Many GABAergic effects of ethanol likely result from the ability of ethanol to enhance presynaptic GABA release in spinal cord (Ziskind-Conhaim et al. 2003), amygdala (Roberto et al. 2003; 2004), hippocampus (Ariwodola and Weiner 2004), and cerebellum (Criswell and Breese 2005) An ethanol-induced increase in GABA release would be expected to modulate all subtypes of GABAA receptors and could clearly contribute to the behavioral effects of ethanol mediated by GABAA receptors in brain. This effect of ethanol exhibits regional and neuronal specificity (Criswell et al. 2008), suggesting that it may contribute to heterogeneity of ethanol interactions. Moreover, chronic exposure to GABA alters GABAA receptor α1 subunit expression (Calkin and Barnes 1994; Montpied et al. 1991a), internalization (Tehrani and Barnes 1997), and decreases GABAA receptor-mediated inhibition (Roca et al. 1990), similar to the effects of ethanol on GABAA receptor α1 subunit expression (Kumar et al. 2003). Thus, ethanol-induced increases in GABA release likely contribute to ethanol-induced changes in GABAA receptor surface expression that appear to be involved in ethanol tolerance, dependence, and withdrawal.
