Alteration of gene expression has been linked to persistent behavioral changes in alcohol- or drug-dependent individuals in both animal and human studies (Edenberg et al., 2005; Heilig & Koob, 2007; Hwang, Stewart, Zhang, Lumeng, & Li, 2004; Liang et al., 2010; Zhou et al., 2011). In the “post-dependent” rats generated by intermittent alcohol vapor intoxication and withdrawal, Meinhardt et al. (2013) identified a pronounced deficit of the metabotropic glutamate receptor II (mGluR2) in the pyramidal neurons of the infralimbic cortex. Among a group of glutamatergic genes that showed enriched downregulation of expression, Grm2, which encodes for mGluR2, was one of the genes that were most significantly affected, although the expression of Grm3, which encodes mGluR3, the other member of the group II metabotropic glutamate receptors, was not altered in this region. Reduction of extracellular glutamate levels in the NAc, which was readily observed in control rats upon systemic injection of mGluR2/mGluR3 agonists, was also absent in the post-dependent rats, consistent with the lack of mGluR2 function as a presynaptic receptor to downregulate glutamate release upon activation. The role of mGluR2
