Clozapine and haloperidol in an animal model of sensorimotor gating deficits in schizophrenia

Prepulse inhibition (PPI) of the acoustic startle response is a measure of sensorimotor gating that is impaired in both schizophrenic patients and in rats treated with dopamine agonists. The disruption of PPI by the dopamine agonist apomorphine (APO) is reversed by antipsychotic agents, including the atypical antipsychotic clozapine. Across a range of compounds, the ability of antipsychotics to restore PPI in APO-treated rats correlates significantly with their clinical potency. Since few animal models predict antipsychotic potency for clozapine, we further characterized the effects of clozapine and the typical antipsychotic haloperidol on APO-disrupted and baseline PPI in rats. The APO-induced disruption of PPI caused by intense (15 dB over background) prepulses was reversed in a dose-dependent manner by both clozapine and haloperidol. When weak (1-5 dB over background) prepulses were used, clozapine and haloperidol increased baseline PPI in control animals. Both APO-disrupted and baseline PPI may be useful in screening both typical and atypical antipsychotic agents.