Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons
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-m...
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| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/92325 https://orcid.org/0000-0002-3854-5968 |
| _version_ | 1826205595950120960 |
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| author | 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 Niswender, Kevin D. Appasani, Raghu Horvath, Monika C. Neve, Rachael L. Worley, Paul F. Snyder, Solomon H. Hurd, Yasmin L. Cheer, Joseph F. Han, Ming-Hu Russo, Scott J. Nestler, Eric J. |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences 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 Niswender, Kevin D. Appasani, Raghu Horvath, Monika C. Neve, Rachael L. Worley, Paul F. Snyder, Solomon H. Hurd, Yasmin L. Cheer, Joseph F. Han, Ming-Hu Russo, Scott J. Nestler, Eric J. |
| author_sort | Mazei-Robison, Michelle S. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:15:36Z |
| format | Article |
| id | mit-1721.1/92325 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:15:36Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/923252022-10-01T14:04:12Z Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons 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 Niswender, Kevin D. Appasani, Raghu Horvath, Monika C. Neve, Rachael L. Worley, Paul F. Snyder, Solomon H. Hurd, Yasmin L. Cheer, Joseph F. Han, Ming-Hu Russo, Scott J. Nestler, Eric J. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Neve, Rachael L. 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. 2014-12-16T16:50:42Z 2014-12-16T16:50:42Z 2011-12 2011-10 Article http://purl.org/eprint/type/JournalArticle 08966273 1097-4199 http://hdl.handle.net/1721.1/92325 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. https://orcid.org/0000-0002-3854-5968 en_US http://dx.doi.org/10.1016/j.neuron.2011.10.012 Neuron 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. application/pdf Elsevier Elsevier |
| spellingShingle | 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 Niswender, Kevin D. Appasani, Raghu Horvath, Monika C. Neve, Rachael L. Worley, Paul F. Snyder, Solomon H. Hurd, Yasmin L. Cheer, Joseph F. Han, Ming-Hu Russo, Scott J. Nestler, Eric J. Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons |
| title | Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons |
| title_full | Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons |
| title_fullStr | Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons |
| title_full_unstemmed | Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons |
| title_short | Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons |
| title_sort | role for mtor signaling and neuronal activity in morphine induced adaptations in ventral tegmental area dopamine neurons |
| url | http://hdl.handle.net/1721.1/92325 https://orcid.org/0000-0002-3854-5968 |
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