Chronic ethanol exposure up-regulates NMDA receptor function and down-regulates GABAA receptor function (see Crews et al. 1996 for review). Since many neurons contain both NMDA and GABAA receptors and ethanol modulates both NMDA and GABAA receptors, interactions between these receptors may play an important role in GABAA receptor adaptation following ethanol administration. For example, administration of dizocilpine (a potent non-competitive antagonist of the NMDA receptor) to rats, like ethanol, increases membrane expression of GABAA receptor α4 subunits in hippocampus (Matthews et al. 2000b). The effect on GABAA receptors following NMDA receptor activation is mediated by intracellular Ca2+, since the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid (BAPTA) blocks the down-regulation of GABAA receptors following NMDA receptor activation (Robello et al. 1997). In addition, the application of glutamate in hippocampal cultures leads to translocation of PKCα and PKCγ to the plasma membrane and cytoplasmic organelles, respectively, while PKCε localization remains unaltered (Buchner et al. 1999; Etoh et al. 1991). Therefore, interactions of NMDA and GABAA receptors via intracellular signaling pathways may play a vital role in GABAA receptor adaptation following chronic ethanol administration. In
