Brain monoamine oxidase A inhibition in cigarette smokers

Joanna S. Fowler, Nora D. Volkow, Gene Jack Wang, Naomi Pappas, Jean Logan, Colleen Shea, David Alexoff, Robert R. MacGregor, David J. Schlyer, Ivana Zezulkova, Alfred P. Wolf

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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 [11C]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 [11C]clorgyline binding to MAO inhibition. MAO A levels were quantified by using the model term λk3 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 λk3 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 λk3 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.

Original languageEnglish
Pages (from-to)14065-14069
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
StatePublished - 26 Nov 1996
Externally publishedYes


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