title: Abuse potential of non-nicotine tobacco smoke components: acetaldehyde, nornicotine, cotinine, and anabasine.
abstract: BACKGROUND
  This review identified published animal studies evaluating the possible abuse potential of acetaldehyde, nornicotine, cotinine, and anabasine based on five commonly used paradigms. These include their effects on midbrain dopamine (DA) levels, drug discrimination and substitution for known drugs of abuse, place conditioning, self-administration behavior, and somatic withdrawal symptoms.
  
  
  RESULTS
  Acetaldehyde had mixed effects on midbrain DA levels and drug discrimination; however, it consistently produced a conditioned place preference and supported self-administration. The single available study on withdrawal found that cessation of acetaldehyde administration resulted in a somatic withdrawal syndrome. Nornicotine increased DA in the midbrain, especially in the nucleus accumbens. Although there are no data on place conditioning, it substituted for nicotine in drug discrimination testing, partially substituted for cocaine and amphetamine, and, though only a single study, supported self-administration. Anabasine increased midbrain DA levels and that it partially substituted for nicotine in drug discrimination testing. Cotinine increased midbrain DA levels and substituted for nicotine.
  
  
  CONCLUSIONS
  The existing literature suggests that acetaldehyde and nornicotine likely possess abuse potential, with anabasine having possible abuse potential. Although some cotinine data were available, it was insufficient to draw conclusions about possible abuse potential. Further research is needed to determine the role of minor alkaloids on tobacco dependence.
authors.affiliation: U.S. Food and Drug Administration, Rockville, MD 20850, USA. allison.hoffman@fda.hhs.gov
authors.forename: Allison C
authors.initials: AC
authors.lastname: Hoffman
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Evans
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology*; D000691:Anabasine / Q000494:pharmacology*; D000818:Animals; D003367:Cotinine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012907:Smoking / Q000009:adverse effects*; D013375:Substance Withdrawal Syndrome; D014029:Tobacco Use Disorder
chemical_list: D009538:Nicotine; C005311:nornicotine; D000079:Acetaldehyde; D003367:Cotinine; D000691:Anabasine; D004298:Dopamine