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Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation

  1. Ming Chen
  2. Yanfang Zhao
  3. Hualan Yang
  4. Wenjie Luan
  5. Jiaojiao Song
  6. Dongyang Cui
  7. Yi Dong
  8. Bin Lai
  9. Lan Ma
  10. Ping Zheng  Is a corresponding author
  1. Fudan Univeristy, China
  2. Fudan University, China
Research Article
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Cite this article as: eLife 2015;4:e09275 doi: 10.7554/eLife.09275

Abstract

One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors.

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Author details

  1. Ming Chen

    State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Yanfang Zhao

    State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Hualan Yang

    State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Wenjie Luan

    State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Jiaojiao Song

    State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Dongyang Cui

    State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Yi Dong

    State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Bin Lai

    State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Lan Ma

    State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan Univeristy, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Ping Zheng

    State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai, China
    For correspondence
    pzheng@shmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experimental procedures conformed to Fudan University as well as international guidelines on the ethical use of animals and all efforts were made to minimize the number of animals used and their suffering.

Reviewing Editor

  1. Wolfram Schultz, University of Cambridge, United Kingdom

Publication history

  1. Received: June 8, 2015
  2. Accepted: July 24, 2015
  3. Accepted Manuscript published: July 24, 2015 (version 1)
  4. Version of Record published: August 17, 2015 (version 2)

Copyright

© 2015, Chen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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