In a rat study, a synthetic version of the melanotan-I peptide called [Nle4,D-Phe7]alpha-MSH helped the animals recover better after a brain injury. The treated rats moved less in a rotation test and performed better on sensorimotor tasks. The peptide also reduced the size of the brain lesion and seemed to promote supportive brain cell growth.

Rats subjected to diencephalic hemisection were s.c. treated with alpha-MSH (20 micrograms/rat daily) or with [Nle4,D-Phe7]alpha-MSH (10 micrograms/rat every other day) for two weeks starting on day 3 after lesion. Apomorphine-induced (1 mg/kg s.c.) rotational behavior was studied on days 7, 14 and 21 after lesion, and a sensorimotor test battery was carried out on days 3, 10, 17 and 24 after lesion. [Nle4,D-Phe7]alpha-MSH greatly reduced rotational behavior and significantly improved sensorimotor performance. Histological studies showed that treatment with alpha-MSH and, even more markedly, with [Nle4,D-Phe7]alpha-MSH reduced the size of the lesion and the pseudoinflammatory reaction, and caused a marked proliferation and hypertrophy of astroglia. Binding studies showed that no supersensitivity of striatal dopamine receptors developed on the lesioned side of alpha-MSH- and [Nle4,D-Phe7]alpha-MSH-treated rats. The present results seem to further support the trophic role of MSH peptides on nerve tissue.