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Plasma concentrations of nicotine in rats during tolerance and chronic exposure studies

European Journal of Drug Metabolism and Pharmacokinetics volume 13, pages 247–252 (1988)Cite this article

Summary

A convenient GC/MS method for the quantitation of nicotine is described. Brief and rapid tolerance to the hypertensive action of nicotine was observed during acute administration. Rats continuously exposed to (+)- or (-)-nicotine for 6 days showed significant dose-related suppression of water intake and body-weight decreases for the initial 4 days; then water consumption slowly returned to control levels, while body weight increased, but failed to reach control levels. During the withdrawal period, water consumption rose to levels significantly higher than that of the tartaric acid and water controls. Body weight during the withdrawal phase continued to increase but remained below those of control animals. Blood concentration of nicotine during acute tolerance was found to be 64.3 ± 17.8 ng/ml whereas the saline controls showed levels of 0.67 ± 0.67 ng/ml. Nicotine levels which were not detectable before the administration of nicotine, were elevated and constant during days 1 and 6 of the infusion period (320 ± 80 ng/ml of plasma) and fell to below levels of detectability 24 hr after the termination of the infusion.

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References

  1. Aceto M.D., Tucker S.M., Ferguson G.S., Hinson J.R. (1986): Rapid and brief tolerance to (+)- and ( − )-nicotine in un anaesthetized rats. Eur. J. Pharmacol., 132, 213–218.

    Article  PubMed  CAS  Google Scholar 

  2. Aceto M.D., Tucker S.M., Ferguson G.S., Hinson J.R. (1987): Chronic nicotine exposure : Studies on water intake, body weight, blood pressure and behaviour. Natl. Inst Drug Abuse Res. Monogr. Ser., 76, 327–333.

    CAS  Google Scholar 

  3. Aceto M.D., Martin B.R., Uwaydah W.M. et al. (1979): Optically pure (+)-nicotine from (±)-nicotine and biological comparisons with (−)-nicotine. J. Med. Chem., 22, 174.

    Article  PubMed  CAS  Google Scholar 

  4. Weeks J.R., Davis J.D. (1964): Intravenous cannulas for rats. J. Appl. Physiol., 19, 540.

    PubMed  CAS  Google Scholar 

  5. Weeks J.A., Jones J.A. (1960): Routine direct measurement of arterial pressure in unanaesthetized rats. Proc. Soc. Exp. Biol. Med., 104, 646.

    PubMed  CAS  Google Scholar 

  6. Teiger D.I. (1974): Induction of physical dependence on morphine, codeine and meperidine in the rat by continuous infusion. J. Pharmacol. Exp. Ther. 190, 408–415.

    PubMed  CAS  Google Scholar 

  7. Siegel S. (1956): Nonparametric statistics for the behavioural sciences. New York: McGraw-Hill, p.312.

    Google Scholar 

  8. Horstmann M. (1985): Simple high-performance liquid chromatographic method for rapid determination of nicotine and cotinine in urine. J. Chromatogr., 344, 391–396.

    Article  PubMed  CAS  Google Scholar 

  9. Russell M.A.H., Feyerabend C. (1978): Cigarette smoking : A dependence on a high nicotine boli. Drug. Metab. Rev., 8, 29.

    Article  PubMed  CAS  Google Scholar 

  10. U.S. Department of Health, Education and Welfare (1979): Smoking and Health : A report of the Surgeon General. Washington, DC : U.S. Gov.

    Google Scholar 

  11. Kännel W.B. (1978): American Heart Association report of the ad hoc committee on cigarette smoking and cardiovascular disease. Circulation, 57, 404.

    Google Scholar 

  12. Spain D.V., Bradess V.A. (1970): Sudden death from coronary heart disease. Chest, 8, 58.

    Google Scholar 

  13. Pomerleau D.F., Pomerleau C.S. (1984): Neuroregulators and reinforcement of smoking: Towards a biobehavioural explanation. Neurosci. Biobehav. Rev., 8, 503–513.

    Article  PubMed  CAS  Google Scholar 

  14. Goldberg S.R., Spealman R.D. (1983): Suppression of behaviour by intravenous injections of nicotine or by electric shocks in squirrel monkeys: Effects of chlordiazepoxide and mecamylamine. J. Pharmacol. Exp. Ther., 224, 334.

    PubMed  CAS  Google Scholar 

  15. Henningfield J.E., Goldberg S.R. (1983): Control of behaviour by intravenous nicotine injections in human subject. Pharmacol. Biochem. Behav., 19, 1021.

    Article  PubMed  CAS  Google Scholar 

  16. Jasinski D.R., Henningfield J.E., Hickey J.E., Johnson R.E. (1982): Progress Report of the NIDA Addiction Research Center, Baltimore, Maryland. Natl. Inst Drug Abuse Res. Monogr. Ser., 43, 92.

    Google Scholar 

  17. Falkebom S., Larsson C., Nordberg A. (1981): Chronic nicotine exposure in rat: A behavioural and biochemical study of tolerance. Drug Alcohol Depend., 8, 51.

    Article  Google Scholar 

  18. Clarke P.B.S., Kumar R. (1984): Some effects of nicotine on food and water intake in undeprived rats. Br. J. Pharmacol. 82, 223.

    Google Scholar 

  19. Wager-Srdar S.A., Levine A.S., Moriey J.E. Hoidal Jr., Niewoehner D.E. (1984): Effects of cigarette smoke and nicotine on feeding and energy. Physiol. Behav., 32, 389.

    Article  PubMed  CAS  Google Scholar 

  20. Schiffman S.M. (1979): The tobacco withdrawal syndrome. NIDA Res. Monog., 23, 158.

    Google Scholar 

  21. Wack J.R., Rodin J. (1982): Smoking and its effects on body weight and the system of caloric regulation. Am. J. Clin. Nutr., 35, 366.

    PubMed  CAS  Google Scholar 

  22. Little C.C. (1904) : Why do people think quitting smoking affects their appetite or their weight? Apothecary (Special) No. 35.

  23. Levin E.D., Morgan M.M., Galvez C., Ellison G.D. (1987): Chronic nicotine and withdrawal effects on body weight and food and water consumption in female rats. Physiol. Behav., 39, 441–444.

    Article  PubMed  CAS  Google Scholar 

  24. Grunberg M.E. (1982): The effects of nicotine and cigarette smoking on food consumption and taste preferences. Addict Behav. 7, 317.

    Article  PubMed  CAS  Google Scholar 

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Affiliations

  1. Medical College of Virginia, Virginia Commonwealth University, MCV Box 613, 23298-0613, Richmond, VA, USA

    B. F. Thomas, E. R. Bowman, S. M. Tucker & M. D. Aceto

Authors
  1. B. F. Thomas
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  2. E. R. Bowman
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  3. S. M. Tucker
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  4. M. D. Aceto
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Thomas, B.F., Bowman, E.R., Tucker, S.M. et al. Plasma concentrations of nicotine in rats during tolerance and chronic exposure studies. Eur. J. Drug Metab. Pharmacokinet. 13, 247–252 (1988). https://doi.org/10.1007/BF03190086

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  • DOI: https://doi.org/10.1007/BF03190086

Key words

  • (+)-Nicotine
  • (−)-Nicotine
  • Tolerance
  • Chronic Exposure
  • Plasma Levels