Brain monoamine oxidase A
inhibition in cigarette smokers
by
Fowler JS, Volkow ND, Wang GJ, Pappas N,
Logan J, Shea C, Alexoff D, MacGregor RR,
Schlyer DJ, Zezulkova I, Wolf AP
Chemistry Department,
Brookhaven National Laboratory,
Upton, NY 11973-5000, USA.
fowler@simbrain.chm.bnl.gov
J Addict Dis 1998; 17(1):23-34

ABSTRACT

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 lambda k3 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 k3 values for the whole brain were 0.18 +/- 0.04 and 0.13 +/- 0.03 ccbrain (mlplasma)-1 min-1 for nonsmokers and smokers, respectively; P < 0.0003). Tranyl-cypromine treatment reduced lambda k3 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.

MAOIs
Nicotine
Tobacco
Smoking
Cotinine
Selegiline
Clorgyline
Dopamine
Cigarettes
Tranylcypromine
Free-base nicotine
Parkinson's disease
Smoking and MAO-B
Nicotine: an antidepressant?
Nicotine and the cannabinoid system
Nicotine and monoamine oxidase inhibitors
Nicotine, pleasure, and reward sensitization

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