Ghorbani_2025_Res.Pharm.Sci_20_218

BACKGROUND AND PURPOSE: Melatonin is a product of the pineal gland, which regulates the circadian cycle. Neurotoxicity is the most important side effect of methamphetamine (Met) abuse during pregnancy. This study aimed to explore the effect of Met exposure during gestation and lactation periods on the learning and memory of offspring mice. The protective effect of melatonin and the role of oxidative stress and acetylcholinesterase were also investigated. EXPERIMENTAL APPROACH: The pregnant mice were randomly divided into 2 groups. Saline or Met (5 mg/kg) was injected daily during pregnancy and lactation. After the lactation period, the offspring mice of each group were divided into 2 subgroups, and saline or melatonin (10 mg/kg) was orally (gavage) administered to the offspring mice from the post-delivery (PD) day 21 up to PD Day 60. The offspring mice were examined in the passive avoidance (PA) test. Finally, oxidative stress markers and acetylcholinesterase (AchE) activity were measured in the brains. FINDINGS/RESULTS: As a result, Met decreased delay and light time while increasing the frequency of entry and time in the dark region of PA. However, melatonin alleviated the impairing effect of Met on PA performance. Meanwhile, the administration of Met increased malondialdehyde while decreasing superoxide dismutase and thiol content. Furthermore, AchE activity was significantly increased in Met-treated mice. Melatonin reversed the levels of antioxidants, lipid peroxidation, and AchE activity in the brain. CONCLUSION AND IMPLICATIONS: Together, these results suggested that melatonin may be a potential therapeutic agent for alleviating Met-induced memory impairment by restoring redox hemostasis and AchE.