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Sanna E, Talani G, Obili N, et al. Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α(4)/δ GABA(A) Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice. Front Neurosci. 2011;5:15doi: 10.3389/fnins.2011.00015.
Sanna, E., Talani, G., Obili, N., Mascia, M. P., Mostallino, M. C., Secci, P. P., Pisu, M. G., Biggio, F., Utzeri, C., Olla, P., Biggio, G., & Follesa, P. (2011). Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α(4)/δ GABA(A) Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice. Frontiers in neuroscience, 515. https://doi.org/10.3389/fnins.2011.00015
Sanna, Enrico, et al. "Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α(4)/δ GABA(A) Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice." Frontiers in neuroscience vol. 5 (2011): 15. doi: https://doi.org/10.3389/fnins.2011.00015
Sanna E, Talani G, Obili N, Mascia MP, Mostallino MC, Secci PP, Pisu MG, Biggio F, Utzeri C, Olla P, Biggio G, Follesa P. Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α(4)/δ GABA(A) Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice. Front Neurosci. 2011 Feb 10;5:15. doi: 10.3389/fnins.2011.00015. eCollection 2011. PMID: 21347217; PMCID: PMC3039156.
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Front Neurosci. 2011 Feb 10;5:15. doi: 10.3389/fnins.2011.00015. eCollection 2011.

Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α(4)/δ GABA(A) Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice.

Frontiers in neuroscience

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

Affiliations

  1. Section of Neuroscience, Department of Experimental Biology, Center of Excellence for the Neurobiology of Dependence, University of Cagliari Monserrato, Cagliari, Italy.

PMID: 21347217 PMCID: PMC3039156 DOI: 10.3389/fnins.2011.00015

Abstract

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(A)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(A)R. The gene expression of the α(4) and δ subunits was increased in the hippocampus of SI C57BL/6J mice; the expression of the γ(2) subunit was decreased whereas that of the α(1) 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(4) subunit but not those of the δ and γ(2) subunits induced by SI. In addition, EtOH self-administration did not block the SI-induced changes in GABA(A)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(4) subunit but not other neurochemical, molecular, and functional modifications induced by SI prolonged mild stress.

Keywords: GABAA receptor; allopregnanolone; ethanol; gene expression; hippocampus; patch-clamp; social isolation; stress

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