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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >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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Pharmacological blockade of corticotropin-releasing hormone receptor 1 (CRH1R) reduces voluntary consumption of high alcohol concentrations in non-dependent Wistar rats

机译：促肾上腺皮质激素释放激素受体1（CRH1R）的药理阻断作用可减少非依赖性Wistar大鼠自愿戒除高浓度酒精

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Background: 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. Methods: 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. Results: 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. Conclusions: 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.
机译：背景：促肾上腺皮质激素释放激素（CRH）系统的失调与过量饮酒和依赖性的发展有关。本研究的目的是评估在间歇性（隔日）饮水模型中，非依赖性Wistar大鼠逐步升至高酒精摄入量时是否也募集了CRH系统。方法：我们比较了在两瓶免费选择的饮酒模式中间歇性和连续使用20％（v / v）酒精的情况。每个实验组总共进行二十四小时的暴露后，我们评估了戒酒的症状，包括焦虑样行为和对压力的敏感性。测试了选择性CRH1受体（CRH1R）拮抗剂antalarmin（0、10、20 mg / kg，i.p.）的酒精消耗量。结果：间歇性使用20％的酒精导致未选的Wistar大鼠将其自愿摄入量提高到较高且稳定的水平，而持续暴露的动物则保持较低的消耗量。这些人群的身体退缩迹象没有差异。此外，在基础条件下或约束压力下研究类似焦虑的行为时均未发现差异。尽管如此，由于两组动物都发现减少了20％的酒精摄入量，而不考虑酒精暴露的方案，因此观察到了对CRH1R antalarmin治疗的敏感性。此外，当将安塔拉明注射到暴露于间歇性10％（v / v）酒精的动物中时，是有效的，而不能抑制连续10％的酒精摄入。结论：当达到持续高水平摄入时，药理学上的CRH1R阻断作用降低了饮酒量，这表明当非依赖对象消耗高剂量的乙醇时，CRH系统起着关键作用。这支持CRH系统不仅维持依赖状态，而且还参与了向依赖的过渡的观点。

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