Department of Pharmaceutical Sciences, Western University of Health Sciences, USA.
J Psychopharmacol. 2020 Dec;34(12):1382-1392. doi: 10.1177/0269881120937543. Epub 2020 Jul 20.
Enhancement in cognitive impulsivity and the resulting alterations in decision making serve as a contributing factor for the development and maintenance of substance-use disorders. Nicotine-induced increases in impulsivity has been previously reported in male humans and rodents. Although the potential for sex differences in nicotine-induced impulsivity has not been examined.
In the present study, male and female Sprague Dawley rats were submitted to a delay discounting task, in which several consecutive measures of self-control were taken. Firstly, rats were tested with vehicle, and next with nicotine doses of 0.4 and 0.8 mg/kg. Thereafter, chronic treatment with bupropion started, and the animals were tested again. Half the animals continued to receive 0.8 mg/kg of nicotine, while the rest received nicotine and also a daily dose of 30 mg/kg of bupropion.
When the animals were first tested with nicotine, female rats showed a significant nicotine dose dependent increase of impulsive behaviour, whereas male rats only showed a decrease on their elections of the larger but delayed reward under the highest dose of 0.8 mg/kg of nicotine. Treatment with bupropion blocked the effect of nicotine on decision making in female rats, as they showed results close to their baseline levels. On the other hand, bupropion did not affect the nicotine-induced delay discounting in male rats.
These findings demonstrate sexually dimorphic effects of nicotine on cognitive impulsivity which may help to shed light on nicotine use vulnerabilities observed in women.
认知冲动的增强以及由此导致的决策改变是物质使用障碍发展和维持的一个促成因素。先前有研究报道,尼古丁可引起人类和啮齿动物冲动性增加。尽管尚未研究尼古丁诱导的冲动性是否存在性别差异。
在本研究中,雄性和雌性 Sprague Dawley 大鼠接受了延迟折扣任务,在此任务中进行了多次连续的自我控制测量。首先,大鼠接受载体处理,然后接受 0.4 和 0.8mg/kg 的尼古丁剂量处理。此后,开始进行丁胺苯丙酮慢性治疗,然后再次对动物进行测试。一半的动物继续接受 0.8mg/kg 的尼古丁,而其余的动物则接受尼古丁和每天 30mg/kg 的丁胺苯丙酮。
当动物首次接受尼古丁测试时,雌性大鼠表现出明显的剂量依赖性冲动行为增加,而雄性大鼠仅在接受最高剂量 0.8mg/kg 的尼古丁时,对较大但延迟的奖励的选择减少。丁胺苯丙酮治疗阻断了尼古丁对雌性大鼠决策的影响,使它们的结果接近基线水平。另一方面,丁胺苯丙酮对雄性大鼠的尼古丁诱导的延迟折扣没有影响。
这些发现表明尼古丁对认知冲动性具有性别二态效应,这可能有助于阐明女性中观察到的尼古丁使用易感性。