Hippocampal GluA1-Containing AMPA Receptors Mediate Context-Dependent Sensitization to Morphine
Glutamatergic systems, including AMPA receptors (AMPARs), are involved in opiate-induced neuronal and behavioral plasticity, although the mechanisms underlying these effects are not fully understood. In the present study, we investigated the effects of repeated morphine administration on AMPAR expre...
| Main Authors: | , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Society for Neuroscience
2012
|
| Online Access: | http://hdl.handle.net/1721.1/73169 https://orcid.org/0000-0002-3854-5968 |
| _version_ | 1826216333358923776 |
|---|---|
| author | Neve, Rachael L. Xia, Yan Portugal, George S. Fakira, Amanda K. Melyan, Zara Lee, H. Thomas Russo, Scott J. Liu, Jie Morón, Jose A. |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Neve, Rachael L. Xia, Yan Portugal, George S. Fakira, Amanda K. Melyan, Zara Lee, H. Thomas Russo, Scott J. Liu, Jie Morón, Jose A. |
| author_sort | Neve, Rachael L. |
| collection | MIT |
| description | Glutamatergic systems, including AMPA receptors (AMPARs), are involved in opiate-induced neuronal and behavioral plasticity, although the mechanisms underlying these effects are not fully understood. In the present study, we investigated the effects of repeated morphine administration on AMPAR expression, synaptic plasticity, and context-dependent behavioral sensitization to morphine. We found that morphine treatment produced changes of synaptic AMPAR expression in the hippocampus, a brain area that is critically involved in learning and memory. These changes could be observed 1 week after the treatment, but only when mice developed context-dependent behavioral sensitization to morphine in which morphine treatment was associated with drug administration environment. Context-dependent behavioral sensitization to morphine was also associated with increased basal synaptic transmission and disrupted hippocampal long-term potentiation (LTP), whereas these effects were less robust when morphine administration was not paired with the drug administration environment. Interestingly, some effects may be related to the prior history of morphine exposure in the drug-associated environment, since alterations of AMPAR expression, basal synaptic transmission, and LTP were observed in mice that received a saline challenge 1 week after discontinuation of morphine treatment. Furthermore, we demonstrated that phosphorylation of GluA1 AMPAR subunit plays a critical role in the acquisition and expression of context-dependent behavioral sensitization, as this behavior is blocked by a viral vector that disrupts GluA1 phosphorylation. These data provide evidence that glutamatergic signaling in the hippocampus plays an important role in context-dependent sensitization to morphine and supports further investigation of glutamate-based strategies for treating opiate addiction. |
| first_indexed | 2024-09-23T16:46:03Z |
| format | Article |
| id | mit-1721.1/73169 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:46:03Z |
| publishDate | 2012 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/731692022-09-29T21:21:24Z Hippocampal GluA1-Containing AMPA Receptors Mediate Context-Dependent Sensitization to Morphine Neve, Rachael L. Xia, Yan Portugal, George S. Fakira, Amanda K. Melyan, Zara Lee, H. Thomas Russo, Scott J. Liu, Jie Morón, Jose A. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Neve, Rachael L. Glutamatergic systems, including AMPA receptors (AMPARs), are involved in opiate-induced neuronal and behavioral plasticity, although the mechanisms underlying these effects are not fully understood. In the present study, we investigated the effects of repeated morphine administration on AMPAR expression, synaptic plasticity, and context-dependent behavioral sensitization to morphine. We found that morphine treatment produced changes of synaptic AMPAR expression in the hippocampus, a brain area that is critically involved in learning and memory. These changes could be observed 1 week after the treatment, but only when mice developed context-dependent behavioral sensitization to morphine in which morphine treatment was associated with drug administration environment. Context-dependent behavioral sensitization to morphine was also associated with increased basal synaptic transmission and disrupted hippocampal long-term potentiation (LTP), whereas these effects were less robust when morphine administration was not paired with the drug administration environment. Interestingly, some effects may be related to the prior history of morphine exposure in the drug-associated environment, since alterations of AMPAR expression, basal synaptic transmission, and LTP were observed in mice that received a saline challenge 1 week after discontinuation of morphine treatment. Furthermore, we demonstrated that phosphorylation of GluA1 AMPAR subunit plays a critical role in the acquisition and expression of context-dependent behavioral sensitization, as this behavior is blocked by a viral vector that disrupts GluA1 phosphorylation. These data provide evidence that glutamatergic signaling in the hippocampus plays an important role in context-dependent sensitization to morphine and supports further investigation of glutamate-based strategies for treating opiate addiction. 2012-09-25T16:29:49Z 2012-09-25T16:29:49Z 2011-11 2011-09 Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/73169 Xia, Y. et al. “Hippocampal GluA1-Containing AMPA Receptors Mediate Context-Dependent Sensitization to Morphine.” Journal of Neuroscience 31.45 (2011): 16279–16291. Copyright © 2011 by the Society for Neuroscience https://orcid.org/0000-0002-3854-5968 en_US http://dx.doi.org/10.1523/jneurosci.3835-11.2011 Journal of Neuroscience 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 Society for Neuroscience SFN |
| spellingShingle | Neve, Rachael L. Xia, Yan Portugal, George S. Fakira, Amanda K. Melyan, Zara Lee, H. Thomas Russo, Scott J. Liu, Jie Morón, Jose A. Hippocampal GluA1-Containing AMPA Receptors Mediate Context-Dependent Sensitization to Morphine |
| title | Hippocampal GluA1-Containing AMPA Receptors Mediate Context-Dependent Sensitization to Morphine |
| title_full | Hippocampal GluA1-Containing AMPA Receptors Mediate Context-Dependent Sensitization to Morphine |
| title_fullStr | Hippocampal GluA1-Containing AMPA Receptors Mediate Context-Dependent Sensitization to Morphine |
| title_full_unstemmed | Hippocampal GluA1-Containing AMPA Receptors Mediate Context-Dependent Sensitization to Morphine |
| title_short | Hippocampal GluA1-Containing AMPA Receptors Mediate Context-Dependent Sensitization to Morphine |
| title_sort | hippocampal glua1 containing ampa receptors mediate context dependent sensitization to morphine |
| url | http://hdl.handle.net/1721.1/73169 https://orcid.org/0000-0002-3854-5968 |
| work_keys_str_mv | AT neverachaell hippocampalglua1containingampareceptorsmediatecontextdependentsensitizationtomorphine AT xiayan hippocampalglua1containingampareceptorsmediatecontextdependentsensitizationtomorphine AT portugalgeorges hippocampalglua1containingampareceptorsmediatecontextdependentsensitizationtomorphine AT fakiraamandak hippocampalglua1containingampareceptorsmediatecontextdependentsensitizationtomorphine AT melyanzara hippocampalglua1containingampareceptorsmediatecontextdependentsensitizationtomorphine AT leehthomas hippocampalglua1containingampareceptorsmediatecontextdependentsensitizationtomorphine AT russoscottj hippocampalglua1containingampareceptorsmediatecontextdependentsensitizationtomorphine AT liujie hippocampalglua1containingampareceptorsmediatecontextdependentsensitizationtomorphine AT moronjosea hippocampalglua1containingampareceptorsmediatecontextdependentsensitizationtomorphine |