Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy

Patricia E. Grebenstein, Danielle Burroughs, Samuel A. Roiko, Paul R. Pentel, Mark G. LeSage

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)181-193
Number of pages13
JournalDrug and alcohol dependence
StatePublished - Jun 1 2015

Bibliographical note

Funding Information:
Funding for this study was provided by NIH / NIDA grant R01-026444 (MGL) and a career development award (MGL) and postdoctoral fellowship (PEG) from the Minneapolis Medical Research Foundation. These funding institutions had no role in the study design, data collection, data analysis, interpretation of the data, manuscript preparation, or decisions to submit the manuscript for publication.


  • Behavioral economics
  • Nicotine self-administration
  • Pharmacokinetics
  • Rat
  • Reinforcement threshold
  • Tobacco control policy

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