For NMDA receptors, again the changes are offsetting: Grin2c is the most highly expressed NMDAR2 receptor and was the only NMDA subunit with increased expression; Grin2b, Grin2d and Grin3a had decreased expression. Alcohol acts as an allosteric modulator of NMDA receptors, and can decrease glutamate signaling by decreasing the mean open time of the channel. Grin1, Grin2a and Grin2b all contain ethanol-sensitive domains (Zhao et al., 2015), but of these only Grin2b expression was decreased. Replacing Grin2b subunits by Grin2c subunits could result in NMDA receptors that are less sensitive to ethanol. Gria4, the most highly expressed AMPA receptor, was increased 1.4 fold and Grid2 was increased 1.7-fold in the PAG; these were the only 2 glutamate receptors with no offsetting changes in other subunits of the same class. AMPA receptors are also inhibited by ethanol (Wirkner et al., 2000), so the increase in Gria4 may be compensatory.
