 2018S). Given a previously documented macronutrient preference for sugar and fat, a high-fat, high-sugar diet (‘sweet-fat diet'), which contained 19% protein, 36.2% carbohydrates and 44.8% fat by calories and 4.6 kcal g −1 (Teklad Diets 06415, South Easton, MA, USA), was used in this study to model BE in the rats. Following surgery, described below, 24 animals were randomly assigned into one of three intervention groups ( n =8 animals per group) at the initiation of the study using a simple randomization. Group size was based on prior studies using DBS in rodent models of appetitive behavior. 19 , 20 Some animals had to be killed ( N =6) over the course of the study for health reasons (for example, head-cap failure) and were removed from their respective groups for the analysis. As a result, the final group numbers for the intervention groups, described in more detail below, were as follows: ‘chronic BE state' (stim ( N =12), sham ( N =6)) and ‘relapse to BE' (sham → sham (N =6), stim → sham ( N =5), stim → stim ( N =7)). All experiments were carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23) revised in 1996 and were approved by the Institutional Animal Care and Use Committee of Dartmouth College.

Following habituation to the animal facility (1 week), and before exposure to the sweet-fat diet, rats were implanted with bipolar electrodes. The animals were anesthetized with isoflurane inhalation (5% induction, 2% maintenance) and mounted in a stereotaxic frame. Custom bipolar electrodes (Plastics One, Roanoke, VA, USA) were implanted bilaterally into the NAc core, according to the following coordinates (relative to bregma: 1.2 mm anterior, 2.8 mm lateral and 7.6 mm ventral to the brain surface). Electrodes were implanted at a 4-degree angle to the perpendicular. Four stainless steel skull screws were placed around the implant sites. Mechanical etching using a razor blade was employed to increase the surface area of the rat skull, to which dental cement was applied (Dentsply, York, PA, USA). Animals were allowed to recover from the surgery for 1-week before the start of experiments.

BE paradigm

Acquisition of the chronic be state.

The method used to induce BE in this study is a modification of previously published models, using a limited access protocol. 21 , 22 , 23 Briefly, ‘sweet-fat diet' pellets were provided to the rats in addition to house chow and water within stimulation chambers daily for 2-h. Intake of the sweet-fat diet, regular chow and water was measured within the 2-h period. The previous 22-h consumption of house chow and water was also measured. Rats were tethered with external wires through a commutator to the stimulator before starting the binge sessions each day. This protocol was continued until a stable level of sweet-fat diet intake was obtained, at which point animals were considered to be in a chronic BE state (with <10% variation in sweet-fat diet intake over four consecutive sessions).

Relapse to the chronic BE state

Relapse, defined as the resumption of bingeing behavior during self-imposed or forced abstinence in humans, was modeled here in rats. Rats that had established a chronic BE state underwent 1 month of forced abstinence from BE without exposure to the cues previously associated with the binge sessions—including the sweet-fat pellets and the binge chambers. Relapse was assessed during the initial session in which the animals returned to the binge chambers and were given access to the sweet-fat pellets. Our model of ‘relapse' was adapted from previously published cue-induced relapse models that used conditioned stimulus cues to induce reinstatement of operant responding after extinction. 24 , 25 To more closely model relapse in clinical populations, however, we used a period of forced abstinence from both the unconditioned stimulus (consumption of the sweet-fat diet) and the associated conditioned stimuli (exposure to the binge chamber, tethering and olfactory cues associated with the food) without altering their association through extinction.

A current-controlled stimulator (S11, Grass Instruments, Quincy, MA, USA) with optical isolation units (PSIU6, Grass Technologies, Quincy, MA, USA) was used to generate a continuous train of monophasic pulses (60-μs pulse width at 150 Hz). The output of the stimulus isolator was monitored using a factory-calibrated oscilloscope (TPS2002C, Tektronix, Beaverton, OR, USA). The administered current output from this constant current stimulator was calibrated to 150 μA. During binge sessions in which animals received active stimulation, the stimulator was turned on immediately before animals had access to the sweet-fat pellet and turned off at the completion of the 2-h binge session. Rats were then disconnected from external wires and returned to home cages. The selection of parameters (pulse width, frequency and current intensity) was based on recent basic science and clinical work. 26 , 27 , 28 , 29

Intervention in the chronic BE state

Once animals reached the chronic BE state (described above), three 2-h binge sessions with intervention (‘intervention sessions') were run with each animal receiving either active or sham stimulation depending on their group assignment. The final number of animals per group after health exclusions for the sham group (no active stimulation) was 6 rats and for the active stimulation group was 12 rats. To assess for any residual effect of stimulation in subsequent binge sessions, all animals underwent three additional binge sessions without stimulation (‘post-intervention sessions') after the three intervention sessions. After the post-intervention sessions, animals remained in their home cage with ad libitum access to house chow and water for 1 month without access to the sweet-fat diet, exposure to the binge chamber or handling other than for cage changes.

Intervention in the relapse to the chronic BE state

When rats restarted binge sessions (in the relapse to the chronic BE state), they immediately entered three intervention sessions, followed by post-intervention sessions. The stimulation group from the previous chronic binge state experiments ( N =12) was further divided, based on prior group assignment, into two subgroups that received either sham stimulation (stim → sham, N =5) or active DBS (stim → stim, N =7) during intervention sessions in the relapse to chronic BE state. The sham group from the chronic BE state experiment continued to receive sham stimulation (sham → sham, N =6) during intervention sessions in the relapse to chronic BE state ( Figure 1a ). These final group numbers reflect initial group assignment ( N =8) minus the number of animals removed in each group during the course of the study because of health concerns.

Experimental design and acquisition of the chronic binge-eating state. ( a ) Experimental design illustrating the behavioral states and corresponding progression of group sizes. White and black boxes denote sessions of no stimulation (sham), whereas gray boxes represent active stimulation. PI, pre-intervention; I, intervention; Post I, Post intervention. ( b ) Electrode locations displayed on representative coronal plates spanning the anterior–posterior dimension (A–P coordinates shown) using the following group symbol pairs: •, Stim→Stim; ▪, Stim→Sham; Δ, Sham→Sham. ( c ) Acquisition of bingeing behavior in all 18 animals showing the variation in binge size (kcal) across sessions. Binge sizes are displayed in kcal for comparison with the previously published model. Group averages in each session are shown with horizontal gray line. ( d ) Plot of binge size (g) versus body weight (g) in the chronic binge-eating state for all animals showing no significant relationship ( R =0.0094, P =0.977).

Verification of electrode placement

At the conclusion of the study, rats were injected with a lethal dose of sodium pentobarbital 200 mg kg −1 and perfused transcardially with normal saline (0.9% NaCl), and then with 4% paraformaldehyde fixative in 0.1 m phosphate-buffered saline. Electrodes then were removed. Whole brains were extracted from the crania, post-fixed for 24 h and then submerged in 20% sucrose in 0.1 m PBS for 48 h. Brains were frozen and cut by cryostat into 40-μm coronal sections, which then were mounted on glass slides and stained using cresyl violet. 30 Electrode locations for all rats included in the study ( N =18) are displayed in Figure 1b .

Data analysis

Percent change in food intake from pre-intervention sessions in the chronic BE state ((grams consumed in the intervention session−average grams consumed in pre-intervention sessions)/average grams consumed in pre-intervention sessions × 100) was calculated for all sessions after a chronic BE state was achieved (<10% variation over four consecutive sessions). Intervention and post-intervention session data for both the chronic BE state and the relapse to chronic BE state were analyzed using two-way repeated-measures analysis of variance (RMANOVA), using time (session number) and intervention group (sham ( N =6) versus stimulation ( N =12)) as independent variables. When the analysis indicated that differences existed between intervention groups, post hoc pairwise comparisons between groups were made using the Bonferroni adjustment. When RMANOVA analysis indicated that significant differences existed, pairwise comparisons were tested at each session to help interpret significant group differences as well as group × time interactions from the RMANOVAs using a one-way ANOVA followed by post hoc analyses between groups on each day using the Tukey adjustment. Significance was determined at P <0.05. Data are expressed as mean (M)±s.e.m.

Acquisition of BE

Implanted and tethered rats acquired binge behavior in ~8 days ( Figure 1c ), only a two to three session delay as compared with data from previously published unimplanted and tethered animals. As in the previously published model, animals in this study did not consume any of the house chow during the binge sessions despite its availability (data not shown). Water consumption was highly variable during the binge session and neither correlated with binge size nor did it significantly vary with interventions (data not shown). Binge sizes during the final three sessions shown in Figure 1c approximate the values observed when animals reached the chronic BE state (defined above) and illustrate the normal animal-to-animal variation. This inter-animal variation in binge size during a chronic BE state has been previously described by others with the outer quintiles defined as BE prone and BE resistant. 31 , 32 Interestingly, when binge sizes in the chronic BE state were plotted with the corresponding animal weights, there was no significant correlation ( R =0.0094, P =0.977; Figure 1d ). Therefore, we did not normalize binge size by animal weight in subsequent analyses.

Chronic BE state

The data shown in Figure 2a were analyzed using a repeated-measures ANOVA with a group (stimulation and sham stimulation) × session (three intervention and three post-intervention session) design. There was a main effect for group (F(1,17)=8.12, P =0.012), an interaction effect between group and session (F(1,16)=26.63, P <0.0001) and a main effect for session (F(1,16)=15.35, P =0.001). The primary finding ( Figure 2a ) was a reduction in binge size with bilateral NAc core DBS compared with sham stimulation. In addition, however, the data also highlighted the within-animal and between-animal variances across the intervention and post-intervention sessions ( Figures 2b and c ).

