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Impact of short access nicotine self-administration on expression of α4β2* nicotinic acetylcholine receptors in non-human primates

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Abstract

Rationale

Although nicotine exposure upregulates the α4β2* subtype of nicotinic acetylcholine receptors (nAChRs), the upregulation of nAChRs in non-human primates voluntarily self-administering nicotine has never been demonstrated.

Objectives

The objective of the study is to determine if short access to nicotine in a non-human primate model of nicotine self-administration is sufficient to induce nAChRs upregulation.

Methods

We combined a nicotine self-administration paradigm with in vivo measure of α4β2* nAChRs using 2-[18F]fluoro-A-85380 (2-FA) and positron emission tomography (PET) in six squirrel monkeys. PET measurement was performed before and after intravenous nicotine self-administration (unit dose 10 μg/kg per injection). Monkeys were trained to self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Intermittent access (1 h daily per weekday) to nicotine was allowed for 4 weeks and levels of α4β2* nAChRs were measured 4 days later.

Results

This intermittent access was sufficient to induce upregulation of α4β2* receptors in the whole brain (31 % upregulation) and in specific brain areas (+36 % in amygdala and +62 % in putamen).

Conclusions

These results indicate that intermittent nicotine exposure is sufficient to produce change in nAChRs expression.

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Authors and Affiliations

  1. Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), 33 Russell Street, Toronto, ON, Canada, M5S 2S1

    Bernard Le Foll

  2. Departments of Family and Community Medicine, Pharmacology, Psychiatry, Institute of Medical Sciences, University of Toronto, Toronto, Canada

    Bernard Le Foll

  3. Ambulatory Care and Structured Treatment Program, Centre for Addiction and Mental Health, Toronto, Canada

    Bernard Le Foll

  4. Preclinical Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA

    Bernard Le Foll & Steven R. Goldberg

  5. Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA

    Svetlana I. Chefer, Alane S. Kimes, Elliot A. Stein & Alexey G. Mukhin

  6. The Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Disease, NIH, Fort.Detrick, Frederick, MD, 21702, USA

    Svetlana I. Chefer

  7. Office of the Clinical Director (retired), Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA

    Alane S. Kimes

  8. Department Psychiatry and Behavioral Sciences and Center for Smoking Cessation, Duke University Medical Center, 2424 Erwin Road, Suite 201, Durham, NC, 27705, USA

    Alexey G. Mukhin

Authors
  1. Bernard Le Foll
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  2. Svetlana I. Chefer
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  3. Alane S. Kimes
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  4. Elliot A. Stein
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  5. Steven R. Goldberg
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  6. Alexey G. Mukhin
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Corresponding author

Correspondence to Bernard Le Foll.

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The authors declare that they have no conflict of interest.

Financial support

This study was supported by the Intramural Research Program of the National Institute on Drug Abuse, NIH, DHHS.

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Steven R. Goldberg In memoriam

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Le Foll, B., Chefer, S.I., Kimes, A.S. et al. Impact of short access nicotine self-administration on expression of α4β2* nicotinic acetylcholine receptors in non-human primates. Psychopharmacology 233, 1829–1835 (2016). https://doi.org/10.1007/s00213-016-4250-9

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  • DOI: https://doi.org/10.1007/s00213-016-4250-9

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