Examination of drug-induced and isolation-induced disruptions of prepulse inhibition as models to screen antipsychotic drugs

Psychopharmacology (Berl). 1995 Nov;122(1):15-26. doi: 10.1007/BF02246437.


Prepulse inhibition (PPI) of an acoustic startle response is impaired in schizophrenics. PPI can also be studied in the rat, and is impaired by dopamine (DA) D2/3 receptor agonists such as apomorphine. This disruption is reversed by DA antagonists, leading to proposals that this approach may be a useful means to identify novel antipsychotics. There is also evidence to suggest a role of serotonergic (5-HT) and glutamatergic systems in schizophrenia, and accordingly PPI can be disrupted by the 5-HT2 agonist DOI, and the non-competitive NMDA antagonist, dizocilpine. In the present study we have examined the effect of four antipsychotic drugs, haloperidol (0.1-0.3 mg/kg), raclopride (0.03-0.3 mg/kg), risperidone (0.3-3 mg/kg) and clozapine (0.0001-10 mg/kg), against the PPI disruptions induced by apomorphine (0.5 mg/kg), DOI (3 mg/kg) and dizocilpine (0.15 mg/kg). Furthermore, these drugs have been examined for their ability to restore a PPI deficit produced by housing rats under conditions of social isolation. All drugs except clozapine reversed an apomorphine-induced disruption. However, clozapine and risperidone, but not raclopride and haloperidol, reversed a DOI-induced disruption. Only risperidone was effective in restoring a PPI deficit produced by dizocilpine. In contrast to the drug-induced disruptions which were differentially sensitive to the various neuroleptics, isolation-induced disruptions were restored by each drug. These results support the idea that non-drug induced disruptions of PPI, such as social isolation, may be a more viable approach to identify novel antipsychotics.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Drug Evaluation, Preclinical / methods*
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Receptors, Serotonin / physiology
  • Reflex, Startle / drug effects*
  • Reflex, Startle / physiology
  • Social Isolation


  • Antipsychotic Agents
  • Receptors, Dopamine
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Serotonin