CaMKIIα-GluA1 Activity Underlies Vulnerability to Adolescent Binge Alcohol Drinking

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.

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.

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.

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.