Pharmacological blockade of corticotropin-releasing hormone receptor 1 (CRH1R) reduces voluntary consumption of high alcohol concentrations in non-dependent Wistar rats.
Pharmacological blockade of corticotropin-releasing hormone receptor 1 (CRH1R) reduces voluntary consumption of high alcohol concentrations in non-dependent Wistar rats.
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DOI：
10.1016/j.pbb.2011.10.016
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发表时间：
2012-01
影响因子：
3.6
通讯作者：
Heilig, Markus
中科院分区：
文献类型：
--
作者：
Cippitelli, Andrea;Damadzic, Ruslan;Singley, Erick;Thorsell, Annika;Ciccocioppo, Roberto;Eskay, Robert L.;Heilig, Markus
促肾上腺皮质激素释放激素（CRH）系统的失调与过度饮酒和依赖的发展有关。本研究的目的是评估CRH系统是否也招募时，非依赖性Wistar大鼠升级到高酒精摄入量的间歇性（隔日）饮酒模型。我们比较了间歇性和连续访问20%（v/v）的酒精在两瓶自由选择饮酒范例。在每个实验组总共20次24小时暴露后，我们评估了酒精戒断的迹象，包括焦虑样行为和对压力的敏感性。选择性CRH 1受体（CRH 1 R）拮抗剂antalarmin（0、10、20 mg/kg，i. p.）进行了酒精摄入量测试间歇性接触20%的酒精导致非选择性Wistar大鼠将其自愿摄入量提高到较高且稳定的水平，而连续暴露的动物则保持较低的消费量。这些组在身体戒断体征方面没有差异。此外，没有发现差异时，焦虑样行为进行了研究，无论是在基础条件下或以下约束压力。然而，观察到对CRH 1 R antalarmin治疗的敏感性，因为无论酒精暴露方案如何，在两组动物中均发现酒精摄入量减少20%。此外，antalarmin是有效的，当注射到动物暴露于间歇性10%（v/v）酒精，而它不能抑制10%的连续酒精摄入。CRH 1 R的药理学阻断减少饮酒时，持续高水平的摄入量，这表明CRH系统发挥了关键作用时，高剂量的乙醇消耗的非依赖性科目。这支持了CRH系统不仅维持依赖状态，而且参与向依赖的过渡的概念。
A dysregulation of the corticotropin-releasing hormone (CRH) system has been implicated in the development of excessive alcohol consumption and dependence. The aim of the present study was to evaluate whether the CRH system is also recruited when non-dependent Wistar rats escalate to high alcohol intake in the intermittent (alternate days) model of drinking. We compared intermittent and continuous access to 20% (v/v) alcohol in a two-bottle free choice drinking paradigm. Following a total of twenty 24-hour exposures for every experimental group, we assessed signs of alcohol withdrawal, including anxiety-like behavior and sensitivity to stress. The selective CRH1 receptor (CRH1R) antagonist antalarmin (0, 10, 20 mg/kg, i.p.) was tested on alcohol consumption. Intermittent access to 20% alcohol led non-selected Wistar rats to escalate their voluntary intake to a high and stable level, whereas continuously exposed animals maintained a lower consumption. These groups did not differ in physical withdrawal signs. In addition, no differences were found when anxiogenic-like behavior was studied, neither under basal conditions or following restraint stress. Nevertheless, sensitivity to the treatment with the CRH1R antalarmin was observed since a reduction of 20% alcohol intake was found in both groups of animals regardless of the regimen of alcohol exposure. In addition, antalarmin was effective when injected to animals exposed to intermittent 10% (v/v) alcohol whereas it failed to suppress 10% continuous alcohol intake. Pharmacological blockade of CRH1R reduced alcohol drinking when sustained high levels of intake were achieved suggesting that the CRH system plays a key role when high doses of ethanol are consumed by non-dependent subjects. This supports the notion that CRH system not only maintains the dependent state but also engages the transition to dependence.
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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：
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作者：
通讯作者：
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影响因子：
13.5
作者：
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通讯作者：
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影响因子：
2.3
作者：
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通讯作者：
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影响因子：
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作者：
Gehlert, Donald R.;Cippitelli, Andrea;Heilig, Markus
通讯作者：
Heilig, Markus
DOI：
10.1111/j.1530-0277.2010.01392.x
发表时间：
2011-04-01
影响因子：
3.2
作者：
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通讯作者：
Ciccocioppo, Roberto