5-HT3 receptors and neurotransmitter release in the CNS: a nerve ending story?

Serotonin (5-HT) 5-HT3 receptors are ligand-gated ion channels, which are g enerally thought to be involved in the presynaptic modulation of neurotrans mitter release. However, analysis of published data reveals that most of th e evidence for the alleged presynaptic role of 5-HT3 receptors in modulatin g CNS neurotransmitter release is not compelling. Nevertheless, 5-HT3 recep tors are present in nerve terminals from some brain regions. The increased basic knowledge of the cellular physiology of central 5-HT3 receptor ligand -gated ion channels provides opportunities for a detailed characterization of the specific presynaptic effects of 5 HT3 receptors. Such reconsideratio n is required for the full appreciation of the functional role of 5-HT3 rec eptors in the CNS.