5-HT(3) receptors and neurotransmitter release in the CNS: a nerve ending story?

Serotonin (5-HT) 5-HT(3) receptors are ligand-gated ion channels, which are generally thought to be involved in the presynaptic modulation of neurotransmitter release. However, analysis of published data reveals that most of the evidence for the alleged presynaptic role of 5-HT(3) receptors in modulating CNS neurotransmitter release is not compelling. Nevertheless, 5-HT(3) receptors are present in nerve terminals from some brain regions. The increased basic knowledge of the cellular physiology of central 5-HT(3) receptor ligand-gated ion channels provides opportunities for a detailed characterization of the specific presynaptic effects of 5-HT(3) receptors. Such reconsideration is required for the full appreciation of the functional role of 5-HT(3) receptors in the CNS.