Chronic binge-eating state. ( a ) Binge size in DBS intervention group (gray circles) versus sham intervention group (black squares) across three intervention sessions (I1-3) and three post-intervention sessions (P1-3). Asterisks highlight sessions with significant differences between the sham and stimulation groups ( P <0.05). ( b ) Individual rat binge sizes in the sham group across sessions shown in a . ( c ) Individual rat binge sizes ( N =7) in the stimulation group that showed a reduction in binge size (>10% reduction in binge size on any intervention day) across sessions shown in a . ( d ) Individual rat binge sizes ( N =5) in the stimulation group that failed to show a reduction in binge size across sessions shown in a . ( e ) Plot of pre-intervention binge size in the chronic binge-eating state (grams) versus average percent reduction in binge size in the stimulation group showing no significant relationship ( N =12; R =−0.018, P =0.957). ( f ) Average percent reduction in binge size, binned by electrode location along the anterior–posterior axis ( N =8 per group). Error bars in all panels: ±s.e.m.

In order to determine which sessions were significantly different between groups, a subsequent session-by-session analysis of between-group differences using ANOVA was performed. This analysis showed a significant difference between the active stimulation group and the sham group on the 3 days of stimulation (I1 F(1,17)=13.033, P =0.002; I2 F(1,17)=11.232, P =0.004; I3 F(1,17)=10.253, P =0.006) but not on the post-stimulation days (P1 F(1,17)=0.83, P =0.376); P2 F(1,17)=0.65, P =0.43; P3 F(1,17)=0.06 P =0.81; Figure 2a ). There was no significant difference in water consumption during the binge sessions between groups, consistent with prior work (data not shown). House chow consumption during the binge session was not included in the analysis because, as in the previously published model, 21 it was not consumed during the binge sessions.

Although these data are promising, as noted above, the variability in treatment response observed in the active stimulation group both between-subjects and within-subjects from session to session was notable (See Figures 2b and d ). In an effort to generate preliminary data to guide future explorations into the intersubject variation in treatment outcomes, we performed a pair of post hoc regression analyses to assess: (1) the relationship between the pre-intervention binge size in the chronic BE state and the average percent reduction in binge size ( Figure 2e ) and (2) the impact of electrode location within the NAc core along the anterior–posterior axis in relation to average percent reduction in binge size ( Figure 2f ). There was no correlation between the percent reduction in binge size with DBS and the pre-intervention binge size in the chronic BE state ( R =−0.018, P =0.957). In addition, although a trend existed toward a larger reduction in binge size with electrode placement in the posterior third of the NAc core, there was no significant group effect on binge reduction with ANOVA (F(1,23)=4.11, P =0.056).

Relapse to chronic BE state

As shown in Figure 3 , BE in animals administered DBS to the NAc core was similar to BE in sham animals assessed longitudinally within the relapse to chronic BE state. Unexpectedly, binge size did not appear to be significantly reduced by DBS in the ‘relapse' to chronic BE state as compared with the chronic BE state. The data shown in Figure 3 were analyzed using a RMANOVA with a group (stim→stim, stim→sham and sham→sham) × session (three intervention and one post-intervention session) design. No main effect of group (F(2,15)=2.97, P =0.082) was observed, with no interaction between groups and session (F(2,15)=1.17, P =0.34), or a main effect of session (F(1,15)=0.21, P =0.656). Therefore, despite the apparent increase in binge size from their previous baseline in the sham→sham group on the first day of relapse, a one-way ANOVA was not run to assess group differences during the first session, given the lack of significant effect of group in the RMANOVA.

Relapse to the chronic binge-eating state. Percent change from the pre-intervention chronic binge-eating state for the three intervention groups: Stim →Stim (gray square), Stim→Sham (red circle), Sham→Sham (black triangle). R1-3 are intervention days and PR1 is the first post-intervention day with all groups getting sham stimulation. Error bars: ±s.e.m.

The NAc is critical in mediating reward-seeking behaviors, including BE. 33 DBS of this brain region has been shown to reduce consumption of cocaine, morphine, alcohol and high-fat chow. 19 , 20 , 26 , 34 In this study, we used a limited access model of BE in which rats were allowed 2 h to consume a highly palatable and calorically dense sweet-fat diet. As we hypothesized, NAc core DBS, administered during the 2-h limited access period, reduced binge size in the chronic BE state. However, NAc core DBS was not effective in the relapse to the chronic BE state with no significant difference seen between groups.

Taken together, the work presented here and by Halpern et al. 19 suggests that stimulation of the NAc produces a significant reduction in binge size in a chronic BE model despite differences in animal species (mouse versus rat), subregion of the NAc targeted (unilateral shell versus bilateral core) and the type of palatable food (high-fat versus sweet-fat). Moreover, both studies show that binge reduction does not continue beyond the sessions in which the animals receive stimulation. Interestingly, both studies also highlight that when behavioral context changes from a chronic BE state to alternative behaviors of palatable food consumption (that is, diet-induced obesity or a binge relapse model), the impact of NAc DBS appears to be less robust.

In the diet-induced obesity model used in the Halpern study, the decreased effectiveness of NAc DBS to reduce palatable food consumption over time may be related to continuous stimulation, which has been shown to induce differential network modulation compared with acute stimulation. The evolving DBS-induced network changes demonstrated by Ewing and Grace 35 may explain why in some circumstances the treatment outcomes diminish with continuous stimulation, whereas others, like improvement of depression symptoms with subgenual cingulate DBS, take time to develop. Future work is needed to determine how continuous stimulation of the NAc core compares with stimulation in the NAc shell to reduce weight in a diet-induced obesity model.

In the relapse to chronic BE state, the decreased efficacy of NAc stimulation may stem from an increased drive/motivation to consume the palatable food. This is consistent with prior studies using a cue-induced model of relapse to substances of abuse that have shown an ‘incubation of craving' with prolonged abstinence driving enhanced responding for drug when animals are re-exposed to previously associated cues. 24 , 36 , 37 Although cue-induced craving was not assessed here, it is possible that a similar underlying mechanism contributed to the decreased efficacy of DBS to reduce binge size during these sessions. To achieve the eventual goal of using focal neural modulation to simultaneously treat a spectrum of dysfunctional food consumption (BE, overeating and obesity), and to prevent relapse to these behaviors, further characterization using other behavioral paradigms will be needed to improve treatment outcomes.

Whereas most studies employing NAc DBS in rats to reduce appetitive behaviors have focused on the shell subregion, 38 , 39 , 40 , 41 some studies such as ours have assessed the effects of high-frequency DBS of the NAc core on consumptive behaviors. Alcohol drinking in rats was significantly reduced when animals received DBS of the NAc core, 20 , 41 and chronic high-frequency stimulation of the NAc core significantly reduced conditioned place preference for morphine. 34 Interestingly, some studies have failed to show NAc subregion specificity of treatment outcomes, as demonstrated by Hamilton et al. in their investigation of cocaine-induced reinstatement of cocaine self-administration. 42 Taken together, this body of work suggests that modulation of the NAc (core as well as shell) using DBS or another non-invasive stimulation method should continue to be investigated for the treatment of appetitive behaviors.

A number of potential limitations should be noted. In terms of our primary outcome, one main concern stems from the type of stimulation that we used (monophasic). This type of waveform is no longer used clinically as it can be more damaging (with chronic stimulation) than biphasic stimulation. For this study, limiting the stimulation period to the binge session appeared to prevent significant unintentional lesioning of adjacent tissue, with no significant lesions observed during histologic examination. However, we cannot rule out some degree of local damage as a confounding factor in the outcome of this study. A second concern relates to the fact that the group sizes were not equal at the conclusion of the study because of unbalanced exclusions between treatment groups because of animal health over the duration of the study. Third, a fourth arm of the study (sham → stim) would have been useful in addressing the effects of stimulation in the relapse experiments if a significant effect had been identified. However, as the effect of stimulation in the chronic BE state did not persist beyond the treatment sessions, the contribution of stimulation that occurred more than 30 days before the relapse sessions was probably minimal. Prior work has also demonstrated no long-term influence of NAc DBS on locomotor activity, suggesting that our results were probably not because of motor effects of the DBS. 43

Data from this study highlight an important limitation still impeding more widespread use of focal neural modulation: the variable and even unpredictable treatment outcomes. Preliminary evaluation of potential sources that could contribute to variance in DBS outcomes for BE revealed no significant correlations within the cohort of animals investigated. The variance in DBS outcomes could not be accounted for by either inter-animal variance in baseline binge size or electrode placement within the NAc core along the anterior–posterior axis. However, as this study was not explicitly designed to identify and test sources that could contribute to variance in DBS treatment outcomes for BE, and, moreover, post hoc analyses did reveal a trend toward significance, further studies will be needed to directly investigate whether variations in electrode placement within the NAc could underlie the observed DBS outcome variance.

We acknowledge that interindividual heterogeneity in binge size, known to exist in the Sprague–Dawley rat population, could theoretically underlie the observed variation in DBS outcomes in the chronic BE state. This behavioral heterogeneity has been well documented in the literature, where the outer quintiles of binge size variation have been defined as BE prone (upper quintile—BE prone) and BE resistant (lowest quintile—BE resistant). 31 , 32 Interestingly, however, differences in the pre-intervention binge size of animals in the chronic BE state did not correlate with the percent reduction in binge size induced by DBS. Therefore, future studies will be needed to better understand how variations in baseline binge size, electrode placement, stimulation parameters or natural variation in reward circuit function may relate to variations in DBS treatment outcomes to reduce BE.

As in this animal model of BE, the hope for advancing focal neural modulation lies within potential personalization, such that an individual's unique brain circuit dysfunction being targeted by DBS could be used as an intermediate marker to guide optimization of electrode placement and selection of stimulation variables. While a significant body of work has helped identify relevant circuits, more work is needed to characterize the relevant features of BRC activity that drive dysfunctional appetitive behavior. Further studies that capture circuit activity during behaviors of interest while stimulation parameters are manipulated and stimulation targets are varied will yield valuable information. Until these domains can be captured with adequate detail (behavior, circuit function and their modulation by variations in electrode placement and stimulation parameters), our ability to manipulate neural circuits in behaviorally meaningful ways will likely remain rudimentary. A more complete delineation of the inter-relationship of these domains could help guide the design of a closed loop system that could concurrently modulate stimulation parameters, adapting to each individual's circuit activity and its changes over time in order to allow for more nuanced and individually tuned focal neural modulation.

