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Influence of experimental history on nicotine self-administration in squirrel monkeys

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Abstract

Rationale

Methods for establishing robust long-term self-administration of intravenous (i.v.) nicotine, the primary psychoactive agent in tobacco, are not well-established in laboratory animals.

Objective

Here, we examine the use of a fading procedure to establish robust and consistent i.v. nicotine self-administration under second-order schedule conditions in squirrel monkeys.

Methods

First, self-administration behavior was developed in two groups of male squirrel monkeys using a second-order fixed-interval 5-min schedule with fixed-ratio 5 units (FI 5-min (FR5: S)). Comparable performances were maintained by i.v. cocaine (0.032 mg/kg/injection (inj); group A, n = 3) and the combination of food delivery (20–30 % condensed milk) and 0.01 mg/kg/inj i.v. nicotine (group B, n = 3). Subsequently, the concentration of condensed milk was gradually reduced to zero in the second group and self-administration behavior was maintained by i.v. nicotine alone. Next, self-administration of a range of doses of i.v. nicotine (0.001–0.032 mg/kg/inj) and, in additional experiments, the minor tobacco alkaloid anatabine (0.01–0.18 mg/kg/inj) was studied in both groups.

Results

Results show that nicotine and anatabine had reinforcing effects in both groups. However, optimal doses of nicotine and anatabine maintained significantly higher rates of i.v. self-administration behavior in subjects trained with the fading procedure than in subjects provided with a history of cocaine-maintained responding.

Conclusion

These results illustrate conditions under which robust i.v. nicotine self-administration can be established in squirrel monkeys and the influence of prior experimental history in the expression of reinforcing effects of nicotine and anatabine.

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Abbreviations

ANOVA:

Analysis of variance

FI:

Fixed-interval

FR:

Fixed-ratio

TO:

Time-out

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Acknowledgments

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

Authorship contributions

R.I. Desai and J Bergman participated in research design for behavioral experiments. R.I. Desai and K.A. Sullivan conducted the experiment. R.I. Desai and K.A. Sullivan performed behavioral data analysis. R.I. Desai, K.A. Sullivan, and J Bergman wrote or contributed to the writing of the manuscript. S.J. Kohut provided in vitro binding data for anatabine. R.I. Desai acquired funding for the research.

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Authors and Affiliations

  1. Preclinical Pharmacology Laboratory, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA

    Rajeev I. Desai, Katherine A. Sullivan, Stephen J. Kohut & Jack Bergman

Authors
  1. Rajeev I. Desai
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  2. Katherine A. Sullivan
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  3. Stephen J. Kohut
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  4. Jack Bergman
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Corresponding author

Correspondence to Rajeev I. Desai.

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Role of funding source

This work was supported by NIH/NIDA grant DA031231. The funding source had no further role in the following: study design, collection of data, analysis of data, interpretation of data, and 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 of research or professional services, and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.

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The authors declare that they have no conflict of interest.

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Desai, R.I., Sullivan, K.A., Kohut, S.J. et al. Influence of experimental history on nicotine self-administration in squirrel monkeys. Psychopharmacology 233, 2253–2263 (2016). https://doi.org/10.1007/s00213-016-4274-1

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  • DOI: https://doi.org/10.1007/s00213-016-4274-1

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