Brain monoamine oxidase A inhibition in cigarette smokers
Brain monoamine oxidase A inhibition in cigarette smokers
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DOI：
10.1073/pnas.93.24.14065
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发表时间：
1996-11-26
影响因子：
11.1
通讯作者：
Wolf, AP
中科院分区：
文献类型：
--
作者：
Fowler, JS;Volkow, ND;Wolf, AP
一些研究已经证明了吸烟和抑郁之间的密切联系。据报道，在体外和动物实验中，香烟烟雾会抑制单胺氧化酶（MAO） A，而且MAO A抑制剂是有效的抗抑郁药，因此我们验证了吸烟者大脑中MAO A会减少的假设。我们用[C-11]氯络碱和正电子发射断层扫描（PET）比较了15名不吸烟者和16名当前吸烟者的脑MAO A。在基线PET扫描后，4名非吸烟者也接受抗抑郁药MAO抑制剂，tranyylcypromine（10毫克/天，连续3天）治疗，然后重新扫描以评估[C-11] clyline结合对MAO抑制的敏感性。MAO A水平通过使用模型项lambda k(3)来量化，该模型项是脑MAO A浓度的函数。在所有被检查的大脑区域中，吸烟者的MAO A明显低于不吸烟者（平均降低28%）。非吸烟者和吸烟者全脑平均λ k(3)值分别为0.18 +/- 0.04和0.13 +/- 0.03 cc（脑）（ml（血浆））（-1）min(-1)；P < 0.0003)。在不同的脑区，丙基环丙胺治疗使λ k(3)平均降低了58%。我们的研究结果表明，暴露在烟草烟雾中与大脑MAO a的显著减少有关，而这种减少大约是短暂使用丙基环丙胺治疗所产生的减少的一半。这表明，MAO A抑制需要被视为抑郁症患者吸烟率高和制定更有效的戒烟策略的潜在贡献变量。
Several studies have documented a strong association between smoking and depression. Because cigarette smoke has been reported to inhibit monoamine oxidase (MAO) A in vitro and in animals and because MAO A inhibitors are effective antidepressants, we tested the hypothesis that MAO A would be reduced in the brain of cigarette smokers. We compared brain MAO A in 15 nonsmokers and 16 current smokers with [C-11]clorgyline and positron emission tomography (PET). Four of the nonsmokers were also treated with the antidepressant MAO inhibitor drug, tranylcypromine (10 mg/day for 3 days) after the baseline PET scan and then rescanned to assess the sensitivity of [C-11]clorgyline binding to MAO inhibition. MAO A levels were quantified by using the model term lambda k(3) which is a function of brain MAO A concentration. Smokers had significantly lower brain MAO A than nonsmokers in all brain regions examined (average reduction, 28%). The mean lambda k(3) values for the whole brain were 0.18 +/- 0.04 and 0.13 +/- 0.03 cc(brain) (ml(plasma))(-1) min(-1) for nonsmokers and smokers, respectively; P < 0.0003). Tranylcypromine treatment reduced lambda k(3) by an average of 58% for the different brain regions. Our results show that tobacco smoke exposure is associated with a marked reduction in brain MAO A, and this reduction is about half of that produced by a brief treatment with tranylcypromine. This suggests that MAO A inhibition needs to be considered as a potential contributing variable in the high rate of smoking in depression and in the development of more effective strategies for smoking cessation.