In this study, use of DBS in a rat model that combines a chronic BE state with a relapse to BE provides evidence that BE behavior can be manipulated by acute DBS within the NAc core. The results provide additional preclinical support for the potential utilization of focal neural modulation of the BRC to reduce binge behavior in patients.

Acknowledgments

This work was supported by funds from the Department of Psychiatry at the Geisel School of Medicine at Dartmouth (AIG), the Hitchcock Foundation (WTD) and an LRP grant from the NIH NIDDK (WTD).

By way of disclosure, in the past 3 years, Dr Green has received research grants from Novartis, Janssen and Alkermes to support research studies, and has served as an uncompensated consultant to Otsuka and Alkermes and as an (uncompensated) member of a data safety monitoring group for Eli Lilly. The remaining authors declare no conflicts of interest.

• Kessler RC, Berglund PA, Chiu WT, Deitz AC, Hudson JI, Shahly V et al. The prevalence and correlates of binge eating disorder in the World Health Organization World Mental Health Surveys: 2013 . Biol Psychiatry 2014; 73 : 492–496. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants . Lancet 2011; 377 : 557–567. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Nestler EJ. Is there a common molecular pathway for addiction ? Nat Neurosci 2005; 8 : 1445–1449. [ PubMed ] [ Google Scholar ]
• Luigjes J, van den Brink W, Feenstra M, van den Munckhof P, Schuurman PR, Schippers R et al. Deep brain stimulation in addiction: a review of potential brain targets . Mol Psychiatry 2012; 17 : 572–583. [ PubMed ] [ Google Scholar ]
• Volkow ND, Wang GJ, Fowler JS, Telang F. Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology . Philos Trans R Soc Lond B Biol Sci 2008; 363 : 3191–3200. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Michaelides M, Thanos PK, Volkow ND, Wang GJ. Dopamine-related frontostriatal abnormalities in obesity and binge-eating disorder: emerging evidence for developmental psychopathology . Int Rev Psychiatry 2012; 24 : 211–218. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Johnson PM, Kenny PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats . Nat Neurosci 2010; 13 : 635–641. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Muller UJ, Voges J, Steiner J, Galazky I, Heinze HJ, Moller M et al. Deep brain stimulation of the nucleus accumbens for the treatment of addiction . Ann N Y Acad Sci 2013; 1282 : 119–128. [ PubMed ] [ Google Scholar ]
• Pierce RC, Vassoler FM. Deep brain stimulation for the treatment of addiction: basic and clinical studies and potential mechanisms of action . Psychopharmacology (Berl) 2013; 229 : 487–491. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Halpern CH, Torres N, Hurtig HI, Wolf JA, Stephen J, Oh MY et al. Expanding applications of deep brain stimulation: a potential therapeutic role in obesity and addiction management . Acta Neurochir (Wien) 2011; 153 : 2293–2306. [ PubMed ] [ Google Scholar ]
• Goodman WK, Foote KD, Greenberg BD, Ricciuti N, Bauer R, Ward H et al. Deep brain stimulation for intractable obsessive compulsive disorder: pilot study using a blinded, staggered-onset design . Biol Psychiatry 2010; 67 : 535–542. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N et al. Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression . Neuropsychopharmacology 2008; 33 : 368–377. [ PubMed ] [ Google Scholar ]
• Muller UJ, Sturm V, Voges J, Heinze HJ, Galazky I, Heldmann M et al. Successful treatment of chronic resistant alcoholism by deep brain stimulation of nucleus accumbens: first experience with three cases . Pharmacopsychiatry 2009; 42 : 288–291. [ PubMed ] [ Google Scholar ]
• Toft M, Lilleeng B, Ramm-Pettersen J, Skogseid IM, Gundersen V, Gerdts R et al. Long-term efficacy and mortality in Parkinson's disease patients treated with subthalamic stimulation . Mov Disord 2011; 26 : 1931–1934. [ PubMed ] [ Google Scholar ]
• Avena NM, Bocarsly ME. Dysregulation of brain reward systems in eating disorders: neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia nervosa . Neuropharmacology 2012; 63 : 87–96. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Richard JM, Castro DC, Difeliceantonio AG, Robinson MJ, Berridge KC. Mapping brain circuits of reward and motivation: in the footsteps of Ann Kelley . Neurosci Biobehav Rev 2013; 37 : 1919–1931. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Burton AC, Nakamura K, Roesch MR. From ventral-medial to dorsal-lateral striatum: Neural correlates of reward-guided decision-making . Neurobiol Learn Mem 2014; 117 : 51–59. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Hamani C, Temel Y. Deep brain stimulation for psychiatric disease: contributions and validity of animal models . Sci Transl Med 2012; 4 : 142rv–148r. [ PubMed ] [ Google Scholar ]
• Halpern CH, Tekriwal A, Santollo J, Keating JG, Wolf JA, Daniels D et al. Amelioration of binge eating by nucleus accumbens shell deep brain stimulation in mice involves D2 receptor modulation . J Neurosci 2013; 33 : 7122–7129. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Henderson MB, Green AI, Bradford PS, Chau DT, Roberts DW, Leiter JC. Deep brain stimulation of the nucleus accumbens reduces alcohol intake in alcohol-preferring rats . Neurosurg Focus 2010; 29 : E12. [ PubMed ] [ Google Scholar ]
• Berner LA, Avena NM, Hoebel BG. Bingeing, self-restriction, and increased body weight in rats with limited access to a sweet-fat diet . Obesity (Silver Spring) 2008; 16 : 1998–2002. [ PubMed ] [ Google Scholar ]
• Corwin RL. Binge-type eating induced by limited access in rats does not require energy restriction on the previous day . Appetite 2004; 42 : 139–142. [ PubMed ] [ Google Scholar ]
• Corwin RL, Buda-Levin A. Behavioral models of binge-type eating . Physiol Behav 2004; 82 : 123–130. [ PubMed ] [ Google Scholar ]
• Marchant NJ, Li X, Shaham Y. Recent developments in animal models of drug relapse . Curr Opin Neurobiol 2013; 23 : 675–683. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Grimm JW, Barnes J, North K, Collins S, Weber R. A general method for evaluating incubation of sucrose craving in rats . J Vis Exp 2011; 57 : e3335. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Vassoler FM, Schmidt HD, Gerard ME, Famous KR, Ciraulo DA, Kornetsky C et al. Deep brain stimulation of the nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug seeking in rats . J Neurosci 2008; 28 : 8735–8739. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Bewernick BH, Kayser S, Sturm V, Schlaepfer TE. Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy . Neuropsychopharmacology 2012; 37 : 1975–1985. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C et al. Deep brain stimulation for treatment-resistant depression . Neuron 2005; 45 : 651–660. [ PubMed ] [ Google Scholar ]
• Benazzouz A, Hallett M. Mechanism of action of deep brain stimulation . Neurology 2000; 55 : S13–S16. [ PubMed ] [ Google Scholar ]
• Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates . 6th edn, Academic Press/Elsevier: Amsterdam, Boston, 2007. [ Google Scholar ]
• Boggiano MM, Artiga AI, Pritchett CE, Chandler-Laney PC, Smith ML, Eldridge AJ. High intake of palatable food predicts binge-eating independent of susceptibility to obesity: an animal model of lean vs obese binge-eating and obesity with and without binge-eating . Int J Obes (Lond) 2007; 31 : 1357–1367. [ PubMed ] [ Google Scholar ]
• Hildebrandt BA, Klump KL, Racine SE, Sisk CL. Differential strain vulnerability to binge eating behaviors in rats . Physiol Behav 2014; 127 : 81–86. [ PubMed ] [ Google Scholar ]
• Wang GJ, Geliebter A, Volkow ND, Telang FW, Logan J, Jayne MC et al. Enhanced striatal dopamine release during food stimulation in binge eating disorder . Obesity (Silver Spring) 2011; 19 : 1601–1608. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Liu HY, Jin J, Tang JS, Sun WX, Jia H, Yang XP et al. Chronic deep brain stimulation in the rat nucleus accumbens and its effect on morphine reinforcement . Addict Biol 2008; 13 : 40–46. [ PubMed ] [ Google Scholar ]
• Ewing SG, Grace AA. Long-term high frequency deep brain stimulation of the nucleus accumbens drives time-dependent changes in functional connectivity in the rodent limbic system . Brain Stimulation 2013; 6 : 274–285. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Counotte DS, Schiefer C, Shaham Y, O'Donnell P. Time-dependent decreases in nucleus accumbens AMPA/NMDA ratio and incubation of sucrose craving in adolescent and adult rats . Psychopharmacology (Berl) 2013; 231 : 1675–1684. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Grimm JW, Hope BT, Wise RA, Shaham Y. Neuroadaptation. Incubation of cocaine craving after withdrawal . Nature 2001; 412 : 141–142. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Wilden JA, Qing KY, Hauser SR, McBride WJ, Irazoqui PP, Rodd ZA. Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell . J Neurosurg 2014; 120 : 997–1005. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Vassoler FM, White SL, Hopkins TJ, Guercio LA, Espallergues J, Berton O et al. Deep brain stimulation of the nucleus accumbens shell attenuates cocaine reinstatement through local and antidromic activation . J Neurosci 2013; 33 : 14446–14454. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• van der Plasse G, Schrama R, van Seters SP, Vanderschuren LJ, Westenberg HG. Deep brain stimulation reveals a dissociation of consummatory and motivated behaviour in the medial and lateral nucleus accumbens shell of the rat . PLoS One 2012; 7 : e33455. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Knapp CM, Tozier L, Pak A, Ciraulo DA, Kornetsky C. Deep brain stimulation of the nucleus accumbens reduces ethanol consumption in rats . Pharmacol Biochem Behav 2009; 92 : 474–479. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Hamilton J, Lee J, Canales JJ. Chronic unilateral stimulation of the nucleus accumbens at high or low frequencies attenuates relapse to cocaine seeking in an animal model . Brain Stimulation 2015; 8 : 57–63. [ PubMed ] [ Google Scholar ]
• Guo L, Zhou H, Wang R, Xu J, Zhou W, Zhang F et al. DBS of nucleus accumbens on heroin seeking behaviors in self-administering rats . Drug Alcohol Depend 2013; 129 : 70–81. [ PubMed ] [ Google Scholar ]

