Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine: effects of route and ethanol coadministration
Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine: effects of route and ethanol coadministration
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DOI：
10.1007/s00213-014-3681-4
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发表时间：
2015-02-01
影响因子：
3.4
通讯作者：
Engleman, Eric A.
中科院分区：
文献类型：
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作者：
Katner, Simon N.;Toalston, Jamie E.;Engleman, Eric A.
尼古丁和乙醇是常见的共滥用药物，而含有尼古丁的乙醇产品越来越受欢迎。然而，对乙醇和尼古丁共滥用大鼠模型中细胞外尼古丁和可替宁水平的时间变化知之甚少。本研究的目的是确定酒精偏好大鼠(P)和Wistar大鼠皮下（SC）和灌胃（IG）尼古丁后脑内尼古丁和可替宁水平的时间变化。采用体内微透析法从伏隔核壳（NACsh）中收集透析液样品，测定尼古丁和可替宁含量，雌性P和Wistar大鼠皮下注射(-)-尼古丁（0.18、0.35和0.70 mg/kg），雌性P大鼠IG注射(-)-尼古丁（0.35和0.70 mg/kg） 15% （v/v）乙醇或水。SC尼古丁产生的尼古丁和可替宁透析液水平分别高达51和14 ng/ml。IG给药15% EtOH + 0.70 mg/kg尼古丁的P大鼠，最大尼古丁和可替宁透析液水平分别为19和14 ng/ml，水中给药0.70 mg/kg尼古丁的P大鼠，最大尼古丁和可替宁水平分别为21和25 ng/ml。在IG给药后15分钟和45分钟内分别检测到尼古丁和可替宁水平。总的来说，本研究的结果表明，尼古丁被迅速吸附并产生相应的尼古丁及其药理活性代谢物可替宁的细胞外脑浓度。脑部持续高浓度的可替宁可能导致尼古丁成瘾。
Nicotine and ethanol are commonly coabused drugs, and nicotine-laced ethanol products are growing in popularity. However, little is known about time-course changes in extracellular nicotine and cotinine levels in rat models of ethanol and nicotine coabuse.The objective of the present study was to determine the time-course changes in brain levels of nicotine and cotinine following subcutaneous (SC) and intragastric (IG) nicotine administration in alcohol-preferring (P) and Wistar rats.In vivo microdialysis was used to collect dialysate samples from the nucleus accumbens shell (NACsh) for nicotine and cotinine determinations, following SC administration of (-)-nicotine (0.18, 0.35, and 0.70 mg/kg) in female P and Wistar rats or IG administration of (-)-nicotine (0.35 and 0.70 mg/kg) in 15 % (v/v) ethanol or water in female P rats.SC nicotine produced nicotine and cotinine dialysate levels as high as 51 and 14 ng/ml, respectively. IG administration of 15 % EtOH + 0.70 mg/kg nicotine in P rats resulted in maximal nicotine and cotinine dialysate levels of 19 and 14 ng/ml, respectively, whereas administration of 0.70 mg/kg nicotine in water resulted in maximal nicotine and cotinine levels of 21 and 25 ng/ml, respectively. Nicotine and cotinine levels were detectable within the first 15 and 45 min, respectively, after IG administration.Overall, the results of this study suggest that nicotine is rapidly adsorbed and produces relevant extracellular brain concentrations of nicotine and its pharmacologically active metabolite, cotinine. The persisting high brain concentrations of cotinine may contribute to nicotine addiction.