Binge ethanol-drinking potentiates corticotropin releasing factor R1 receptor activity in the ventral tegmental area.
Binge ethanol-drinking potentiates corticotropin releasing factor R1 receptor activity in the ventral tegmental area.
复制标题
暴饮暴食的乙醇增强腹侧侧侧侧区域的皮质激素释放因子R1受体活性。
DOI：
10.1111/acer.12153
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Bonci A
中科院分区：
文献类型：
--
作者：
Sparta DR;Hopf FW;Gibb SL;Cho SL;Stuber GD;Messing RO;Ron D;Bonci A
Corticotropin releasing factor (CRF) and urocortin play an important role in many stress responses and also can regulate ethanol intake. Adaptations in CRF signaling in the central amygdala promote ethanol consumption after long-term ethanol intake in dependent animals and also after brief periods of binge ethanol intake. Thus, even brief episodes of ethanol consumption can alter the function of the CRF system, allowing CRF to regulate ethanol intake. Here, we examined whether brief binge ethanol consumption leads to CRF receptor adaptations within the ventral tegmental area (VTA), a structure involved in signaling rewarding and aversive events and important in the development and expression of drug and alcohol addiction. We utilized a mouse model of binge drinking known as drinking in the dark (DID), where C57BL/6J mice drink approximately ~6 gkg/4 hours and achieve blood ethanol concentrations of approximately 100 mg/dL, which is equivalent to binge drinking in humans. We used ex vivo whole-cell recordings from putative VTA dopamine neurons to examine CRF regulation of NMDA receptor (NMDAR) currents. We also examined the impact of CRF receptor antagonist injection in the VTA on binge ethanol intake. Ex vivo whole-cell recordings from putative VTA dopamine neurons showed enhanced CRF–mediated potentiation of NMDA receptor (NMDAR) currents in juvenile mice that consumed ethanol in the DID procedure. CRF-induced potentiation of NMDAR currents in ethanol drinking mice was blocked by administration of CP-154,526 (3 μM), a selective CRF1 receptor antagonist. Furthermore, intra-VTA infusion of CP-154,526 (1 μg) significantly reduced binge ethanol consumption in adult mice. These results were not due to alterations of VTA NMDAR number or function, suggesting that binge drinking may enhance signaling through VTA CRF1 receptors onto NMDARs. Altered CRF1R-mediated signaling in the VTA promotes binge-like ethanol consumption in mice, which supports the idea that CRF1Rs may therefore be a promising pharmacological target for reducing binge drinking in humans.
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影响因子：
16.2
作者：
Lüscher C;Malenka RC
通讯作者：
Malenka RC
DOI：
10.1038/npp.2009.209
发表时间：
2010-05
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1111/j.1530-0277.2011.01610.x
发表时间：
2012-02-01
影响因子：
3.2
作者：
Kaur, Simranjit;Li, Ju;Ryabinin, Andrey E.
通讯作者：
Ryabinin, Andrey E.
影响因子：
5.5
作者：
JOHNSON, SW;NORTH, RA
通讯作者：
NORTH, RA
DOI：
10.1523/jneurosci.2246-11.2011
发表时间：
2011-07-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Adamantidis AR;Tsai HC;Boutrel B;Zhang F;Stuber GD;Budygin EA;Touriño C;Bonci A;Deisseroth K;de Lecea L
通讯作者：
de Lecea L