CRF(1) Receptor-Dependent Increases in Irritability-Like Behavior During Abstinence from Chronic Intermittent Ethanol Vapor Exposure.
CRF(1) Receptor-Dependent Increases in Irritability-Like Behavior During Abstinence from Chronic Intermittent Ethanol Vapor Exposure.
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DOI：
10.1111/acer.13484
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
George O
中科院分区：
文献类型：
--
作者：
Kimbrough A;de Guglielmo G;Kononoff J;Kallupi M;Zorrilla EP;George O
在人类中，从乙醇中戒断的情绪和身体迹象是常见的。这些症状中的许多，包括焦虑样和抑郁样行为，已经在乙醇依赖的动物模型中得到表征。目前在动物模型中测量戒断的几种行为测试的一个问题是，随着时间的推移，它们通常不能在受试者中重复。此外，人类乙醇戒断最常见的症状之一，即易怒，尚未在动物模型中得到很好的表征。促肾上腺皮质激素释放因子（CRF）-CRF 1受体系统已被认为是关键的焦虑样行为的出现在酒精依赖，但该系统的作用，在易怒样行为尚未得到表征。本研究比较了慢性间歇性乙醇蒸汽暴露（CIE）诱导的乙醇依赖性对大鼠急性戒断和长期戒断过程中的瓶刷试验的应激样行为的影响。训练大鼠在操作室中自我给予乙醇，然后使其处于非依赖状态或通过CIE产生依赖。在瓶刷试验中，对未处理、非依赖和依赖大鼠进行了酒精戒断8 h和2周的过敏样行为检测。依赖性和非依赖性大鼠的单独队列用于检查特异性CRF 1受体拮抗剂R121919对易怒样行为的影响。依赖性大鼠表现出乙醇摄入量增加相比，自己的前CIE基线和非依赖性大鼠。在这两个时间点的禁欲，乙醇依赖性大鼠表现出增加的攻击性反应相比，幼稚和nondependent大鼠。R121919减少了依赖性和非依赖性大鼠的易怒样行为，但依赖性大鼠对R121919更敏感。易怒样行为是一种临床相关的和可靠的测量消极情绪状态，部分介导的CRF-CRF 1系统的激活，并保持在酒精依赖大鼠长期禁欲升高。
In humans, emotional and physical signs of withdrawal from ethanol are commonly seen. Many of these symptoms, including anxiety-like and depression-like behavior, have been characterized in animal models of ethanol dependence. One issue with several current behavioral tests that measure withdrawal in animal models is they are often not repeatable within subjects over time. Additionally, irritability, one of the most common symptoms of ethanol withdrawal in humans, has not been well characterized in animal models. The corticotropin-releasing factor (CRF)-CRF1 receptor system has been suggested to be critical for the emergence of anxiety-like behavior in ethanol dependence, but the role of this system in irritability-like behavior has not been characterized. The present study compared the effects of chronic intermittent ethanol vapor exposure (CIE)-induced ethanol dependence on irritability-like behavior in rats using the bottle-brush test during acute withdrawal and protracted abstinence. Rats were trained to self-administer ethanol in operant chambers and then either left in a nondependent state or made dependent via CIE. Naive, nondependent, and dependent rats were tested for irritability-like behavior in the bottle-brush test 8 h and 2 weeks into abstinence from ethanol. Separate cohorts of dependent and nondependent rats were used to examine the effect of the specific CRF1 receptor antagonist R121919 on irritability-like behavior. Dependent rats exhibited escalated ethanol intake compared with their own pre-CIE baseline and nondependent rats. At both time-points of abstinence, ethanol-dependent rats exhibited increased aggressive-like responses compared with naive and nondependent rats. R121919 reduced irritability-like behavior in both dependent and nondependent rats, but dependent rats were more sensitive to R121919. Irritability-like behavior is a clinically relevant and reliable measure of negative emotional states that is partially mediated by activation of the CRF-CRF1 system and remains elevated during protracted abstinence in ethanol-dependent rats.
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酒精中毒的一二拳：中央杏仁核的作用/kappa-阿片受体。
影响因子：
10.6
作者：
Kissler, Jessica L.;Sirohi, Sunil;Reis, Daniel J.;Jansen, Heiko T.;Quock, Raymond M.;Smith, Daniel G.;Walker, Brendan M.
通讯作者：
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影响因子：
2.7
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通讯作者：
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影响因子：
4.2
作者：
FRYE, GD;ELLIS, FW
通讯作者：
ELLIS, FW
DOI：
10.1111/j.1530-0277.2008.00678.x
发表时间：
2008-09-01
影响因子：
3.2
作者：
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通讯作者：
Koob, G. F.
影响因子：
3.4
作者：
BALDWIN, HA;RASSNICK, S;BRITTON, KT
通讯作者：
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