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 dis crepant reports related to the ability of clozapine to restore prepuls e inhibition (PPI) of acoustic startle in apomorphine (APO)-treated ra ts. Changes in PPI after APO and clozapine were compared in Sprague-Da wley (SD) versus Wistar rats. In SD rats, intraperitoneal administrati on of clozapine (4-12 mg/kg) completely reversed the PPI-disruptive ef fects of APO (0.5 mg/kg), with significant effects evident at the lowe st dose of clozapine. Compared to SD rats, Wistars exhibited a relativ ely weaker (but statistically significant) disruption of PPI with the same or higher doses of APO and were also less sensitive to the PPI-re storative effects of clozapine. Clozapine administered via subcutaneou s route completely restored PPI after APO treatment in SD rats. Discre pant findings with this model can be attributed to differences in mt s train; SD rats exhibit patterns of drug responses in this model that a re optimal for examining profiles of putative atypical antipsychotics. (C) 1998 American College of Neuropsychopharmacology. Published by El sevier Science Inc.