Persistent Reversal of Enhanced Amphetamine Intake by Transient CaMKII Inhibition
Amphetamine exposure transiently increases Ca2+/calmodulin-dependent protein kinase II (CaMKII) α expression in the nucleus accumbens (NAcc) shell and this persistently increases local GluA1 S831 phosphorylation and enhances behavioral responding to the drug. Here we assessed whether transiently int...
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| Format: | Article |
| Language: | en_US |
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Society for Neuroscience
2013
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| Online Access: | http://hdl.handle.net/1721.1/79759 https://orcid.org/0000-0002-3854-5968 |
| _version_ | 1826209383518830592 |
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| author | Loweth, Jessica A. Li, Dongdong Cortright, James J. Wilke, Georgia Jeyifous, Okunola Neve, Rachael L. Bayer, K. Ulrich Vezina, Paul |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Loweth, Jessica A. Li, Dongdong Cortright, James J. Wilke, Georgia Jeyifous, Okunola Neve, Rachael L. Bayer, K. Ulrich Vezina, Paul |
| author_sort | Loweth, Jessica A. |
| collection | MIT |
| description | Amphetamine exposure transiently increases Ca2+/calmodulin-dependent protein kinase II (CaMKII) α expression in the nucleus accumbens (NAcc) shell and this persistently increases local GluA1 S831 phosphorylation and enhances behavioral responding to the drug. Here we assessed whether transiently interfering with CaMKII signaling using a dominant-negative CaMKIIα mutant delivered to the NAcc shell with herpes simplex viral vectors could reverse these long-lasting biochemical and behavioral effects observed following exposure to amphetamine. As expected, transient expression of CaMKIIα K42M in the NAcc shell produced a corresponding transient increase in CaMKIIα and decrease in pCaMKIIα (T286) protein levels in this site. Remarkably, this transient inhibition of CaMKII activity produced a long-lasting reversal of the increased GluA1 S831 phosphorylation levels in NAcc shell and persistently blocked the enhanced locomotor response to and self-administration of amphetamine normally observed in rats previously exposed to the drug. Together, these results indicate that even transient interference with CaMKII signaling may confer long-lasting benefits in drug-sensitized individuals and point to CaMKII and its downstream pathways as attractive therapeutic targets for the treatment of stimulant addiction. |
| first_indexed | 2024-09-23T14:21:38Z |
| format | Article |
| id | mit-1721.1/79759 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:21:38Z |
| publishDate | 2013 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/797592022-09-29T08:56:27Z Persistent Reversal of Enhanced Amphetamine Intake by Transient CaMKII Inhibition Loweth, Jessica A. Li, Dongdong Cortright, James J. Wilke, Georgia Jeyifous, Okunola Neve, Rachael L. Bayer, K. Ulrich Vezina, Paul Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Neve, Rachael L. Amphetamine exposure transiently increases Ca2+/calmodulin-dependent protein kinase II (CaMKII) α expression in the nucleus accumbens (NAcc) shell and this persistently increases local GluA1 S831 phosphorylation and enhances behavioral responding to the drug. Here we assessed whether transiently interfering with CaMKII signaling using a dominant-negative CaMKIIα mutant delivered to the NAcc shell with herpes simplex viral vectors could reverse these long-lasting biochemical and behavioral effects observed following exposure to amphetamine. As expected, transient expression of CaMKIIα K42M in the NAcc shell produced a corresponding transient increase in CaMKIIα and decrease in pCaMKIIα (T286) protein levels in this site. Remarkably, this transient inhibition of CaMKII activity produced a long-lasting reversal of the increased GluA1 S831 phosphorylation levels in NAcc shell and persistently blocked the enhanced locomotor response to and self-administration of amphetamine normally observed in rats previously exposed to the drug. Together, these results indicate that even transient interference with CaMKII signaling may confer long-lasting benefits in drug-sensitized individuals and point to CaMKII and its downstream pathways as attractive therapeutic targets for the treatment of stimulant addiction. Peter F. McManus Charitable Trust National Institutes of Health (U.S.) (Grant R01 DA09397) National Institutes of Health (U.S.) (Grant T32 DA07255) National Institutes of Health (U.S.) (Grant F31 DA022834) National Institutes of Health (U.S.) (Grant F31 DA022834) 2013-08-01T18:53:27Z 2013-08-01T18:53:27Z 2013-01 2012-10 Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/79759 Loweth, J. A., D. Li, J. J. Cortright, G. Wilke, O. Jeyifous, R. L. Neve, K. U. Bayer, and P. Vezina. “Persistent Reversal of Enhanced Amphetamine Intake by Transient CaMKII Inhibition.” Journal of Neuroscience 33, no. 4 (January 23, 2013): 1411-1416. https://orcid.org/0000-0002-3854-5968 en_US http://dx.doi.org/10.1523/jneurosci.4386-13.2013 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 | Loweth, Jessica A. Li, Dongdong Cortright, James J. Wilke, Georgia Jeyifous, Okunola Neve, Rachael L. Bayer, K. Ulrich Vezina, Paul Persistent Reversal of Enhanced Amphetamine Intake by Transient CaMKII Inhibition |
| title | Persistent Reversal of Enhanced Amphetamine Intake by Transient CaMKII Inhibition |
| title_full | Persistent Reversal of Enhanced Amphetamine Intake by Transient CaMKII Inhibition |
| title_fullStr | Persistent Reversal of Enhanced Amphetamine Intake by Transient CaMKII Inhibition |
| title_full_unstemmed | Persistent Reversal of Enhanced Amphetamine Intake by Transient CaMKII Inhibition |
| title_short | Persistent Reversal of Enhanced Amphetamine Intake by Transient CaMKII Inhibition |
| title_sort | persistent reversal of enhanced amphetamine intake by transient camkii inhibition |
| url | http://hdl.handle.net/1721.1/79759 https://orcid.org/0000-0002-3854-5968 |
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