ABSTRACT
In the 30 years since the differentiation of M and D receptors (Gaddum and Picarelli, 1957), it has become clear that multiple 5-hydroxytryptamine (5-HT) receptors exist. The heterogeneity of 5-HT receptors has become even more apparent in the past decade. To a significant degree, the appreciation of this fact is a direct result of the development of radio ligand binding techniques (Snyder, 1983). At the present time, at least five 5-HT binding site subtypes have been differentiated by radioligand techniques in brain homogenates (Fillion, 1983; Leysen, 1983; Fuller, 1984; Hamon et aI., 1984; Peroutka, 1987). Anatomic studies using auto radiographic techniques have also confirmed that a variety of serotonergic recognition sites, with distinct regional localizations, exist in the central nervous system (Biegon et aI., 1982; Pazos and Palacios, 1985; Pazos et aI., 1985a; Hoyer et aI., 1986a; 1986b). The identification and characterization of these 5-HT receptor subtypes has, and will continue to have, multiple clinical implications. For example, neuropsychiatric disorders such as anxiety, depression and hallucinosis have been specifically linked to specific 5-HT receptor subtypes in the central nervous system. As evidenced by this publication, 5-HT has also been linked to the regulation of aggression and impulse control. This review will summarize data concerning the pharma-
Preliminary Binding Studies Bennett and Aghajanian (1974) were the first investigators to successfully radiolabel 5-HT receptors. The binding of 3H-d-Iysergic acid diethylamide (d-LSD) was saturable, reversible, stereoselective and displayed high affinity (KD = 7.5 nM) for its membrane recognition site. The binding sites also displayed appropriate regional variations since brain regions with the highest density of receptors were areas known to receive a dense projection of 5-HT neuronal terminals. These findings were soon extended and confirmed by other laboratories (Bennett and Snyder, 1975; Lovell and Freedman, 1976).
