Department of Psychology, George Mason University, Fairfax, VA 22030, USA.
Psychopharmacology (Berl). 2012 Jan;219(1):73-82. doi: 10.1007/s00213-011-2378-1. Epub 2011 Jul 1.
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.
研究表明,青少年时期对尼古丁奖赏效应的敏感性增加,而压力与该年龄段吸烟起始风险增加有关。压力可能通过增强尼古丁的奖赏特性导致青少年尼古丁使用增加。促肾上腺皮质释放因子 1 型受体(CRF-R1)介导生理和行为应激反应。它们也可能介导应激诱导的与尼古丁奖赏相关的多个神经基质活性的增强。
本研究旨在使用偏向性条件位置偏爱(CPP)程序确定急性应激源暴露对青少年雄性大鼠单次尼古丁条件位置偏爱的影响,以及 CRF-R1 在这种影响中的作用。
在位置条件形成前 24 小时给予单次间歇性足底电击,可剂量依赖性地促进尼古丁(0.2、0.4 和 0.6 mg/kg)的 CPP 获得。在足底电击暴露前 30 分钟预先给予 CP-154,526(20 mg/kg),一种选择性 CRF-R1 拮抗剂,可显著减弱先前应激促进尼古丁 CPP 获得的作用。CP-154,526 预处理对在非应激条件下产生 CPP 的尼古丁剂量进行条件训练的动物没有影响,这表明 CRF-R1 在应激后具有特定作用。
总之,结果表明,在青少年时期,尼古丁奖赏会因最近的应激源暴露而增强,这种增强涉及 CRF-R1 信号转导。此类研究的信息可用于指导预防和治疗青少年尼古丁依赖的努力。