Binge Drinking: In Search of its Molecular Target via the GABA(A) Receptor.
Binge Drinking: In Search of its Molecular Target via the GABA(A) Receptor.
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DOI：
10.3389/fnins.2011.00123
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发表时间：
2011
影响因子：
4.3
通讯作者：
June HL Sr
中科院分区：
文献类型：
--
作者：
Yang AR;Liu J;Yi HS;Warnock KT;Wang M;June HL Jr;Puche AC;Elnabawi A;Sieghart W;Aurelian L;June HL Sr
狂饮，临床上常被称为问题或危险饮酒，是一种过量饮酒的模式，其特征是血液酒精浓度在2小时内≥0.08 g%。本研究表明，GABAA受体α1亚基的过度表达有助于酗酒，并进一步证明这种参与与α1受体亚基的神经解剖学定位有关。利用单纯疱疹病毒扩增子载体传递小干扰RNA (siRNA)，我们发现α1亚基特异性siRNA （pHSVsiLA1）在高酒精饮酒大鼠的腹侧白质（VP）中引起了基因表达、受体密度和酗酒的深刻、长期和选择性的减少。以类似方式将siRNA （pHSVsiNC）传递到VP中，未能改变基因表达、受体密度或酗酒。然而，α1基因的沉默并不能改变大量的糖或水的摄入。这些结果与我们之前的研究一起，提供了令人信服的证据，证明含有α1的GABAA受体亚基在过度饮酒的暴饮暴食模式的调节中起着关键作用。总的来说，这些数据可能有助于开发基于基因的治疗过度饮酒的新药理学方法。
Binge drinking, frequently referred to clinically as problem or hazardous drinking, is a pattern of excessive alcohol intake characterized by blood alcohol levels ≥0.08 g% within a 2-h period. Here, we show that overexpression of α1 subunits of the GABAA receptor contributes to binge drinking, and further document that this involvement is related to the neuroanatomical localization of α1 receptor subunits. Using a herpes simplex virus amplicon vector to deliver small interference RNA (siRNA), we showed that siRNA specific for the α1 subunit (pHSVsiLA1) caused profound, long-term, and selective reduction of gene expression, receptor density, and binge drinking in high-alcohol drinking rats when delivered into the ventral pallidum (VP). Scrambled siRNA (pHSVsiNC) delivered similarly into the VP failed to alter gene expression, receptor density, or binge drinking. Silencing of the α1 gene in the VP, however, failed to alter binge sucrose or water intake. These results, along with our prior research, provide compelling evidence that the α1-containing GABAA receptor subunits are critical in the regulation of binge-like patterns of excessive drinking. Collectively, these data may be useful in the development of gene-based and novel pharmacological approaches for the treatment of excessive drinking.
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影响因子：
56.9
作者：
CLONINGER, CR
通讯作者：
CLONINGER, CR
影响因子：
7.6
作者：
June, HL;Foster, KL;Skolnick, P
通讯作者：
Skolnick, P
影响因子：
9.8
作者：
Edenberg, HJ;Dick, DM;Begleiter, H
通讯作者：
Begleiter, H
影响因子：
2.9
作者：
Kaufmann, WA;Humpel, C;Marksteiner, J
通讯作者：
Marksteiner, J
DOI：
10.1111/j.1530-0277.1995.tb00966.x
发表时间：
1995-08-01
影响因子：
3.2
作者：
DEVAUD, LL;MORROW, AL;DUNCAN, GE
通讯作者：
DUNCAN, GE