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Reduced nicotine reward in obesity: cross-comparison in human and mouse

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Abstract

Rationale

Tobacco use and obesity lead to significant morbidity and mortality.

Objective

This study was conducted to investigate the factors maintaining smoking behavior in lean and obese individuals by utilizing a mouse/human cross-validation model of nicotine reward.

Methods

In humans, a cigarette choice paradigm was used to examine the relative reinforcing value of nicotine in obese and non-obese smokers. Conditioned place preference (CPP) for nicotine was assessed in mice fed standard low fat rodent chow and mice rendered obese by a high fat diet.

Results

In humans, obese smokers self-administered nicotine via cigarettes significantly less often than non-obese smokers and showed attenuated hedonic effects of nicotine-containing cigarettes compared to denicotinized cigarettes. Similarly, mice exposed to a high fat diet did not exhibit nicotine CPP, relative to control mice. mRNA levels for mu-opiate and leptin receptors were also downregulated in the ventral tegmental area of these mice.

Conclusions

Together, these studies provide the first evidence for reduced nicotine reward in obese subjects and suggest that this may be mediated by dietary influences on the endogenous opioid system.

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Acknowledgements

This work was supported in part by National Institute on Drug Abuse Grant DA-11649-01A2 (JAB) and 1F31 DA 015949 (CLW) and a Transdisciplinary Tobacco Use Research Center grant from the National Cancer Institute and National Institute on Drug Abuse P5084718 (CL). The authors acknowledge Dr. Margaret Rukstalis for her input on the nicotine choice paradigm, Dr. Neal Benowitz for his helpful feedback and for cotinine assays, Susan Kucharski and Angela Pinto for their assistance with data management, Misty Godfrey for animal husbandry, and Maryanne Foster for assistance with manuscript preparation.

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Authors and Affiliations

  1. Department of Pharmacology, 125 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA, 19104-6084, USA

    Julie A. Blendy & Carrie L. Walters

  2. Department of Psychiatry, Tobacco Use Research Center, 3535 Market Street Suite 4100, Philadelphia, PA, 19104, USA

    Andrew Strasser, Freda Patterson & Caryn Lerman

  3. Department of Psychiatry, WPIC, University of Pittsburgh School of Medicine, 3811 O’Hara Street, Pittsburgh, PA, 15213, USA

    Kenneth A. Perkins

  4. Department of Psychiatry, Children’s Hospital of Philadelphia, 3440 Market Street, Suite 200, Philadelphia, PA, 19104, USA

    Robert Berkowitz

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  1. Julie A. Blendy
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  2. Andrew Strasser
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  3. Carrie L. Walters
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  4. Kenneth A. Perkins
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  5. Freda Patterson
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  7. Caryn Lerman
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Correspondence to Julie A. Blendy or Caryn Lerman.

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Blendy, J.A., Strasser, A., Walters, C.L. et al. Reduced nicotine reward in obesity: cross-comparison in human and mouse. Psychopharmacology 180, 306–315 (2005). https://doi.org/10.1007/s00213-005-2167-9

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  • DOI: https://doi.org/10.1007/s00213-005-2167-9

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