The cannabinoid antagonist SR 141716A (Rimonabant) reduces the increase of extra-cellular dopamine release in the rat nucleus accumbens induced by a novel high palatable food

The assumption of a novel high palatable food (a candied cherry) occurs concomitantly with an increase in the concentration of extra-cellular dopamine and its main metabolite 3,4-dihydroxy-phenylacetic acid (DOPAC) by about 45% in the dialysate obtained by intracerebral microdialysis from the shell of the nucleus accumbens of male rats. Such increase was reversed by SR 141716A (Rimonabant), a selective cannabinoid CB1 receptor antagonist (0.3 mg/kg i.p. and 1 mg/kg i.p.), which also reduces the assumption of the high palatable food, when given 15 min before exposure to the candied cherry. SR 141716A effects on extracellular dopamine and DOPAC were prevented by WIN 55,212-2 (0.3 mg/kg i.p.) or HU 210 (0.1 mg/kg i.p.) given 15 min before SR 141716A. The present results show for the first time that SR 141716A reduces the increase in extra-cellular dopamine induced by a novel high palatable food in the nucleus accumbens. This confirms that cannabinoid CB1 receptors play a key role in food intake and/or appetite and suggests that the mesolimbic dopaminergic system is involved at least in part, in the effects of cannabinoid receptor agonists and antagonists on food intake and/or appetite.