GABAA receptors in the posterior, but not anterior, ventral tegmental area mediate Ro15-4513-induced attenuation of binge-like ethanol consumption in C57BL/6J female mice.
GABAA receptors in the posterior, but not anterior, ventral tegmental area mediate Ro15-4513-induced attenuation of binge-like ethanol consumption in C57BL/6J female mice.
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DOI：
10.1016/j.bbr.2011.02.014
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发表时间：
2011-06-20
影响因子：
2.7
通讯作者：
Boehm, Stephen L., II
中科院分区：
文献类型：
--
作者：
Melon, Laverne C.;Boehm, Stephen L., II
关键词：
在对自然和药物奖赏（包括酒精）的研究中，GABAA受体已被证明可调节中脑被盖区（VTA）的多巴胺能输出。Ro 15 -4513，咪唑并苯二氮卓衍生物和GABAA受体的变构调节剂，可靠地拮抗酒精的行为效应。各种酒精消耗模型显示，急性给药后，酒精消耗行为减少。在本研究中，Ro 15 -4513全身给药，或微量注射到前或后腹侧被盖区，探讨GABAA受体在这一地区的作用，在调制高模式的酒精消费的C57 BL/6 J近交系小鼠在黑暗中饮酒（DID）模型。在药物操作之前，动物可以连续6天接触乙醇2小时。在接近的第七天之前，立即将小鼠全身（I. P.）或位点特异性施用的Ro 15 -4513。全身Ro 15 -4513（10 mg/kg）减少了DID范例中的暴食样乙醇摄入。此外，Ro 15 -4513微量注射到后腹侧被盖区后，乙醇摄入量逐步减少，最高剂量显著降低乙醇摄入量。在VTA前部微量注射后未发现任何影响，全身或后部VTA Ro 15 -4513对5%蔗糖溶液或水的消耗也无影响。目前的研究结果支持Ro 15 -4513敏感的VTA-GABAA受体在调节酗酒样乙醇消耗中的作用。此外，这里的工作增加了越来越多的文献表明，在VTA的区域异质性。
GABAA receptors have been shown to modulate dopaminergic output from the Ventral Tegmental Area (VTA) in studies of both natural and drug rewards, including alcohol. Ro15-4513, the imidazobenzodiazepine derivative and allosteric modulator at the GABAA receptor, reliably antagonizes the behavioral effects of alcohol. Various models of alcohol consumption show a decrease in consummatory behaviors, specific to ethanol, following acute administration of the drug. In the present study, Ro15-4513 was systemically administered, or microinjected into the anterior or posterior VTA, to explore the role of GABAA receptors at this region in modulating the high pattern of alcohol consumption by C57BL/6J inbred mice in the Drinking in the Dark (DID) model. Animals had 2 hour access to ethanol for 6 days prior to drug manipulations. Immediately before the seventh day of access, mice were systemically (I.P.) or site-specifically administered Ro15-4513. Systemic Ro15-4513 (at 10mg/kg) decreased binge-like ethanol intake in the DID paradigm. Additionally, there was a stepwise decrease in consumption following Ro15-4513 microinjection into the posterior VTA, with the highest dose significantly decreasing ethanol intake. There was no effect found following microinjection into the anterior VTA, nor was there an effect of systemic or intra-posterior VTA Ro15-4513 on consumption of a 5% sucrose solution or water. The present findings support a role for Ro15-4513 sensitive VTA-GABAA receptors in modulating binge-like ethanol consumption. Moreover, the work here adds to the growing body of literature suggesting regional heterogeneity in the VTA.
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影响因子：
6.1
作者：
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DOI：
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发表时间：
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影响因子：
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