|Abstract: ||According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), binge eating disorder (BED) is an eating disorder characterized by repetitive episodes of uncontrolled and excessive food consumption (binge eating), in a short period of time, without the inappropriate
compensatory behaviors for limiting weight gain. BED is a stable condition that is associated with
elevated psychiatric comorbidity, including depression and anxiety.
A large body of evidence supports a contribution of the endocannabinoid system in the modulation
of energy balance by controlling food intake through central and peripheral mechanisms. The cannabinoid CB1 receptor is abundantly expressed in the central nervous system and induces inhibition of neurotransmission through modulation of presynaptic neurotransmitter release. CB1
receptors inverse agonists inhibit food intake through both central and peripheral mechanisms while, in contrast, cannabinoid agonists stimulate food intake in humans and induce beneficial effects in acquired immune deficiency syndrome related to anorexia, suggesting altered
endocannabinoid neurotransmission in anorectic conditions. A possible involvement of the endocannabinoid system in the pathogenesis of BED and other eating disorders has recently been supported by independent experimental evidence. Elevated plasma levels of anandamide were found in women affected by AN and BED. Moreover, anandamide levels were inversely correlated with plasma leptin concentrations.
On the basis of these evidence, the aim of this thesis was to study whether and which elements of the endocannabinoid system might be correlated with the binge eating behavior, which brain areas are specifically involved, and if pharmacological treatments specific for the endocannabinoid
system (i.e. agonists, antagonists, inverse agonists of cannabinoid receptors, inhibitors of endocannabinoid metabolisms) are be able, besides to modify the state of BED induced in laboratory animals, to restore a correct functionality of the endocannabinoid system.
Furthermore an analysis of the behavioral profile of animals with BED has been evaluated before
the start of drug treatment by means of different mazes in which is possible to study anxiety and depression.
Binge eating behavior was induced in animals by giving them a sporadic (3 days/week) and limited (2h) access to a high fat diet (margarine) in addition to a continuous access to chow and water. In these animals, the intake of margarine becomes significantly greater than in animals with limited
daily access to margarine and remains stable over prolonged periods of time. As revealed by forced swim test, animals with binge eating behavior did not show a depressive like behavior compared to control animals. However, using the elevated plus maze, an anxiety like behavior was highlighted in those animals before access to margarine (Pre - binge phase) that it was significantly reduced after
the consumption of this palatable food (Post - binge phase). Results showed that an increase of the
endocannabinoid signaling by CB1 agonists or by inhibitors of endocannabinoid metabolism did not modify the binge eating behavior presents in our animals. On the contrary, a decrease of the endocannabinoid signaling by CB1 receptors inverse agonist/antagonist rimonabant, was able to
alter this behavior when given chronically. As regards the CB1 receptor density, no difference has been highlighted between animals showing binge eating behavior and control group. In conclusion, negative modulation of the endocannabinoid signal may represent an important strategy in the treatment of Binge Eating Disorder.|