Effects of MAO inhibition and a combination of minor alkaloids, β-carbolines, and acetaldehyde on nicotine self-administration in adult male rats

Tracy T. Smith, Matthew B. Schaff, Laura E. Rupprecht, Rachel L. Schassburger, Deanne M. Buffalari, Sharon E. Murphy, Alan F. Sved, Eric C. Donny

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Introduction: 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.

Original languageEnglish (US)
Article number5706
Pages (from-to)243-252
Number of pages10
JournalDrug and alcohol dependence
StatePublished - Oct 1 2015

Bibliographical note

Funding Information:
Research reported in this publication was supported by the National Institute on Drug Abuse and FDA Center for Tobacco Products (CTP) (U54 DA031659 awarded to E.C.D.) The funding source had no other role other than financial support. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. Funding for Tracy Smith was provided by the National Institute on Drug Abuse ( F31 DA037643 ).

Publisher Copyright:
© 2015 Elsevier Ireland Ltd.


  • Monoamine oxidase inhibition
  • Nicotine
  • Non-nicotine tobacco constituents
  • Regulatory science
  • Self-administration
  • Tobacco policy


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