Alpha-melanocyte stimulating hormone antagonizes antidepressant-like effect of neuropeptide Y in Porsolt's test in rats.

The physiological and functional interaction between neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (alpha-MSH) with reference to anxiety and food intake is well documented. An attempt has been made to study the influence of melanocortin (MC) system on NPY induced antidepressant-like effect in rats using Porsolt's forced swim test as the behavioral paradigm. NPY (0.40-2.10 ng/rat), NPY Y1 and Y5 receptors agonist [Leu(31), Pro(34)]-NPY (0.20-0.60 ng/rat) or selective MC4 receptors antagonist HS014 (0.01-0.07 ng/rat) dose dependently elicited antidepressant-like effect. On the other hand, alpha-MSH (100-400 ng/rat) resulted in high immobility suggestive of depression. Antidepressant-like effect of NPY (1.00-2.10 ng/rat) or [Leu(31), Pro(34)]-NPY (0.40-0.60 ng/rat) was significantly reversed by prior treatment of alpha-MSH (100 ng/rat). While antidepressant action of NPY (0.40-1.00 ng/rat) or [Leu(31), Pro(34)]-NPY (0.20-0.40 ng/rat) was enhanced by concurrent administration of HS014 (0.01 ng/rat), the locomotor activity in all the treatment groups was unaffected. These results suggest the possibility that MC and NPYergic systems may interact and regulate the depression via MC4 and NPY Y1 or Y5 receptors.