title: Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy.
abstract: BACKGROUND
  The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations.
  
  
  METHODS
  The present study examined these issues in a rodent nicotine self-administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined.
  
  
  RESULTS
  Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds.
  
  
  CONCLUSIONS
  These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction.
authors.affiliation: Department of Medicine, Minneapolis Medical Research Foundation, 701 Park Ave., Minneapolis, MN 55415, United States; Department of Medicine, University of Minnesota School of Medicine, 420 Delaware St. SE, Minneapolis, MN 55455, United States.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Grebenstein
authors.affiliation: Department of Medicine, Minneapolis Medical Research Foundation, 701 Park Ave., Minneapolis, MN 55415, United States.
authors.forename: Danielle
authors.initials: D
authors.lastname: Burroughs
authors.affiliation: Department of Neuroscience, Gillette Children's Specialty Healthcare, 183 University Ave E, Saint Paul, MN 55101, United States.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Roiko
authors.affiliation: Department of Medicine, Minneapolis Medical Research Foundation, 701 Park Ave., Minneapolis, MN 55415, United States; Department of Medicine, University of Minnesota School of Medicine, 420 Delaware St. SE, Minneapolis, MN 55455, United States; Department of Pharmacology, University of Minnesota School of Medicine, 6-120 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455, United States.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Pentel
authors.affiliation: Department of Medicine, Minneapolis Medical Research Foundation, 701 Park Ave., Minneapolis, MN 55415, United States; Department of Medicine, University of Minnesota School of Medicine, 420 Delaware St. SE, Minneapolis, MN 55455, United States; Department of Psychology, University of Minnesota, N218 Elliot Hall, 75 E River Rd., Minneapolis, MN 55455, United States. Electronic address: lesag002@umn.edu.
authors.forename: Mark G
authors.initials: MG
authors.lastname: LeSage
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D005260:Female; D007206:Individuality; D008297:Male; D009538:Nicotine / Q000493:pharmacokinetics / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D011237:Predictive Value of Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000517:prevention & control* / Q000523:psychology*
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine
keywords: Behavioral economics; Nicotine self-administration; Pharmacokinetics; Rat; Reinforcement threshold; Tobacco control policy