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Alcohol Clin Exp Res. 2015 Sep;39(9):1680-90. doi: 10.1111/acer.12819. Epub 2015 Aug 6.

CaMKIIα-GluA1 Activity Underlies Vulnerability to Adolescent Binge Alcohol Drinking.

Author information

1
Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina.
2
Curriculum in Neurobiology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina.
3
Department of Psychiatry, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina.
4
Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina.

Abstract

BACKGROUND:

Binge drinking during adolescence is associated with increased risk for developing alcohol use disorders; however, the neural mechanisms underlying this liability are unclear. In this study, we sought to determine whether binge drinking alters expression or phosphorylation of 2 molecular mechanisms of neuroplasticity, calcium/calmodulin-dependent kinase II alpha (CaMKIIα) and the GluA1 subunit of AMPA receptors (AMPARs) in addiction-associated brain regions. We also asked whether activation of CaMKIIα-dependent AMPAR activity escalates binge-like drinking.

METHODS:

To address these questions, CaMKIIαT286 and GluA1S831 protein phosphorylation and expression were assessed in the amygdala and striatum of adolescent and adult male C57BL/6J mice immediately after voluntary binge-like alcohol drinking (blood alcohol >80 mg/dl). In separate mice, effects of the CaMKIIα-dependent GluA1S831 phosphorylation (pGluA1S831 )-enhancing drug tianeptine were tested on binge-like alcohol consumption in both age groups.

RESULTS:

Binge-like drinking decreased CaMKIIαT286 phosphorylation (pCaMKIIαT286 ) selectively in adolescent amygdala with no effect in adults. Alcohol also produced a trend for reduced pGluA1S831 expression in adolescent amygdala but differentially increased pGluA1S831 in adult amygdala. No effects were observed in the nucleus accumbens or dorsal striatum. Tianeptine increased binge-like alcohol consumption in adolescents but decreased alcohol consumption in adults. Sucrose consumption was similarly decreased by tianeptine pretreatment in both ages.

CONCLUSIONS:

These data show that the adolescent and adult amygdalae are differentially sensitive to effects of binge-like alcohol drinking on plasticity-linked glutamate signaling molecules. Tianeptine-induced increases in binge-like drinking only in adolescents suggest that differential CaMKIIα-dependent AMPAR activation may underlie age-related escalation of binge drinking.

KEYWORDS:

Adolescence; Alcohol; Binge; CaMKII; GluA1

PMID:
26247621
PMCID:
PMC4558330
DOI:
10.1111/acer.12819
[Indexed for MEDLINE]
Free PMC Article

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