Pharmacological modulation of the endocannabinoid signalling alters binge‐type eating behaviour in female rats

Abstract

Background and Purpose Binge eating disorder (BED) is characterized by excessive food intake during short periods of time. Recent evidence suggests that alterations in the endocannabinoid signalling could be involved in the pathophysiology of BED. In this study, we investigated whether pharmacological manipulation of endocannabinoid transmission may be effective in modulating the aberrant eating behaviour present in a validated rat model of BED. Experimental Approach Binge‐type eating was induced in female rats by providing limited access to an optional source of dietary fat (margarine). Rats were divided into three groups, all with ad libitum access to chow and water: control (C), with no access to margarine; low restriction (LR), with 2 h margarine access 7 days a week; high restriction (HR), with 2 h margarine access 3 days a week. Key Results Compared with the LR group, the HR group consumed more margarine and this was accompanied by an increase in body weight. The cannabinoid CB1/CB2 receptor agonist Δ9‐tetrahydrocannabinol significantly increased margarine intake selectively in LR rats, while the fatty acid amide hydrolase inhibitor URB597 showed no effect. The CB1 receptor inverse agonist/antagonist rimonabant dose‐dependently reduced margarine intake in HR rats. Notably, in HR rats, chronic treatment with a low dose of rimonabant induced a selective long‐lasting reduction in margarine intake that did not develop tolerance, and a significant and persistent reduction in body weight. Conclusions and Implications Chronic pharmacological blockade of CB1 receptors reduces binge eating behaviour in female rats and may prove effective in treating BED, with an associated significant reduction in body weight. Linked Articles This article is part of a themed section on Cannabinoids. To view the other articles in this section visit &

Differential expression of CART in feeding and reward circuits in binge eating rat model

“…Although the usefulness of rimonabant in the treatment of obesity has been debated, it is found to be effective in the treatment of BE [19,20]. In the present study, acute treatment with rimonabant, prior to the BE, significantly decreased consumption of HFSPD.…”

“…Daily [18,33,34] or even alternate day [35,36] access to palatable diet for 2-h has been shown to produce BE in rats. However, it is suggested that development of binging is enhanced and remain stable for longer period when it is offered only 3 times per week than for 2-h each day [19,35]. In addition, when the palatable diet is comprised of sugar and fat, daily or alternate day access increases binging behavior to the same degree [18].…”

“…We also investigated the effects of CART and CART antibody on the consumption of normal or binge diet. Moreover, blockade of cannabinoid 1 (CB1) receptors by rimonabant reduced BE behavior in rats and therefore usefulness of the agent in the treatment of BE disorder was suggested [19]. Pataky et al [20] reported effective use of rimonabant in the treatment of obese patients with BE disorder, however, the underlying mechanism were not explained.…”

Endocannabinoid signalling in reward and addiction

“…Although two small clinical trials did not show Δ9-THC efficacy 176 a larger trial demonstrated small but significant weight gain in women with severe anorexia nervosa following 4 weeks treatment with Dronabinol 188 . Conversely, in binge eating disorder the CB 1 R antagonist Rimonabant significantly reduces binge eating and promotes weight loss with only modest presentation of psychiatric side effects 189, 190 .…”

Endocannabinoids and Metabolic Disorders

“…For instance, chronic administration of rimonabant reduced feeding behavior in an animal model of binge eating disorder (Scherma et al 2013) and the same drug was able to decrease body weight and binge eating behavior in obese patients affected by binge eating disorder (Pataky et al 2013). In contrast, Verty and collaborators were able to demonstrate that Δ 9 -THC attenuated weight loss in a rodent model of activity-based anorexia through a mechanism that likely involves a decrease in energy expenditure (Verty et al 2011).…”