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Nicotinic effects of tobacco smoke constituents in nonhuman primates

Abstract

Rationale

Recent studies in rodents suggest that non-nicotine constituents of tobacco smoke (e.g., minor tobacco alkaloids) may promote tobacco consumption—either through their own pharmacological effects or by augmenting the effects of nicotine. However, there is scant information on the behavioral pharmacology of minor tobacco alkaloids in primate species.

Objective

The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine, anabasine, anatabine, myosmine, and cotinine exhibit nicotine-like behavioral effects in squirrel monkeys.

Methods

Initial experiments were conducted to determine the effects of nicotine (0.032–1.0 mg/kg) and the minor tobacco alkaloids nornicotine (1–1.8 mg/kg), anabasine (0.1–1.0 mg/kg), anatabine (10–32 mg/kg), myosmine (0.32–1.8 mg/kg), and cotinine (10–180 mg/kg) on food-maintained performance (n = 4). Next, the ability of tobacco alkaloids to substitute for the α4β2-selective nicotinic agonist (+)-epibatidine in drug discrimination experiments was evaluated in a separate group of monkeys (n = 4).

Results

Results show that nicotine and each minor tobacco alkaloid except cotinine (a) produced dose-related decreases in food-maintained responding; (b) substituted for (+)-epibatidine and, in additional experiments, produced additive effects when combined with nicotine; (c) induced emesis or tremor at doses that reduced food-maintained responding and had (+)-epibatidine-like discriminative-stimulus effects; and (d) based on correlation with reported receptor binding affinities, likely produced their behavioral effects through α4β2 receptor mechanisms.

Conclusion

Selected minor tobacco alkaloids have nicotinic-like effects that may contribute to tobacco consumption and addiction.

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Abbreviations

ANOVA:

Analysis of variance

FR:

Fixed ratio

TO:

Timeout

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Acknowledgments

We thank Dr. Roger Spealman for his comments on an earlier version of this manuscript.

Role of funding source

This work was supported by NIH/NIDA grant DA031231. The funding source had no further role in study design, collection of data, analysis of data, interpretation of data, writing, and submission of report for publication. The authors declare that, except for income received from our primary employer and, for JB, from LWW for editorial duties, no other financial support or compensation has been received from any individual or corporate entity over the past 3 years research or professional services, and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.

Conflict of interest

The authors declare that they have no competing interests.

Authorship contributions

R.I. Desai and J Bergman participated in research design for behavioral experiments. R.I. Desai, M.R. Doyle, and S.L. Withey conducted the experiment. R.I. Desai, M.R. Doyle, and S.L. Withey performed behavioral data analysis. R.I. Desai and J. Bergman wrote or contributed to the writing of the manuscript. R.I. Desai acquired funding for the research.

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Correspondence to Rajeev I. Desai.

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Desai, R.I., Doyle, M.R., Withey, S.L. et al. Nicotinic effects of tobacco smoke constituents in nonhuman primates. Psychopharmacology 233, 1779–1789 (2016). https://doi.org/10.1007/s00213-016-4238-5

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  • DOI: https://doi.org/10.1007/s00213-016-4238-5

Keywords

  • Nicotine
  • Minor tobacco alkaloids
  • Drug discrimination
  • Food-maintained behavior
  • Nonhuman primates
  • Nornicotine
  • Anabasine
  • Anatabine
  • Myosmine
  • Epibatidine