EXAMINATION OF DRUG-INDUCED AND ISOLATION-INDUCED DISRUPTIONS OF PREPULSE INHIBITION AS MODELS TO SCREEN ANTIPSYCHOTIC-DRUGS

Prepulse inhibition (PPI) of an acoustic startle response is impaired in schizophrenics. PPI can also be studied in the rat, and is impaired by dopamine (DA) D-2/3 receptor agonists such as apomorphine. This di sruption is reversed by DA antagonists, leading to proposals that this approach may be a useful means to identify novel antipsychotics. Ther e is also evidence to suggest a role of serotonergic (5-HT) and glutam atergic systems in schizophrenia, and accordingly PPI can be disrupted by the 5-HT2 agonist DOI, and the non-competitive NMDA antagonist, di zocilpine. In the present study we have examined the effect of four an tipsychotic drugs, haloperidol (0.1-0.3 mg/kg), raclopride (0.03-0.3 m g/kg), risperidone (0.3-3 mg/kg) and clozapine (0.0001-10 mg/kg), agai nst the PPI disruptions induced by apomorphine (0.5 mg/kg), DOI (3 mg/ kg) and dizocilpine (0.15 mg/kg). Furthermore, these drugs have been e xamined for their ability to restore a PPI deficit produced by housing rats under conditions of social isolation. All drugs except clozapine reversed an apomorphine-induced disruption. However, clozapine and ri speridone, but not raclopride and haloperidol, reversed a DOI-induced disruption. Only risperidone was effective in restoring a PPI deficit produced by dizocilpine. In contrast to the drug-induced disruptions w hich were differentially sensitive to be various neuroleptics, isolati on-induced disruption were restored by each drug. These results suppor t the idea that non-drug induced disruptions of PPI, such as social is olation, may be a more viable approach to identify novel antipsychotic s.