In the previous decade, non-human primates (Cynomolgus macaques) have been a powerful model to study the effects of long-term EtOH consumption (Vivian et al. 2001). Ongoing research in the Weiner lab has provided the first evidence of neuroadaptations in the GABAergic synapses in monkey hippocampus (Weiner et al. 2005). In this paradigm of EtOH self-administration, cynomolgus macaques are trained to self administer a 4% EtOH solution on an operant panel and then given 22 h daily access to the EtOH solution. Control subjects were age-and sex-matched animals that had free access to food and water but were not exposed to the operant panels. The preliminary in vitro electrophysiologic findings revealed a significant increase in paired-pulse facilitation (PPF) of GABAA IPSCs in dentate granule cells in slices prepared immediately following the last day of 18 months of daily EtOH drinking. Their 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
