γ-Melanotropin and brain function

In view of the close structural similarity between the pro-opiocortin fragment, gamma-MSH, and ACTH/MSH-type peptides, the behavioural profile of gamma-MSH was explored. Attention was first focused on behavioural procedures in which ACTH/MSH-related neuropeptides have been found effective. It was found that gamma-MSH and ACTH-like neuropeptides had opposite effects on avoidance behaviour. In this respect the activity of gamma-MSH resembles that of opiate antagonists rather than that of beta-endorphin. Accordingly, ACTH(1-24) induced excessive grooming which is blocked by opiate antagonists and is attenuated by gamma-MSH. In addition, gamma-MSH injected into the periaqueductal grey matter of the brainstem of opiate-naive rats elicited symptoms reminiscent of those seen after opiate withdrawal. Gamma-MSH attenuated several effects of intracerebroventricularly administered beta-endorphin (e.g. antinociception, hypothermia, alpha-MSH release) and decreased the acquisition of heroin self-administration. Although gamma-MSH at rather high doses displaced naloxone from its specific binding sites in brain homogenates, it did not interfere with beta-endorphin-induced effects on in vitro muscle preparations (guinea-pig ileum; rat rectum). Interestingly, gamma-MSH induced relaxation of the rat rectum in vitro. It is postulated that gamma-MSH may attenuate beta-endorphin-induced effects by acting via gamma-MSH receptor sites (functional antagonism), although a pharmacological antagonism cannot be excluded as yet.