Visualization of a novel serotonin recognition site (5-HT_1D) in the human brain by autoradiography

The localization of a novel serotonin (5-hydroxytryptamine, 5-HT) recognition site named 5-HT_1D was studied by autoradiography in human postmortem brain material. Serotonin-1 sites were labeled with [³H]5-HT. The different subpopulations of 5-HT₁ sites were investigated by the use of unlabeled selective compounds. 8-OH-DPAT (8-hydroxy-2-[N,N-di-n-propyl-amino]tetralin) was used to block [³H]5-HT binding to 5-HT_1A, the β-blocker (-)-21 009 (4-[3-ter-butyl-amino-2-hydroxy-propoxy]indol-2-carbonic acid isopropyl ester) to 5-HT_1B and the ergoline mesulergine to 5-HT_1C recognition sites. 5-HT_1D sites were defined as the binding sites remaining when both 8-OH-DPAT and mesulergine were added to the incubation medium. Under these conditions, 5-HT_1D sites represented a high proportion of total [³H]5-HT binding sites in the basal ganglia and substantia nigra. Lower proportions were observed in other brain areas such as the hippocampal formation and raphé nuclei. 5-HT_1D sites thus represent the majority of 5-HT₁ binding sites in the striatonigral pathway in man. This localization suggests an involvement of these sites in the mediation of serotoninergic mechanisms in basal ganglia functions and a possible role in brain diseases where these areas are known to be involved.