The majority of work on chronic EtOH effects on glutamatergic transmission has focused on changes in glutamate receptors, particularly in light of the sensitivity of these receptors to acute EtOH actions (see previous discussion). Chronic EtOH exposure generally produces an increase in the function of NMDARs and in NMDAR-mediated glutamatergic synaptic transmission (Cebere et al. 1999; Grover et al. 1998; Gulya et al. 1991; Lack et al. 2007; Smothers et al. 1997) (Fig. 1d). Initial studies examined effects of receptor activation on neuronal calcium and nitric oxide signals either in preparations made from EtOH-exposed animals or in cultured neurons treated with EtOH in the medium (Grover et al. 1998; Gulya et al. 1991; Chandler et al. 1997; Iorio et al. 1992; Smothers et al. 1997). Exposure to EtOH for days to weeks increased NMDAR agonist-induced increases in intracellular calcium. These 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
