Clozapine's effects on phencyclidine-induced disruption of prepulse inhibition of the acoustic startle response.

The reduction in magnitude of the startle reflex in response to a loud noise produced by prior presentation of a stimulus of lower intensity is known as prepulse inhibition (PPI). PPI may be disrupted by a variety of drugs, most notably by dopaminergic agonists such as apomorphine and by phencyclidine (PCP), and related noncompetitive N-methyl-D-aspartate (NMDA) antagonists. Apomorphine-induced disruption of PPI is antagonized by both typical and atypical neuroleptics. The present study examined the effects of the atypical neuroleptic, clozapine, alone and in combination with PCP, on PPI in rats. The results of previous studies suggest that disruption of PPI by PCP and similar drugs is not sensitive to antagonism by typical neuroleptics such as haloperidol. The results of the present study show that clozapine's effect on PCP-induced disruption of PPI is also limited. The failure of clinically effective antipsychotics of diverse chemical classes to block the effects of PCP on PPI of acoustic startle suggest that the effects of PCP in this procedure may represent a model of attentional deficits observed in treatment-resistant schizophrenia.