Adolescent Exposure to Nicotine and Ethanol Attenuates Adult Nicotine Reward Sensitivity in Rats

Adolescence is a sensitive developmental stage in which exposure to addictive substances can produce long-lasting changes in the neural circuits that regulate reward. Nicotine and ethanol are frequently co-used among adolescents, and converging evidence suggests that these drugs interact to modulate mesolimbic dopamine transmission. The present study investigated how chronic exposure to nicotine, ethanol, or their combination during adolescence influences adult conditioned place preference (CPP) for nicotine. Male Wistar-Imamichi rats were assigned to four groups: Control (no drug exposure), Nicotine (0.20 mg/kg/day, s.c., PND 28-41), EtOH (voluntary 20% ethanol intake), and Co-use (nicotine + ethanol). After maturation, all animals underwent CPP with 0.08 mg/kg nicotine using an unbiased procedure. We hypothesized that adolescent drug exposure would enhance vulnerability to nicotine reward in adulthood. Contrary to this hypothesis, only the Control group exhibited significant CPP, whereas no nicotine-induced preference was observed in any drug-exposed group. These findings emphasize the complexity of developmental drug interactions and suggest that adolescent exposure to addictive substances does not uniformly increase vulnerability to nicotine reward.