Epping-Jordan M P, Watkins S S, Koob G F, Markou A
The Scripps Research Institute, Department of Neuropharmacology, La Jolla, California 92037, USA.
Nature. 1998 May 7;393(6680):76-9. doi: 10.1038/30001.
Tobacco smoking is a worldwide public health problem. In the United States alone, over 400,000 deaths and $50 billion in medical costs annually are directly attributed to smoking. Accumulated evidence indicates that nicotine is the component of tobacco smoke that leads to addiction, but the means by which nicotine produces addiction remain unclear. Nicotine is less effective as a positive reinforcer than other drugs of abuse in non-dependent animals. Nevertheless, nicotine-withdrawal symptoms, including depressed mood, anxiety, irritability and craving in dependent subjects may contribute to the addictive liability of nicotine. We show here that spontaneous nicotine withdrawal in rats resulted in a significant decrease in brain reward function, as measured by elevations in brain reward thresholds, which persisted for four days. Further, systemic injections of a competitive nicotinic-receptor antagonist led to a dose-dependent increase in brain reward thresholds in chronic nicotine-treated rats. The decreased function in brain reward systems during nicotine withdrawal is comparable in magnitude and duration to that of other major drugs of abuse, and may constitute an important motivational factor that contributes to craving, relapse and continued tobacco consumption in humans.
吸烟是一个全球性的公共卫生问题。仅在美国，每年就有超过40万人死亡，医疗费用高达500亿美元，这些都直接归因于吸烟。越来越多的证据表明，尼古丁是烟草烟雾中导致成瘾的成分，但尼古丁产生成瘾的方式仍不清楚。在非依赖动物中，尼古丁作为一种阳性强化剂的效果不如其他滥用药物。然而，尼古丁戒断症状，包括依赖者的情绪低落、焦虑、易怒和渴望，可能会导致尼古丁的成瘾性。我们在此表明，大鼠的自发尼古丁戒断导致大脑奖赏功能显著下降，通过大脑奖赏阈值的升高来衡量，这种下降持续了四天。此外，对慢性尼古丁处理的大鼠全身注射竞争性烟碱受体拮抗剂会导致大脑奖赏阈值剂量依赖性增加。尼古丁戒断期间大脑奖赏系统功能的下降在程度和持续时间上与其他主要滥用药物相当，可能构成一个重要的动机因素，导致人类的渴望、复吸和持续吸烟。
