LESION STUDY OF THE DISTRIBUTION OF SEROTONIN 5-HT4 RECEPTORS IN RAT BASAL GANGLIA AND HIPPOCAMPUS

The regional distribution of 5-hydroxytryptamine (5-HT4) receptors lab elled with [H-3]GR113808 was examined in rat basal ganglia and hippoca mpus after specific lesions. Lesion of serotonin neurons induced by in jections of 5,7-dihydroxytryptamine into the dorsal and medial raphe n uclei resulted in increased 5-HT4 receptor binding in most regions exa mined, compared with controls. More precisely, there was a 78% increas e in the rostral but no change in the caudal part of caudate-putamen, and 83% and 54% increases in the shell and core of the nucleus accumbe ns respectively. In the substantia nigra, the increase in 5-HT4 bindin g was larger (72%) than that in the globus pallidus (32%). In the hipp ocampus, 63%, 30% and 28% increases were measured in CA2, CA1 and CA3 respectively. Following lesion of dopamine neurons by intranigral inje ction of 6-hydroxydopamine, increased 5-HT4 receptor binding was obser ved in the caudal (59%), but not the rostral part or caudate-putamen, as well as in the globus pallidus (93%). Since no decreases in 5-HT4 r eceptor density were detected after the dopamine lesion, it was conclu ded that these receptors are not expressed in dopamine neurons. Kainic acid lesions of the caudate-putamen were associated with dramatic loc al decreases in 5-HT4, receptor binding on the injected side (-89%), w hich suggested that striatal neurons express 5-HT4 receptors. Correspo nding decreases of 72 and 20% in receptor density were detected in glo bus pallidus and substantia nigra, consistent with a presumed localiza tion of 5-HT4 receptors on striatal GABA neurons projecting to these r egions. in the substantia nigra, the decrease in [H-3]GR113808 binding was localized to the pars lateralis, indicating that striatal neurons belonging to the cortico-striato-nigro-tectal pathway, and containing GABA and dynorphin, express 5-HT4 receptors.