effects could be observed at EtOH concentrations that did not alter neuronal viability and did not affect baseline intracellular calcium levels. Furthermore, changes in responses to NMDAR activation were consistently larger than changes in the effects of activation of other ionotropic glutamate receptors (Chandler et al. 1997; Gulya et al. 1991; Smothers et al. 1997). Direct examination of ion current through the NMDAR pore has revealed effects consistent with a chronic EtOH-induced upregulation of NMDAR function (Floyd et al. 2003; Grover et al. 1998). An increase in the component of current mediated by NR2B-containing receptors has also been observed (Floyd et al. 2003; Kash et al. 2009; Roberto et al. 2004b, 2006). Interestingly, acute EtOH inhibition of NMDARs in most brain regions is still intact or even increased after chronic in vivo exposure (Floyd et al. 2003; Roberto et al. 2006; Roberto et al. 2004b), although a small decrease in inhibition was observed in medial septum/diagonal band neurons (Grover et al. 1998). Evidence of tolerance to EtOH inhibition during acute exposure has also been observed in hippocampal slices (Grover et al. 1994; Miyakawa et al. 1997). Overall, it appears that NMDAR function is still suppressed during intoxication even after prolonged
