The Main Features of Central 5-HT_1A Receptors

Abstract

Soon after the development of binding assays using [³H]5-hydroxytryptamine ([³H]5-HT) to label the specific recognition sites for serotonin on membranebound receptors in the central nervous system (CNS), differences from one brain area to another were noted which suggested the existence of several distinct classes of binding sites. In particular, comparison of the fate of [³H]5- HT high-affinity binding sites in the rat brain after the selective degeneration of serotoninergic neurones due to the intra-raphe infusion of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) showed that both the hippocampal and striatal sites are located on postsynaptic targets of serotoninergic projections (Nelson et al. 1978), where they are subjected, however, to differential adaptive changes after the lesion. Thus a significant increase in the density of [³H]5-HT high-affinity binding sites was noted in the hippocampus but not in the striatum (Nelson et al. 1978). Studies of the pharmacological properties of [³H]5-HT high-affinity binding also revealed that the radioactive indoleamine probably recognises several distinct high-affinity sites in brain membranes. Indeed, inhibition of [³H]5-HT high-affinity binding by drugs such as methiothepin and quipazine yielded (apparent) Hill coefficients of less than 1.0, as expected of the heterogeneity of corresponding binding sites (Nelson et al. 1978).