TY  - JOUR
PY  - 2015//
TI  - CaMKIIα-GluA1 activity underlies vulnerability to adolescent binge alcohol drinking
JO  - Alcoholism: clinical and experimental research
A1  - Agoglia, Abigail E.
A1  - Holstein, Sarah E.
A1  - Reid, Grant
A1  - Hodge, Clyde W.
SP  - 1680
EP  - 1690
VL  - 39
IS  - 9
N2  - 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. <br><br>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. <br><br>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. <br><br>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.<p />  <p>Language: en</p>
LA  - en
SN  - 0145-6008
UR  - http://dx.doi.org/10.1111/acer.12819
ID  - ref1
ER  -