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Introduction: While cigarette smoking rates have been steadily decreasing over the past decade, there has been a dramatic increase in nicotine use via e-cigarettes, especially during adolescence. Adolescent e-cigarette use is associated with a greater risk of future cigarette smoking, and increased rates of cigarette smoking in individuals who may have otherwise never tried cigarettes. In humans and rodents, early initiation of nicotine use has been associated with greater consumption, dependence, and persistent nicotine use. The present study sought to investigate the long-lasting effect of daily high-dose nicotine exposure during adolescence on nicotine consumption in adulthood.Method: Male Sprague-Dawley rats were exposed daily to nicotine (1.0 mg/kg, subcutaneous), or vehicle (1 ml/kg saline, subcutaneous) during adolescence (post-natal day [P] 28-41). Adult nicotine self-administration (0.02 mg/kg/infusion, intravenous) was assessed beginning on P75 on fixed-ratio 1 (FR1), fixed-interval 1min (FI1), and progressive ratio (PR) schedules of reinforcement.Results: Adolescent nicotine pre-exposure did not affect adult nicotine self-administration on the simple FR1 schedule, however increased intake and responding for nicotine was observed when a short delay was implemented on an FI1 schedule of reinforcement. Conclusions:Adolescence is a critical period when the brain is especially vulnerable to the effects of nicotine. Nicotine exposure in adolescence enhances susceptibility to increased nicotine ✉