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.
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.
|Moore, Catherine F; Sabino, Valentina; Koob, George F et al. (2017) Neuroscience of Compulsive Eating Behavior. Front Neurosci 11:469|
|Valenza, Marta; DiLeo, Alyssa; Steardo, Luca et al. (2016) Ethanol-related behaviors in mice lacking the sigma-1 receptor. Behav Brain Res 297:196-203|
|Ferragud, Antonio; Howell, Adam D; Moore, Catherine F et al. (2016) The Trace Amine-Associated Receptor 1 Agonist RO5256390 Blocks Compulsive, Binge-like Eating in Rats. Neuropsychopharmacology :|
|Iemolo, Attilio; Seiglie, Mariel; Blasio, Angelo et al. (2016) Pituitary adenylate cyclase-activating polypeptide (PACAP) in the central nucleus of the amygdala induces anxiety via melanocortin receptors. Psychopharmacology (Berl) 233:3269-77|
|Iemolo, Attilio; Ferragud, Antonio; Cottone, Pietro et al. (2015) Pituitary Adenylate Cyclase-Activating Peptide in the Central Amygdala Causes Anorexia and Body Weight Loss via the Melanocortin and the TrkB Systems. Neuropsychopharmacology 40:1846-55|
|Seiglie, Mariel P; Smith, Karen L; Blasio, Angelo et al. (2015) Pituitary adenylate cyclase-activating polypeptide induces a depressive-like phenotype in rats. Psychopharmacology (Berl) 232:3821-31|
|Blasio, Angelo; Valenza, Marta; Iyer, Malliga R et al. (2015) Sigma-1 receptor mediates acquisition of alcohol drinking and seeking behavior in alcohol-preferring rats. Behav Brain Res 287:315-22|
|Giuliano, Chiara; Cottone, Pietro (2015) The role of the opioid system in binge eating disorder. CNS Spectr 20:537-45|
|Smith, Karen L; Rao, Rahul R; Velázquez-Sánchez, Clara et al. (2015) The uncompetitive N-methyl-D-aspartate antagonist memantine reduces binge-like eating, food-seeking behavior, and compulsive eating: role of the nucleus accumbens shell. Neuropsychopharmacology 40:1163-71|
|Valenza, Marta; Steardo, Luca; Cottone, Pietro et al. (2015) Diet-induced obesity and diet-resistant rats: differences in the rewarding and anorectic effects of D-amphetamine. Psychopharmacology (Berl) 232:3215-26|
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