Abstract
•METH causes neuroinflammation, abnormal neurogenesis, and cognitive impairment with notable sexual dimorphism.•Exercise is a behavioral intervention that offers protection against METH-induced toxicity.•The protective effect of physical exercise against METH-induced toxicity depends on the activity level.
One of the outcomes of methamphetamine (METH) misuse is impaired hippocampal function. In addition, regular physical exercise has been proposed as an effective behavioral intervention with numerous health benefits, particularly in the treatment of drug misuse. In this study, we evaluated the impact of physical exercise on METH-induced neurotoxicity and inflammation in male and female adult mice. Importantly, we assessed whether the protective effects of exercise vary depending on activity levels. Our findings indicate that METH causes neuroinflammation, abnormal neurogenesis, and cognitive impairment in mice, with notable sexual dimorphism in response to METH toxicity. In addition, the protective effect of physical exercise against METH-induced neuroinflammation and neurogenesis impairment depended on the activity level. Overall, our results indicate the importance of introducing tailored physical exercise protocols into treatment and recovery strategies for individuals who misuse psychoactive substances, such as METH.