Brain nitric oxide metabolites in rats preselected for nicotine preference and intake
Brain nitric oxide metabolites in rats preselected for nicotine preference and intake
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DOI：
10.1016/j.neulet.2013.04.027
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发表时间：
2013-06-17
影响因子：
2.5
通讯作者：
Pogun, Sakire
中科院分区：
文献类型：
--
作者：
Keser, Aysegul;Nesil, Tanseli;Pogun, Sakire
尼古丁成瘾是一个严重的健康问题，导致全世界数以百万计的可预防的死亡。气体信使分子一氧化氮（NO）在成瘾中起着关键作用，尼古丁增加了大脑中的一氧化氮代谢物（NOx）。了解尼古丁偏好和摄入量的个体差异背后的因素对于制定有效的戒烟治疗策略非常重要。本研究旨在通过测量一氧化氮的稳定代谢物来评估一氧化氮的活性。在预先选择尼古丁偏好的大鼠中，一氧化氮在三个大脑区域表达高水平的尼古丁乙酰胆碱受体。大鼠（n = 88）从青少年或成年开始，自由选择两瓶口服尼古丁/水；对照动物在相同的条件下只喝水。暴露12周或6周后，测定海马、额叶皮质和杏仁核中的氮氧化物（亚硝酸盐+硝酸盐）水平。由于大鼠在口服尼古丁治疗期间是单独饲养的，因此也将幼稚大鼠纳入研究，以评估隔离应激的效果。隔离应激使海马中的氮氧化物含量增加。尼古丁偏好对一氧化氮活性没有显著影响，但与成年大鼠相比，青春期接触的大鼠额叶皮层中的氮氧化物水平更高。我们的研究结果表明，在青春期接触尼古丁，无论摄入多少尼古丁，都会导致大鼠额叶皮层的NO活性升高，这种情况会持续到成年。2013爱思唯尔爱尔兰有限公司版权所有。
Nicotine addiction is a serious health problem resulting in millions of preventable deaths worldwide. The gas messenger molecule nitric oxide (NO) plays a critical role in addiction, and nicotine increases nitric oxide metabolites (NOx) in the brain. Understanding the factors which underlie individual differences in nicotine preference and intake is important for developing effective therapeutic strategies for smoking cessation. The present study aimed to assess NO activity, by measuring its stable metabolites, in three brain regions that express high levels of nicotinic acetylcholine receptors in rats preselected for nicotine preference. Rats (n = 88) were exposed to two-bottle, free choice of oral nicotine/water starting either as adolescents or adults; control animals received only water under identical conditions. Following 12 or six weeks of exposure, levels of NOx (nitrite + nitrate), were determined in the hippocampus, frontal cortex, and amygdala. Since the rats were singly housed during oral nicotine treatment, naive rats were also included in the study to evaluate the effect of isolation stress. Isolation stress increased NOx in the hippocampus. Nicotine preference did not have a significant effect on NO activity, but rats with adolescent exposure had higher NOx levels in the frontal cortex compared to adult-onset rats. Our findings suggest that nicotine exposure during adolescence, regardless of the amount of nicotine consumed, results in higher NO activity in the frontal cortex of rats, which persists through adulthood. (C) 2013 Elsevier Ireland Ltd. All rights reserved.