Abstract
Alcohol consumption in adolescence causes multiple acute negative changes in neural and behavioral function that persist well into adulthood and possibly throughout life. The medial prefrontal cortex (mPFC) and dorsal hippocampus are critical for executive function and memory and are especially vulnerable to adolescent ethanol exposure. We have reported that astrocytes, particularly in the mPFC, change both in morphology and synaptic proximity during adolescence. Moreover, adolescent intermittent ethanol (AIE) exposure produces enduring effects on both astrocyte function and synaptic proximity in the adult hippocampal formation, and the latter effect was reversed by the clinically used agent gabapentin (Neurontin), an anticonvulsant and analgesic that is an inhibitor of the VGCC α2δ1 subunit. These findings underscore the importance of investigating AIE effects on astrocytes in the mPFC, a region that undergoes marked changes in structure and connectivity during adolescence. Using astrocyte-specific viral labeling and immunohistochemistry, mPFC astrocytic morphology and colocalization with AMPA-(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) glutamate receptor 1 (GluA1), an AMPA receptor subunit and established neuronal marker of excitatory synapses, were assessed to quantify the proximity of astrocyte processes with glutamatergic synaptic puncta. AIE exposure significantly reduced astrocyte-synaptic proximity in adulthood, an effect that was reversed by sub-chronic gabapentin treatment in adulthood. There was no effect of AIE on astrocytic glutamate homeostasis machinery or neuronal synaptic proteins in the mPFC. These findings indicate a possible glial-neuronal mechanism underlying the effects of AIE on frontal lobe-mediated behaviors and suggest a specific therapeutic approach for the amelioration of those effects.