title: Inhibition of monoamine oxidase B in the brains of smokers.
abstract: 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.
authors.affiliation: Brookhaven National Laboratory, Upton, New York 11973, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Fowler
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
authors.forename: G J
authors.initials: GJ
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Pappas
authors.forename: J
authors.initials: J
authors.lastname: Logan
authors.forename: R
authors.initials: R
authors.lastname: MacGregor
authors.forename: D
authors.initials: D
authors.lastname: Alexoff
authors.forename: C
authors.initials: C
authors.lastname: Shea
authors.forename: D
authors.initials: D
authors.lastname: Schlyer
authors.forename: A P
authors.initials: AP
authors.lastname: Wolf
authors.forename: D
authors.initials: D
authors.lastname: Warner
authors.forename: I
authors.initials: I
authors.lastname: Zezulkova
authors.forename: R
authors.initials: R
authors.lastname: Cilento
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology; D012907:Smoking / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D009538:Nicotine; D008995:Monoamine Oxidase; D005947:Glucose; D004298:Dopamine