Background: In our previous study, we demonstrated that oak hydroalcoholic extract improves memory impairment in a postpartum depression model due to its antioxidant properties. The purpose of this study is to further investigate the effect of oak on another amnesia model and explore the mediating role of cholinergic muscarinic receptors. Objectives: This study investigated the effect of hydroalcoholic extract of oak fruit on amnesia induced by morphine in the presence and absence of cholinergic muscarinic receptors, as well as changes in serum biochemical factors. Methods: In this experimental study, adult male mice were divided into groups: Control and morphine-receiving (5 and 7.5 mg/kg) groups to induce amnesia after training. In the groups receiving 7.5 mg/kg morphine, oak extract (1 and 10 mg/kg) was administered one day after training and continued for one week. Atropine (0.1 and 1 mg/kg) was injected only on the first day after training and before the oak extract injection. Passive avoidance memory was evaluated 1, 3, and 7 days after training using a step-down device. Motor activity was assessed using the open field test. Blood biochemical factors, including triglycerides, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total antioxidant capacity (TAC), were measured after one week of injections. Results: Morphine (7.5 mg/kg) impaired memory on days 1 and 7 (P < 0.05), while oak extract (1 and 10 mg/kg) improved memory (P < 0.001). Additionally, the oak extract maintained its enhancing effect even in the presence of atropine, a cholinergic muscarinic system antagonist. Oak extract significantly increased HDL and TAC levels but did not affect LDL, cholesterol, and triglyceride levels. Conclusions: These findings suggest that oak extract can improve morphine-induced amnesia due to its antioxidant effect, without involving the cholinergic system. Additionally, oak extract can increase beneficial lipids without affecting harmful lipids.
