As described above, the adaptive changes in GABAA receptor expression are thought to lead to a pronounced hypofunction of GABAergic neurotransmission and possibly the development of tolerance to the in vitro acute effects of EtOH on these synapses. In the hippocampus, there is a decrease in the threshold for seizure induction by the GABAA receptor antagonist pentylenetetrazole (Kokka et al. 1993) and a decrease in GABAA receptor activity in hippocampal slices that also lasts for at least 40 days after the last EtOH dose (Cagetti et al. 2003; Kang et al. 1996; Liang et al. 2004, 2009). Using analysis of tetrodotoxin (TTX)-resistant mIPSCs recorded from CA1 pyramidal neurons of chronic EtOH exposed and control rats, this group demonstrated a significant decrease in the amplitude and decay of these responses (Cagetti et al. 2003) possibly reflecting the observed alteration in the expression of α1 and α4 subunits. The mIPSC frequency is also slightly decreased, suggesting that chronic EtOH exposure may also be associated with a presynaptic decrease in GABA release at these synapses (see later section). Importantly, the pharmacological alterations in
