5-HT(3) RECEPTORS IN THE RAT CENTRAL-NERVOUS-SYSTEM ARE MAINLY LOCATED ON NERVE-FIBERS AND TERMINALS

Autoradiographic and membrane binding studies with [H-3](R,S)- or [H-3 ](S)-zacopride were performed in combination with lesions using variou s neurotoxins in an attempt to identify which neuronal cell types are endowed with 5-HT3 receptors in the rat central nervous system. Lesion s of noradrenergic (by DSP-4), dopaminergic (by 6-hydroxydopamine) and serotonergic (by 5,7-dihydroxytryptamine) systems had little effect g enerally on the density of 5-HT3 receptors labelled with [H-3](R,S)- o r [H-3](S)-zacopride in various regions of the brain and the spinal co rd. The only exception was the amygdala where a significant loss (appr oximately -20%) of 5-HT3 receptors labelled by [H-3](R,S)-zacopride wa s associated with the selective lesion of serotonergic fibres by 5,7-d ihydroxytryptamine. Microinjection of kainic or ibotenic acid into the dorsal and ventral hippocampus reduced the density of 5-HTIA receptor s labelled with [H-3]8-OH-DPAT (approximately -45%) as expected from t heir known location on intrinsic neuronal cell bodies and/or dendrites . In contrast, the same lesion did not affect 5-HT3 receptors, suggest ing their location on fibres 'en passage'. At the spinal level, 5-HT3 receptors were found to exist on primary afferent fibres terminating w ithin the superficial layers of the dorsal horn, as shown by the marke d reduction in the local autoradiographic labelling by [H-3](S)-zacopr ide after either dorsal rhizotomy (-81%) or neonatal capsaicin treatme nt (-72%). These data suggest that 5-HT3 receptors in the central nerv ous system are generally located presynaptically on nerve terminals or fibres of non-monoaminergic neurones.