SEROQUEL (ICI-204,636) RESTORES PREPULSE INHIBITION OF ACOUSTIC STARTLE IN APOMORPHINE-TREATED RATS - SIMILARITIES TO CLOZAPINE

Seroquel (ICI 204,636) is a mixed D-2/5HT(2) antagonist with a preclin ical profile suggestive of potential antipsychotic efficacy. We compar ed seroquel to clozapine in an animal model of sensorimotor gating def icits in shizophrenic patients. Like schizophrenic patients, rats trea ted with apomophrine (APO) exhibit deficits in prepulse inhibition (PP I) of acoustic startle. The ability of antipsychotics to restore PPI i n APO-treated rats correlates (R(s) = 0.991) with their clinical poten cy. Seroquel and clozapine both restore PPI in APO-treated rats. Seroq uel's restoration of PPI in apomorphine-treated rats follows simple mo notonic ascending dose-response properties, and is not accompanied by consistent changes in startle reflex amplitude. Seroquel's profile in this PPI model mimics that of other antipsychotics.