Electrophysiology of Central Serotonin Receptor Subtypes

The possibility that multiple serotonin (5-HT) receptors exist in the CNS was first suggested by microiontophoretic studies in the cerebral cortex (Roberts and Straughan, 1967) and subcortical regions (Haigler and Aghajanian, 1974). In these early experiments, putative 5-HT antagonists, such as methysergide and cinanserin, blocked excitatory but not inhibitory effects of 5-HT, indicating that at least two types of 5-HT receptors may be present in the brain, one for excitation and one for inhibition. Subsequently, radioligand-binding techniques disclosed the presence of multiple 5-HT binding sites in the brain. As reviewed elsewhere in this volume, this conclusion derives from the finding that the neuroleptic agent [3H]spiperone labels 5-HT binding sites in the frontal cortex (Creese and Snyder, 1978; Leysen and Laduron, 1977; Leysen et al., 1978) that exhibit features distinct from those sites labeled by [3H]5-HT itself (Peroutka and Snyder, 1979). At the [3H] spiperone-labeled site, putative 5-HT antagonists display nanomolar affinities, whereas 5-HT and 5-HT agonists bind in the micromolar concentration range (Peroutka and Snyder, 1983). Conversely, 5-HT and certain 5-HT agonists display more potent binding affinities than antagonists at the [3H]5-HT-labeled site.