Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors

Abstract

Rationale: Central cannabinoid systems have been implicated in appetite regulation by the respective hyperphagic actions of exogenous cannabinoids, such as delta9-THC, and hypophagic effects of selective cannabinoid receptor antagonists.

Objective: This study examined whether an endogenous cannabinoid, anandamide, could induce overeating, via a specific action at central (CB1) cannabinoid receptors.

Methods: Pre-satiated male rats (n=18), received subcutaneous injections of anandamide (0.5, 1.0, 5.0, 10.0 mg/kg) before 3-h, nocturnal food intake tests. In a second series of intake tests (n=8), anandamide injection (1.0 mg/kg) was preceded by injection of the specific CB1 receptor antagonist, SR141716 (0.1, 0.5, 1.0 mg/kg SC).

Results: All doses of anandamide induced significant overeating, with 1.0 mg/kg being most potent. Additionally, hyperphagia induced by 1.0 mg/kg anandamide was dose-dependently attenuated by SR141716 pretreatment.

Conclusion: This first demonstration of anandamide-induced, CB -mediated, overeating provides important evidence for the involvement of a central cannabinoid system in the normal control of eating.