Prepulse inhibition as a screening test for potential antipsychotics

Abstract

Abstract Startle response amplitude is greatly reduced by a low intensity pulse presented 100 msec prior to the startle stimulus. The magnitude of this prepulse inhibition (PPI) is reduced in schizophrenic patients. In rats, apomorphine disrupts PPI; haloperidol antagonizes apomorphine's effects. We tested the antipsychotic drugs haloperidol, chlorpromazine, clozapine, and risperidone, and the non‐antipsychotic psychopharmacological agents diazepam, buspirone, and imipramine for their ability to antagonize apomorphine's effects on PPI of the acoustic startle reflex. Haloperidol, chlorpromazine, and risperidone antagonized apomorphine's blockade of PPI. Clozapine antagonized apomorphine's effect only at a dose that decreased startle amplitude by 82%. Imipramine and diazepam did not antagonize apomorphine's effect at behaviorally relevant doses. Buspirone weakly antagonized apomorphine blockade of PPI, but, like apomorphine, disrupted PPI when given alone. These results suggest that this PPI test may provide a useful screening procedure for compounds wtih antipsychotic activity. However, the lack of a robust clozapine effect needs to be investigated.