Olanzapine Sensitization and Clozapine Tolerance: From Adolescence to Adulthood in the Conditioned Avoidance Response Model

摘要: Disruption of conditioned avoidance response (CAR) in rodents is one trademark feature many antipsychotic drugs. In adult rats, repeated olanzapine (OLZ) treatment causes an enhanced disruption (sensitization), whereas clozapine (CLZ) a decreased (tolerance). The present study addressed (1) whether OLZ sensitization and CLZ tolerance can be induced adolescent (2) the extent to which adolescence persists into adulthood. Male Sprague–Dawley rats (approximate postnatal days (∼P) 43–47) were first treated with (1.0 or 2.0 mg/kg, subcutaneously (sc)) (10 20 mg/kg, sc) daily for 5 consecutive CAR model. They then tested expression either (∼P 50) after they matured adults 76 92) challenge test during all injected lower dose (0.5 mg/kg) (5.0 mg/kg). When adolescence, previously showed stronger inhibition than those vehicle (ie, sensitization). contrast, weaker tolerance). adulthood, was still detectable at both time points 92), only on ∼P 76, manifested intertrial crossing. Performance prepulse fear-induced 22 kHz ultrasonic vocalizations adulthood not altered by drug treatment. Collectively, these findings suggest that atypical induce long-term specific alteration effect despite brain maturation. As drugs are being increasingly used children adolescents past two decades, from this important understanding impacts behavioral developments. This work also has implications clinical practice involving treatments terms choice, dose, schedule.