The DBA/2J strain and prepulse inhibition of startle: a model system to test antipsychotics?

Rationale: Prepulse inhibition (PPI) of the startle response in mice is inc reasingly used as a paradigm of sensory gating with potential predictive an d construct validity towards schizophrenia. Objectives: Establishment of a mouse PPI paradigm in which typical and atypical antipsychotic drugs direct ly improve a low performance PPI. Methods: Three strains of mice - C57B1/6J , 129S6/SvEvTac and DBA/2J - were tested in a startle paradigm with three p repulse intensities, 2, 4 and 8 dB above background. Results: Under these c onditions, risperidone (0, 0.25, 0.5 and 1 mg/kg i.p.) and clozapine (0, 1, 3 and 9 mg/kg i.p.) improved PPI in all three strains, with order of effec t in DBA/2J > 129S6SvEvTac > C57B1/6J. The DBA/2J strain showed larger PPI- enhancing effects, without disturbing the basal startle response. Two alpha (7) nicotinic receptor agonists, GTS-21 (1-10 mg/kg i.p.) and AR-R17779 (1 -10 mg/kg i.p.) were inactive in the PPI procedure in DBA/2J mice. Conclusi ons: DBA/2J mice were very sensitive to the psychotic-like effects of atypi cal (clozapine) and typical (risperidone) antipsychotics, and this strain i s proposed as a model to directly measure sensory gating properties of drug s. alpha (7) Nicotinergic receptor agonists were ineffective in this PPI pa radigm.