Chunk #53 — Chronic administration of ethanol — Alterations in GABAA receptor subunit expression, localization, and trafficking — Alterations in synaptic localization of receptors
Given the important role of synaptic vs. extrasynaptic GABAA receptors in acute ethanol effects, it is important to understand the role of these receptor populations following chronic ethanol exposure. Cagetti et al. (2003) found changes in synaptic GABAA receptor function in the hippocampus of rats that had undergone chronic intermittent ethanol (CIE) treatment followed by 2 days of withdrawal. CIE treatment decreases the frequency, rise time, amplitude, and decay time of mIPSCs in pyramidal neurons from CA1, an overall change in GABAA receptor function that is consistent with increased neuronal excitability. Interestingly, CIE eliminated the effects of diazepam on the mIPSCs and increased mIPSC sensitivity to the α4 subunit-selective benzodiazepine Ro15-4513. These pharmacological changes are consistent with a decreased expression of α1-GABAA receptors and an increased expression of α4-GABAA receptors in the synapse. Brief exposure (48–72 h) to the neuroactive 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
