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.
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.
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DOI：
10.3389/fnins.2011.00015
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发表时间：
2011
影响因子：
4.3
通讯作者：
Follesa P
中科院分区：
文献类型：
--
作者：
Sanna E;Talani G;Obili N;Mascia MP;Mostallino MC;Secci PP;Pisu MG;Biggio F;Utzeri C;Olla P;Biggio G;Follesa P
断奶后社会隔离（SI）是一种以行为和神经化学改变为特征的长期轻度应激模型。我们用SI在C57BL/6J小鼠中研究了自由选择饮酒模式下乙醇（EtOH）对海马γ-氨基丁酸A型受体（GABAARs）基因表达和功能的影响，以及神经活性类固醇在EtOH作用中的作用。SI应激诱导海马3α-羟基-5α-孕-20-one （3α,5α-TH PROG）明显减少，并与GABAAR的分子和功能改变有关。SI C57BL/6J小鼠海马α4、δ亚基基因表达增加；γ - 2亚基表达量降低，α - 1亚基表达量不变。C57BL/6J小鼠齿状回（DG）颗粒细胞的片钳记录显示，α-(4,5,6,7-四氢异恶唑[5,4-c]吡啶-3-醇（THIP）诱导的强直电流比对照C57BL/6J小鼠增强。在SI C57BL/6J小鼠中观察到的这些神经化学、分子和功能变化与EtOH摄入量和EtOH偏好增加有关。然而，EtOH消耗的增加并没有恢复SI引起的海马3α，5α-TH PROG的减少。EtOH可抑制SI诱导的α4亚基基因表达的变化，而对δ和γ2亚基基因表达的变化无抑制作用。此外，EtOH自我给药并未阻断si诱导的海马颗粒细胞中gabaar介导的张力抑制的变化，但增加了DG颗粒细胞中基底gabaar能sIPSCs的频率。我们的结论是，自我给药EtOH选择性地消除了α4亚基的增加，而不是SI长期轻度应激引起的其他神经化学、分子和功能改变。
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 (GABAARs) 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 GABAAR. The gene expression of the α4 and δ subunits was increased in the hippocampus of SI C57BL/6J mice; the expression of the γ2 subunit was decreased whereas that of the α1 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 α4 subunit but not those of the δ and γ2 subunits induced by SI. In addition, EtOH self-administration did not block the SI-induced changes in GABAAR-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 α4 subunit but not other neurochemical, molecular, and functional modifications induced by SI prolonged mild stress.
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影响因子：
5.3
作者：
Ariwodola, OJ;Weiner, JL
通讯作者：
Weiner, JL
影响因子：
3.4
作者：
Cruz, Fabio C.;Quadros, Isabel M.;Planeta, Cleopatra da S.;Miczek, Klaus A.
通讯作者：
Miczek, Klaus A.
DOI：
10.1111/j.1530-0277.2006.00247.x
发表时间：
2006-12-01
影响因子：
3.2
作者：
Gustafsson, Lisa;Nylander, Ingrid
通讯作者：
Nylander, Ingrid
影响因子：
3.4
作者：
Hall, FS;Huang, S;Linnoila, M
通讯作者：
Linnoila, M
DOI：
10.1073/pnas.1137276100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Carta, M;Ariwodola, OJ;Valenzuela, CF
通讯作者：
Valenzuela, CF