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Sham feeding corn oil increases accumbens dopamine in the rat

• Nu-Chu Liang ,
• Andras Hajnal , and
• Ralph Norgren

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• This is the final version - click for previous version

Both real and sham feeding of sucrose increase dopamine (DA) overflow in the nucleus accumbens (NAc). Fat is another constituent of foods that is inherently preferred by humans and rodents. We examined the affect of sham feeding corn oil in rats that were food and water deprived overnight. Rats were implanted with guide cannulas aimed at the NAc, as well as gastric fistulas. On alternate days, they were trained to sham lick 100% corn oil or distilled water (dH 2 O) for 20 min in the morning. Twenty-minute microdialysis samples were taken before, during, and after sham licking. DA and monoamines were analyzed by reverse-phase HPLC with coulometric detection. The results show that DA release in the NAc was significantly increased during sham licking of corn oil compared with the prior baseline (157.5 ± 18.8%, n = 12). During sham licking of dH 2 O, DA release in the NAc was not changed (93.0 ± 4.0%, n = 15). This experiment demonstrates that sham feeding of corn oil releases accumbens DA in a manner similar to ingestion of sucrose. Although both stimuli may have an olfactory component, sucrose is a gustatory, and 100% corn oil appears to be a trigeminal stimulus. Thus these data support the hypothesis that different sensory modalities produce reward using the same or closely related substrates in the forebrain.

although the exact role of mesolimbic dopamine (DA) in reward remains controversial, considerable evidence demonstrates that both natural ( 26 , 27 , 35 ) and nonnatural ( 36 ) rewards release DA in this system. DA neurons in the ventral tegmental area (VTA) project predominantly to the nucleus accumbens (NAc) ( 3 , 22 ). Intake of palatable foods, such as chocolate ( 35 ) and shortcake ( 14 , 15 ), results in an increase of extracellular DA in the NAc. Among the constituents of these foods, sucrose has been tested most because it has inherent rewarding properties. In our laboratory, we have demonstrated that both real ( 4 , 5 ) and sham ( 7 ) feeding of sucrose increase DA overflow in the NAc. During sham feeding, sucrose solution is drained out from the stomach by a gastric fistula and so the postingestive effects of sucrose are excluded. Thus the result of the sucrose sham feeding experiment indicates that the orosensory effects of sucrose alone are sufficient to increase extracellular levels of NAc DA.

Fat is another macronutrient that appears to be inherently preferred by both humans and rodents. Rats prefer 25, 50, and 100% corn oil emulsions to water. Using corn oil emulsions, Smith and colleagues demonstrated that sham intake of corn oil is an inverted-U function of concentration in both preweanling ( 1 , 29 ) and adult ( 17 , 29 ) rats. Furthermore, systemic application of the DA receptor antagonists SCH-23390 and raclopride dose dependently decrease the intake of corn oil emulsions without affecting the latency to sham feed or producing obvious motor impairment ( 33 , 34 ). These results support the hypothesis that the rewarding effects of oral corn oil are mediated by central dopaminergic activity, but do not specify the site of the effect. A more direct support for this hypothesis requires measuring mesolimbic DA levels during orosensory stimulation with corn oil. Therefore, in the present study, we used microdialysis in combination with reverse-phase HPLC to investigate DA levels in the medial shell of NAc during sham feeding of 100% corn oil emulsion. Some of these data were presented at the annual meeting of the Society for Neuroscience in Washington, D.C. in 2005 ( 12 ).

A total of 43 male Sprague-Dawley rats (275–325 g, Charles River, Wilmington, MA) were used in five iterations of this study. They were individually housed on a 12:12-h light-dark schedule with ad libitum tap water and standard laboratory diet [rodent diet (W) 8604; Harlan Teklad, Madison, WI]. For the implantation of gastric fistulas and microdialysis cannulas, the subjects were food deprived overnight, then treated with atropine sulfate (0.15 mg/kg ip), and, 20 min later, anesthetized with pentobarbital sodium (50 mg/kg ip). Each rat was fitted with a stainless steel gastric fistula and bilateral, 21-gauge stainless steel guide cannula aimed above the posterior medial NAc (A 1.0 mm, L 1.0 mm from the bregma, and V 4.0 mm from the skull; see Ref. 23 ). The design and implantation of the gastric cannulas are described elsewhere ( 28 ). The guide cannulas were fixed to the skull using stainless steel screws (Fillister head 1–72 × 1/8 in.; Small Parts) and dental acrylic. All the procedures in this experiment were approved by the Institutional Animal Care and Use Committee of the Pennsylvania State University College of Medicine and comply with the American Physiological Society's “Guiding Principles for Research Involving Animals and Human Beings.”

After 7–10 days recovery, the rats were transferred to individual hanging cages that had a longitudinal slot in the floor and were placed on an 18-h food and water deprivation regimen. One hour before the sham licking training session (7:30 AM), the stomach was flushed with lukewarm water. A flexible tube was screwed in the gastric fistula and passed through the slot to drain solutions. On alternative days, the subjects received distilled water (dH 2 O) or 100% corn oil emulsion [100 ml corn oil blended with 0.75 ml Tween-80 (Sigma-Aldrich, St. Louis, MO)] for 20 min (9:00–9:20 AM). They were then allowed 2–3 h (12:00–3:00 PM) real intake of normal powder chow and dH 2 O. Each rat had 6 to 10 training trials with dH 2 O and 100% corn oil emulsion. They were then transferred to one of the six microdialysis chambers and received the same training regimen for 4–7 more days. On the last day of training in the chamber, the concentric microdialysis probes with 2-mm active membrane were implanted bilaterally in the medial shell of the NAc through the guide cannulas. The active membrane of the probes consisted of cellulose tubing (20-kDa cutoff, 0.2-mm OD × 2-mm length; Spectrum, Ranch Dominguez, CA; see Ref. 5 for details). The probes were perfused with artificial cerebrospinal fluid [aCSF (in mM): 145 NaCl, 2.7 KCl, 1.2 CaCl 2 , 1.0 MgCl 2 , and 2.0 Na 2 HPO 4 in HPLC-grade water (Fisher Scientific, Pittsburgh, PA) adjusted to pH 7.4] through a microdialysis swivel (model 375/D/22QE; Instech Laboratories, Plymouth Meeting, PA) at a rate of 1.0 μl/min using microsyringe pumps (model A99; Razel Scientific Instruments, Stamford, CT). On the test days, 20-min dialysis samples were taken before, during, and after sham licking. Because of the limits of the microdialysis probes, each subject had at most three test days. At the end of the experiment, the rats were killed with an overdose of pentobarbital sodium (150 mg/kg ip), then perfused transcardially with 0.9% saline solution followed by 10% formalin. The brains were frozen, serially sectioned at 50 μm, and stained with cresyl violet to verify placement of the microdialysis probes. DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) from microdialytic samples (20 μl) were analyzed by reverse-phase HPLC with coulometric detection (analytic cell: model 5014B, electrode 1: −175 mV; electrode 2: +175 mV; guard cell: model 5020: +300 mV; CoulArray system; ESA, Chelmsford, MA). The chromatograms were recorded and analyzed off-line by the ESA data system on a PC.

After exclusions for poor placement ( n = 4), malfunctioning probes ( n = 20), and inadequate fistula drainage ( n = 7), data from 12 rats with a total of 15 probes were included in the results. The probes excluded for location were in the rostral shell of NAc (β + 2.50 mm, n = 2), lateral to the NAc core (β + 1.20 mm, n = 1), and dorsal to the core (β + 1.70 mm, n = 1). During sham licking of dH 2 O and corn oil, DA overflow at these sites was unchanged or increased somewhat (data not shown). Because the subject numbers were small, the results were not analyzed further. The successful probes were located between 1.00 and 1.40 mm anterior to β in the medial shell of NAc ( Fig. 1 ). Sham intake of both dH 2 O and corn oil emulsion increased during training. There was a significant trial effect and a stimulus times trial interaction [ F (5,110) = 13.64, P < 0.001; F (5,110) = 7.29, P < 0.001]. The dH 2 O intake reached peak on the third training trial (20.08 ± 3.18 ml/20 min) and then decreased in the following trials. In contrast, corn oil emulsion intake increased continuously with mean intake reaching 22.33 ± 1.89 ml/20 min by the sixth trial. On the first trial in the microdialysis chamber, both dH 2 O and corn oil emulsion intakes decreased significantly compared with the prior training trial (dH 2 O: 16.92 ± 3.41 ml vs. 7 ± 1.11 ml, t -test, P < 0.02; corn oil emulsion: 22.33 ± 1.89 ml vs. 12.47 ± 2.43 ml, t -test, P < 0.005). Although the dH 2 O intake was smaller than the corn oil emulsion intake on the first trial in the chamber, the difference was not quite significant ( t -test, P = 0.053). During the dialysis tests, however, sham intakes of corn oil and dH 2 O were statistically identical (corn oil vs. dH 2 O: 13.97 ± 2.08 ml vs. 11.73 ± 1.39 ml; t -test, P = 0.37).

Fig. 1. Localizations of the microdialysis probes. Microdialysis sites in the nucleus accumbens (NAc) are drawn in the sections of the rat brain's left hemisphere. The active membranes of the probes (0.2 mm × 2 mm), depicted with gray bars, were located between 1.40 and 1.00 mm rostral to the bregma in the medial shell of the NAc based on the atlas of Paxinos and Watson ( 23 ).

For neurochemistry data analysis, the raw results from the chromatograms were converted to a percentage of the mean value of the three baseline samples taken before the sham licking sessions. These normalized data for DA, DOPAC, and HVA were analyzed by separate two-way ANOVAs (stimulus × sample/time), followed by post hoc Newman-Kuels tests when justified.

