Brain monoamine oxidase A inhibition in cigarette smokers.
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.
Fowler
J S
JS
Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. fowler@simbrain.chm.bnl.gov
Volkow
N D
ND
Wang
G J
GJ
Pappas
N
N
Logan
J
J
Shea
C
C
Alexoff
D
D
MacGregor
R R
RR
Schlyer
D J
DJ
Zezulkova
I
I
Wolf
A P
AP
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology*; D002250:Carbon Radioisotopes; D003010:Clorgyline / Q000378:metabolism*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D009928:Organ Specificity; D012016:Reference Values; D012907:Smoking / Q000503:physiopathology*; D014055:Tomography, Emission-Computed; D014191:Tranylcypromine / Q000494:pharmacology
D002250:Carbon Radioisotopes; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D014191:Tranylcypromine; D008995:Monoamine Oxidase; D003010:Clorgyline