Chunk #54 — Chronic administration of ethanol — Alterations in GABAA receptor subunit expression, localization, and trafficking — Alterations in synaptic localization of receptors
steroid 3α,5α-THP may cause a similar effect since there is a decrease in the decay time of mIPSCs recorded in hippocampal CA1 pyramidal cells (Hsu et al. 2003). The decrease in mIPSC decay time was blocked by infusion of α4 subunit antisense oligonucleotides into the hippocampus, suggesting that this change in synaptic GABAA receptor kinetics is due to an increase in synaptic α4 subunit expression. Additionally, tonic current is also modified after chronic ethanol exposure. Specifically, the effects of various GABAA receptor modulators on tonic currents are reduced or ablated after CIE treatment (Liang et al. 2004). Indeed, GABAA receptor ligands with selectivity for α4-GABAA receptors exerted decreased effects on extrasynaptic currents as well as increased effects on synaptic currents. Electron microscopy revealed an increase in synaptic localization of α4, but not δ subunits on the dentate granule cells of CIE rats (Liang et al. 2006). Taken together, these studies show that translocation of α4-GABAA receptors from an extrasynaptic to synaptic localization may represent a mechanism of GABAA receptor adaptation to ethanol exposure.
