title: Effects of MAO inhibition and a combination of minor alkaloids, β-carbolines, and acetaldehyde on nicotine self-administration in adult male rats.
abstract: BACKGROUND
  Although nicotine is the primary reinforcing constituent in cigarettes, there is evidence that other constituents in cigarette smoke may interact with nicotine to reinforce smoking behavior.
  
  
  METHODS
  The present experiments investigated whether a novel combination of these cigarette smoke constituents would increase nicotine self-administration in adult male rats. The constituents included five minor alkaloids (anabasine, nornicotine, cotinine, myosmine, and anatabine), two β-carbolines (harman and norharman), and acetaldehyde. All doses were indexed to be proportional to concentrations in cigarette smoke given a standard dose of nicotine used in rodent self-administration, or ten times higher than this standard. To model MAO inhibition seen in chronic smokers, some groups received separate injections of tranylcypromine prior to each self-administration session.
  
  
  RESULTS
  Tranylcypromine increased low-dose nicotine self-administration independent of other smoke constituents, which had no effect on self-administration behavior. The effect of tranylcypromine was confirmed across a large range of reinforcement schedules. The effect of tranylcypromine on low-dose nicotine self-administration was observed regardless of whether the injection was delivered 1-h or 23-h prior to the self-administration session, consistent with the interpretation that MAO inhibition was responsible for the increase in self-administration, instead of acute off-target effects.
  
  
  CONCLUSIONS
  These data suggest that this cocktail of constituents does not significantly alter the primary reinforcing effects of nicotine, but constituents that inhibit MAO may increase the primary reinforcing effects of nicotine, especially at low doses.
authors.affiliation: Department of Psychology, University of Pittsburgh, United States.
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Smith
authors.affiliation: Department of Neuroscience, University of Pittsburgh, United States.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Schaff
authors.affiliation: Department of Neuroscience, University of Pittsburgh, United States.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Rupprecht
authors.affiliation: Department of Neuroscience, University of Pittsburgh, United States.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Schassburger
authors.affiliation: Department of Neuroscience, University of Pittsburgh, United States.
authors.forename: Deanne M
authors.initials: DM
authors.lastname: Buffalari
authors.affiliation: College of Biological Sciences, University of Minnesota, United States.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Murphy
authors.affiliation: Department of Psychology, University of Pittsburgh, United States; Department of Neuroscience, University of Pittsburgh, United States.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Sved
authors.affiliation: Department of Psychology, University of Pittsburgh, United States. Electronic address: edonny@pitt.edu.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Donny
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D012055:Reinforcement Schedule; D012646:Self Administration; D014191:Tranylcypromine / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D002243:Carbolines; D008996:Monoamine Oxidase Inhibitors; D014191:Tranylcypromine; D009538:Nicotine; D000079:Acetaldehyde
keywords: Monoamine oxidase inhibition; Nicotine; Non-nicotine tobacco constituents; Regulatory science; Self-administration; Tobacco policy