Elhassan Sagi, Bagdas Deniz, Damaj M Imad
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA.
Experimental Animals Breeding and Research Center, Faculty of Medicine, Uludag University, Bursa, Turkey.
Nicotine Tob Res. 2017 Jun 1;19(6):763-766. doi: 10.1093/ntr/ntx045.
Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal.
Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal.
Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse.
The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence.
啮齿动物研究表明，尼古丁代谢物以及降烟碱和可替宁等烟草次要生物碱可能通过增强尼古丁的奖赏和强化作用来促进吸烟。然而，关于这些烟草次要生物碱对尼古丁戒断影响的信息却很少。本研究旨在确定烟草次要生物碱降烟碱和可替宁在自发尼古丁戒断小鼠模型中是否表现出类似尼古丁的行为效应。
给小鼠输注尼古丁或生理盐水，持续14天。在第15天，即移除微型泵18 - 24小时后进行实验。在测试前10分钟，对尼古丁依赖的ICR雄性小鼠进行急性注射尼古丁（0.05和0.5毫克/千克）、降烟碱（2.5和25毫克/千克）或可替宁（5和50毫克/千克），以确定其对躯体体征、焦虑样行为和戒断自发痛觉过敏体征的影响。
尼古丁和烟草次要生物碱降烟碱而非可替宁，能使小鼠尼古丁戒断体征出现剂量依赖性逆转。
高剂量的烟草次要生物碱和尼古丁代谢物降烟碱具有类似烟碱的作用，可能导致烟草消费和依赖。
