Discrepant findings of clozapine effects on prepulse inhibition of startle: is it the route or the rat?

Studies examined methodological differences that might account for discrepant reports related to the ability of clozapine to restore prepulse inhibition (PPI) of acoustic startle in apomorphine (APO)-treated rats. Changes in PPI after APO and clozapine were compared in Sprague. Dawley (SD) versus Wistar rats. In SD rats, intraperitoneal administration of clozapine (4-12 mg/kg) completely reversed the PPI-disruptive effects of APO (0.5 mg/kg), with significant effects evident at the lowest dose of clozapine. Compared to SD rats, Wistars exhibited a relatively weaker (but statistically significant) disruption of PPI with the same or higher doses of APO and were also less sensitive to the PPI-restorative effects of clozapine. Clozapine administered via subcutaneous route completely restored PPI after APO treatment in SD rats. Discrepant findings with this model can be attributed to differences in rat strain; SD rats exhibit patterns of drug responses in this model that are optimal for examining profiles of putative atypical antipsychotics.