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dc.contributor.authorLoweth, Jessica A.
dc.contributor.authorLi, Dongdong
dc.contributor.authorCortright, James J.
dc.contributor.authorWilke, Georgia
dc.contributor.authorJeyifous, Okunola
dc.contributor.authorNeve, Rachael L.
dc.contributor.authorBayer, K. Ulrich
dc.contributor.authorVezina, Paul
dc.date.accessioned2013-08-01T18:53:27Z
dc.date.available2013-08-01T18:53:27Z
dc.date.issued2013-01
dc.date.submitted2012-10
dc.identifier.issn0270-6474
dc.identifier.issn1529-2401
dc.identifier.urihttp://hdl.handle.net/1721.1/79759
dc.description.abstractAmphetamine 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.en_US
dc.description.sponsorshipPeter F. McManus Charitable Trusten_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R01 DA09397)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant T32 DA07255)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant F31 DA022834)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant F31 DA022834)en_US
dc.language.isoen_US
dc.publisherSociety for Neuroscienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1523/jneurosci.4386-13.2013en_US
dc.rightsArticle 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.en_US
dc.sourceSFNen_US
dc.titlePersistent Reversal of Enhanced Amphetamine Intake by Transient CaMKII Inhibitionen_US
dc.typeArticleen_US
dc.identifier.citationLoweth, 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.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.mitauthorNeve, Rachael L.en_US
dc.relation.journalJournal of Neuroscienceen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsLoweth, J. A.; Li, D.; Cortright, J. J.; Wilke, G.; Jeyifous, O.; Neve, R. L.; Bayer, K. U.; Vezina, P.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-3854-5968
mit.licensePUBLISHER_POLICYen_US


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