The results showed that sham licking corn oil stimulated accumbens DA flux, while licking dH 2 O did not. The percent increase in DA overflow, however, was not correlated with the volume of oil consumed ( r = −0.17). Two-way ANOVAs (stimulus × sample) revealed that there were stimulus [ F ( 1 , 25 ) = 10.17, P < 0.004], sample [ F (8,200) = 2.85, P < 0.006], and stimulus times sample [ F (8,200) = 2.52, P < 0.02] effects. After 20-min of sham corn oil intake, DA levels were significantly higher than baseline and higher than DA levels after dH 2 O intake (corn oil vs. dH 2 O: 157.5 ± 18.8% vs. 93.0 ± 4.0%, P < 0.001; Fig. 2 ). DA levels continued to be significantly higher for 20 min after oil intake ceased (corn oil vs. dH 2 O sample 5: 141.9 ± 21.7% vs. 96.0 ± 5.4%, P < 0.05). Two-way ANOVAs demonstrated that DOPAC and HVA levels also were higher than baseline after sham licking of corn oil. There were stimulus [DOPAC: F ( 1 , 25 ) = 8.98, P < 0.007; HVA: F ( 1 , 25 ) = 8.53, P < 0.008] and sample [DOPAC: F (8,200) = 2.67, P < 0.009; HVA: F (8,200) = 5.89, P < 0.001] effects in both cases, but no interaction between stimulus and sample [DOPAC: F (8,200) = 1.17, P = 0.32; HVA: F (8,200) = 1.08, P = 0.38].

Fig. 2. Extracellular levels of dopamine (DA; top ), 3,4-dihydroxyphenylacetic acid (DOPAC; middle ), and homovanillic acid (HVA, bottom ) in the NAc before, during, and after sham licking of distilled water (dH 2 O) and corn oil. Licking corn oil stimulated DA flux in the NAc. This effect lasted at least 20 min after the end of the corn oil bout. Sham licking of corn oil also increased DOPAC and HVA overall, but none of the post hoc comparisons was significant. *Significant post hoc tests for differences from baseline samples and from sham water intake ( P < 0.05; #significant difference in sample 5 when the rats ingested water in sample 4 compared with corn oil in the same period, P < 0.05).

This experiment has demonstrated that sham licking of 100% corn oil increases DA and its metabolites in the NAc. The design controlled for licking behavior because the rats received dH 2 O and corn oil on alternative days and ingested similar amounts. The DA activation during licking corn oil, therefore, was unlikely to result from differential oromotor activity. Because the rats were sham feeding to minimize gastrointestinal feedback, the nutritive component in the corn oil should not contribute to the increased DA overflow in the NAc. The results support the hypothesis that the oral sensory properties of corn oil drive accumbens dopaminergic activity.

Sham licking of a gustatory stimulus, sucrose, stimulates accumbens DA overflow as a function of concentration ( 7 ). The effects of 0.3 M sucrose and 100% corn oil on DA overflow in the NAc did not differ (156.05 ± 11.78% and 157.5 ± 18.8%, respectively, Ref. 6 ). Behaviorally, rats prefer 100% corn oil to 10% sucrose (≅0.24 M, Ref. 33 ). Theoretically, if both the behavioral and neurochemical indexes reflected the same underlying reward mechanisms, the measures would match. In fact, it is unlikely that either NAc DA overflow or preference reflect reward similarly because the construct cannot be defined precisely, especially in neural terms ( 20 ). Nevertheless, the results from the present study and the sucrose studies ( 4 , 5 , 7 ) support the hypothesis that the reward produced via different sensory modalities are mediated by the same or closely related substrates in the forebrain.

Anatomical studies have demonstrated direct and indirect connections between the forebrain gustatory relays and the mesolimbic DA areas, including the NAc and the ventral tegmental area (VTA) ( 3 , 13 , 19 , 22 ). Those forebrain and hindbrain connections provide possible substrates for DA activation in the accumbens and may also be involved in the hedonic effects of taste ( 19 ). Hajnal and Norgren ( 6 ) demonstrated that lesions in the secondary taste relay and the parabrachial nuclei (PBN), but not in the gustatory thalamus, blunt the DA overflow during sucrose licking. This result implies that the hedonic information of the sucrose taste reaches the NAc via the PBN and the limbic forebrain circuits.

DA flux occurs in other areas during tasks involving ingestive behavior but not always directly in register with oral stimulation. DA release in the striatum occurred during operant learning for food reward but peaked around the lever-press task rather than reward consumption ( 18 ). Extracellular DA in the medial prefrontal cortex (MPC) was increased in response to presentation of a neutral stimulus, a plastic box, which had been associated with a palatable food. The same neutral stimulus, however, did not modify extracellular DA in the medial NAc ( 2 ). In the MPC, DA appears to be essential for attention and working memory-related learning. In an eight-arm radial maze task, MPC DA efflux increased in the absence of food reward ( 24 ). These and other studies indicate that increased accumbens DA release during sham intake is not just a general response to food, but one facet of the complex, highly orchestrated neural activity that accompanies rewarded behavior.

The sensory mechanisms by which corn oil is detected are not known. The best candidates are olfaction, taste, and the oral somatosensory system. Rats made anosmic by nasal instillation of ZnSO 4 still discriminated fats, such as margarine and lard mixed with food ( 17 ). After olfactory bulbectomy, rats still preferentially ingest 0.5 and 1% corn oil ( 25 ). Anosmic mice can show conditioned place preference to 100% corn oil ( 30 ). Although preference for 1 and 3% corn oil is decreased in anosmic mice, their preference for the higher concentrations of 5 and 10% is not affected ( 30 ). These results suggest that an olfactory mechanism is not necessary for processing oral oil stimulation. Recent studies suggest that fatty acids are important for the gustatory recognition of fats. Rats can detect free fatty acids and acquire a conditioned aversion to them ( 16 ). In addition, a fatty acid transporter, CD36, is located on the taste cells ( 11 ). Although provocative, this evidence does not prove that taste is responsible for detecting oils or dietary fats. The main reason is that the dietary fats consist mainly of triglycerides, and triglycerides need to be digested first to become fatty acids. Although lingual lipase can hydrolyze triglycerides to free fatty acids ( 10 ), how effective this mechanism is for the gustatory recognition of dietary lipids remains unknown. In rats, addition of a potent lipase inhibitor diminished preference for a triacylglyceride solution. This effect, however, did not occur when the lipase inhibitor was added to a corn oil emulsion ( 10 ). Furthermore, rats with lesions in the secondary gustatory nucleus, the PBN, fail to learn aversions to taste stimuli but do learn to avoid 100% corn oil ( 21 ). Thus it is possible that the olfactory or the gustatory systems are not essential for processing the sensory and hedonic aspects of corn oil. This would leave the trigeminal system as the best candidate.

The intraoral trigeminal system, however, does not project directly to the limbic or DA systems. The mandibular branch of the trigeminal nerve innervates the anterior tongue, lower teeth, and much of the intraoral mucosa ( 9 , 31 , 32 ). The maxillary branch distributes to the hard and soft palate. The axons of these nerves project to the mediodorsal principal and spinal trigeminal sensory nuclei as well as the nucleus of the solitary tract (NST) ( 9 , 31 , 32 ). In contrast to the anterior oral cavity, somatosensory information from the posterior oral cavity reaches the brain through the glossopharyngeal nerve. Tactile information detected by the glossopharyngeal nerve is also carried to the NST ( 8 ). There is little if any evidence of direct projections to the mesolimbic areas from the trigeminal system. The NST and the spinal trigeminal nuclei project strongly to the parabrachial nuclei. Thus it is possible that intraoral somatosensory activity reaches the ventral forebrain via the PBN ( 13 , 32 , 37 ). Electrophysiological confirmation of this possibility is lacking and, as mentioned above, behavioral evidence suggests that, at minimum, additional routes exist ( 21 ). The current experiment demonstrates that sham licking of corn oil releases accumbens DA much the same way as does sucrose ingestion. The central pathways that are critical for this effect can be determined using experiments parallel to those used to narrow the sucrose hedonic response down to the parabrachial ventral pathway ( 6 ).

This research was supported by National Institutes of Health Grants DC-00240, DC-05435, and DK-065709, and a Pennsylvania Tobacco Settlement Grant.

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The authors thank N. Acharya for assistance with the microdialysis and Dr. W. M. Margas for HPLC.

