title: Prepulse inhibition of the startle reflex and response to antipsychotic treatments in two outbred mouse strains in comparison to the inbred DBA/2 mouse.
abstract: BACKGROUND
  Naturally low prepulse inhibition (PPI) in DBA/2 mice is increased by marketed antipsychotics and compounds acting at novel targets relevant to schizophrenia. Whether other mouse strains with naturally low PPI respond similarly and could be translational models of schizophrenia is unknown.
  
  
  OBJECTIVE
  Baseline levels of PPI were determined in outbred CF-1 and Black Swiss mice. CF-1 and Black Swiss mice were then compared to DBA/2 mice for their responses to typical (haloperidol) and atypical (clozapine) antipsychotics and to compounds with potential antipsychotic activity, a histamine H(3) receptor antagonist (thioperamide) and a glycine transporter-1 inhibitor (SSR504734).
  
  
  RESULTS
  CF-1 and Black Swiss mice had naturally low PPI, similar to the level in C57BL/6 mice, but higher than that in DBA/2 mice. Haloperidol (0.3-1 mg/kg) increased PPI in DBA/2, CF-1, and Black Swiss mice. Clozapine (3 mg/kg) increased PPI in DBA/2 and CF-1 mice, but not in Black Swiss mice. Thioperamide (10-30 mg/kg) and SSR504734 (30 mg/kg) increased PPI only in DBA/2 mice. Strain differences in PPI responsiveness were not due to differences in brain concentrations of the tested compounds.
  
  
  CONCLUSIONS
  CF-1 mice with naturally low PPI may be useful for testing typical and atypical antipsychotics while Black Swiss mice only responded to a typical antipsychotic. DBA/2 mice remain the only strain with naturally low PPI that responds to marketed antipsychotics, as well as to compounds with novel mechanisms of action. Thus, DBA/2 mice may be the strain of choice for screening novel chemical entities for their ability to increase PPI.
authors.affiliation: EnVivo Pharmaceuticals, Inc, 480 Aresenal St, Watertown, MA 02472, USA. dgfloodpa@gmail.com
authors.forename: Dorothy G
authors.initials: DG
authors.lastname: Flood
authors.forename: Eva
authors.initials: E
authors.lastname: Zuvich
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Marino
authors.forename: Maciej
authors.initials: M
authors.lastname: Gasior
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013216:Reflex, Startle / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D013045:Species Specificity
chemical_list: D014150:Antipsychotic Agents