Multiple serotonin receptors: too many, not enough, or just the right number?

In this manuscript, current knowledge about central nervous system serotonin (5-HT) receptors is discussed with an emphasis toward describing the functional significance of the multiple 5-HT receptors. Five characteristics of 5-HT receptors, which are hypothesized to contribute to this functional significance, are discussed: (a) 5-HT has varying affinity and potency for the different receptor subtypes; (b) multiple transduction pathways are used by the different receptor subtypes; (c) receptor subtypes differ in their susceptibility to agonist-mediated desensitization/downregulation; (d) receptor subtypes interact in mediating cellular responses to the neurotransmitter; and (e) receptor subtypes respond differently to changes in the physiological environment. It is hypothesized that these characteristics of the multiple neurotransmitter receptors provide the nervous system with a capacity for coding and decoding of 5-HT-mediated neuronal transmission that could not take place with a single neurotransmitter receptor. Serotonergic regulation of female reproduction and regulation of glucocorticoid release are used to illustrate the integrative potential deriving from the existence of multiple 5-HT receptors.