• 1 Ackerman SH , Albert M, Shindledecker RD, Gayle C, and Smith GP. Intake of different concentrations of sucrose and corn oil in preweanling rats. Am J Physiol Regul Integr Comp Physiol 262 : R624–R627, 1992 . Link | Web of Science  |  Google Scholar
• 2 Bassareo V and Di Chiara G. Differential influence of associative and nonassociative learning mechanisms on the responsiveness of prefrontal and accumbal dopamine transmission to food stimuli in rats fed ad libitum. J Neurosci 17 : 851–861, 1997 . Crossref | PubMed | Web of Science  |  Google Scholar
• 3 Geisler S and Zahm DS. Afferents of the ventral tegmental area in the rat-anatomical substratum for integrative functions. J Comp Neurol 490 : 270–294, 2005 . Crossref | PubMed | Web of Science  |  Google Scholar
• 4 Hajnal A and Norgren R. Accumbens dopamine mechanisms in sucrose intake. Brain Res 904 : 76–84, 2001 . Crossref | PubMed | Web of Science  |  Google Scholar
• 5 Hajnal A and Norgren R. Repeated access to sucrose augments dopamine turnover in the nucleus accumbens. Neuroreport 13 : 2213–2216, 2002 . Crossref | PubMed | Web of Science  |  Google Scholar
• 6 Hajnal A and Norgren R. Taste pathways that mediate accumbens dopamine release by sapid sucrose. Physiol Behav 84 : 363–369, 2005 . Crossref | PubMed | Web of Science  |  Google Scholar
• 7 Hajnal A , Smith GP, and Norgren R. Oral sucrose stimulation increases accumbens dopamine in the rat. Am J Physiol Regul Integr Comp Physiol 286 : R31–R37, 2004 . Link | Web of Science  |  Google Scholar
• 8 Hamilton RB and Norgren R. Central projections of gustatory nerves in the rat. J Comp Neurol 222 : 560–577, 1984 . Crossref | PubMed | Web of Science  |  Google Scholar
• 9 Jacquin MF , Semba K, Egger MD, and Rhoades RW. Organization of HRP-labeled trigeminal mandibular primary afferent neurons in the rat. J Comp Neurol 215 : 397–420, 1983 . Crossref | PubMed | Web of Science  |  Google Scholar
• 10 Kawai T and Fushiki T. Importance of lipolysis in oral cavity for orosensory detection of fat. Am J Physiol Regul Integr Comp Physiol 285 : R447–R454, 2003 . Link | Web of Science  |  Google Scholar
• 11 Laugerette F , Passilly-Degrace P, Patris B, Niot I, Febbraio M, Montmayeur JP, and Besnard P. CD36 involvement in orosensory detection of dietary lipids, spontaneous fat preference, and digestive secretions. J Clin Invest 115 : 3177–3184, 2005 . Crossref | PubMed | Web of Science  |  Google Scholar
• 12 Liang NC , Hajnal A, and Norgren R. Sham feeding corn oil increases accumbens dopamine in the rat (Abstract). Soc Neuorsci Abstract Viewer : 532.7, 2005 . Google Scholar
• 13 Lundy RFJ and Norgren R. Gustatory system. In: The Rat Nervous System , edited by Paxinos G. San Diego, CA: Academic, 2004 , p. 891–921. Google Scholar
• 14 Martel P and Fantino M. Influence of the amount of food ingested on mesolimbic dopaminergic system activity: a microdialysis study. Pharmacol Biochem Behav 55 : 297–302, 1996 . Crossref | PubMed | Web of Science  |  Google Scholar
• 15 Martel P and Fantino M. Mesolimbic dopaminergic system activity as a function of food reward: a microdialysis study. Pharmacol Biochem Behav 53 : 221–226, 1996 . Crossref | PubMed | Web of Science  |  Google Scholar
• 16 McCormack DN , Clyburn VL, and Pittman DW. Detection of free fatty acids following a conditioned taste aversion in rats. Physiol Behav 87 : 582–594, 2006 . Crossref | PubMed | Web of Science  |  Google Scholar
• 17 Mindell S , Smith GP, and Greenberg D. Corn oil and mineral oil stimulate sham feeding in rats. Physiol Behav 48 : 283–287, 1990 . Crossref | PubMed | Web of Science  |  Google Scholar
• 18 Nakazato T . Striatal dopamine release in the rat during a cued lever-press task for food reward and the development of changes over time measured using high-speed voltammetry. Exp Brain Res 166 : 137–146, 2005 . Crossref | PubMed | Web of Science  |  Google Scholar
• 19 Norgren R , Grigson P, Hajnal A, and Lundy RFJ. Motivational modulation of taste. In: Limbic and Association Cortical Systems: Basic, Clinical and Computational Aspects , edited by Ono T, Matsumoto G, Llinas R, Berthoz A, Norgren R, Nishijo H, and Tamura R. Amsterdam: Elsevier Science, 2003 , p. 319–334. Google Scholar
• 20 Norgren R , Hajnal A, and Mungarndee SS. Gustatory reward and the nucleus accumbens. Physiol Behav. In press. Google Scholar
• 21 Norgren R , Li B, and Wheeler D. Medial and lateral parabrachial nucleus lesions affect learned aversions and sodium appetite differently (Abstract). Appetite 37 : 155, 2001 . Google Scholar
• 22 Oades RD and Halliday GM. Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity. Brain Res 434 : 117–165, 1987 . Crossref | PubMed | Web of Science  |  Google Scholar
• 23 Paxinos G and Watson C. The Rat Brain in Stereotaxic Coordinates. San Diego, CA: Academic, 2005 . Google Scholar
• 24 Phillips AG , Ahn S, and Floresco SB. Magnitude of dopamine release in medial prefrontal cortex predicts accuracy of memory on a delayed response task. J Neurosci 24 : 547–553, 2004 . Crossref | PubMed | Web of Science  |  Google Scholar
• 25 Ramirez I . Role of olfaction in starch and oil preference. Am J Physiol Regul Integr Comp Physiol 265 : R1404–R1409, 1993 . Link | Web of Science  |  Google Scholar
• 26 Smith GP . Accumbens dopamine is a physiological correlate of the rewarding and motivating effects of food. In: Handbook of Behavioral Neurobiology (2nd ed.), edited by Stricker EM and Woods SC. New York: Kluwer Academic/Plenum, 2004 , p. 15–42. Google Scholar
• 27 Smith GP . Dopamine and food reward. In: Progress in Psychobiology and Physiological Psychology , edited by Morrison A and Fluharty S. New York: Academic, 1995 , p. 83–144. Google Scholar
• 28 Smith GP . Sham feeding in rats with chronic, reversible gastric fistulas. In: Current Protocols in Neuroscience. New York: Wiley, 1999 , p. 1–6. Google Scholar
• 29 Smith GP and Greenberg D. Orosensory stimulation of feeding by oils in preweanling and adult rats. Brain Res Bull 27 : 379–382, 1991 . Crossref | PubMed | Web of Science  |  Google Scholar
• 30 Takeda M , Sawano S, Imaizumi M, and Fushiki T. Preference for corn oil in olfactory-blocked mice in the conditioned place preference test and the two-bottle choice test. Life Sci 69 : 847–854, 2001 . Crossref | PubMed | Web of Science  |  Google Scholar
• 31 Takemura M , Sugimoto T, and Sakai A. Topographic organization of central terminal region of different sensory branches of the rat mandibular nerve. Exp Neurol 96 : 540–557, 1987 . Crossref | PubMed | Web of Science  |  Google Scholar
• 32 Waite P . Trigeminal sensory system. In: The Rat Nervous System (3rd ed.), edited by Paxinos G. San Diego, CA: Academic, 2004 , p. 817–851. Google Scholar
• 33 Weatherford SC , Greenberg D, Gibbs J, and Smith GP. The potency of D-1 and D-2 receptor antagonists is inversely related to the reward value of sham-fed corn oil and sucrose in rats. Pharmacol Biochem Behav 37 : 317–323, 1990 . Crossref | PubMed | Web of Science  |  Google Scholar
• 34 Weatherford SC , Smith GP, and Melville LD. D-1 and D-2 receptor antagonists decrease corn oil sham feeding in rats. Physiol Behav 44 : 569–572, 1988 . Crossref | PubMed | Web of Science  |  Google Scholar
• 35 Wilson C , Nomikos GG, Collu M, and Fibiger HC. Dopaminergic correlates of motivated behavior: importance of drive. J Neurosci 15 : 5169–5178, 1995 . Crossref | PubMed | Web of Science  |  Google Scholar
• 36 Wise RA and Rompre PP. Brain dopamine and reward. Annu Rev Psychol 40 : 191–225, 1989 . Crossref | PubMed | Web of Science  |  Google Scholar
• 37 Yoshida A , Chen K, Moritani M, Yabuta NH, Nagase Y, Takemura M, and Shigenaga Y. Organization of the descending projections from the parabrachial nucleus to the trigeminal sensory nuclear complex and spinal dorsal horn in the rat. J Comp Neurol 383 : 94–111, 1997 . Crossref | PubMed | Web of Science  |  Google Scholar

