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Research ArticleResearch Article: New Research, Disorders of the Nervous System

Upregulation of nAChRs and Changes in Excitability on VTA Dopamine and GABA Neurons Correlates to Changes in Nicotine-Reward-Related Behavior

Austin T. Akers, Skylar Y. Cooper, Zachary J. Baumgard, Gabriella P. Casinelli, Alicia J. Avelar and Brandon J. Henderson
eNeuro 28 September 2020, 7 (5) ENEURO.0189-20.2020; DOI: https://doi.org/10.1523/ENEURO.0189-20.2020
Austin T. Akers
Department of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV 25703
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Skylar Y. Cooper
Department of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV 25703
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  • ORCID record for Skylar Y. Cooper
Zachary J. Baumgard
Department of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV 25703
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Gabriella P. Casinelli
Department of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV 25703
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Alicia J. Avelar
Department of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV 25703
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Brandon J. Henderson
Department of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV 25703
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Abstract

Previous reports indicate that nicotine reward is mediated through α4β2*, α6β2*, and α4α6β2* nicotinic acetylcholine receptors (nAChRs; * indicates that additional nAChR subunits may be present). Little is known about α4α6β2* nAChR involvement in reward and reinforcement because of a lack of methods that allow the direct investigation of this particular nAChR subtype. Here, we use male and female mice that contain α4-mCherry and α6-GFP nAChR subunits to show that concentrations of nicotine sufficient to evoke reward-related behavior robustly upregulate α4* and α4α6* nAChRs on midbrain dopamine (DA) and GABA neurons. Furthermore, the extent of α4α6* nAChR upregulation on ventral tegmental area (VTA) DA neurons aligns with the magnitude of nicotine reward-related behavior. We also show that the upregulation of nAChRs is accompanied by a functional change in firing frequency of both DA and GABA neurons in the VTA that is directly linked to nicotine reward-related behavior.

  • excitability
  • nicotine
  • nicotinic receptor
  • reward
  • upregulation

Footnotes

  • The authors declare no competing financial interests.

  • This work was supported by the National Institutes on Drug Abuse at the National Institutes of Health Grant DA040047 (to B.J.H.). Research reported in this publication was supported by National Institute on Drug Abuse and Food and Drug Administration Center for Tobacco Products Grant DA046335 (to B.J.H.). Funding was also provided by the PhRMA Foundation (Predoctoral Fellowship in Pharmacology/Toxicology to S.Y.C.) and startup funds to B.J.H. by the Marshall University Research Corporation.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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eneuro: 7 (5)
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September/October 2020
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Upregulation of nAChRs and Changes in Excitability on VTA Dopamine and GABA Neurons Correlates to Changes in Nicotine-Reward-Related Behavior
Austin T. Akers, Skylar Y. Cooper, Zachary J. Baumgard, Gabriella P. Casinelli, Alicia J. Avelar, Brandon J. Henderson
eNeuro 28 September 2020, 7 (5) ENEURO.0189-20.2020; DOI: 10.1523/ENEURO.0189-20.2020

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Upregulation of nAChRs and Changes in Excitability on VTA Dopamine and GABA Neurons Correlates to Changes in Nicotine-Reward-Related Behavior
Austin T. Akers, Skylar Y. Cooper, Zachary J. Baumgard, Gabriella P. Casinelli, Alicia J. Avelar, Brandon J. Henderson
eNeuro 28 September 2020, 7 (5) ENEURO.0189-20.2020; DOI: 10.1523/ENEURO.0189-20.2020
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Keywords

  • excitability
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  • nicotinic receptor
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