Comparison of chronic ethanol and chronic intermittent ethanol treatments on the expression of GABA_A and NMDA receptor subunits

We examined the mRNA and protein levels of GABA_A and NMDA receptor (NMDAR) subunits in cultured mouse cortical neurons following exposure to chronic ethanol (CE) or chronic intermittent ethanol (CIE), and after 5 days of withdrawal. With respect to GABA_A receptor mRNA, both treatments decreased the levels of α1 and α2 subunits, and increased the level of α4. However, only CE treatment caused parallel changes in the protein levels; α2 and α4 protein levels did not change after CIE. Both treatments did not alter β2 and β3 mRNA levels, but they increased β2/3 protein levels. The γ2 subunit mRNA levels decreased with both treatments, but protein levels did not change. Most of the changes returned to control levels after withdrawal, except for the γ2 subunit protein, which was lower than controls. In the case of NMDAR subunit, both treatments greatly increased the levels of NR2B mRNA, but barely altered NR1 mRNA and polypeptide levels. CIE treatment caused a relatively higher increase in NR2B protein, and this was the only sustained increase after long-term withdrawal. Taken together, our results show that CIE regimen has less pronounced effects on GABA_A receptor expression, but increases NR2B expression more dramatically than CE treatment in cultured cortical neurons. These differential effects on subunit expression may result in altered receptor structure and function as a result of ethanol exposure.