AUTHOR NOTES

• Address for reprint requests and other correspondence: Nu-Chu Liang, Dept. of Neural and Behavioral Sciences, College of Medicine, The Pennsylvania State Univ., 500 Univ. Drive, Hershey, PA 17033 (e-mail: [email protected] )
• Licking microstructure in response to novel rewards, reward devaluation and dopamine antagonists: Possible role of D1 and D2 medium spiny neurons in the nucleus accumbens 1 Oct 2024 | Neuroscience & Biobehavioral Reviews, Vol. 165
• Ventral Tegmental Area Amylin Receptor Activation Differentially Modulates Mesolimbic Dopamine Signaling in Response to Fat versus Sugar 28 May 2024 | eneuro, Vol. 11, No. 6
• The Obese Brain 31 July 2024
• C57bl/6 Mice Show Equivalent Taste Preferences toward Ruminant and Industrial Trans Fatty Acids 24 January 2023 | Nutrients, Vol. 15, No. 3
• Fatty acids composition and in vivo biochemical effects of Aleurites moluccana seed (Candlenut) in obese wistar rats 8 June 2022 | Diabetology & Metabolic Syndrome, Vol. 14, No. 1
• Prefrontal Cortical Control of Activity in Nucleus Accumbens Core Is Weakened by High-Fat Diet and Prevented by Co-Treatment with N-Acetylcysteine: Implications for the Development of Obesity 3 September 2022 | International Journal of Molecular Sciences, Vol. 23, No. 17
• Role of the striatal dopamine, GABA and opioid systems in mediating feeding and fat intake 1 Aug 2022 | Neuroscience & Biobehavioral Reviews, Vol. 139
• Perinatal exposure to a high-fat diet alters proopiomelanocortin, neuropeptide Y and dopaminergic receptors gene expression and the food preference in offspring adult rats 1 January 2022 | Brazilian Journal of Biology, Vol. 82
• GABAB receptor signaling in the caudate putamen is involved in binge-like consumption during a high fat diet in mice 29 September 2021 | Scientific Reports, Vol. 11, No. 1
• Patterned Feeding of a Hyper-Palatable Food (Oreo Cookies) Reduces Alcohol Drinking in Rats 20 October 2021 | Frontiers in Behavioral Neuroscience, Vol. 15
• Ordinaries 10 July 2021 | Journal of Bioeconomics, Vol. 23, No. 2
• Midbrain and Lateral Nucleus Accumbens Dopamine Depletion Affects Free-choice High-fat high-sugar Diet Preference in Male Rats 1 Jul 2021 | Neuroscience, Vol. 467
• Obesity and dietary fat influence dopamine neurotransmission: exploring the convergence of metabolic state, physiological stress, and inflammation on dopaminergic control of food intake 28 June 2021 | Nutrition Research Reviews, Vol. 136
• Whole‐brain efferent and afferent connectivity of mouse ventral tegmental area melanocortin‐3 receptor neurons 10 September 2020 | Journal of Comparative Neurology, Vol. 529, No. 6
• Impact of High Fat Diet and Ethanol Consumption on Neurocircuitry Regulating Emotional Processing and Metabolic Function 26 January 2021 | Frontiers in Behavioral Neuroscience, Vol. 14
• Highly Palatable Foods Are Addictive 1 October 2021
• Layers of signals that regulate appetite 1 Oct 2020 | Current Opinion in Neurobiology, Vol. 64
• A Role for GLP-1 in Treating Hyperphagia and Obesity 9 June 2020 | Endocrinology, Vol. 161, No. 8
• Diet-Induced Obesity Alters the Circadian Expression of Clock Genes in Mouse Gustatory Papillae 30 June 2020 | Frontiers in Physiology, Vol. 11
• Dopamine and Addiction 4 Jan 2020 | Annual Review of Psychology, Vol. 71, No. 1
• Insulin resistance and obesity 1 Jan 2020
• Fat Addiction: Psychological and Physiological Trajectory 15 November 2019 | Nutrients, Vol. 11, No. 11
• GABAB Receptor Signaling in the Mesolimbic System Suppresses Binge-like Consumption of a High-Fat Diet 1 Oct 2019 | iScience, Vol. 20
• A chronic LPS-induced low-grade inflammation fails to reproduce in lean mice the impairment of preference for oily solution found in diet-induced obese mice 1 Apr 2019 | Biochimie, Vol. 159
• Neural vulnerability factors for obesity 1 Mar 2019 | Clinical Psychology Review, Vol. 68
• Lindsey A. Schier and 
• Alan C. Spector
• Food additives, food and the concept of ‘food addiction’: Is stimulation of the brain reward circuit by food sufficient to trigger addiction? 1 Dec 2018 | Pathophysiology, Vol. 25, No. 4
• Sugar Addiction: From Evolution to Revolution 7 November 2018 | Frontiers in Psychiatry, Vol. 9
• A high-refined carbohydrate diet facilitates compulsive-like behavior in mice through the nitric oxide pathway 1 Nov 2018 | Nitric Oxide, Vol. 80
• Voluntary Corn Oil Ingestion Increases Energy Expenditure and Interscapular UCP1 Expression Through the Sympathetic Nerve in C57BL/6 Mice 7 October 2018 | Molecular Nutrition & Food Research, Vol. 62, No. 22
• Maternal Overnutrition Programs Central Inflammation and Addiction-Like Behavior in Offspring 20 Jun 2018 | BioMed Research International, Vol. 2018
• Pharmacological Interventions for Obesity: Current and Future Targets 7 May 2018 | Current Addiction Reports, Vol. 5, No. 2
• Conditioned flavor preferences in animals: Merging pharmacology, brain sites and genetic variance 1 Mar 2018 | Appetite, Vol. 122
• Oleoylethanolamide: The role of a bioactive lipid amide in modulating eating behaviour 10 November 2017 | Obesity Reviews, Vol. 19, No. 2
• Evaluation of Palatability of Sake paired with Dishes-A New Endeavor 1 Jan 2018 | JOURNAL OF THE BREWING SOCIETY OF JAPAN, Vol. 113, No. 5
• Food Addiction and Binge Eating: Lessons Learned from Animal Models 11 January 2018 | Nutrients, Vol. 10, No. 1
• Lipids in Eating and Appetite Regulation – A Neuro‐Cognitive Perspective 5 December 2017 | European Journal of Lipid Science and Technology, Vol. 119, No. 12
• Amylin receptor activation in the ventral tegmental area reduces motivated ingestive behavior 1 Sep 2017 | Neuropharmacology, Vol. 123
• Effects of bingeing on fat during adolescence on the reinforcing effects of cocaine in adult male mice 1 Feb 2017 | Neuropharmacology, Vol. 113
• The Relationship Between Drugs of Abuse and Palatable Foods: Pre-clinical Evidence Towards a Better Understanding of Addiction-Like Behaviors 30 June 2017
• Endocannabinoid Signaling in Reward and Addiction: From Homeostasis to Pathology 31 May 2017
• Physiologic and Neural Controls of Eating 1 Dec 2016 | Gastroenterology Clinics of North America, Vol. 45, No. 4
• Food Reward and Appetite Regulation in Children 13 October 2016
• A sad mood increases attention to unhealthy food images in women with food addiction 1 May 2016 | Appetite, Vol. 100
• Association of Oral Fat Sensitivity with Body Mass Index, Taste Preference, and Eating Habits in Healthy Japanese Young Adults 1 Jan 2016 | The Tohoku Journal of Experimental Medicine, Vol. 238, No. 2
• Gustatory Salivation Is Associated with Body Mass Index, Daytime Sleepiness, and Snoring in Healthy Young Adults 1 Jan 2016 | The Tohoku Journal of Experimental Medicine, Vol. 240, No. 2
• The role of dopamine in the pursuit of nutritional value 1 Dec 2015 | Physiology & Behavior, Vol. 152
• Maternal nicotine exposure during lactation alters food preference, anxiety-like behavior and the brain dopaminergic reward system in the adult rat offspring 1 Oct 2015 | Physiology & Behavior, Vol. 149
• Alterations in sucrose sham-feeding intake as a function of diet-exposure in rats maintained on calorically dense diets 1 Sep 2015 | Appetite, Vol. 92
• Exposure to nicotine increases dopamine receptor content in the mesocorticolimbic pathway of rat dams and offspring during lactation 1 Sep 2015 | Pharmacology Biochemistry and Behavior, Vol. 136
• Concurrent maternal and pup postnatal tobacco smoke exposure in Wistar rats changes food preference and dopaminergic reward system parameters in the adult male offspring 1 Aug 2015 | Neuroscience, Vol. 301
• Increased palatable food intake and response to food cues in intrauterine growth-restricted rats are related to tyrosine hydroxylase content in the orbitofrontal cortex and nucleus accumbens 1 Jul 2015 | Behavioural Brain Research, Vol. 287
• Obesity and the Neurocognitive Basis of Food Reward and the Control of Intake 1 Jul 2015 | Advances in Nutrition, Vol. 6, No. 4
• Corn oil, but not cocaine, is a more effective reinforcer in obese than in lean Zucker rats 1 May 2015 | Physiology & Behavior, Vol. 143
• Distinctive striatal dopamine signaling after dieting and gastric bypass 1 May 2015 | Trends in Endocrinology & Metabolism, Vol. 26, No. 5
• Neural Responses to Macronutrients: Hedonic and Homeostatic Mechanisms 1 May 2015 | Gastroenterology, Vol. 148, No. 6
• Neurochemical Components of Undereating and Overeating 31 July 2015
• Intestinal lipid–derived signals that sense dietary fat 2 February 2015 | Journal of Clinical Investigation, Vol. 125, No. 3
• Comparison of sucrose and ethanol-induced c-Fos-like immunoreactivity in the parabrachial nuclei and accumbens nucleus 1 Mar 2015 | Journal of Biomedical Research, Vol. 16, No. 1
• A high multivitamin diet fed to Wistar rat dams during pregnancy increases maternal weight gain later in life and alters homeostatic, hedonic and peripheral regulatory systems of energy balance 1 Feb 2015 | Behavioural Brain Research, Vol. 278
• c-Fos induction in mesotelencephalic dopamine pathway projection targets and dorsal striatum following oral intake of sugars and fats in rats 1 Feb 2015 | Brain Research Bulletin, Vol. 111
• The early origins of food preferences: targeting the critical windows of development 22 January 2015 | The FASEB Journal, Vol. 29, No. 2
• The endocannabinoid system 1 Jan 2015
• The opioid system contributes to the acquisition of reinforcement for dietary fat but is not required for its maintenance 1 Jan 2015 | Physiology & Behavior, Vol. 138
• “Eating addiction”, rather than “food addiction”, better captures addictive-like eating behavior 1 Nov 2014 | Neuroscience & Biobehavioral Reviews, Vol. 47
• Overlap of food addiction and substance use disorders definitions: Analysis of animal and human studies 1 Oct 2014 | Neuropharmacology, Vol. 85
• Is fat taste ready for primetime? 1 Sep 2014 | Physiology & Behavior, Vol. 136
• Hormonal and neural mechanisms of food reward, eating behaviour and obesity 24 June 2014 | Nature Reviews Endocrinology, Vol. 10, No. 9
• Neuroadaptations in the Striatal Proteome of the Rat Following Prolonged Excessive Sucrose Intake 15 March 2014 | Neurochemical Research, Vol. 39, No. 5
• Why fat is so preferable: from oral fat detection to inducing reward in the brain 4 March 2014 | Bioscience, Biotechnology, and Biochemistry, Vol. 78, No. 3
• Behavioral palatability of dietary fatty acids correlates with the intracellular calcium ion levels induced by the fatty acids in GPR120-expressing cells 1 Jan 2014 | Biomedical Research, Vol. 35, No. 6
• Gut–brain nutrient signaling. Appetition vs. satiation 1 Dec 2013 | Appetite, Vol. 71
• Increased Levels of Extracellular Dopamine in the Nucleus Accumbens and Amygdala of Rats by Ingesting a Low Concentration of a Long-Chain Fatty Acid 22 May 2014 | Bioscience, Biotechnology, and Biochemistry, Vol. 77, No. 11
• Effects of chronic mild stress on rats selectively bred for behavior related to bipolar disorder and depression 1 Jul 2013 | Physiology & Behavior, Vol. 119
• A fatty gut feeling 1 Jul 2013 | Trends in Endocrinology & Metabolism, Vol. 24, No. 7
• Endocannabinoid signaling in the gut mediates preference for dietary unsaturated fats 5 March 2013 | The FASEB Journal, Vol. 27, No. 6
• Pharmacological modulation of the endocannabinoid signalling alters binge‐type eating behaviour in female rats 27 May 2013 | British Journal of Pharmacology, Vol. 169, No. 4
• Flavor-Independent Maintenance, Extinction, and Reinstatement of Fat Self-Administration in Mice 1 May 2013 | Biological Psychiatry, Vol. 73, No. 9
• Electroretinographic detection of human brain dopamine response to oral food stimulation 20 June 2013 | Obesity, Vol. 21, No. 5
• Intermittent access to sweet high-fat liquid induces increased palatability and motivation to consume in a rat model of binge consumption 1 Apr 2013 | Physiology & Behavior, Vol. 114-115
• Molecular Aspects of Obesity and Insulin Resistance in Metabolic Syndrome and Neurological Disorders 23 April 2013
• The neurobiology of food intake in an obesogenic environment 17 July 2012 | Proceedings of the Nutrition Society, Vol. 71, No. 4
• Food and Fluid Intake 26 September 2012
• Cheng-Shu Li ,
• Sooyoung Chung ,
• Da-Peng Lu , and
• Young K. Cho
• Joost Overduin ,
• Dianne P. Figlewicz ,
• Jennifer Bennett-Jay ,
• Sepideh Kittleson , and
• David E. Cummings
• Dysregulation of brain reward systems in eating disorders: Neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia nervosa 1 Jul 2012 | Neuropharmacology, Vol. 63, No. 1
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• Cognitive and neuronal systems underlying obesity 1 Jun 2012 | Physiology & Behavior, Vol. 106, No. 3
• The gut–brain dopamine axis: A regulatory system for caloric intake 1 Jun 2012 | Physiology & Behavior, Vol. 106, No. 3
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• Dietary Factors Affect Food Reward and Motivation to Eat 1 Jan 2012 | Obesity Facts, Vol. 5, No. 2
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• Hedonic and incentive signals for body weight control 22 February 2011 | Reviews in Endocrine and Metabolic Disorders, Vol. 12, No. 3
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• Obesogenic diets may differentially alter dopamine control of sucrose and fructose intake in rats 1 Jul 2011 | Physiology & Behavior, Vol. 104, No. 1
• Similarities in hypothalamic and mesocorticolimbic circuits regulating the overconsumption of food and alcohol 1 Jul 2011 | Physiology & Behavior, Vol. 104, No. 1
• Hans-Rudolf Berthoud ,
• Natalie R. Lenard , and
• Andrew C. Shin
• Reciprocal responsiveness of nucleus accumbens shell and core dopamine to food- and drug-conditioned stimuli 27 November 2010 | Psychopharmacology, Vol. 214, No. 3
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• The study of food addiction using animal models of binge eating 1 Dec 2010 | Appetite, Vol. 55, No. 3
• Dopamine and binge eating behaviors 1 Nov 2010 | Pharmacology Biochemistry and Behavior, Vol. 97, No. 1
• Neuropharmacology of learned flavor preferences 1 Nov 2010 | Pharmacology Biochemistry and Behavior, Vol. 97, No. 1
• Reduced accumbens dopamine in Sprague–Dawley rats prone to overeating a fat-rich diet 1 Oct 2010 | Physiology & Behavior, Vol. 101, No. 3
• Central dopaminergic circuitry controlling food intake and reward: implications for the regulation of obesity 4 August 2010 | WIREs Systems Biology and Medicine, Vol. 2, No. 5
• Intragastric infusion of glucose enhances the rewarding effect of sorbitol fatty acid ester ingestion as measured by conditioned place preference in mice 1 Mar 2010 | Physiology & Behavior, Vol. 99, No. 4
• Reward-related Neuroadaptations Induced by Food Restriction 1 Jan 2010
• Altered orosensory sensitivity to oils in CCK-1 receptor deficient rats 1 Jan 2010 | Physiology & Behavior, Vol. 99, No. 1
• Fat and Obesity from a Neurophysiological Perspective 1 Jan 2010 | Oleoscience, Vol. 10, No. 10
• Blood oxygenation level-dependent response to intragastric load of corn oil emulsion in conscious rats 9 Dec 2009 | NeuroReport, Vol. 20, No. 18
• Preference for High-Fat Food in Animals 8 September 2010
• Baclofen, raclopride, and naltrexone differentially affect intake of fat and sucrose under limited access conditions 1 Sep 2009 | Behavioural Pharmacology, Vol. 20, No. 5-6
• High-fat diet decreases tyrosine hydroxylase mRNA expression irrespective of obesity susceptibility in mice 1 May 2009 | Brain Research, Vol. 1268
• Preference for dietary fat induced by release of beta-endorphin in rats 1 May 2009 | Life Sciences, Vol. 84, No. 21-22
• Imaging of Brain Dopamine Pathways 1 Mar 2009 | Journal of Addiction Medicine, Vol. 3, No. 1
• Sugar and Fat Bingeing Have Notable Differences in Addictive-like Behavior 1 Mar 2009 | The Journal of Nutrition, Vol. 139, No. 3
• ΔFosB-Mediated Alterations in Dopamine Signaling Are Normalized by a Palatable High-Fat Diet 1 Dec 2008 | Biological Psychiatry, Vol. 64, No. 11
• Underweight rats have enhanced dopamine release and blunted acetylcholine response in the nucleus accumbens while bingeing on sucrose 1 Oct 2008 | Neuroscience, Vol. 156, No. 4
• Molecular Mechanisms of Fat Preference and Overeating 23 October 2008 | Annals of the New York Academy of Sciences, Vol. 1141, No. 1
• A high‐fat diet prevents and reverses the development of activity‐based anorexia in rats 27 February 2008 | International Journal of Eating Disorders, Vol. 41, No. 5
• Maternal high fat diet during the perinatal period alters mesocorticolimbic dopamine in the adult rat offspring: reduction in the behavioral responses to repeated amphetamine administration 16 November 2007 | Psychopharmacology, Vol. 197, No. 1
• High-Fat Diet Exposure Increases Dopamine D2 Receptor and Decreases Dopamine Transporter Receptor Binding Density in the Nucleus Accumbens and Caudate Putamen of Mice 17 October 2007 | Neurochemical Research, Vol. 33, No. 3
• Activation of dopamine D1‐like receptors in nucleus accumbens is critical for the acquisition, but not the expression, of nutrient‐conditioned flavor preferences in rats 10 March 2008 | European Journal of Neuroscience, Vol. 27, No. 6
• Maternal Fat Intake and Offspring Brain Development 1 Jan 2008
• Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake 1 Jan 2008 | Neuroscience & Biobehavioral Reviews, Vol. 32, No. 1
• GPR expression in the rat taste bud relating to fatty acid sensing 1 Jan 2007 | Biomedical Research, Vol. 28, No. 1
• Why Is Fat so Tasty? Chemical Reception of Fatty Acid on the Tongue 1 Jan 2007 | Journal of Nutritional Science and Vitaminology, Vol. 53, No. 1

