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Thalamic glutamate decreases with cigarette smoking

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Abstract

Rationale

Findings from animal studies and human PET imaging indicate that nicotine and cigarette smoking affect glutamate (Glu) and related neurochemical markers in the brain and imply that smoking reduces extracellular Glu. As Glu release is mediated by nicotinic acetylcholine receptors (nAChRs), which are present at high concentrations in the thalamus, we examined the effects of smoking on thalamic Glu.

Objective

To determine the effects of tobacco smoking on thalamic glutamate levels.

Methods

Thalamic Glu levels were measured in vivo in 18 smokers and 16 nonsmokers using proton magnetic resonance spectroscopic imaging (1H MRSI) at 1.5 T.

Results

Mean Glu levels did not differ significantly between the subject groups. However, within smokers, Glu levels were negatively correlated with self-reports of both cigarettes/day over the last 30 days (r = −0.64, p = 0.006) and pack-years of smoking (r = −0.66, p = 0.005).

Conclusions

Consistent with expectations based on preclinical studies, within smokers, cigarettes/day and pack-years are associated with reduced Glu in thalamus, a brain region rich in nAchRs. These results encourage work on candidate glutamatergic therapies for smoking cessation and suggest a noninvasive metric for their action in the brain.

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Acknowledgments

This work was supported by the National Institute on Drug Abuse (P20DA022539, R01DA020726, R03DA20512, and R21DA023192) (EDL and JON), NIMH grants T32MH073517 and K23MH094613 (ELN), the National Center for Research Resources (NIH M01RR00865, UCLA GCRC), and endowments from the Katherine K. and Thomas P. Pike Chair in Addiction Studies, and the Marjorie M. Greene Trust. The research support for projects other than the one reported here was supplied to Dr. Edythe D. London under UCLA Contract (number 20063287) with Philip Morris USA. All experimental procedures comply with the current laws of the USA.

Conflict of interest

None of the authors has a financial relationship with any organization that sponsored this research and none of the sponsors had any involvement with the design, collection, analysis, writing of the manuscript, or the decision to submit the manuscript for publication. The authors have full control of all primary data and agree to allow the journal to review the data if requested.

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Authors and Affiliations

  1. Division of Child & Adolescent Psychiatry, UCLA Semel Institute for Neuroscience, 760 Westwood Plaza, Box 175919, Los Angeles, CA, 90024-1759, USA

    Joseph O’Neill, Marc C. Tobias, Matthew Hudkins & Erika L. Nurmi

  2. Department of Psychiatry and Biobehavioral Sciences, UCLA Semel Institute for Neuroscience, Los Angeles, CA, USA

    Eugene Y. Oh & Edythe D. London

  3. Biostatistics Core, UCLA Semel Institute for Neuroscience, Los Angeles, CA, USA

    Gerhard S. Hellemann

  4. UCLA Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, Los Angeles, CA, USA

    Edythe D. London

  5. UCLA Brain Research Institute, David Geffen School of Medicine, Los Angeles, CA, 90024, USA

    Edythe D. London

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  1. Joseph O’Neill
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  2. Marc C. Tobias
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  3. Matthew Hudkins
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Correspondence to Joseph O’Neill.

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O’Neill, J., Tobias, M.C., Hudkins, M. et al. Thalamic glutamate decreases with cigarette smoking. Psychopharmacology 231, 2717–2724 (2014). https://doi.org/10.1007/s00213-014-3441-5

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