SEROQUEL - ELECTROPHYSIOLOGICAL PROFILE OF A POTENTIAL ATYPICAL ANTIPSYCHOTIC

Extracellular single unit recording techniques were employed to compar e the effects of seroquel with the reference antipsychotic (AP) agents clozapine and haloperidol in electrophysiological tests that may pred ict AP activity. Seroquel and clozapine were differentially more activ e in reversing the inhibitory actions of d-amphetamine on mesolimbic ( A10) than nigrostriatal (A9) dopamine (DA)-containing neurons, whereas haloperidol exhibited the opposite selectivity. In cell population st udies, acute treatment with seroquel and clozapine selectively increas ed the number of spontaneously active A10 DA cells, which was found to correlate with the ability of both these drugs to cause depolarizatio n inactivation (DI) of A10 DA cells following repeated (28 day) admini stration. This profile of activity was unlike that of haloperidol, whi ch acutely caused a nonselective increase in the number of active A9 a nd A10 DA cells, associated with the ability of this agent to cause DI of both A9 and A10 DA cells after repeated treatment. Since DI of A10 DA cells may be correlated with AP efficacy whereas DI of A9 DA cells may predict the ability of an AP to cause extrapyramidal side effects (EPS) and tardive dyskinesia (TD), seroquel, like clozapine, may be a n atypical AP with a reduced likelihood for producing EPS/TD.