산화 스트레스 조절이 코카인 및 신타케인 유발 행동에 미치는 영향

Effects of Oxidative Stress Modulation on Cocaine- and Synthacaine-induced Behavior

Oxidative stress has emerged as a critical mediator in the neurobiological mechanisms underlying drug addiction, affecting neuronal integrity, neurotransmission, and reward circuitry. Reactive oxygen species (ROS), produced excessively following drug exposure, induce oxidative damage and neuroadaptive changes that contribute significantly to substance use disorders. Although endogenous antioxidant systems, including superoxide dismutase, catalase, glutathione peroxidase (GPX), and peroxiredoxin (PRDX), act to counterbalance ROS-induced damage, their precise roles in addiction remain underexplored. This study investigates whether impaired antioxidant defenses contribute to enhanced stimulant sensitivity using glutathione peroxidase-1 (GPX1) knockout (KO) and peroxiredoxin-6 (PRDX6) overexpression (OE) mouse models. GPX1 KO mice exhibited enhanced conditioned place preference (CPP) to cocaine and synthacaine, suggesting increased vulnerability due to impaired antioxidant defense. Conversely, PRDX6 OE mice demonstrated heightened locomotor responses following cocaine administration, reflecting complex regulatory mechanisms involving antioxidant systems in stimulant-induced behavioral adaptations. Taken together, this study suggests that antioxidant-based strategies to restore the balance of oxidative stress pathways may provide an important therapeutic target for stimulant-induced behavior.