Behavioral effects of [4-Norleucine, 7-D-Phenylalanine]-α-melanocyte-stimulating hormone

The behavioral effects of α-melanocyte stimulating hormone (α-MSH) were compared to an α-MSH analogue that had a norleucine substituted for methionine in the four position and a D-phenylalanine substituted for L-phenylalanine in the seven position. [Nle⁴,D-Phe⁷]-α-MSH has previously been shown to be a superpotent agonist on melanocytes [17]. The present experiments indicate that [Nle⁴,D-Phe⁷]-α-MSH is equipotent to α-MSH in inducing grooming when administered intraventricularly. In contrast, the analogue has the opposite effect of α-MSH on performance of a visual discrimination task. α-MSH improves visual performance whereas [Nle⁴,D-Phe⁷]-α-MSH attenuates such performance. The contrasting activities of [Nle⁴,D-Phe⁷]-α-MSH on the physiological processes described suggest that this analogue may interact with three distinct melanotropin receptors in different ways. On melanocyte receptors the melanotropin analogue is a superagonist, on CNS melanotropin receptors involved in grooming it is equipotent to α-MSH, and on CNS receptors involved in attention, learning and memory [Nle⁴,D-Phe⁷]-α-MSH may be an antagonist of endogenous melanotropin.