Background One of the mechanisms associated with morphine neurotoxicity is oxidative stress. Jujube fruit extract may reduce oxidative stress due to its antioxidant properties. Objective This study aims to investigate the protective effect of jujube fruit extract on the Acetylcholinesterase (AchE) activity and oxidative stress in the cortex and serum of morphine-treated male rats. Materials and Methods In this experimental study, 42 male Wistar rats were randomly divided into six groups of 7 which were given oral administration of jujube extract (100 and 200 mg/kg) and intraperitoneal injection of 0.5 mg/kg morphine for 30 days. After blood collection, separation of the serum, and homogenization of brain tissue, the activities of Catalase (CAT), AchE, and Superoxide Dismutase (SOD) enzymes were assessed. Collected data were analyzed using one-way ANOVA. Results Oral administration of jujube extract at doses of 100 and 200 mg/kg significantly increased the activity of AchE, CAT, and SOD in the serum and cortex of rats compared to morphine injection (P<0.01). Oral administration of 200 mg/kg jujube extract plus morphine injection significantly increased the activity of cortical AchE compared to morphine injection alone (P<0.01). Conclusion Jujube extract can prevent the side effects of morphine in the cortex by increasing antioxidant activity
