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Reinforcement enhancement by nicotine in adult rats: behavioral selectivity and relation to mode of delivery and blood nicotine levels

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Abstract

Rationale

Reinforcement-enhancing effects of nicotine occur in human subjects and laboratory rats. However, the doses used in animal studies typically exceed smoking-associated levels of exposure, and generalized behavioral activation by nicotine can potentially confound data interpretation.

Methods

During daily 60-min sessions, male adult rats pressed an “active” lever to illuminate a brief cue light. Pressing on either the active or inactive lever retracted both levers for 60 s. Nicotine (0.025–0.2 mg/kg) was given either by continuous intravenous (IV) infusion, or spaced IV pulses (3-s or 30-s/pulse), or pre-session subcutaneous (SC) injection.

Results

Almost all rats responded preferentially for the cue light for several weeks. After several home-cage nicotine injections, reinforcement enhancement occurred even within the first nicotine test session. Nicotine increased active lever responding without altering inactive lever responding, with effects reliably observed at doses as low as 0.1 mg/kg SC or 0.1 mg/kg/session IV. Within the session, the 0.1 mg/kg dose maximally increased active lever responding by 2–3-fold, coinciding with serum levels of 25 ng/ml. Intravenous nicotine (tested at 0.1 mg/kg/60-min session) was equally effective whether delivered by continuous infusion or in a series of equally spaced 0.003 mg/kg pulses each of 3-s or 30-s duration.

Conclusions

Low doses of nicotine can potentiate responding for a primary sensory reinforcer without producing a generalized increase in lever pressing. Reinforcer enhancement by nicotine generalized to several modes of drug delivery, appeared to track circulating levels of drug, and occurred even at serum levels within the daytime range of moderate cigarette smokers.

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Acknowledgements

The study was supported by a Natural Science and Engineering Research Council of Canada (NSERC) Discovery Grant (155055, to P.B.S.C), and a Canadian Institutes of Health Research of Canada Operating Grant (MOP-10516, to P.B.S.C.). P.B.S.C. is a member of the Center for Studies in Behavioral Neurobiology at Concordia University, Montreal. The authors have no financial relationship with the organizations that sponsored this research. All experiments comply with the current laws of Canada.

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  1. Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Building Rm. 1320, 3655 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada

    Annie Constantin & Paul B. S. Clarke

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  1. Annie Constantin
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  2. Paul B. S. Clarke
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Correspondence to Paul B. S. Clarke.

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Constantin, A., Clarke, P.B.S. Reinforcement enhancement by nicotine in adult rats: behavioral selectivity and relation to mode of delivery and blood nicotine levels. Psychopharmacology 235, 641–650 (2018). https://doi.org/10.1007/s00213-017-4778-3

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  • DOI: https://doi.org/10.1007/s00213-017-4778-3

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