5-HT 3 receptors in the rat central nervous system are mainly located on nerve fibres and terminals

Abstract

Autoradiographic and membrane binding studies with[ 3H](R,S)-or[ 3H](S)-zacopride were performed in combination with lesions using various neurotoxins in an attempt to identify which neuronal cell types are endowed with 5-HT 3 receptors in the rat central nervous system. Lesions of noradrenergic (by DSP-4), dopaminergic (by 6-hydroxydopamine) and serotonergic (by 5,7-dihydroxytrptamine) system had little effect generally on the density of 5-HT 3 receptors labelled with[ 3H](S)-or [ 3H](S)-zacopride in various regions of the brain and only exception was the amyglada where a significant loss (∼-20%) of 5-HT 3 receptors labelled by[ 3H](R,S)-zacopride was associated with the selective lesion of serotonergic fibres by 5,7-dihydroxytryptamine. Microinjection of kainic or ibotenic acid into the dorsal and ventral hippocampus reduced the density of 5-HT 1A receptors labelled with[ 3H]8-OH-DPAT (∼-45%) as expected from their known location on intrinsic neuronal cell bodies and/or dendrites. In contrast, the same lesion did not effect 5-HT 3 receptors, suggesting their location on fibres ‘en passage’. At the spinal level, 5-HT 3 receptors were found to exist on primary afferent fibres terminating within the superficial layers of the dorsal horn, as shown by the marked reduction in the local autoradiographic labelling by[ 3H](S)-zacopride after either dorsal rhizotoomy (−81%) or neonatal capsaicin treatment (−72%). These data suggest that 5-HT 3 receptors in the central nervous system are generally located presynaptically on nerve terminals of non-monoaminergic neurones.