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5 μg/kg/inf). We successfully show that adolescent but not adult, nicotine exposure enhances cocaine self-administration in male rats. Furthermore, we illustrate early adolescent but not adult nicotine exposure enhances fentanyl self-administration, independent of sex. Overall, our findings highlight that adolescence is a unique period of development that is vulnerable to nicotine-induced enhancement for cocaine and fentanyl self-administration in rats.Discovery of neural mechanisms underlying neuropsychiatric disorders within the aging