Behavioral profile of ψ-MSH: Relationship with acta and β-endorphin action

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