Ethanol effects on N-methyl-D-aspartate receptors in the bed nucleus of the stria terminalis

Abstract

The extended amygdala is a series of interconnected, embryologically similar series of nuclei in the brain that are thought to play key roles in aspects of alcohol dependence, specifically in stress-induced increases in alcohol-seeking behaviors. Plasticity of excitatory transmission in these and other brain regions is currently an intense area of scrutiny as a mechanism underlying aspects of addiction. N-methyl-D-aspartate (NMDA) receptors (NMDARs) play a critical role in plasticity at excitatory synapses and have been identified as major molecular targets of ethanol. Thus, this article will explore alcohol and NMDAR interactions first at a general level and then focusing within the extended amygdala, in particular on the bed nucleus of the stria terminalis (BNST).

Figure 1.

The acute and chronic effects of ethanol in control and GluN2B KO mice in the BNST. (A) Basally, our data suggests that many BNST synapses are populated by AMPARs and NMDARs (GluN2A- and GluN2B-containing). During acute ethanol application to the slice, there is an inhibition of glutamate transmission. Our work has shown that this is specific to the NMDARs that are GluN2B-containing because no ethanol inhibition occurs in slices from GluN2B KO mice (B). (C) Following chronic intermittent ethanol, we find enhancement of long-term potentiation (LTP) that is GluN2B dependent because this effect is absent in GluN2B KO mice (D). We postulate that this LTP enhancement results from increased synaptic GluN2B-containing receptors. Further, our data illustrate that extrasynaptic GluN2B-containing receptors contribute to synaptic signaling (although the mechanism is unknown) to enhance LTP after chronic intermittent ethanol.