title: Drug-induced potentiation of prepulse inhibition of acoustic startle reflex in mice: a model for detecting antipsychotic activity?
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: F. Hoffmann-La Roche Ltd., Preclinical CNS Research, Basel, Switzerland. abdel@igbmc.u-strasbg.fr
authors.forename: A M
authors.initials: AM
authors.lastname: Ouagazzal
authors.forename: F
authors.initials: F
authors.lastname: Jenck
authors.forename: J L
authors.initials: JL
authors.lastname: Moreau
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006185:Habituation, Psychophysiologic; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011619:Psychotropic Drugs / Q000494:pharmacology; D013216:Reflex, Startle / Q000187:drug effects*; D013045:Species Specificity; D013268:Stimulation, Chemical
chemical_list: D014150:Antipsychotic Agents; D011619:Psychotropic Drugs