Stereological investigation of 5-HT3 receptors in the substantia nigra and dorsal raphe nucleus in the rat

Abstract

Serotonin (5-HT) is a common neurotransmitter in mammals, playing a central role in the regulation of various processes such as sleep, perception, cognitive and autonomic functions in the nervous system. Previous studies have demonstrated that 5-HT type 3 (5-HT3) receptors are expressed in either or both the substantia nigra (SN) and the dorsal raphe nucleus (DRN) in humans, marmosets, rats and Syrian hamsters. Here, we quantify the distribution of 5-HT3 receptors across these regions in the adult rat. Fluorescent immunohistochemistry was performed on sections of rat brain covering the entire rostro-caudal extent of the SN and DRN with antibodies specific to the 5-HT3A receptor subunit, as well as others targeting the monoaminergic markers tyrosine hydroxylase (TH) and the 5-HT transporter (SERT). The number of 5-HT3A receptor-positive, TH-positive (n = 28,428 ± 888, Gundersen’s m = 1 coefficient of error [CE] = 0.05) and SERT-positive (n = 12,852 ± 462, CE = 0.06) cells were estimated in both the SN and the DRN using stereology. We found that 5-HT3A receptor-positive cells are present in the SNr (n = 1250 ± 64, CE = 0.24), but they did not co-localise with TH-positive cells, nor were they present in the SNc. In contrast, no 5-HT3A receptor-positive cells were found in the DRN. These results support the presence of 5-HT3 receptors in the SN, but not in the DRN, and do not support their expression on monoaminergic cells within these two brain areas.