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The effects of oral nicotine administration and abstinence on sleep in male C57BL/6J mice

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Abstract

Background

Sleep disturbances are common in smoking cessation attempts and are predictive of relapse. Despite this knowledge, there is no established animal model to study the effect of nicotine abstinence on sleep and EEG parameters.

Objectives

The present study was conducted to characterize sleep and wakefulness in male C57BL/6J mice during periods of oral nicotine administration and abstinence.

Methods

Male C57BL/6J mice were implanted with EEG/EMG recording devices. EEG/EMG data were recorded continuously for a period of 4 weeks. At the beginning of week 2, 200 μg/ml of nicotine was added to the 0.2% saccharin vehicle drinking solution. Following a 2-week period of oral nicotine administration, abstinence was initiated by excluding the nicotine from the 0.2% saccharin vehicle drinking solution. EEG/EMG were analyzed at pre-nicotine baseline, during nicotine administration, and on days 1, 2, and 5 of abstinence from nicotine.

Results

Oral nicotine administration decreased total sleep time during the active phase, consistent with the stimulant actions of nicotine. In contrast, NREM sleep quantity was increased during the active phase on nicotine abstinence day 1 and REM sleep was decreased during days 2 and 5 of abstinence. Further, sleep fragmentation was increased during the inactive phase on all days of abstinence. Oral nicotine administration and abstinence from nicotine also altered EEG relative power frequencies during the inactive and active phase.

Conclusions

Both oral nicotine administration and abstinence lead to sleep disturbances in mice. Similarities between this model and human reports on the effect of nicotine/nicotine withdrawal on sleep support its utility in examining the molecular mechanisms that modulate the relationship between sleep, nicotine, and nicotine abstinence/withdrawal.

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Funding

Grant #: T32DA017637-12, National Institute on Drug Abuse.

Title: Research Training–Genetics of Substance Abuse.

PI: John K. Hewitt.

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Authors and Affiliations

  1. Department of Psychology and Neuroscience, The University of Colorado Boulder, Institute for Behavioral Genetics, 1480 30th Street, Boulder, CO, 80309, USA

    Hunter L. Mathews

  2. Department of Integrative Physiology, The University of Colorado Boulder, Institute for Behavioral Genetics, 1480 30th Street, Boulder, CO, 80309, USA

    Jerry A. Stitzel

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  1. Hunter L. Mathews
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Correspondence to Hunter L. Mathews.

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All procedures were approved by the University of Colorado’s Institutional Animal Care and Use Committee and followed the National Institutes of Health guide for the care and use of laboratory animals.

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The authors declare that they have no conflict of interest.

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Mathews, H.L., Stitzel, J.A. The effects of oral nicotine administration and abstinence on sleep in male C57BL/6J mice. Psychopharmacology 236, 1335–1347 (2019). https://doi.org/10.1007/s00213-018-5139-6

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  • DOI: https://doi.org/10.1007/s00213-018-5139-6

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