Of mice and flies: commonalities among 5-HT receptors

Pharmacological studies as well as molecular cloning of 5-HT receptors have revealed a multiplicity of receptor subtypes, not only in mammals but, as discussed in this review by René Hen, also in molluscs and arthropods. Most of these receptors belong to the G protein-coupled receptor family, and their mechanism of action involves modulating levels of second messengers such as cAMP, IP3 and Ca2+. Rather than being specialized in a particular physiological function, a given receptor may be expressed in multiple neurons throughout the brain but always in the same compartment in these neurons. The 5-HT1B receptor, for example, is generally localized presynaptically on neuronal terminals, where it inhibits neurotransmitter release. A widespread distribution of 5-HT receptors might explain how 5-HT can modulate the multiple neuronal circuits that underlie complex behaviours.