CLOZAPINES 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 vari ety of drugs, most notably by dopaminergic agonists such as apomorphin e and by phencyclidine (PCP), and related noncompetitive N-methyl-D-as partate (NMDA) antagonists. Apomorphine-induced disruption of PPI is a ntagonized by both typical and atypical neuroleptics. The present stud y examined the effects of the atypical neuroleptic, clozapine, alone a nd in combination with PCP, on PPI in rats. The results of previous st udies suggest that disruption of PPI by PCP and similar drugs is not s ensitive to antagonism by typical neuroleptics such as haloperidol. Th e results of the present study show that clozapine's effect on PCP-ind uced disruption of PPI is also limited. The failure of clinically effe ctive antipsychotics of diverse chemical classes to block the effects of PCP on PPI of acoustic startle suggest that the effects of PCP in t his procedure may represent a model of attentional deficits observed i n treatment-resistant schizophrenia.