RATIONALE: Many people come in contact with psychoactive drugs, yet not all of them become addicts. Epidemiology shows that a late approach with cigarette smoking is associated with a lower probability to develop nicotine dependence. Exposure to nicotine during periadolescence, but not similar exposure in the postadolescent period, increases nicotine self-administration in rats, but underlying mechanisms remain poorly understood. OBJECTIVE: We investigated whether exposure to nicotine during or after adolescence would alter rewarding properties of the same drug at adulthood, as assessed by place conditioning. MATERIALS AND METHODS: Periadolescent (PND 34-43) or postadolescent (PND 60-69) rats were injected with saline or nicotine (0.4 mg kg(-1)) for 10 days. The rats received three pairings with saline and three pairings with nicotine (0, 0.3, or 0.6 mg kg(-1)) 5 weeks after pretreatment. The rats were then tested for place conditioning in a drug-free state. RESULTS: Upon first exposure to the apparatus, animals pretreated with nicotine during adolescence showed elevated novelty-induced activation. The 0.3 (but not the 0.6) mg kg(-1) dose failed to produce both ongoing locomotor sensitization and place conditioning in animals pretreated with nicotine following adolescence. This suggests a rightward shift in the dose-response curve, namely, a reduced efficacy of nicotine. Conversely, the same dose was effective in saline-pretreated controls and noteworthy in rats pretreated during adolescence. CONCLUSION: Exposure following the adolescent period might diminish the risk to develop nicotine dependence. As for human implications, findings are consistent with a reduced vulnerability to nicotine addiction in people who start smoking late in their life.