Research using both in vivo and in vitro models has established that both acute and chronic exposure to alcohol affects the NMDA receptor. Acutely, alcohol acts as an NMDA antagonist (Tomberg, 2010), leading to significant decreases in the size of NMDA excitatory post-synaptic potentials (EPSPs) (Nie et al., 1994) and inhibition of NMDA-dependent long-term potentiation (LTP) (Puglia and Valenzuela, 2010). Chronic exposure to alcohol leads to an increased density of receptors and facilitation of NMDA receptor functioning, due to receptor subunit phosphorylation and increased expression of various NMDA receptor subunit mRNAs (Nagy, 2008b). Significantly increased expression after chronic alcohol exposure has been observed in NR1 subunit mRNA in the amygdala (Floyd et al., 2003) and protein in the hippocampus (Maler et al., 2005), in NR2A and NR2B subunit mRNA in the cortex and hippocampus (Follesa and Ticku, 1995) and protein in the hippocampus (Maler et al., 2005). After a 48-hour withdrawal period, NR1, NR2A, and NR2B mRNA levels returned to baseline in the hippocampus and cortex (Follesa and Ticku, 1995), and protein levels were returned to baseline in the amygdala
