The inverse agonist of CB1 receptor SR141716 blocks compulsive eating of palatable food.

Dieting and the increased availability of highly palatable food are considered major contributing factors to the large incidence of eating disorders and obesity. This study was aimed at investigating the role of the cannabinoid (CB) system in a novel animal model of compulsive eating, based on a rapid palatable diet cycling protocol. Male Wistar rats were fed either continuously a regular chow diet (Chow/Chow, control group) or intermittently a regular chow diet for 2 days and a palatable, high-sucrose diet for 1 day (Chow/Palatable). Chow/Palatable rats showed spontaneous and progressively increasing hypophagia and body weight loss when fed the regular chow diet, and excessive food intake and body weight gain when fed the palatable diet. Diet-cycled rats dramatically escalated the intake of the palatable diet during the first hour of renewed access (7.5-fold compared to controls), and after withdrawal, they showed compulsive eating and heightened risk-taking behavior. The inverse agonist of the CB1 receptor, SR141716 reduced the excessive intake of palatable food with higher potency and the body weight with greater efficacy in Chow/Palatable rats, compared to controls. Moreover, SR141716 reduced compulsive eating and risk-taking behavior in Chow/Palatable rats. Finally, consistent with the behavioral and pharmacological observations, withdrawal from the palatable diet decreased the gene expression of the enzyme fatty acid amide hydrolase in the ventromedial hypothalamus while increasing that of CB1 receptors in the dorsal striatum in Chow/Palatable rats, compared to controls. These findings will help understand the role of the CB system in compulsive eating.