The MC4 receptor mediates α-MSH induced release of nucleus accumbens dopamine

Strong evidence suggests a functional link between the melanocortin and dopamine systems. α-Melanocyte stimulating hormone (α-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 α- 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 α-MSH on dopamine transmission may be mediated by the MC4 receptor.