Chronic ethanol administration alters immunoreactivity for GABA(A) receptor subunits in rat cortex in a region-specific manner

Background: Chronic ethanol administration has a plethora of physiological effects. Among the most consistently observed findings is a change in the e xpression pattern of gamma-aminobutyric acid type A (GABA(A)) receptor subu nits in the rat brain cortex. These findings led to the hypothesis of "subu nit substitution" to account for changes in receptor function without chang es in receptor number. Methods: We used subunit (alpha 1 and alpha 4) specific antibodies and a co mbination of immunohistochemistry and immunoblotting to examine subregions of cortex (prefrontal, cingulate, motor, parietal, and piriform) for their response to 2 weeks of forced ethanol administration. Results: Overall, cortical immunoreactivity for the al subunit was decrease d and for the alpha 4 subunit increased whether measured immunohistochemica lly or by immunoblotting. Piriform cortex exhibited a bidirectional change in GABA(A) receptor alpha 1 and alpha 4 immunoreactivity, similar to that p reviously observed in preparations of whole cortex. However, in parietal co rtex declines in alpha 1 immunoreactivity (55 +/- 12% control value [CV] an d 88.3 +/- 4.3% CV; immunohistochemistry and immunoblotting, respectively) were not accompanied by concomitant increases in alpha 4 immunoreactivity ( 104 +/- 8% CV and 116 +/- 9.3% CV; immunohistochemistry and immunoblotting, respectively). Conversely, alpha 4 immunoreactivity increased in cingulate cortex (210 +/- 30% CV and 134 +/- 9.5% CV; immunohistochemistry and immun oblotting, respectively) without a decline in alpha 1 immunoreactivity (90 +/- 4% CV and 91.3 +/- 3.9% CV; immunohistochemistry and immunoblotting, re spectively). Prefrontal and motor cortex exhibited GABA(A) receptor subunit peptide alterations, but these changes varied with the method of analysis. Conclusions: These findings demonstrate that ethanol dependence results in nonuniform changes in GABA(A) receptor subunit peptide levels across the ra t brain cortex and suggest that mechanisms which subserve functional change s in receptor activity may vary in accordance with anatomic or cellular dif ferences within the cortex.