The glutamate ionotropic receptor NMDA Type Subunit 2B (GRIN2B) and the glutamate ionotropic receptor AMPA Type Subunit 1 (GRIA1) were identified as hub genes in transcriptome analysis of human alcoholic prefrontal cortex (Farris and Mayfield, 2014). GRIN2B was up-regulated in the hippocampus of human alcoholics (Zhou et al., 2011). Analysis of frontal cortex modules also revealed up-regulated genes involved in synaptic transmission in alcoholics, particularly at glutamatergic synapses (Ponomarev et al., 2012). Genes from this alcohol-responsive module included GRIN1, dynamin (DNM1), syntaxin (STX1A), synapsin 1 (SYN1), synaptophysin (SYP), and the vesicular glutamate transporter 1 (VGLUT1, SLC17A7). The GC content of the glutamatergic genes was greater than average, suggesting coordinated synaptic up-regulation in alcohol abusers (Ponomarev et al., 2012). Two additional up-regulated genes from this module, GIPC1 and MIB2, have roles in glutamate transmission and are respectively involved in NMDA receptor trafficking and ubiquitination of the NMDA NR2B subunit (Jurd et al., 2008; Yi et al., 2007). Up-regulation of NR2B-NMDA receptor activity within the dorsomedial striatum by alcohol contributed to synaptic dysregulation and excessive alcohol intake and relapse drinking in rats
