finding is consistent with a decrease in release probability (see later section) and is in agreement with the decrease in mIPSC frequency observed in rats following chronic intermittent EtOH exposure (Cagetti et al. 2003). Interestingly, there was lack of tolerance for both the acute facilitatory effect of EtOH and flunitrazepam on evoked GABAA IPSCs (Weiner et al. 2005). Using the same paradigm of EtOH self-administration, whole-cell patch clamp recordings on acutely dissociated amygdala neurons from EtOH-exposed cynomolgus macaques showed a decrease in the effect of flunitrazepam on the currents gated by exogenous GABA application compared with amygdala neurons from control animals (Anderson et al. 2007; Floyd et al. 2004). However, the modest inhibition of GABA-gated currents induced by acute EtOH was not affected by the chronic EtOH consumption. In addition, mRNA expression levels for the β, γ, and δ subunits in total amygdala RNA isolated from control and EtOH-drinking animals were measured. Chronic EtOH significantly reduced amygdala β1 and γ2 subunit expression. Overall, these findings demonstrate that chronic EtOH self-administration reduces the benzodiazepine sensitivity of amygdala GABAA receptors and this reduced sensitivity may reflect decreased expression of the γ subunit.
