Systemic administration of ghrelin induces conditioned place preference and stimulates accumbal dopamine

Ghrelin, preferably via hypothalamic circuits, is known to play a role in the control of energy balance, body weight homeostasis and appetite. In addition, it has recently been found that ghrelin injection into key structures of the mesolimbic dopamine (DA) system increases food intake in rodents and induces locomotor stimulation as well as accumbal DA overflow in mice. Thus, centrally administered ghrelin activates the mesolimbic DA system. However, ghrelin is mainly produced in and secreted from peripheral tissues. The present series of experiments were therefore undertaken to investigate the effects of peripherally injected ghrelin on mesolimbic DA system activity and, herewith, associated behaviours. It was found that intraperitoneal administration of ghrelin (0.33 mg/kg) induces locomotor stimulation, conditioned place preference and accumbal DA-overflow in mice. In conclusion, peripherally produced ghrelin, e.g. in the stomach, may activate the mesolimbic DA system. This suggests that the pre-prandial rise in plasma ghrelin may, via this system, increase the incentive value for motivated behaviours such as food seeking.