EVIDENCE FOR AN INTERACTION BETWEEN CB1 CANNABINOID AND METABOTROPIC GLUTAMATE RECEPTOR IN REGULATING FOOD INTAKE IN RATS

Both the central cannabinoidergic and glutamatergic systems have been implicated in regulating food intake. Agonists of either pathway are known to stimulate food intake in mammals. Conversely, the central cannabinoid receptor antagonists and glutamate antagonists decrease food intake in rodents. Peripheral injection of glutamate increase food intake in mammals. The interaction between these systems in modulating food intake in rats has not yet been examined. In this study, we attempted to provide evidence for interactions between CB1cannabinoid and metabotropic glutamate receptors in regulating feeding behavior in rats. Male wistar rats received intrapritoneal injections of AM281(CB1 receptor antagonist),ACEA (CB1 receptor agonist), 2R,4R- APDC(metabotropic receptor agonist), LY341495 (metabotropic receptor antagonist)following 24h food deprivation. Food intake was then recorded for 180 minute. The agonists of both receptor systems significantly increased food intake. IP injection of LY341495 dose dependently decreased intake (P≤0.05). Sub-anorectic doses of CB1 receptor antagonist (AM281) and metabotropic glutamate antagonist (LY341495) synergistically attenuated baseline feeding when combined. Sub-maximal doses of ACEA, a CB1 Receptor agonist, and metabotropic receptor agonis(2R,4R-APDC) caused a significant increase in food intake. These findings suggest the involvement of CB1 cannabinoud receptors in the regulation of food intake, possibly through metabotropic Glutamate receptors.