NMDA receptors vary in their response to ethanol depending on which subunits make up the receptor, reviewed in (Lovinger and Roberto, 2013). Binge drinking decreased the expression of Grin2b (encoding NR2B; −1.6-fold) and increased Grin2c (encoding NR2C, +2.6-fold) (Table 1). NR2C-containing receptors are less sensitive to inhibition by ethanol than those that contain NR2B (Lovinger and Roberto, 2013), so this shift in ratio should result in decreased sensitivity of the NMDA receptors to ethanol in the DRN, decreasing its inhibitory effects and potentially increasing tolerance to ethanol’s intoxicating effects. Furthermore, the net increased expression of glutamate receptor genes in combination with a net decreased expression of GABAA receptor genes (Table 1) could result in a higher excitatory tone regulating the DRN.
