Objective: Opioid dependence is a chronic and complex disorder characterized by relapse and remission. Chronic administration of morphine causes symptoms of physical and psychological dependence. The purpose of the present study was to investigate the effect of anti-addictive drugs such as bupropion and varenicline on morphine dependence and naloxone precipitated withdrawal syndrome in a rat model. Materials and Methods: To assess the physical dependence of morphine, Wistar albino rats were intraperitoneal (i.p.) administered increasing doses of morphine twice daily for 5 days, 4 hours after a single dose of morphine on day 6, and 15 minutes before subcutaneous (s.c.) naloxone (2 mg/kg, s.c.) administration to elicit withdrawal symptoms. Physical dependence was evaluated by giving intraperitoneal bupropion (5, 10 and 20 mg/kg, i.p.) and varenicline (0.5. 1 and 2 mg/kg, s.c) for 15 minutes. Results: The morphine-dependent rats had significantly more withdrawal symptoms than naive control rats. The results demonstrated administration of bupropion and varenicline during induction of morphine dependence attenuated the most of the severity of withdrawal symptoms. Co-administration of bupropion reduced withdrawal symptoms such as jumping, wet dog shaking, weight loss and total withdrawal symptoms. Co-administration of varenicline was found to be effective on withdrawal symptoms such as bupropion, but had no effect on weight loss. Conclusion: These outcomes provide preliminary data that bupropion and varenicline could be used as a candidate drugs to attenuate morphine withdrawal symptoms.