The mechanisms underlying the increase in NMDAR function are still under investigation, but several interesting facets of the story have already emerged. Analysis of receptor function and pharmacology, as well as examination of receptor subunit expression and location, indicate that receptors containing the NR2B subunit are the subtypes most strongly affected by chronic EtOH exposure (Carpenter-Hyland et al. 2004; Floyd et al. 2003; Kash et al. 2009; Roberto et al. 2004b) (Fig. 1d). The molecular basis of increased NR2B function is less clear. While some investigators have reported increases in NR2B mRNA expression following chronic alcohol exposure in vitro (Hu et al. 1996; Snell et al. 1996), and in vivo (Follesa and Ticku 1995; Kash et al. 2009; Roberto et al. 2006) such increases have not been observed in every brain region (Cebere et al. 1999; Floyd et al. 2003; Läck et al. 2005). Increases in NR2B, and to a lesser extent NR2A, protein expression have also been observed using immunologic techniques after both in vitro and in vivo EtOH exposure (Kash et al. 2005; Obara et al. 2009; Snell
