AUTHOR=Sanna Enrico , Talani Giuseppe , Obili Nicola , Mascia Maria Paola , Mostallino Maria Cristina , Secci Pietro Paolo , Pisu Maria Giuseppina , Biggio Francesca , Utzeri Cinzia , Olla Pierluigi , Biggio Giovanni , Follesa Paolo 

TITLE=Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α4/δ GABAA Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice

JOURNAL=Frontiers in Neuroscience

VOLUME=5

YEAR=2011

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2011.00015

DOI=10.3389/fnins.2011.00015

ISSN=1662-453X

ABSTRACT=<p>Post-weaning social isolation (SI) is a model of prolonged mild stress characterized by behavioral and neurochemical alterations. We used SI in C57BL/6J mice to investigate the effects of ethanol (EtOH) in the free-choice drinking paradigm on gene expression and function of γ-aminobutyric acid type A receptors (GABA<sub>A</sub>Rs) and the role of neuroactive steroids in the actions of EtOH in the hippocampus. SI stress induced a marked reduction in hippocampal 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG) and was associated with molecular and functional changes of the GABA<sub>A</sub>R. The gene expression of the α<sub>4</sub> and δ subunits was increased in the hippocampus of SI C57BL/6J mice; the expression of the γ<sub>2</sub> subunit was decreased whereas that of the α<sub>1</sub> did not change. Patch-clamp recordings in dentate gyrus (DG) granule cells obtained from SI C57BL/6J mice revealed a greater enhancement of tonic currents induced by α-(4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridin-3-ol (THIP) compared to that in control C57BL/6J mice. These neurochemical, molecular and functional changes observed in SI C57BL/6J mice were associated with an increased EtOH intake and EtOH preference. Nevertheless, the increase in EtOH consumption did not restore the reduction in hippocampal 3α,5α-TH PROG induced by SI. EtOH self-administration blocked the changes in gene expression of the α<sub>4</sub> subunit but not those of the δ and γ<sub>2</sub> subunits induced by SI. In addition, EtOH self-administration did not block the SI-induced changes in GABA<sub>A</sub>R-mediated tonic inhibition in hippocampal granule cells but increased the frequency of basal GABAergic sIPSCs in DG granule cells. We conclude that self-administration of EtOH selectively abolishes the increase of α<sub>4</sub> subunit but not other neurochemical, molecular, and functional modifications induced by SI prolonged mild stress.</p>