Gasior Maciej, Jaszyna Maria, Munzar Patrik, Witkin Jeffrey M, Goldberg Steven R
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Psychopharmacology (Berl). 2002 Aug;162(4):385-95. doi: 10.1007/s00213-002-1113-3. Epub 2002 Jun 7.
Caffeine and nicotine are the main psychoactive ingredients of coffee and tobacco, respectively, with a high frequency of concurrent use in humans.
The aim of the present study was to examine the interaction of caffeine and nicotine in rats trained to discriminate nicotine from saline.
Two groups of male Sprague-Dawley rats ( n=8 per group) were trained to discriminate 0.4 mg/kg nicotine, SC, from saline under a fixed ratio schedule of food presentation. One group of rats was chronically exposed to caffeine (1.0 mg/ml) dissolved in their drinking water whereas the other group was exposed to tap water. Effects of IP injections of caffeine on nicotine-lever selection were subsequently examined. In separate groups of rats exposed to the same caffeine-drinking or water-drinking regimen, effects of caffeine pretreatment on nicotine plasma levels were evaluated.
Although caffeine (1.0-30.0 mg/kg) did not generalize to nicotine when administered alone, it markedly potentiated discriminative-stimulus effects of the threshold dose of nicotine (0.05 mg/kg) in both water- and caffeine-drinking rats. Nicotine plasma levels were, however, not affected by acute or chronic caffeine exposure.
Caffeine appears to enhance the discriminative-stimulus effects of the threshold dose of nicotine by a pharmacodynamic rather than a pharmacokinetic interaction. This suggests that caffeine consumption may be a contributing factor in the onset, maintenance of and relapse to tobacco dependence.
咖啡因和尼古丁分别是咖啡和烟草的主要精神活性成分,在人类中同时使用的频率很高。
本研究的目的是检测咖啡因和尼古丁在经过训练能区分尼古丁和生理盐水的大鼠中的相互作用。
两组雄性Sprague-Dawley大鼠(每组n = 8)在固定比率的食物呈现模式下接受训练,以区分皮下注射的0.4mg/kg尼古丁和生理盐水。一组大鼠长期饮用溶解有咖啡因(1.0mg/ml)的水,而另一组饮用自来水。随后检测腹腔注射咖啡因对尼古丁杠杆选择的影响。在分别接受相同咖啡因饮水或自来水饮水方案的大鼠组中,评估咖啡因预处理对尼古丁血浆水平的影响。
虽然单独给予咖啡因(1.0 - 30.0mg/kg)时不会与尼古丁产生交叉反应,但它能显著增强阈值剂量尼古丁(0.05mg/kg)对饮水大鼠和饮用咖啡因大鼠的辨别刺激作用。然而,尼古丁血浆水平不受急性或慢性咖啡因暴露的影响。
咖啡因似乎通过药效学而非药代动力学相互作用增强了阈值剂量尼古丁的辨别刺激作用。这表明饮用咖啡因可能是烟草依赖的起始、维持和复发的一个促成因素。