Of particular clinical importance is the development of tolerance and dependence to EtOH, and it is likely that adaptive changes in synaptic function in response to ethanol’s actions on GABAA receptors play a role in this process. Indeed, it is well known that chronic EtOH treatment can lead to tolerance and physical dependence (Chandler et al. 1998) and withdrawal following long-term EtOH consumption is associated with increased neuronal excitability (Kliethermes 2005; Weiner and Valenzuela 2006). These alterations have been hypothesized to represent, in part, a compensatory adaptation to the in vitro acute facilitatory effects of EtOH on GABAergic synapses (Siggins et al. 2005; Weiner and Valenzuela 2006). Few studies have reported the effects of long-term EtOH exposure on GABAergic synaptic transmission looking at both postsynaptic and presynaptic mechanisms using in vitro brain slice methods.
