Antagonism of phencyclidine-induced deficits in prepulse inhibition by the putative atypical antipsychotic olanzapine.
V P Bakshi, M A Geyer
Psychopharmacology November 1995 DOI: 10.1007/bf02246096 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Animals (rats) treated with PCP or dizocilpine |
| Interventions | Olanzapine Phencyclidine (PCP) Dizocilpine (MK-801) |
| Dose | Olanzapine 0, 1.25, 2.5, 5.0 or 10.0 mg/kg; PCP 1.5 mg/kg; dizocilpine 0.1 mg/kg |
| Measures | Prepulse inhibition (PPI) of the startle reflex, baseline startle reactivity |
| Key findings | At the two highest doses tested (5.0 and 10.0 mg/kg), olanzapine significantly increased prepulse inhibition in animals whose gating deficits were induced by PCP (1.5 mg/kg) or dizocilpine (0.1 mg/kg), without affecting PPI or baseline startle reactivity when given alone. The authors argue this supports olanzapine being functionally similar to clozapine and potentially useful as an atypical antipsychotic. |
Abstract
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.
Citations in the library
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- Time course of the attenuation effect of repeated antipsychotic treatment on prepulse inhibition disruption induced by repeated phencyclidine treatment. Pharmacology, Biochemistry, and Behavior June 2011
- T-817MA, a novel neurotrophic compound, ameliorates phencyclidine-induced disruption of sensorimotor gating. Psychopharmacology April 2008
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