Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites

doi:10.1016/0006-8993(86)90902-9

Brain Research

Volume 376, Issue 1, 18 June 1986, Pages 85-96

https://doi.org/10.1016/0006-8993(86)90902-9 Get rights and content

Abstract

The presence, pharmacological properties and anatomical distribution of serotonin-1A and serotonin-1B receptor subtypes were studied in the human brain by both radioligand binding assays and autoradiographic procedures. Frontal cortices and hippocampi from human brains obtained at autopsy without evidence of neurological disease were used in this study. [³H]5-HT was used to label both 5-HT_1A and 5-HT_1B receptor subtypes. 5-HT_1A receptors were selectively labeled by [³H]8-hydroxy-2[di-N-propylamino]tetralin, while 5-HT_1B receptors were labeled by (-)-[¹²⁵I]iodocyanopindolol ([¹²⁵I]CYP) in the presence of 30 μM isoprenaline. The pharmacological profile of 5-HT_1A receptors in human brain tissue was very similar to those previously found in rat and pig brain tissues. The general anatomical distribution of these sites was also similar to that found in the rat brain, although some differences were observed when analyzed at the microscopic level. In contrast to 5-HT_1A receptors, it was not possible to identify 5-HT receptors having the pharmacological properties of 5-HT_1B sites in the human brain, using either [³H]5-HT or [¹²⁵I]CYP as ligands. The absence of identifiable 5-HT_1B receptors in human brain preparations, a fact previously found in pig brain tissue, is discussed in terms of the existence of species differences in brain serotonin receptors.

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The distribution of serotonin-1 (5-HT₁) receptors in the rat brain was studied by light microscopic quantitative autoradiography. Receptors were labeled with [³H]serotonin (5-[³H]HT), 8-hydroxy-2-[H-dipropylamino-³H]tetralin (8-OH-[³H]DPAT), [³H]LSD and [³H]mesulergine, and the densities quantified by microdensitometry with the aid of a computer-assisted image-analysis system. Competition experiments for 5-[³H]HT binding by several serotonin-1 agonizts led to the identification of brain areas enriched in each one of the three subtypes of 5-HT₁ recognition sites already described (5-HT_1A, 5-HT_1B, 5-HT_1C). The existence of these׳selective׳ areas allowed a detailed pharmacological characterization of these sites to be made in a more precise manner than has been attained in membrane-binding studies. While 5-[³H]HT labeled with nanomolar affinity all the 5-HT₁ subtypes, the other ³H-labeled ligands labeled selectively 5-HT_1A (8-OH-[³H]DPAT), 5-HT_1C ([³H]mesulergine) and both of them ([³H]LSD). Very high concentrations of 5-HT₁ receptors were localized in the choroid plexus, lateroseptal nucleus, globus pallidus and ventral pallidum, dentate gyrus, dorsal subiculum, olivary pretectal nucleus, substantia nigra, reticular and external layer of the entorhinal cortex. The different fields of the hippocampus (CA₁–CA₄), some nuclei of the amygdaloid complex, the hypothalamic nuclei and the dorsal raphé, among others, also presented high concentrations of sites. Areas containing intermediate densities of 5-HT₁ receptors included the claustrum, olfactory tubercle, accumbens, central gray and lateral cerebellar nucleus. The nucleus caudate-putamen and the cortex, at the different levels studied, presented receptor densities ranging from intermediate to low. Finally, in other brain areas-pons, medulla, and spinal cord-only low or very low concentrations of 5-HT₁ receptors were found. From the areas strongly enriched in 5-HT₁ sites, dentate gyrus and septal nucleus contained 5-HT_1A sites, while globus pallidus, dorsal subiculum, substantia nigra and olivary pretectal nucleus were enriched in 5-HT_1B. The sites in the choroid plexus, which presented the highest density of receptors in the rat brain, were of the 5-HT_1C subtype. The distribution of 5-HT₁ receptors reported here is discussed in correlation with the distribution of serotoninergic neurons and fibers, the related anatomical pathways and the effects which appear to be mediated by these sites. © 1985.This article is part of a Special Issue entitled SI:50th Anniversary Issue.
This article is part of a Special Issue entitled SI:50th Anniversary Issue.

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Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites

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Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT_1A recognition sites. Apparent absence of 5-HT_1B recognition sites