Antagonism of phencyclidine-induced deficits in prepulse inhibition by the putative atypical antipsychotic olanzapine
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Prepulse inhibition (PPI) of the startle reflex provides an operational measure of sensorimotor gating. Deficits in PPI are observed in schizophrenia patients and can be modelled in animals by administration of noncompetitive NMDA antagonists such as phencyclidine (PCP) or dizocilpine (MK-801). Previous studies indicate that the atypical antipsychotic clozapine restores PPI in PCP-treated animals while the typical antipsychotic haloperidol does not. Olanzapine (LY170053) is a novel putative atypical antipsychotic that shares many pharmacological and behavioral properties with clozapine. The present study assessed the ability of olanzapine (0, 1.25, 2.5, 5.0 or 10.0 mg/kg) to antagonize deficits in PPI produced by PCP (1.5 mg/kg) and dizocilpine (0.1 mg/kg). At the two highest doses, olanzapine significantly increased PPI in PCP- and dizocilpine-treated animals without affecting PPI or baseline startle reactivity by itself. These results support the notion that olanzapine is functionally similar to clozapine and may have utility as an atypical antipsychotic agent.
Key wordsSchizophrenia Clozapine Startle Sensorimotor gating NMDA Dizocilpine
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- Beasely CM, Tollefson G, Tran P, Satterlee W, Sanger T, Hamilton, S and the Olanzapine HGAD Study Group (1995) Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology (in press)Google Scholar
- Coward DM (1992) General pharmacology of clozapine. Br J Psychiatry 160 [Suppl 17]:5–11Google Scholar
- Geyer MA, Swerdlow NR, Mansbach RS, Braff DL (1990) Startle response models of sensorimotor gating and habituation deficits in schizophrenia. Brain Res Bull 25:485–498Google Scholar
- Moore NA, Calligaro DO, Wong DT, Bymaster F, Tye NC (1993) The pharmacology of olanzapine and other new antipsychotic agents. Curr Op Investig Drugs 2:281–293Google Scholar
- Schwarzkopf SB, Al-Amin HA, Ison JR (1994) Clozapine, but not D1/D2 dopamine antagonists, reverses sensorimotor gating deficits and hypermotility induced by an NMDA antagonist: pathophysiologic implications. Soc Neurosci Abstr 20:25Google Scholar