Epidemic eating disorders and obesity, like drug addiction, can be conceptualized as chronic relapsing conditions with alternating periods of abstinence (e.g., dieting to avoid "forbidden" foods) and relapse (uncontrollable eating of palatable foods) that continue despite negative consequences. The increased availability of palatable foods and dieting are believed to be risk factors. Eating disorders and obesity very frequently occur comorbidly with anxiety and mood disorders but the neurobiological link between the two pathological conditions is poorly understood. The applicant has recently proposed a new interpretation of the etiology of compulsive eating and comorbid anxiety and affective disorders: overeating may be generated by the negative emotional state associated with its absence (analogous to excessive intake of drugs and relapse). In this context, there is increasing evidence that the endocannabinoid system plays a role in hedonic feeding and it is believed that its activation is part of a negative feedback system that opposes anxiety. Our preliminary evidences show that the endocannabinoid system in the extended amygdala is recruited during abstinence from palatable food. Therefore, the general hypothesis here is that neuroadaptations in the endocannabinoid system in the extended amygdala sustain palatable food intake via a negative reinforcement mechanism and oppose the negative affective consequences of palatable food withdrawal. The present application uses an integrative behavioral, pharmacological and molecular approach to study i) the role of the endocannabinoid system in the consummatory and motivational components of compulsive eating, ii) the mechanisms which link compulsive eating to anxiety and depressive disorders and the role played by the endocannabinoid system in this context, iii) the neuroadaptational changes in the endocannabinoid machinery in the extended amygdala which contribute to the negative reinforcement mechanisms of compulsive eating.

Public Health Relevance

These experiments will provide critical information about the brain changes that accompany compulsive eating of palatable food and their relevance in the development of comorbid anxiety and mood disorders. Such information is important for the development of more efficacious treatments for eating disorders and obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH091945-03
Application #
8270550
Study Section
Special Emphasis Panel (ZMH1-ERB-L (04))
Program Officer
Winsky, Lois M
Project Start
2010-07-15
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
3
Fiscal Year
2012
Total Cost
$402,188
Indirect Cost
$154,688
Name
Boston University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
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Blasio, Angelo; Steardo, Luca; Sabino, Valentina et al. (2014) Opioid system in the medial prefrontal cortex mediates binge-like eating. Addict Biol 19:652-62
Blasio, Angelo; Rice, Kenner C; Sabino, Valentina et al. (2014) Characterization of a shortened model of diet alternation in female rats: effects of the CB1 receptor antagonist rimonabant on food intake and anxiety-like behavior. Behav Pharmacol 25:609-17
Dore, Riccardo; Valenza, Marta; Wang, Xiaofan et al. (2014) The inverse agonist of CB1 receptor SR141716 blocks compulsive eating of palatable food. Addict Biol 19:849-61
Velázquez-Sánchez, Clara; Ferragud, Antonio; Moore, Catherine F et al. (2014) High trait impulsivity predicts food addiction-like behavior in the rat. Neuropsychopharmacology 39:2463-72
Iemolo, Attilio; Blasio, Angelo; St Cyr, Stephen A et al. (2013) CRF-CRF1 receptor system in the central and basolateral nuclei of the amygdala differentially mediates excessive eating of palatable food. Neuropsychopharmacology 38:2456-66
Cottone, P; Sabino, V; Nagy, T R et al. (2013) Centrally administered urocortin 2 decreases gorging on high-fat diet in both diet-induced obesity-prone and -resistant rats. Int J Obes (Lond) 37:1515-23
Dore, Riccardo; Iemolo, Attilio; Smith, Karen L et al. (2013) CRF mediates the anxiogenic and anti-rewarding, but not the anorectic effects of PACAP. Neuropsychopharmacology 38:2160-9
Sabino, Valentina; Kwak, Jina; Rice, Kenner C et al. (2013) Pharmacological characterization of the 20% alcohol intermittent access model in Sardinian alcohol-preferring rats: a model of binge-like drinking. Alcohol Clin Exp Res 37:635-43
Blasio, Angelo; Iemolo, Attilio; Sabino, Valentina et al. (2013) Rimonabant precipitates anxiety in rats withdrawn from palatable food: role of the central amygdala. Neuropsychopharmacology 38:2498-507

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