Li Sophia, Zou Sheng, Coen Kathleen, Funk Douglas, Shram Megan J, Lê A D
Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Addict Biol. 2014 Mar;19(2):156-64. doi: 10.1111/j.1369-1600.2012.00473.x. Epub 2012 Jul 11.
Stress is an important factor in the initiation and maintenance of smoking in adolescents. Women are more vulnerable to the development of addiction to smoking and have more difficulty quitting than men. Women also showe enhanced responses to stress. Despite these differences, no work has been done examining the effects of stress on the reinforcing efficacy of self-administered nicotine in adolescent rats, or if there are sex differences. Male and female adolescent Long Evans rats were trained to self-administer one of three different intravenous doses of nicotine (7.5, 15, 30 μg/kg/infusion) first on fixed ratio, and then on a progressive ratio (PR) schedule beginning on postnatal day 33. The effect of the pharmacological stressor yohimbine (0.3, 0.6 mg/kg, i.p.) on the reinforcing efficacy of nicotine was then determined using the PR schedule. Yohimbine stimulated nicotine intake and increased PR breakpoints and numbers of infusions received in both male and female adolescent rats. The infusion dose of nicotine was positively associated with yohimbine-induced increases in responding. Female rats showed significantly increased breakpoints at yohimbine doses and nicotine infusion doses at which males did not. The effects of the pharmacological stressor, yohimbine on the reinforcing efficacy of nicotine are therefore linked to sex and nicotine infusion dose. Female rats are more sensitive to stress-induced potentiation of nicotine self-administration.
压力是青少年开始吸烟并持续吸烟的一个重要因素。女性比男性更容易染上烟瘾，而且戒烟也更困难。女性对压力的反应也更强烈。尽管存在这些差异，但尚未有人研究压力对青少年大鼠自我给药尼古丁强化效果的影响，也未研究是否存在性别差异。雄性和雌性青少年朗·埃文斯大鼠首先在固定比率下接受训练，自我给药三种不同静脉注射剂量（7.5、15、30μg/kg/次注射）的尼古丁之一，然后从出生后第33天开始在累进比率（PR）程序下进行训练。然后使用PR程序确定药理应激源育亨宾（0.3、0.6mg/kg，腹腔注射）对尼古丁强化效果的影响。育亨宾刺激了雄性和雌性青少年大鼠的尼古丁摄入量，增加了PR断点以及接受的注射次数。尼古丁的注射剂量与育亨宾诱导的反应增加呈正相关。在育亨宾剂量和尼古丁注射剂量下，雌性大鼠的断点显著增加，而雄性大鼠则没有。因此，药理应激源育亨宾对尼古丁强化效果的影响与性别和尼古丁注射剂量有关。雌性大鼠对压力诱导的尼古丁自我给药增强作用更敏感。
