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.
Wang
R Y
RY
Dept. of Psychiatry and Behavioral Sciences, SUNY at Stony Brook 11794-8790, USA.
Ashby
C R
CR
Zhang
J Y
JY
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D006801:Humans; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology
D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D012701:Serotonin; D003024:Clozapine; D004298:Dopamine