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

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

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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.

Original languageEnglish
Pages (from-to)145-155
Number of pages11
JournalPsychopharmacology
Volume190
Issue number2
DOIs
StatePublished - Feb 2007

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nornicotine
Self Administration
Nicotine

All Science Journal Classification (ASJC) codes

  • Pharmacology

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Effects of nornicotine enantiomers on intravenous S(-)-nicotine self-administration and cardiovascular function in rats. / Stairs, Dustin; Neugebauer, N. M.; Wei, X.; Boustany, C.; Hojahmat, M.; Cassis, L. A.; Crooks, P. A.; Dwoskin, L. P.; Bardo, M. T.

In: Psychopharmacology, Vol. 190, No. 2, 02.2007, p. 145-155.

Research output: Contribution to journalArticle

Stairs, D, Neugebauer, NM, Wei, X, Boustany, C, Hojahmat, M, Cassis, LA, Crooks, PA, Dwoskin, LP & Bardo, MT 2007, 'Effects of nornicotine enantiomers on intravenous S(-)-nicotine self-administration and cardiovascular function in rats', Psychopharmacology, vol. 190, no. 2, pp. 145-155. https://doi.org/10.1007/s00213-006-0610-1
Stairs, Dustin ; Neugebauer, N. M. ; Wei, X. ; Boustany, C. ; Hojahmat, M. ; Cassis, L. A. ; Crooks, P. A. ; Dwoskin, L. P. ; Bardo, M. T. / Effects of nornicotine enantiomers on intravenous S(-)-nicotine self-administration and cardiovascular function in rats. In: Psychopharmacology. 2007 ; Vol. 190, No. 2. pp. 145-155.
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