Effects of acute stress on acquisition of nicotine conditioned place preference in adolescent rats: a role for corticotropin-releasing factor 1 receptors

Studies indicate that adolescence is a time of increased sensitivity to the rewarding effects of nicotine, and that stress is associated with an increased risk for smoking initiation in this age group. It is possible that stress leads to increased nicotine use in adolescence by augmenting its rewarding properties. Corticotropin-releasing factor type 1 receptors (CRF-R1) mediate physiological and behavioral stress responses. They may also mediate stress-induced potentiation of activity in multiple neural substrates implicated in nicotine reward.The aim of the present study was to determine the effect of acute stressor exposure on single trial nicotine conditioned place preference (CPP) in adolescent male rats using a biased CPP procedure and the role of CRF-R1 in this effect.A single episode of intermittent footshock administered 24 h before the start of place conditioning dose-dependently facilitated acquisition of CPP to nicotine (0.2, 0.4, and 0.6 mg/kg). Pretreatment with CP-154,526 (20 mg/kg), a selective CRF-R1 antagonist, 30 min before footshock exposure significantly attenuated the effect of prior stress to facilitate nicotine CPP acquisition. CP-154,526 pretreatment had no effect in animals conditioned with a nicotine dose that produced CPP under non-stress conditions, suggesting a specific role for CRF-R1 following stress.Taken together, the results suggest that during adolescence, nicotine reward is enhanced by recent stressor exposure in a manner that involves signaling at CRF-R1. Information from studies such as this may be used to inform efforts to prevent and treat adolescent nicotine dependence.