Kasten C R, Frazee A M, Boehm S L
Department of Psychology, Indianapolis University Purdue University - Indianapolis, 402 N Blackford St LD 124, Indianapolis, IN 46202, United States.
Department of Psychology, Indianapolis University Purdue University - Indianapolis, 402 N Blackford St LD 124, Indianapolis, IN 46202, United States.
Pharmacol Biochem Behav. 2016 Sep;148:28-37. doi: 10.1016/j.pbb.2016.05.010. Epub 2016 May 27.
Although United States smoking rates have been on the decline over the past few decades, cigarette smoking still poses a critical health and economic threat. Very few treatment options for smoking exist, and many of them do not lead to long-term abstinence. Preclinical models are necessary for understanding the effects of nicotine and developing treatments. Current self-administration models of nicotine intake may require surgical procedures and often result in low levels of intake. Further, they do not lend themselves to investigating treatments. The current study sought to develop a limited-access model of nicotine intake using the Drinking-in-the-Dark paradigm, which results in high levels of binge-like ethanol consumption that can be pharmacologically manipulated. The present study found that mice will consume nicotine under a range of parameters. Intakes under the preferred condition of 0.14mg/ml nicotine in 0.2% saccharin reached over 6mg/kg in two hours and were reduced by an injection of R(+)-baclofen. Mecamylamine did not significantly affect nicotine consumption. As nicotine and ethanol are often co-abused, nicotine intake was also tested in the presence of ethanol. When presented in the same bottle, mice altered nicotine intake under various concentrations to maintain consistent levels of ethanol intake. When nicotine and ethanol were presented in separate bottles, mice greatly reduced their nicotine intake while maintaining ethanol intake. In conclusion, these studies characterize a novel model of limited-access nicotine intake that can be pharmacologically manipulated.
尽管在过去几十年里美国的吸烟率一直在下降，但吸烟仍然对健康和经济构成重大威胁。针对吸烟的治疗选择非常少，而且其中许多并不能导致长期戒烟。临床前模型对于理解尼古丁的作用和开发治疗方法是必要的。目前的尼古丁摄入自我给药模型可能需要手术操作，而且往往导致低水平的摄入量。此外，它们不适合用于研究治疗方法。当前的研究试图使用“黑暗中饮酒”范式开发一种有限接触的尼古丁摄入模型，该范式会导致高水平的类似暴饮暴食的乙醇消费，且这种消费可以通过药物进行控制。本研究发现，小鼠会在一系列参数下摄入尼古丁。在0.2%糖精中0.14mg/ml尼古丁的首选条件下，两小时内摄入量超过6mg/kg，并通过注射R(+)-巴氯芬而减少。美加明对尼古丁消费没有显著影响。由于尼古丁和乙醇经常被共同滥用，在有乙醇存在的情况下也测试了尼古丁摄入情况。当它们放在同一个瓶子里时，小鼠会改变不同浓度下的尼古丁摄入量，以维持乙醇摄入量的一致水平。当尼古丁和乙醇放在单独的瓶子里时，小鼠在维持乙醇摄入量的同时大幅减少了尼古丁摄入量。总之，这些研究描述了一种可以通过药物控制的新型有限接触尼古丁摄入模型。
