Ameliorative effects of varenicline and bupropion on morphine-induced conditioned place preference in rats

Background: Rewarding properties of morphine constitue the principal reasons for drug-craving behaviors which appear during morphine addiction. Varenicline and bupropion were reported to have some positive effects on addictive substances by different studies. In this study, the effects of varenicline and bupropion on morphine rewarding properties were investigated via conditioned place preference (CPP) in rats.Methods: Conditioning was performed by intraperitoneal (i.p.) administration of morphine (10 mg/kg, i.p., 1, 3, 5, and 7 days) and saline (2,4, 6, and 8 days). To evaluate the development of dependence, subcutaneous administration of varenicline (0.5, 1 and 2 mg/kg, s.c.) or bupropion (5, 10 and 20 mg/kg, i.p.) was carried out 15 minutes before the administration of morphine. To evaluate the expression of dependence, varenicline or bupropion was administered 15 minutes before the test on 9th day. To investigate the extinction of the reward effect, drugs were tested daily on days 14, 18, and 22 and evaluated for reinstatement on 23rd day.Results: Systemic morphine administration statistically significant produced CPP. Varenicline and bupropion did not reduce the development of morphine-induced CPP. In addition, varenicline and bupropion decreased expression, reinstatement and accelerated the extinction of morphine-induced CPP. Unlike varenicline, bupropion statistically significant produced CPP and altered locomotor activity.Conclusions: These data suggest that varenicline and bupropion may be useful therapeutic pharmacological agents to reduce morphine dependence. The results of our research provide preliminary evidence to highlight the importance of the effects of varenicline and bupropion on morphine dependence. In the future, it would be appropriate to conduct mechanistic studies to explain the underlying mechanisms by using different methods on the subject.