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

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.

The gamma(2)-MSH peptide mediates a central analgesic effect via a GABA-ergic mechanism that is independent from activation of melanocortin receptors.

Using the latency for tail-flick after thermal stimulation we have assessed the effects of alpha-, gamma(1)- and gamma(2)-MSH on nociceptive threshold in the mice. Intracisternal injections of gamma(2)-MSH induced a distinct analgesia, while gamma(1)-MSH in the same doses gave only a minor analgesia. Intracisternal alpha-MSH instead gave a short-term hyperalgesia.

Behavioural responses of gamma-MSH peptides administered into the rat ventral tegmental area.

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).

Evaluation of behavioural effects of neural melanocortin receptor antagonists injected ICV and in VTA in rats.

The natural melanocortic peptides are known to exert a variety of effects after central administration. Recently, we discovered the first potent and selective substances for the MC4 receptor, i.e.