A cannabinoid receptor antagonist attenuates ghrelin-induced activation of the mesolimbic dopamine system in mice

Abstract Ghrelin has been attributed various physiological processes including food intake and reward regulation, through activation of the mesolimbic dopamine system. Reward modulation involves the mesolimbic dopamine system, consisting of the ventral tegmental area (VTA) dopamine neurons targeting nucleus accumbens (NAc), a system that ghrelin activates through VTA-dependent mechanisms. In the first study, we found that systemic intraperitoneal (ip) administration of rimonabant attenuated intracerebroventricular (icv) ghrelin's ability to cause locomotor stimulation and NAc dopamine release in mice. Ghrelin-induced (icv) chow intake was not altered by rimonabant administration (ip). Finally, we showed that bilateral VTA administration of rimonabant blocks the ability of intra-VTA administered ghrelin to increase locomotor activity, but does not affect food intake in mice. Collectively, these data indicate clear dissociation between regulation of food intake and activation of the mesolimbic dopamine system.