Adolescent morphine exposure induced long-term cognitive impairment and prefrontal neurostructural abnormality in adulthood in mice

Abstract Opioids abuse in adolescence is becoming a pressing public health issue. Although evidence indicates that adolescent opioid exposure contributes to persistent changes in brain development, its long-term consequences in adulthood are still unclear. Here, we established a mouse model of adolescent morphine exposure and used the 5-choice serial reaction time task (5‐CSRTT) combined with behavioral tests to evaluate changes in cognitive behaviors. We found that exposure to morphine during adolescence led to deficits in multidimensional cognitive functions in mice, including attention, information processing speed, and behavior inhibition. Notable, these impairments persisted into adulthood. Furthermore, the morphine-exposed mice exhibited decreased learning efficiency and spatial memory. Adolescent morphine exposure also induced significant and persistent morphological changes and synaptic abnormalities in medial prefrontal cortex (mPFC) neurons, which may be responsible for cognitive impairments in adulthood. Together, our study identifies adolescence as a critical period during which opioid exposure acts profoundly on cognitive development and emphasizes that the disruption of neurons by opioids in adolescence may link mPFC-associated cognitive impairments in adulthood.