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 labelled with [3H]GR113808 was examined in rat basal ganglia and hippocampus after specific lesions. Lesion of serotonin neurons induced by injections of 5,7-dihydroxytryptamine into the dorsal and medial raphe nuclei resulted in increased 5-HT4 receptor binding in most regions examined, compared with controls. More precisely, there was a 78% increase 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 accumbens respectively. In the substantia nigra, the increase in 5-HT4 binding was larger (72%) than that in the globus pallidus (32%). In the hippocampus, 63%, 30% and 28% increases were measured in CA2, CA1 and CA3 respectively. Following lesion of dopamine neurons by intranigral injection of 6-hydroxydopamine, increased 5-HT4 receptor binding was observed in the caudal (59%), but not the rostral part of caudate-putamen, as well as in the globus pallidus (93%). Since no decreases in 5-HT4 receptor density were detected after the dopamine lesion, it was concluded that these receptors are not expressed in dopamine neurons. Kainic acid lesions of the caudate-putamen were associated with dramatic local decreases in 5-HT4 receptor binding on the injected side (-89%), which suggested that striatal neurons express 5-HT4 receptors. Corresponding decreases of 72 and 20% in receptor density were detected in globus pallidus and substantia nigra, consistent with a presumed localization of 5-HT4 receptors on striatal GABA neurons projecting to these regions. In the substantia nigra, the decrease in [3H]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.
Compan
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V
CNRS UPR 9013, Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, Marseille, France.
Daszuta
A
A
Salin
P
P
Sebben
M
M
Bockaert
J
J
Dumuis
A
A
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007211:Indoles / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism; D014018:Tissue Distribution
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D015116:5,7-Dihydroxytryptamine; D016627:Oxidopamine; D007608:Kainic Acid; C082871:GR 113808