Strong evidence suggests a functional link between the melanocortin and dopamine systems. alpha-Melanocyte stimulating hormone (alpha-MSH) induced grooming behaviour, which can be blocked by dopamine receptor antagonists, is associated with increased dopaminergic transmission in the striatal regions. Whether this effect is mediated specifically by melanocortin (MC) receptors has not previously been established. Using in vivo microdialysis on anesthesized rats we have shown that alpha- MSH administered into the ventral tegmental area induced a significant increase in dopamine and DOPAC levels in the nucleus accumbens. This increase was completely blocked by pre-treatment with the MC4 receptor selective antagonist HS131, indicating that the effects of alpha-MSH on dopamine transmission may be mediated by the MC4 receptor.

The behavioural effects induced by alpha-, gamma1- and gamma2-MSH peptides (0.3 and 3 nmole per rat) injected into the left ventral tegmental area (VTA) of rats were compared. alpha- and gamma1-MSH caused grooming of comparable magnitude, and also additional vertical activity (rearing). By contrast gamma2-MSH caused a moderate but stable catalepsy, and practically no grooming. Moreover, intra-VTA pre-treatment with gamma2-MSH, 15 min prior to intra-VTA gamma1-MSH, markedly attenuated both the gamma1-induced grooming and vertical activities. The differences in the behavioural response of the MSH peptides indicate that they act differentially on MC receptors in the VTA.

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