, Volume 122, Issue 2, pp 198–201 | Cite as

Antagonism of phencyclidine-induced deficits in prepulse inhibition by the putative atypical antipsychotic olanzapine

  • Vaishali P. Bakshi
  • Mark A. Geyer
Rapid Communication


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 words

Schizophrenia Clozapine Startle Sensorimotor gating NMDA Dizocilpine 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bakshi VP, Swerdlow NR, Geyer MA (1994) Clozapine antagonizes phencyclidine-induced deficits in sensorimotor gating of the startle response. J Pharmacol Exp Ther 271:787–794PubMedGoogle Scholar
  2. 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
  3. Coward DM (1992) General pharmacology of clozapine. Br J Psychiatry 160 [Suppl 17]:5–11Google Scholar
  4. 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
  5. Hoffman DC (1992) Typical and atypical neuroleptics antagonize MK-801-induced locomotion and stereotypy in rats. J Neural Transm 89:1–10CrossRefGoogle Scholar
  6. Hoffman DC, Donovan H, Cassella JV (1993) The effects of haloperidol and clozapine on the disruption of sensorimotor gating induced by the noncompetitive glutamate antagonist MK-801. Psychopharmacology 111:339–344CrossRefPubMedGoogle Scholar
  7. Johansson C, Jackson DM, Svensson L (1994) The atypical antipsychotic, remoxipride, blocks phencyclidine-induced disruption of prepulse inhibition in the rat. Psychopharmacology 116:437–442CrossRefPubMedGoogle Scholar
  8. Kane J, Honigfeld G, Singer J, Meltzer H (1988) Clozapine for the treatment-resistant schizophrenic. Arch Gen Psychiatry 45:789–796PubMedGoogle Scholar
  9. Moore NA, Tye NC, Axton MS, Risius FC (1992) The behavioral pharmacology of olanzapine, a novel “atypical” antipsychotic agent. J Pharmacol Exp Ther 262:545–551PubMedGoogle Scholar
  10. 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
  11. 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
  12. Swerdlow NR, Geyer MA (1993) Clozapine and halperidol in an animal model of sensorimotor gating deficits in schizophrenia. Pharmacol Biochem Behav: 44:741–744CrossRefPubMedGoogle Scholar
  13. Swerdlow NR, Braff DL, Taaid N, Geyer MA (1994) Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry 51:139–154PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Vaishali P. Bakshi
    • 1
  • Mark A. Geyer
    • 1
  1. 1.Departments of Neurosciences and PsychiatryUniversity of California at San DiegoLa JollaUSA

Personalised recommendations