title: Effects of Monoamine Oxidase Inhibition on the Reinforcing Properties of Low-Dose Nicotine.
abstract: The Food and Drug Administration (FDA) has the authority to regulate cigarette smoke constituents, and a reduction in nicotine content might benefit public health by reducing the prevalence of smoking. Research suggests that cigarette smoke constituents that inhibit monoamine oxidase (MAO) may increase the reinforcing value of low doses of nicotine. The aim of the present experiments was to further characterize the impact of MAO inhibition on the primary reinforcing and reinforcement enhancing effects of nicotine in rats. In a series of experiments, rats responded for intravenous nicotine infusions or a moderately-reinforcing visual stimulus in daily 1-h sessions. Rats received pre-session injections of known MAO inhibitors. The results show that (1) tranylcypromine (TCP), a known MAO inhibitor, increases sensitivity to the primary reinforcing effects of nicotine, shifting the dose-response curve for nicotine to the left, (2) inhibition of MAO-A, but not MAO-B, increases low-dose nicotine self-administration, (3) partial MAO-A inhibition, to the degree observed in chronic cigarette smokers, also increases low-dose nicotine self-administration, and (4) TCP decreases the threshold nicotine dose required for reinforcement enhancement. The results of the present experiments suggest cigarette smoke constituents that inhibit MAO-A, in the range seen in chronic smokers, are likely to increase the primary reinforcing and reinforcement enhancing effects of low doses of nicotine. If the FDA reduces the nicotine content of cigarettes, then variability in constituents that inhibit MAO-A could impact smoking.
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Smith
authors.affiliation: Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Rupprecht
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Samantha N
authors.initials: SN
authors.lastname: Cwalina
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Onimus
authors.affiliation: Department of Biological Sciences, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Murphy
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Donny
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.|Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Sved
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage*; D009538:Nicotine / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration; D014191:Tranylcypromine / Q000008:administration & dosage
chemical_list: D008996:Monoamine Oxidase Inhibitors; D014191:Tranylcypromine; D009538:Nicotine; D008995:Monoamine Oxidase