An examination of protein expression changes in subregions of the Acb and Amyg of chronic ethanol-drinking P rats revealed at 24-h withdrawal that GluN2a expression levels were increased, whereas GluN2b expression levels were decreased in the AcbSh.180 These authors also reported that Homer2a/b, mGlu1, mGlu5, GluN2a, and GluN2b expression levels were all consistently increased in the AcbCo and CeA.180 To test the hypothesized genetic role for the mGlu2 receptor in alcohol dependence, a recent RNA and exome sequencing study revealed that a SNP which creates a stop codon in the mGlu2 gene is present in P, but not NP, rats.202 This stop codon results in the absence of mGlu2 receptors, impaired gluta-matergic synaptic transmission, and altered levels of multiple genes associated with synaptic function. These authors also examined F2 rats from a PxNP–NPxP cross and found that mGlu2 expression levels were significantly and inversely related to ethanol consumption, with decreases in mGlu2 and mGlu2 receptor expression associated with significant increases in ethanol-drinking behavior.202 Similarly, mGlu2 knockout mice display significantly greater ethanol consumption and preference than their wild-type counterparts.202 As mGlu2
