title: Delivery of nicotine in an extract of a smokeless tobacco product reduces its reinforcement-attenuating and discriminative stimulus effects in rats.
abstract: BACKGROUND
  Animal models of tobacco addiction rely on administration of nicotine alone or nicotine combined with isolated constituents. Models using tobacco extracts derived from tobacco products and containing a range of tobacco constituents might more accurately simulate tobacco exposure in humans.
  
  
  OBJECTIVE
  To compare the effects of nicotine alone and an aqueous smokeless tobacco extract in several addiction-related animal behavioral models.
  
  
  METHODS
  Nicotine alone and nicotine dose-equivalent concentrations of extract were compared in terms of their acute effects on intracranial self-stimulation (ICSS) thresholds, discriminative stimulus effects, and effects on locomotor activity.
  
  
  RESULTS
  Similar levels of nicotine and minor alkaloids were achieved using either artificial saliva or saline for extraction, supporting the clinical relevance of the saline extracts used in these studies. Extract produced reinforcement-enhancing (ICSS threshold-decreasing) effects similar to those of nicotine alone at low to moderate nicotine doses, but reduced reinforcement-attenuating (ICSS threshold-increasing) effects at a high nicotine dose. In rats trained to discriminate nicotine alone from saline, intermediate extract doses did not substitute for the training dose as well as nicotine alone. Locomotor stimulant effects and nicotine distribution to brain were similar following administration of extract or nicotine alone.
  
  
  CONCLUSIONS
  The reinforcement-attenuating and discriminative stimulus effects of nicotine delivered in an extract of a commercial smokeless tobacco product differed from those of nicotine alone. Extracts of tobacco products may be useful for evaluating the abuse liability of those products and understanding the role of non-nicotine constituents in tobacco addiction.
authors.affiliation: Minneapolis Medical Research Foundation, 914 South 8th St,. S-3 Labs, 860, Minneapolis, MN 55404, USA. harr0547@umn.edu
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Harris
authors.forename: Irina
authors.initials: I
authors.lastname: Stepanov
authors.forename: Paul R
authors.initials: PR
authors.lastname: Pentel
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lesage
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004193:Discrimination Learning / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration; D014018:Tissue Distribution; D014029:Tobacco Use Disorder / Q000503:physiopathology*; D014030:Tobacco, Smokeless / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D010936:Plant Extracts; D009538:Nicotine