Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons
Name
Mazei-Robison-2011-Role for mTOR Signal.pdf
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1.54 MB
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Checksum (MD5)
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Author(s)
Mazei-Robison, Michelle S.
Koo, Ja Wook
Friedman, Allyson K.
Lansink, Carien S.
Robison, Alfred J.
Vinish, Monika
Krishnan, Vaishnav
Kim, Seyun
Siuta, Michael A.
Galli, Aurelio
Date Issued
December 2011
Journal
Neuron
Publisher
Elsevier
Citation
Mazei-Robison, Michelle S., Ja Wook Koo, Allyson K. Friedman, Carien S. Lansink, Alfred J. Robison, Monika Vinish, Vaishnav Krishnan, et al. “Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons.” Neuron 72, no. 6 (December 2011): 977–990. © 2011 Elsevier Inc.
Version
Final published version
Abstract
While the abuse of opiate drugs continues to rise, the neuroadaptations that occur with long-term drug exposure remain poorly understood. We describe here a series of chronic morphine-induced adaptations in ventral tegmental area (VTA) dopamine neurons, which are mediated via downregulation of AKT-mTORC2 (mammalian target of rapamycin complex-2). Chronic opiates decrease the size of VTA dopamine neurons in rodents, an effect seen in humans as well, and concomitantly increase the excitability of the cells but decrease dopamine output to target regions. Chronic morphine decreases mTORC2 activity, and overexpression of Rictor, a component of mTORC2, prevents morphine-induced changes in cell morphology and activity. Further, local knockout of Rictor in VTA decreases DA soma size and reduces rewarding responses to morphine, consistent with the hypothesis that these adaptations represent a mechanism of reward tolerance. Together, these findings demonstrate a novel role for AKT-mTORC2 signaling in mediating neuroadaptations to opiate drugs of abuse.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.neuron.2011.10.012
