Fully mature mice exposed to low levels of nicotine during periadolescence exhibited reductions in the rewarding and subjective effects of cocaine. These results provide converging validity that periadolescent nicotine exposure can permanently decrease a subject's sensitivity to the reinforcing effects of cocaine. These changes were noted long after exposure, suggesting that nicotine may have altered neural systems mediating drug reward. Since reductions in the rewarding value of abused drugs are associated with increased self-administration, periadolescent nicotine exposure might increase the risk for substance abuse problems. The study thus provides biological support that nicotine might serve a "gateway" function for substance abuse.