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Question: QUESTION 28 Sham eating experiments in rats have demonstrated that... when (how often) we eat can be influenced by conditioned stimuli the kind of food that we eat can be influenced by the calorie content of the food the amount we eat can be influenced by our prior experience with a given food All of the above QUESTION 29 Which of the following is true about

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 Multiple Choice

1. Which of the following definitions of key terms in motivation is INCORRECT?

2. The functions of some peripheral factors in the control of eating can be demonstrated by the sham feeding preparation. But which of the following is NOT true? In the sham feeding preparation:

3. Experiments with rats, monkeys and humans using sham feeding have advanced our knowledge about food intake by demonstrating that:

4. Which one of the following findings would support the glucostatic hypothesis?

5. Which of these statements is correct, regarding how damage to the brain affects eating?

6. Long-term regulation of body weight and fat has been associated with the following hormone:

7. Which of the following is NOT the case with respect to a primate’s secondary cortical taste area?

8. The orbitofrontal cortex:

• Has critical implications for survival.
• Serves a reward-decoding function.
• Plays a very important role in emotion.
• Is not involved in learning which stimuli are foods.

9. Which of the following explanations for the problems of obesity targets environmental factors as the cause?

10. When thinking about the amygdala, which of the following do we find NOT to be the case?

11. Which of the following statements about thirst is UNTRUE?

12. __________ is the term that refers to a decreased volume of blood circulation, and it leads to the behavioural response of _________.

13. Why do we keep drinking even when our bodies are not deprived of water?

14. The pleasantness of touch is located in the _____________.

15. Which, if any, of the factors below has probably NOT influenced human sexual behaviour in evolution?

16. According to sociobiological explanations for sexual behaviour, women seek out partners who will provide the most _____________.

17. Current research considers human sexual behaviour to be motivated by what factors in the brain?

18. Which of the following are actual factors confirming the involvement of the preoptic area in the control of male sexual behaviour?

19. Some research suggests that women are more receptive to external sensory stimuli when they are what?

20. Motivational states are states that lead animals to work toward __________.

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Different sham procedures for rats in traumatic brain injury experiments induce corresponding increases in levels of trauma markers

Affiliation.

• 1 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, China.
• PMID: 23122667
• DOI: 10.1016/j.jss.2012.09.013

Background: In traumatic brain injury animal models, sham or naïve control groups are often used for the analysis of injured animals; however, the existence and/or significance of differences in the control groups has yet to be studied. In addition, recent controversies regarding the decompressive craniectomy trial in which decompressive craniectomies in patients with severe traumatic brain injury and refractory increased intracranial pressure remains unsettled. Although the report demonstrated that the procedure may result in less favorable long-term outcomes despite the decrease in intracranial pressure and shorter length of intensive care unit stay, the study has been criticized, and the debate is still inconclusive partly because of a lack of mechanistic explanation. We have recently discovered epithelial and endothelial tyrosine kinase (Etk) to exhibit upregulation after traumatic neural injury and will compare the effects of craniectomy procedure with those of other procedures inducing different levels of severity.

Materials and methods: Four groups of rats receiving different procedures (controlled cortical impact, craniectomy, bicortical drilling, and unicortical drilling [UD]) were compared. Polymerase chain reaction, Western blot analysis, and immunoflorescence staining of Etk, S100, and glial fibrillary acidic protein levels were used to analyze the results and compare the different groups.

Results: Etk upregulation was statistically significant between craniectomy and UD groups. The level of change for glial fibrillary acidic protein and S100 was only significant when cortex was impacted.

Conclusions: UD may be preferable as a sham control procedure over craniectomy or bicortical drilling. Increases in the expression of Etk in the craniectomy group suggest a possible mechanism by which unfavorable outcome occurs in patients receiving craniectomy procedures.

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