Abstract
The adolescent brain, characterized by its high plasticity, is particularly vulnerable to substance abuse, leading to long-term impacts on brain function and behavior. Methamphetamine (METH), a potent psychostimulant, is associated with severe neurological and psychiatric consequences. While most studies focus on METH exposure in adulthood, little is known about the effects of adolescent METH exposure. In this study, we explored the long-term effects of adolescent METH exposure on brain function and behavior in adulthood using a mouse model. Mice were administered METH for 8 days during adolescence, and their behavior was analyzed in adulthood. METH-exposed mice (METH mice) displayed anxiety-like behaviors, cognitive decline, and increased microglial numbers in the medial prefrontal cortex (mPFC) and dorsal hippocampus (dHIP). Additionally, METH exposure during adolescence induced neuroinflammation in adulthood. Adolescent METH exposure also enhances defensive reactivity to neuroinflammation and oxidative stress by activating the NFE2L2-mediated redox system and promotes neurogenesis in adulthood. These findings suggest that the detrimental effects of adolescent METH exposure extend into adulthood, emphasizing the delayed-onset impact of early exposure to psychostimulants.