Involvement of alpha-MSH in the social isolation induced anxiety- and depression-like behaviors in rat.

Although physical isolation of rats is known to cause anxiety- and depression-like symptoms, the underlying mechanisms are not fully understood. We have attempted to define the role of endogenous melanocortins (MC) in the manifestation of these symptoms. Weaning rats were socially isolated for 6 weeks and subjected to behavioral paradigms like elevated plus maze (EPM), social interaction, and forced swim test (FST). While socially isolated rats spent less time in social interaction, and showed significantly decreased activity in the open arms of the EPM, the immobility time in FST was significantly increased thus reflecting anxiety- and depression-like phenotypes. Intracerebroventricular injection of HS014 (5 or 10 nmol/rat), selective antagonist of MC4 receptors, attenuated these symptoms. This suggested the involvement of endogenous alpha-melanocyte stimulating hormone (alpha-MSH) in anxiety and depression. With a view to determining the neuroanatomical substrates in which the endogenous alpha-MSH may process the related information, profile of the peptide in paraventricular (PVN), arcuate (ARC), dorsomedial hypothalamic-dorsal (DMNd) and -ventral (DMNv) nuclei, and central nucleus of amygdala (CeA) was investigated with immunohistochemistry. While social isolation significantly reduced alpha-MSH-immunoreactivity profile in all these components, re-socialization of the socially isolated rats, over a period of 72 h, resulted in full recovery of the alpha-MSH-immunoreactivity profile; the symptoms of anxiety- and depression-like behaviors were also fully attenuated. We suggest that alpha-MSH in the PVN, ARC, DMNd, DMNv and CeA, acting via MC4 receptors, are involved in manifestation of affective disorders like anxiety and depression.