SEROQUEL RESTORES SENSORIMOTOR GATING IN PHENCYCLIDINE-TREATED RATS

Phencyclidine (PCP) is a psychotomimetic noncompetitive glutamate anta gonist that has been used in studies of the neural substrates of psych osis. Both schizophrenic patients and PCP-treated rats exhibit reduced amounts of prepulse inhibition (PPI) of the startle reflex, which is the normal inhibition of startle that occurs when the startling noise is preceded 30 to 500 msec by a weak prepulse. The present study asses sed the effects of seroquel (ICI 204,636), a mixed D2/5-hydroxytryptam ine(2) antagonist with a preclinical profile suggestive of potential a ntipsychotic efficacy, on the PCP-induced disruption of PPI. Clozapine , risperidone and haloperidol were also studied as comparison compound s. PCP (1.25 mg/kg) significantly reduced PPI, with prepulses that wer e 1 to 12 dB above background. Seroquel and clozapine significantly re stored PPI in PCP-treated rats, whereas haloperidol and risperidone di d not. Similar findings were obtained in studies using separate animal s, a slightly lower dose of PCP (1.0 mg/kg) and a high dose of each of these antipsychotics. Separate studies verified that risperidone and haloperidol restored PPI in apomorphine-treated rats. In the present s tudies, seroquel exhibited a profile consistent with those exhibited b y other ''atypical'' antipsychotics,.