Effects of nornicotine enantiomers on intravenous S(-)-nicotine self-administration and cardiovascular function in rats

D. J. Stairs, N. M. Neugebauer, X. Wei, C. Boustany, M. Hojahmat, L. A. Cassis, P. A. Crooks, L. P. Dwoskin, M. T. Bardo

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Rationale: Previous neurochemical evidence indicates that R(+)-nornicotine is more potent than S(-)-nornicotine in evoking dopamine release in rat nucleus accumbens slices. Objective: The current study tested the hypothesis that R(+)-nornicotine is also more potent than S(-)-nornicotine in selectively decreasing intravenous S(-)-nicotine self-administration in rats. Results: After acute pretreatment (1-10 mg/kg for each enantiomer), R(+)-nornicotine was more potent than S(-)-nornicotine in decreasing S(-)-nicotine self-administration; in contrast, within the same dose range, the nornicotine enantiomers were equipotent in decreasing sucrose-maintained responding. This enantioselectivity does not likely reflect a difference in bioavailability, since similar levels of nornicotine were recovered from the brain 60 min after injection (5.6 mg/kg for each enantiomer). With repeated pretreatment, tolerance did not develop to the rate-decreasing effect of either nornicotine enantiomer (3 or 5.6 mg/kg) with respect to the decrease in S(-)-nicotine self-administration, although the enantioselectivity dissipated across repeated pretreatments. While both enantiomers acutely produced a similar increase in blood pressure and heart rate, tolerance developed to the blood pressure effects of R(+)-nornicotine, but not to the effects of S(-)-nornicotine, across repeated treatments. Conclusion: Both R(+)- and S(-)-nornicotine may have potential utility as a novel tobacco use cessation agent.

Original languageEnglish
Pages (from-to)145-155
Number of pages11
Issue number2
StatePublished - Feb 2007

Bibliographical note

Funding Information:
Acknowledgments This work was supported by USPHS grant DA 016521 to Yaupon Therapeutics. The University of Kentucky holds a patent for nornicotine as a smoking cessation therapy, and the patent is licensed to Yaupon Therapeutics, Inc. P.A.C, L.P.D. and M.T.B. have financial interests in Yaupon.


  • Cardiovascular effects
  • Nicotine self-administration
  • Nornicotine
  • Schedule-controlled behavior
  • Tobacco dependence

ASJC Scopus subject areas

  • Pharmacology


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