Olanzapine antagonizes the acquisition and expression of morphine-induced conditioned place preference in male and female mice

Introduction: Several investigations have indicated that dopamine D-2 receptors could influence morphine reward. The influence of olanzapine (a D-2 dopamine receptor antagonist) on the morphine-induced conditioned place preference (CPP) in male and female mice was investigated in the present study. Methods: The effects of olanzapine on the acquisition and expression of morphine CPP in male and female N-MRI mice (W: 20-25 g) were investigated in the present study. Resultd: Subcutaneous (s.c.) injection of morphine (1-10 mg/kg, three drug sessions) induced place preference both in male and female mice. Intraperitoneal (i.p.) administration of olanzapine (0.5-5 mg/kg) induced place aversion (CPA) in female mice but not in male mice. Administration of olanzapine (1, 2.5, 5 mg/kg, i.p.) reduced both the acquisition and expression of morphine-induced CPP in male and female mice. However, olanzapine (5 mg/kg, i.p.) caused more than 80% mortality in female but not male mice. The effects of olanzapine were reversed by L-arginine (20 mg/kg, i.p.) pre-administration. Conlusion: We conclude that olanzapine reduced morphine effects via different mechanism/s.