Interactions between 5-HT3 receptors and cerebral dopamine function: implications for the treatment of schizophrenia and psychoactive substance abuse

Abstract

This article reviews current knowledge on the interaction between 5-hydroxytryptamine (5-HT), acting at 5-HT3 receptors in the CNS, and cerebral dopamine systems. Since 1987, a growing body of behavioural, neurochemical and electrophysiological evidence from animal studies has demonstrated a clear role for 5-HT3 receptors in the modulation of activity of mesolimbic and mesocortical dopamine neurones. This evidence has led to the suggestion that 5-HT3 receptor antagonists have potential as novel antipsychotic agents and may also find use in the treatment of psychoactive substance abuse. Data emerging from clinical studies generally support this hypothesis and suggest that 5-HT3 antagonists may prove to be among the first agents available to treat schizophrenia which are not dopamine D2 antagonists and hence lack their side-effect problems.