, Volume 169, Issue 3–4, pp 234–239

Reversal of phencyclidine-induced prepulse inhibition deficits by clozapine in monkeys

  • Gary S. Linn
  • Shobhit S. Negi
  • Scott V. Gerum
  • Daniel C. Javitt
Original Investigation



Prepulse inhibition (PPI) of the acoustic startle reflex is a measure of sensorimotor gating, which occurs across species and is deficient in severe neuropsychiatric disorders such as schizophrenia. In monkeys, as in rodents, phencyclidine (PCP) induces schizophrenia-like deficits in PPI. In rodents, in general, typical antipsychotics (e.g. haloperidol) reverse PPI deficits induced by dopamine (DA) agonists (e.g. apomorphine), but not those induced by N-methyl-d-aspartate (NMDA) receptor antagonists [e.g. phencyclidine (PCP)], whereas atypical antipsychotics (e.g. clozapine) reverse PPI deficits induced by DA agonists and NMDA antagonists. However, some discrepancies exist with some compounds and strains of rodents.


This study investigated whether a typical (haloperidol, 0.035 mg/kg) and an atypical (clozapine, 2.5 mg/kg) antipsychotic could be distinguished in their ability to reverse PCP-induced deficits in PPI in eight monkeys (Cebus apella).


First, haloperidol dose was determined by its ability to attenuate apomorphine-induced deficits in PPI. Then, haloperidol and clozapine were tested in eight monkeys with PCP-induced deficits of PPI. Experimental parameters were similar to standard human PPI procedures, with 115 dB white noise startle pulses, either alone or preceded by 120 ms with a prepulse 16 dB above the 70 dB background noise.


Clozapine reversed PCP-induced PPI deficits. In contrast, haloperidol did not significantly attenuate PCP-induced PPI deficits even at doses that significantly attenuated apomorphine effects.


In this primate model, clozapine was distinguishable from haloperidol by its ability to attenuate PCP-induced deficits in PPI. The results provide further evidence that PPI in nonhuman primates may provide an important animal model for the development of novel anti-schizophrenia medications.


Apomorphine Clozapine Haloperidol NMDA receptor Non-human primate model Phencyclidine (PCP) Prepulse inhibition (PPI) Schizophrenia Neuroleptic sensitization Sensorimotor gating 


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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Gary S. Linn
    • 1
    • 2
  • Shobhit S. Negi
    • 1
  • Scott V. Gerum
    • 1
  • Daniel C. Javitt
    • 1
    • 2
  1. 1.The Nathan S. Kline Institute for Psychiatric ResearchOrangeburgUSA
  2. 2.Department of PsychiatryNew York University School of MedicineNew YorkUSA

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