GABA(A) RECEPTOR ALPHA(1), ALPHA(4), AND BETA(3) SUBUNIT MESSENGER-RNA AND PROTEIN EXPRESSION IN THE FRONTAL-CORTEX OF HUMAN ALCOHOLICS

Animal studies have shown that chronic ethanol consumption produces ph ysical dependence upon ethanol and alters gamma-aminobutyric acid-A (G ABA(A)) receptor subunit gene expression in brain. Although extensive investigation has been conducted in animal models, relatively little w ork has been performed directly on human alcoholic brain tissue to det ermine if there are alterations in GABA(A) receptor gene expression. I n this study, GABA(A) receptor alpha(1), alpha(4), and beta(3) subunit mRNA and peptide expression in postmortem frontal cortex from human a lcoholics (n = 15) and age- and sex-matched controls (n = 13) were mea sured by quantitative, competitive reverse transcription polymerase ch ain reaction and Western blot analysis. GABA(A) receptor beta(3) subun it mRNA expression was 35% greater(p < 0.05) in alcoholics, compared w ith nonalcoholic controls. We found no significant difference in alpha (1 )and alpha(4 )subunit mRNA levels between groups. However, there wa s a trend toward greater (21%) alpha(1) subunit mRNA expression. There was no difference in alpha(1), alpha(4), or beta(2/3) subunit peptide levels in frontal cortex between controls and alcoholics. Neither the age of the subjects nor the postmortem interval correlated with mRNA or peptide levels. Blood ethanol content also did not correlate with m RNA or peptide expression in alcoholic samples. These data suggest tha t GABA(A) receptor adaptations, resulting from prolonged alcohol consu mption in human alcoholics, may differ from animal models of alcohol d ependence. These differences may be related to the longevity of alcoho l exposure in human alcoholics, as well as variability in the dependen ce/withdrawaI state of the human subjects. Therefore, further studies in human postmortem brain tissue are warranted.