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First, this study was conducted in males since we have previously shown that adolescent nicotine enhancement of cocaine self-administration is seen in both males and females ( 4.4 Clinical Implications With increasing evidence that aberrant activation of 5-HT systems during adolescence triggers lasting changes in neuronal signaling, use of drugs such as tobacco, e-cigarettes, and antidepressants may permanently alter the course of adolescent brain maturation and neurotransmitter signaling