Hossain Mohammadpour Kargar1* and Yousof Mousavi
Objective: Methamphetamine (Met) is a highly addictive psychostimulant that elevates the amount of dopamine in the brain. Dopamine accumulation leads to oxidative stress and eventually induces brain damage. Alpha-Lipoic Acid (ALA) is a potent natural antioxidant in the body, and reduction of oxidative stress by ALA has been shown in animal models. In this study, we investigated the effects of intraperitoneal administration of alpha-lipoic acid on anxiety-like behaviors, pain perception, and oxidative stress in the periaqueductal gray in Met-induced neurotoxicity.
Methods: Thirty-five male Wistar rats were divided into five equal groups: 1) saline+saline, 2) saline+vehicle (sunflower oil as ALA solvent), 3) Met+vehicle, 4) Met+ALA (10 mg/kg), and 5) Met+ALA (40 mg/kg). Rats received methamphetamine repeatedly (2 × 20 mg/kg, 2 hour interval), and alpha-lipoic acid was injected 30 minutes, 24 hours, and 48 hours after the last methamphetamine injection. We used the tail flick test to evaluate pain perception and the open field test to evaluate anxiety-like behaviors. After the behavioral tests, we anesthetized the rats, extracted their brains, prepared periaqueductal gray matter homogenates, and evaluated Malondialdehyde (MDA) level, Catalase (CAT), and Superoxide Dismutase (SOD) activities.
Results: Met administration not only induced hyperalgesia and anxiety-like behaviors, but also increased MDA levels and reduced CAT and SOD activities in the periaqueductal gray matter area. Treatment with ALA decreased MDA levels, increased CAT and SOD activities, and prevented hyperalgesia and anxiety-like behaviors.
Conclusion: Our results showed that Met administration induced hyperalgesia, anxiety-like behaviors, oxidative stress, and impaired antioxidant defenses in the PAG. Administration of ALA decreased oxidative stress in the periaqueductal gray matter area by elevating SOD and CAT activity and reduced hyperalgesia and anxiety-like behaviors following acute Met administration.
