ABSTRACT
We measured the concentration of brain monoamine oxidase B (MAO B; EC 1.4.3.4) in 8 smokers and compared it with that in 8 non-smokers and in 4 former smokers using positron emission tomography (PET) and deuterium substituted [11C]L-deprenyl ([11C]L-deprenyl-D2) as a radiotracer for MAO B. Smokers had significantly lower brain MAO B than non-smokers as measured by the model term lambda k3 which is a function of MAO B activity. Reductions were observed in all brain regions. Low brain MAO B in the cigarette smoker appears to be a pharmacological rather than a genetic effect since former smokers did not differ from non-smokers. Brain MAO B inhibition by cigarette smoke is of relevance in light of the inverse association between smoking and Parkinson's disease and a high prevalence of smoking in psychiatric disorders and in substance abuse. Though nicotine is at the core of the neuropharmacological actions of tobacco smoke, MAO B inhibition may also be an important variable in understanding and treating tobacco smoke addiction.
Subject(s)
Brain/enzymology , Monoamine Oxidase Inhibitors , Monoamine Oxidase/analysis , Smoke/adverse effects , Smoking/metabolism , Adult , Basal Ganglia/chemistry , Basal Ganglia/drug effects , Basal Ganglia/metabolism , Brain/diagnostic imaging , Brain/metabolism , Carbon Radioisotopes , Deuterium , Female , Fluorodeoxyglucose F18 , Glucose/metabolism , Humans , Male , Middle Aged , Monoamine Oxidase/drug effects , Monoamine Oxidase/metabolism , Nicotine/pharmacology , Selegiline , Smoking/adverse effects , Tomography, Emission-ComputedABSTRACT
The massive health problem associated with cigarette smoking is exacerbated by the addictive properties of tobacco smoke and the limited success of current approaches to cessation of smoking. Yet little is known about the neuropharmacological actions of cigarette smoke that contribute to smoking behaviour, or why smoking is so prevalent in psychiatric disorders and is associated with a decreased risk of Parkinson's disease. Here we report that brains of living smokers show a 40% decrease in the level of monoamine oxidase B (MAO B; EC 1.4.3.4) relative to non-smokers or former smokers. MAO B is involved in the breakdown of dopamine, a neurotransmitter implicated in reinforcing and motivating behaviours as well as movement. MAO B inhibition is therefore associated with enhanced activity of dopamine, as well as with decreased production of hydrogen peroxide, a source of reactive oxygen species. We propose that reduction of MAO B activity may synergize with nicotine to produce the diverse behavioural and epidemiological effects of smoking.
Subject(s)
Brain/enzymology , Monoamine Oxidase/metabolism , Smoking/metabolism , Adult , Aged , Aged, 80 and over , Brain/drug effects , Dopamine/metabolism , Female , Glucose/metabolism , Humans , Male , Middle Aged , Monoamine Oxidase Inhibitors/pharmacology , Nicotine/pharmacology , Selegiline/pharmacology , Tomography, Emission-ComputedABSTRACT
With the described method, a large number of sealed bottles can be tested to determine their effectiveness, integrity, and reliability in preserving an inert atmosphere. The method consists of placing milligram quantities of dry ice into the bottles, capping them, and periodically weighing them on an analytical balance; leaky bottles are detected by a loss in weight. This method can be applied to test a large number of bottles with a minimum of effort and manpower and without complicated instrumentation. The data presented are highly reproducible and correlate well with data from other methods and with the physical defects of the bottles.
