Brain monoamine oxidase A inhibition in cigarette smokers

被引:333
作者
Fowler, JS
Volkow, ND
Wang, GJ
Pappas, N
Logan, J
Shea, C
Alexoff, D
MacGregor, RR
Schlyer, DJ
Zezulkova, I
Wolf, AP
机构
[1] BROOKHAVEN NATL LAB,DEPT MED,UPTON,NY 11973
[2] SUNY STONY BROOK,DEPT PSYCHIAT,STONY BROOK,NY 11794
关键词
D O I
10.1073/pnas.93.24.14065
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:14065 / 14069
页数:5
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