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Habitual nicotine-seeking in rats following limited training

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Abstract

Rationale and objectives

A potential reason that cigarette smoking can persist despite multiple quit attempts is that repeated voluntary nicotine intake may facilitate a transition from goal-directed to habitual behavioral control. Although accelerated habit formation for self-administered ethanol or cocaine has been previously demonstrated, this phenomenon has not been extensively studied with nicotine. We therefore examined the liability of nicotine self-administration to become habitual, while also examining that of orally consumed saccharin as an experimental control.

Methods

Under fixed ratio 1 (FR-1) schedules, male Sprague-Dawley rats (n = 8–11/group) lever-pressed for intravenous (IV) nicotine (30 μg/kg/infusion) for 10 consecutive days, while also lever-pressing for saccharin solution (0.1% w/v, 0.19 mL/delivery) in separate operant sessions. In experiment 1, either nicotine or saccharin was devalued by pairing with the aversive agent lithium chloride (LiCl; 0.15 M, 14.1 mL/kg) prior to extinction and reacquisition testing. In experiment 2, the contingency between lever pressing and delivery of either nicotine or saccharin was degraded in six sessions, followed by extinction testing.

Results

LiCl pairings selectively reduced responding for nicotine (−35% from control) and saccharin (−48%) in reacquisition testing, indicating that both rewards were effectively devalued. During extinction testing, saccharin-seeking responses were reduced by both manipulations (devaluation −30%, degradation −79%), suggesting that responding for saccharin was goal-directed. In contrast, nicotine-seeking responses were not significantly affected by either manipulation (devaluation −4%, degradation −21%), suggesting that responding for nicotine was habitually driven.

Conclusions

Operant responding for IV nicotine may rapidly come under habitual control, potentially contributing to the tenacity of tobacco use.

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Abbreviations

FR:

fixed-ratio

IP:

intraperitoneal

IV:

intravenous

LiCl:

lithium chloride

NSA:

nicotine self-administration

SC:

subcutaneous

SSA:

saccharin self-administration

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Acknowledgements

This project was funded by the CAMH.

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Authors and Affiliations

  1. Neurobiology of Alcohol Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON, M5S 2S1, Canada

    A. Loughlin, D. Funk, K. Coen & A. D. Lê

  2. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    A. Loughlin & A. D. Lê

  3. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    A. D. Lê

Authors
  1. A. Loughlin
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  2. D. Funk
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  3. K. Coen
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  4. A. D. Lê
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Corresponding author

Correspondence to D. Funk.

Ethics declarations

All experimental procedures described were conducted in full compliance with the National Institutes of Health “Principles of Laboratory Animal Care” (8th Edition, 2011) and approved by the local Animal Care Committee of the Centre for Addiction and Mental Health.

Conflicts of interest

The authors declare that they have no competing interests.

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Loughlin, A., Funk, D., Coen, K. et al. Habitual nicotine-seeking in rats following limited training. Psychopharmacology 234, 2619–2629 (2017). https://doi.org/10.1007/s00213-017-4655-0

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