REGULATION OF alpha 4/delta GABA(A) RECEPTORS IN THE HIPPOCAMPUS OF SOCIALLY ISOLATED MICE EXPOSED TO VOLUNTARY ETHANOL CONSUMPTION

FOLLESA, PAOLO;Mostallino MC;Serra M;Sanna E.

2010-01-01

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Abstract

Social isolation in C57BL/6J mice was used as a model of prolonged mild stress to investigate the effects of ethanol (EtOH) in the free-choice drinking paradigm on gene expression and function of GABAA receptor (GABAAR) in the hippocampus. Socially isolated (SI) and group-housed (GH) mice were exposed for 6 weeks to the two-bottle choice (EtOH/H2O). Specific GABAAR subunit expression were measured by RNase protection assay and immunohistochemistry. GABAAR function was evaluated by conventional whole-cell patch clamp recording in brain slices. We found a significant increase in the abundance of both α4 and δ subunits of the GABAAR in the hippocampus of SI mice compared to GH animals. On the contrary the abundance of the α1 subunit mRNA was unchanged in SI mice as compared to GH mice. Voluntary EtOH drinking resulted in a marked increase in δ subunit mRNA levels in GH mice, whereas in SI animals, it completely abolished the increase in α4 subunit mRNA but did not alter that of the δ subunit with respect to the SI mice that consumed only water. Parallel changes in α4 and δ subunit peptides were observed by immunohistochemistry. Patch clamp recording in dentate gyrus granule cells obtained from SI mice revealed a greater enhancement of tonic currents induced by THIP compared to that in GH animals. Voluntary EtOH consumption reduced the increase in tonic current associated with social isolation. These results suggest that voluntary EtOH drinking in SI mice has a selective influence on α4 subunit since it blocks its enhanced expression but fails to alter the up-regulation of δ subunit. Sponsored by NIAAA INIA-Stress Grant #1 U01 AA016670.