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Ghrelin and dopamine: new insights on the peripheral regulation of appetite.

ABSTRACT

A review is provided of current evidence supporting the actions of the stomach-derived peptide ghrelin on ventral tegmental area (VTA) dopamine cells to increase food intake and other appetitive behaviours. Ghrelin is a 28 amino-acid peptide that was first identified as an endogenous ligand to growth hormone secretagogue receptors (GHS-R). In addition to the hypothalamus and brain stem, GHS-R message and protein are distributed throughout the brain, with high expression being detected in regions associated with goal directed behaviour. Of these, the VTA shows relatively high levels of mRNA transcript and protein. Interestingly, ghrelin infusions into the VTA increase food intake dramatically, and stimulate dopamine release from the VTA. Moreover, VTA dopamine neurones increase their activity in response to ghrelin in slice preparations, suggesting that ghrelin increases food intake by modulating the activity of dopaminergic neurones in the VTA. On the basis of these data as well as the fact that VTA dopamine cells respond to other metabolic hormones such as insulin and leptin, it is proposed that VTA dopamine cells, similar to cells in the mediobasal hypothalamus, are first-order sensory neurones that regulate appetitive behaviour in response to metabolic and nutritional signals.