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Effect of menthol on nicotine intake and relapse vulnerability in a rat model of concurrent intravenous menthol/nicotine self-administration

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Abstract

Rationale

Epidemiological data suggest that menthol may increase vulnerability to cigarette/nicotine use and relapse. While menthol’s sensory properties are often attributed as the underlying cause of the enhanced vulnerability, an alternative possibility is that they are mediated via pharmacological interactions with nicotine.

Objective

This study addressed the possibility that menthol enhances nicotine intake and relapse vulnerability via pharmacological interactions with nicotine using a concurrent intravenous menthol/nicotine self-administration procedure.

Methods

Following acquisition, adolescent rats were given 23-h/day access to nicotine (0.01 mg/kg/infusion), nicotine plus menthol (0.16, 0.32, or 0.64 mg/kg/infusion), or menthol alone (0.16, 0.32, 0.64 mg/kg/infusion) for a total of 10 days. Nicotine-seeking was assessed using an extinction/cue-induced reinstatement procedure following 10 days of forced abstinence. We also assessed the effect of menthol (0.32 mg/kg/infusion) on progressive ratio responding for nicotine (0.01 mg/kg/infusion).

Results

Menthol decreased PR responding for nicotine but did not affect self-administration under extended access conditions. The low dose of menthol tended to decrease subsequent extinction responding, and was not different from menthol alone, whereas the high dose decreased reinstatement responding. Although not significant, the highest levels of extinction responding were observed in a minority of rats in the moderate and high menthol–nicotine groups; rats in these groups also took longer to extinguish.

Conclusions

Taken together, these results demonstrate that pharmacological interactions of menthol with nicotine reduce, rather than increase, nicotine’s reinforcing effects and some measures of relapse vulnerability. Importantly, however, moderate and high menthol doses may increase some aspects of relapse vulnerability in a minority of individuals.

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Acknowledgements

We would like to acknowledge Rebecca Beiter and Elizabeth Gasteiger for technical assistance.

Funding

This study was supported by the Virginia Commonwealth University’s Center for the Study of Tobacco Products Pilot Research Program, the University of Virginia’s 4-VA Innovation Grant Project (WJL), and the National Institute on Drug Abuse (R01DA024716; WJL).

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Authors and Affiliations

  1. Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, 22902, USA

    Tanseli Nesil, Syeda Narmeen, Anousheh Bakhti-Suroosh & Wendy J. Lynch

  2. Department of Psychiatry and Neurobehavioral Sciences, PO Box 801402, Charlottesville, VA, 22904, USA

    Wendy J. Lynch

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  1. Tanseli Nesil
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  2. Syeda Narmeen
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  3. Anousheh Bakhti-Suroosh
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  4. Wendy J. Lynch
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Correspondence to Wendy J. Lynch.

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All procedures were conducted in accordance with the guidelines set by the University of Virginia Animal Care and Use Committee.

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The authors declare that they have no conflict of interest.

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Nesil, T., Narmeen, S., Bakhti-Suroosh, A. et al. Effect of menthol on nicotine intake and relapse vulnerability in a rat model of concurrent intravenous menthol/nicotine self-administration. Psychopharmacology 236, 1219–1232 (2019). https://doi.org/10.1007/s00213-018-5128-9

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