Synergistic efects of opioid and cannabinoid antagonists on food intake.

Central cannabinoid systems have been implicated in appetite regulation through the hyperphagic effects of exogenous and endogenous cannabinoids. These effects may involve activation of reward systems and be mediated in part by opioidergic processes. Cannabinoid-opioid interactions in feeding were examined by testing the combined effects on food intake of sub-anorectic doses of selective antagonists for CB1 and opioid receptors. Male rats (n = 8) received subcutaneous injections of naloxone (0, 0.1, 0.5, 1.0 mg/kg) and SR141716 (0, 0.1, 0.5, 1.0 mg/kg) before l-h, nocturnal food (chow) intake tests. Neither naloxone nor SR141716 reliably affected feeding when administered alone. By contrast, combined administration of the two antagonists significantly suppressed chow intake at each dose combination. Joint administration of the highest doses of each antagonist suppressed intake by 73%, a significantly greater effect than produced by either naloxone (32%) or SR141716 alone (17%). The data reveal a synergistic interaction between the effects of naloxone and SR141716 on feeding, provide further evidence of important functional relationships between endogenous cannabinoid and opioid systems, and strengthen the postulated role for endocannabinoids in reward processes contributing to the normal control of appetite.