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

J L Wiley

Pharmacology, Biochemistry, and Behavior December 1994 DOI: 10.1016/0091-3057(94)90259-3 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Animal experimental study Peer reviewed
Population Rats
Interventions Clozapine Phencyclidine (PCP)
Measures Prepulse inhibition (PPI) of acoustic startle
Key findings Clozapine had only a limited effect on PCP-induced disruption of prepulse inhibition in rats. The authors argue that the failure of clinically effective antipsychotics from diverse chemical classes to block PCP's effects on PPI suggests this procedure may model attentional deficits in treatment-resistant schizophrenia.

Abstract

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.

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