Rapid delivery of nicotine promotes behavioral sensitization and alters its neurobiological impact

Background: Nicotine is highly addictive when it is inhaled from tobacco smoke, whereas nicotine replacement products, which usually deliver nicotine orally or transdermally, rarely lead to addiction. It has been proposed that this is due in part to differences in the rate of nicotine delivery to the brain under the two conditions. However, the mechanism by which rapid nicotine delivery facilitates the transition to addiction is not known. The ability of drugs to alter gene regulation and to produce sensitization has been implicated in addiction. We hypothesized, therefore, that varying the rate of nicotine administration may modulate its ability to elicit this form of plasticity. Methods: Animals were treated with repeated intravenous infusions of nicotine over 5, 25, or 100 sec, and their locomotor responses were monitored over treatment days. Results: We found that increasing the rate of intravenous nicotine infusion potentiated its ability to produce locomotor sensitization, and to induce c-fos and arc mRNA expression in mesocorticolimbic structures. Conclusions. We suggest that rapid administration may increase vulnerability to addiction by altering the neurobiological impact of nicotine and promoting a form of neurobebavioral plasticity (i.e., sensitization) that can lead to pathological incentive motivation for drugs.