Immunochemical Identification of Melanocortin and Leptin Receptors on Serotoninergic Neurons in the Rat Midbrain

Abstract

The interaction between the melanocortin, leptin, and serotonin systems of the brain is based on the binding of peptides of the melanocortin family and leptin with types 3 and 4 melanocortin receptors (MC3R and MC4R) and leptin receptors (LepR) located on serotoninergic neurons in different parts of the brain. However, there are few data on the locations of these receptors on serotoninergic neurons and none on their locations in midbrain structures such as the ventral tegmental area (VTA) and dorsal raphe nucleus (DRN). The aim of the immunohistochemical study reported here was to identify MC3R, MC4R, and LepR on serotoninergic neurons immunopositive for tryptophan hydroxylase (TPH) in the VTA and DRN in rats. This is the first study demonstrating that serotoninergic neurons in the VTA and DRN bear all receptor types studied, though different quantities are present. The numbers of TPH-immunopositive neurons bearing MC3R in the VTA and DRN were 32 and 84% greater than the numbers of neurons bearing MC4R. The density of MC3R of serotoninergic neurons was significantly greater. The proportions of TPH-immunopositive neurons carrying LepR in the VTA and DRN were 61 and 75%, respectively, the numbers being comparable with those for MC4R. Thus, this report provides the first evidence that MC3R, MC4R, and LepR are located on serotoninergic neurons in the VTA and DRN, pointing to the possibility that their functional activity is regulated by melanocortin peptides and leptin.