Modulation of the A10 dopamine system: electrophysiological studies of the role of 5-HT3-like receptors.

The distribution of 5-HT3-like receptors is primarily in the mesocorticolimbic structures. We have previously demonstrated that the atypical antipsychotic drug clozapine and a structurally related compound RMI 81,582 differ from other typical antipsychotic drugs in that they are effective 5-HT3 receptor antagonists. Our experimental results suggest that 5-HT3-like receptors play a permissive role in regulating or gating the inhibitory action of dopamine in the mesocorticolimbic areas. We hypothesize that the ability of clozapine to antagonize both 5-HT3-like and dopamine receptors may account for its preferential interaction with the mesocorticolimbic dopamine system and the higher efficacy in treating the schizophrenic symptoms.