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Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine: effects of route and ethanol coadministration

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Abstract

Rationale

Nicotine and ethanol are commonly coabused drugs, and nicotine-laced ethanol products are growing in popularity. However, little is known about time-course changes in extracellular nicotine and cotinine levels in rat models of ethanol and nicotine coabuse.

Objectives

The objective of the present study was to determine the time-course changes in brain levels of nicotine and cotinine following subcutaneous (SC) and intragastric (IG) nicotine administration in alcohol-preferring (P) and Wistar rats.

Methods

In vivo microdialysis was used to collect dialysate samples from the nucleus accumbens shell (NACsh) for nicotine and cotinine determinations, following SC administration of (-)-nicotine (0.18, 0.35, and 0.70 mg/kg) in female P and Wistar rats or IG administration of (-)-nicotine (0.35 and 0.70 mg/kg) in 15 % (v/v) ethanol or water in female P rats.

Results

SC nicotine produced nicotine and cotinine dialysate levels as high as 51 and 14 ng/ml, respectively. IG administration of 15 % EtOH + 0.70 mg/kg nicotine in P rats resulted in maximal nicotine and cotinine dialysate levels of 19 and 14 ng/ml, respectively, whereas administration of 0.70 mg/kg nicotine in water resulted in maximal nicotine and cotinine levels of 21 and 25 ng/ml, respectively. Nicotine and cotinine levels were detectable within the first 15 and 45 min, respectively, after IG administration.

Conclusions

Overall, the results of this study suggest that nicotine is rapidly adsorbed and produces relevant extracellular brain concentrations of nicotine and its pharmacologically active metabolite, cotinine. The persisting high brain concentrations of cotinine may contribute to nicotine addiction.

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Acknowledgments

The skillful technical assistance of Joseph A. McClaren and Curtis D. Bard is gratefully acknowledged. This work was supported by NIH-NIAAA grants AA07611, AA019366, and AA020396.

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The authors declare no conflicts of interest

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Authors and Affiliations

  1. Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, 46202-4887, USA

    Simon N. Katner, Jamie E. Toalston, Michael P. Smoker, Zachary A. Rodd, William J. McBride & Eric A. Engleman

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  1. Simon N. Katner
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  2. Jamie E. Toalston
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  3. Michael P. Smoker
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  4. Zachary A. Rodd
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  5. William J. McBride
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  6. Eric A. Engleman
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Correspondence to Eric A. Engleman.

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Katner, S.N., Toalston, J.E., Smoker, M.P. et al. Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine: effects of route and ethanol coadministration. Psychopharmacology 232, 551–560 (2015). https://doi.org/10.1007/s00213-014-3681-4

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  • DOI: https://doi.org/10.1007/s00213-014-3681-4

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