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 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-HT3 receptors in modulating CNS neurotransmitter release is not compelling. Nevertheless, 5-HT3 receptors 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 reconsideration is required for the full appreciation of the functional role of 5-HT3 receptors in the CNS.