4.2 Article

CaMKII-GluA1 Activity Underlies Vulnerability to Adolescent Binge Alcohol Drinking

期刊

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
卷 39, 期 9, 页码 1680-1690

出版社

WILEY
DOI: 10.1111/acer.12819

关键词

Adolescence; Alcohol; Binge; CaMKII; GluA1

资金

  1. National Institute on Alcohol Abuse and Alcoholism [R37AA014983, P60AA11605]

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BackgroundBinge 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 (CaMKII) and the GluA1 subunit of AMPA receptors (AMPARs) in addiction-associated brain regions. We also asked whether activation of CaMKII-dependent AMPAR activity escalates binge-like drinking. MethodsTo address these questions, CaMKIIT286 and GluA1(S831) 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 >80mg/dl). In separate mice, effects of the CaMKII-dependent GluA1(S831) phosphorylation (pGluA1(S831))-enhancing drug tianeptine were tested on binge-like alcohol consumption in both age groups. ResultsBinge-like drinking decreased CaMKIIT286 phosphorylation (pCaMKII(T286)) selectively in adolescent amygdala with no effect in adults. Alcohol also produced a trend for reduced pGluA1(S831) expression in adolescent amygdala but differentially increased pGluA1(S831) 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. ConclusionsThese 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 CaMKII-dependent AMPAR activation may underlie age-related escalation of binge drinking.

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