Effects of melanocortin receptor agonists and antagonists on exploratory activity: a review

In view of recent interest in the regenerative powers of alpha-melanocyte-stimulating hormone (α-MSH), the effects of melanocortin receptor agonists and antagonists were reviewed in open-field, elevated plus-maze, hole-board, and light-box tests of exploratory activity. In the open-field, low doses of melanocortin receptor agonists increase ambulatory activity and rearing but decrease center zone activity and duration under some conditions. In the elevated plus-maze, MSH receptor agonists generally decrease open arm exploration while MSH receptor antagonists increase open arm exploration, possibly caused by effects in amygdala, medial preoptic area, and ventromedial hypothalamus. Hole-board and light-box test results are preliminary but indicate a similar pattern of an anxiogenic response to melanocortin receptor agonists and an anxiolytic response to antagonists. At low doses, melanocortin receptor agonists are liable to increase general activity, a factor that needs to be taken into account when examining its regenerating action. Melanocortin receptor antagonists decrease anxiety in the elevated plus-maze and thereby may serve a useful function while increasing appetite.