Systemic administration of ghrelin increases extracellular dopamine in the shell but not the core subdivision of the nucleus accumbens.

The gut-hormone ghrelin endogenously binds to the ghrelin receptor (GHS-R) to promote foraging and feeding behaviours mainly via the hypothalamic arcuate nucleus (ARC). GHS-Rs are also expressed in midbrain dopaminergic neurons of the ventral tegmental area (VTA) suggesting that ghrelin may modulate the mesolimbic dopamine (DA) system. In support of this hypothesis, previous results have shown that intraventricular administration of ghrelin in rats increases DA levels in the nucleus accumbens (NAc). In the present study, the systemic doses of ghrelin capable of triggering central activation were first determined, and growth hormone (GH) levels were used as a marker of ghrelin-induced activation. Similar dose regimen was then used to measure ghrelin-induced effects on extracellular levels of monoamines in the shell and core subdivisions of the NAc using microdialysis in freely moving rats. We show that subcutaneous (s.c.) administration of ghrelin produced an increase in basal plasmatic ghrelin concentrations that was paralleled by enhanced GH secretion. In addition, a significant increase in extracellular levels of DA was observed specifically in the NAc shell, with no effect in the core subdivision. Extracellular serotonin (5-HT) levels were also affected in the shell subregion, but without reaching statistical significance. Increased extracellular DA levels in the NAc shell have been typically associated with the acute reinforcing effects of addictive drugs. The present findings therefore suggest that systemic ghrelin may modulate the valence of reinforcers such as food and drugs of abuse by interfering with mesolimbic DA activity.