Endocrine Abstracts

Accumulating evidence suggests that ghrelin’s physiological role extends beyond appetite and energy balance to include reward-seeking behaviour both for food (a natural reward) and chemical drugs. The neurochemical circuitry that links ghrelin to reward behavior and the level of the mesolimbic reward system remains unclear. Ghrelin receptors can be found on the ventral tegmental area (VTA) dopamine neurons. It is not known, however, which dopaminergic projections are relevant for ghrelin’s effects on reward, since VTA dopamine neurons send projections to several brain areas relevant for reward behavior including the nucleus accumbens (NAc), amygdala and prefrontal cortex. We found that food-motivated behaviour assessed in the progressive ratio lever-pressing for sucrose paradigm could be driven from the VTA but not the NAc. Interestingly, pretreatment with either a D1-like or D2 receptor antagonist into the NAc completely blocked the food reward effect of VTA ghrelin, leaving chow intake intact. This suggests a role for the VTA-NAc dopaminergic signaling in food reward behavior but not for food intake. The idea that ghrelin’s effects on food intake and food reward behavior engage different reward circuitry is also supported by studies in which we were able to parse ghrelin’s effects these behaviors pharmacologically using mu-preferring opioid receptor antagonist or an NPY Y1 receptor antagonist. Supported by EC: FP7-HEALTH-2009-241592; FP7-KBBE-2009-3-245009.

Declaration of funding

This work was supported by EC: FP7-HEALTH-2009-241592; FP7-KBBE-2009-3-245009.