Drug-induced potentiation of prepulse inhibition of acoustic startle reflex in mice: a model for detecting antipsychotic activity?

Psychopharmacology (Berl). 2001 Jul;156(2-3):273-83. doi: 10.1007/s002130100763.


Rationale: Schizophrenic patients typically have impaired startle habituation (SH) and prepulse inhibition of the startle reflex (PPI). PPI can be disrupted in rats by psychomimetics, and drug-induced reversal of this deficit is considered to predict potential antipsychotic properties. Certain strains of mice, such as C57BL/6J, naturally display poor PPI.

Objective: To test whether mice spontaneously showing low levels of PPI might prove a useful tool for detecting novel antipsychotics.

Methods: PPI and SH were evaluated in four strains of mice: BALB/cByJ, MORO, 129/SvEv and C57BL/6J. The effects of antipsychotic [haloperidol (1, 3 and 6 mg/kg), clozapine (0.3, 1, 3 and 30 mg/kg) and risperidone (0.1, 0.3 and 1 mg/kg)] and non-antipsychotic [diazepam (3, 10 and 30 mg/kg), buspirone (1, 3 and 10 mg/kg), desipramine (3, 10 and 30 mg/kg), morphine (3, 10 and 30 mg/kg) and scopolamine (0.3, 1 and 3 mg/kg)] drug treatments were studied on PPI.

Results: Haloperidol (6 mg/kg), clozapine (3 and 30 mg/kg), and risperidone (1 mg/kg) all significantly enhanced PPI in C57BL/6J. All non-antipsychotics failed to improve PPI in this strain, except diazepam. Facilitation of PPI was also obtained in the other strains; however, clear interstrain differences were observed depending on the class of antipsychotic used and on the level of prepulse intensity.

Conclusion: Antipsychotic-induced facilitation of PPI is clearly detected in mice naturally exhibiting poor levels of sensorimotor gating (e.g., C57BL/6J), but is also observed in other strains of mice. The use of this procedure as a potential screening test for detecting novel antipsychotic medications is discussed.

Publication types

  • Comparative Study

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Antipsychotic Agents / pharmacology*
  • Drug Evaluation, Preclinical
  • Habituation, Psychophysiologic
  • Male
  • Mice
  • Mice, Inbred Strains
  • Psychotropic Drugs / pharmacology
  • Reflex, Startle / drug effects*
  • Species Specificity
  • Stimulation, Chemical


  • Antipsychotic Agents
  • Psychotropic Drugs