Figure 10.

Hypothetical model of the mechanism leading to increased NR2B-NMDAR activity during the withdrawal period following repeated ethanol exposure. Initial exposure of DMS neurons to ethanol results in a rapid inhibition of the activity of the NR2B-NMDAR channel; however, ethanol withdrawal leads to a long-lasting facilitation of channel activity. Repeated exposure of the DMS to ethanol results in a gradual reduction of the inhibitory action of ethanol on the channel and increased facilitation of the activity of the channel following withdrawal. These changes are likely to be due to long-lasting activation of Fyn kinase, long-lasting phosphorylation of NR2B, and forward trafficking of the subunit to the synaptic membrane.