Persistent reversal of enhanced amphetamine intake by transient CaMKII inhibition.
نویسندگان
چکیده
Amphetamine exposure transiently increases Ca(2+)/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.
منابع مشابه
Brief Communications Persistent Reversal of Enhanced Amphetamine Intake by Transient CaMKII Inhibition
Jessica A. Loweth,1,2 Dongdong Li,2 James J. Cortright,2 Georgia Wilke,2 Okunola Jeyifous,3 Rachael L. Neve,4 K. Ulrich Bayer,5 and Paul Vezina1,2 1Committee on Neurobiology, and Departments of 2Psychiatry and Behavioral Neuroscience and 3Neurobiology, The University of Chicago, Chicago, Illinois 60637, 4Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and 5Department of P...
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عنوان ژورنال:
- The Journal of neuroscience : the official journal of the Society for Neuroscience
دوره 33 4 شماره
صفحات -
تاریخ انتشار 2013