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Psychopharmacology

, Volume 190, Issue 2, pp 145–155 | Cite as

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. BardoEmail author
Original Investigation

Abstract

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.

Keywords

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

Notes

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.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • D. J. Stairs
    • 1
  • N. M. Neugebauer
    • 1
  • X. Wei
    • 2
  • C. Boustany
    • 3
  • M. Hojahmat
    • 4
  • L. A. Cassis
    • 3
  • P. A. Crooks
    • 2
  • L. P. Dwoskin
    • 2
  • M. T. Bardo
    • 1
    Email author
  1. 1.Department of PsychologyUniversity of KentuckyLexingtonUSA
  2. 2.College of PharmacyUniversity of KentuckyLexingtonUSA
  3. 3.Center for Nutritional SciencesUniversity of KentuckyLexingtonUSA
  4. 4.Yaupon Therapeutics Inc.LexingtonUSA

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