Adolescent Alcohol Exposure Alters GABA(A) Receptor Subunit Expression in Adult Hippocampus

作者：Centanni Samuel W; Teppen Tara; Risher Mary Louise; Fleming Rebekah L; Moss Julia L; Acheson Shawn K; Mulholland Patrick J; Pandey Subhash C; Chandler L Judson; Swartzwelder H S^*

来源：Alcoholism: Clinical and Experimental Research , 2014, 38(11): 2800-2808.

DOI：10.1111/acer.12562

• Adolescence
• GABA Receptors
• Chronic Intermittent Ethanol

BackgroundThe long-term consequences of adolescent alcohol abuse that persist into adulthood are poorly understood and have not been widely investigated. We have shown that intermittent exposure to alcohol during adolescence decreased the amplitude of GABA(A) receptor (GABA(A)R)-mediated tonic currents in hippocampal dentate granule cells in adulthood. The aim of this study was to investigate the enduring effects of chronic intermittent alcohol exposure during adolescence or adulthood on the expression of hippocampal GABA(A)Rs. %26lt;br%26gt;MethodsWe used a previously characterized tissue fractionation method to isolate detergent resistant membranes and soluble fractions, followed by Western blots to measure GABA(A)R protein expression. We also measured mRNA levels of GABA(A)R subunits using quantitative real-time polymerase chain reaction. %26lt;br%26gt;ResultsAlthough the protein levels of 1-, 4-, and -GABA(A)R subunits remained stable between postnatal day (PD) 30 (early adolescence) and PD71 (adulthood), the 5-GABA(A)R subunit was reduced across that period. In rats that were subjected to adolescent intermittent ethanol (AIE) exposure between PD30 and PD46, there was a significant reduction in the protein levels of the -GABA(A)R, in the absence of any changes in mRNA levels, at 48hours and 26days after the last ethanol (EtOH) exposure. Protein levels of the 4-GABA(A)R subunit were significantly reduced, but mRNA levels were increased, 26days (but not 48hours) after the last AIE exposure. Protein levels of 5-GABA(A)R were not changed by AIE, but mRNA levels were reduced at 48hours but normalized 26days after AIE. In contrast to the effects of AIE, chronic intermittent ethanol (CIE) exposure during adulthood had no effect on expression of any of the GABA(A)R subunits examined. %26lt;br%26gt;ConclusionsAIE produced both short- and long-term alterations of GABA(A)R subunits mRNA and protein expression in the hippocampus, whereas CIE produced no long-lasting effects on those measures. The observed reduction of protein levels of the -GABA(A)R, specifically, is consistent with previously reported altered hippocampal GABA(A)R-mediated electrophysiological responses after AIE. The absence of effects of CIE underscores the emerging view of adolescence as a time of distinctive vulnerability to the enduring effects of repeated EtOH exposure.

• 出版日期2014-11