Assessment of GABA-B, metabotropic glutamate, and opioid receptor involvement in an animal model of binge drinking.
Assessment of GABA-B, metabotropic glutamate, and opioid receptor involvement in an animal model of binge drinking.
复制标题
评估暴饮动物模型中 GABA-B、代谢型谷氨酸和阿片受体的参与情况。
DOI：
10.1016/j.alcohol.2010.07.009
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Finn,DeborahA
中科院分区：
文献类型：
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作者：
Tanchuck,MichelleA;Yoneyama,Naomi;Ford,MatthewM;Fretwell,AndreaM;Finn,DeborahA
饮酒至醉酒或狂饮是酒精滥用的一个标志性特征。尽管难以在啮齿动物中建模，但预定的高酒精消耗（SHAC）程序在小鼠中产生高的、稳定的乙醇摄入和血液乙醇浓度，达到与狂饮定义一致的水平。本研究的目的是确定药物操作阿片类药物，多巴胺能和γ-氨基丁酸（GABA）能系统对SHAC程序酗酒的影响。在接受蔗糖或乙醇操作性自我给药训练的小鼠中进行平行操作。对于SHAC程序，给予遗传异质性戒断性癫痫发作对照小鼠不同时间段的液体接入，每三天30分钟乙醇会话（总共七天）。在每次乙醇治疗之前，小鼠腹腔内用纳洛酮（0、0.6或1.25mg/kg）、巴氯芬（0、2.5或5.0mg/kg）或2-甲基-6-（苯乙炔基）-吡啶（MPEP; 0、3.0或10.0mg/kg）预处理。对于操作性自我给药程序，训练单独的C57 BL/6小鼠组以完成单次响应要求（在活动杠杆上按压16次），以获得30分钟的乙醇或蔗糖溶液。在自我给药前，小鼠接受相同剂量的纳洛酮、MPEP或巴氯芬预处理，并在中间几天注射盐水。纳洛酮产生了剂量依赖性的减少酗酒，最高剂量也显着减少乙醇和蔗糖的操作性自我管理。两种剂量的巴氯芬都显著降低了酗酒，但较高剂量的巴氯芬也倾向于减少饮水量。最高剂量的巴氯芬也显着降低操作性自我管理的蔗糖。MPEP（10 mg/kg）显著降低了酒精消耗量和蔗糖自我给药。这些结果表明，阿片类药物，多巴胺能，γ-氨基丁酸能系统的操作显着减少狂饮。
Drinking to intoxication or binge drinking is a hallmark characteristic of alcohol abuse. Although hard to model in rodents, the scheduled high alcohol consumption (SHAC) procedure generates high, stable ethanol intake and blood ethanol concentrations in mice to levels consistent with definitions of binge drinking. The purpose of the present studies was to determine the effects of pharmacological manipulation of the opioidergic, glutamatergic, and γ-aminobutyric acid (GABA)ergic systems on binge drinking with the SHAC procedure. Parallel manipulations were conducted in mice trained in operant self-administration of either sucrose or ethanol. For the SHAC procedure, genetically heterogeneous Withdrawal Seizure Control mice were given varying periods of fluid access, with a 30-min ethanol session every third day (total of seven). Mice were pretreated intraperitoneally with naltrexone (0, 0.6, or 1.25mg/kg), baclofen (0, 2.5, or 5.0mg/kg), or 2-methyl-6-(phenylethynyl)-pyridine (MPEP; 0, 3.0, or 10.0mg/kg) before each ethanol session. For the operant self-administration procedure, separate groups of C57BL/6 mice were trained to complete a single response requirement (16 presses on the active lever) to gain 30min of access to an ethanol or a sucrose solution. Mice received pretreatments of the same doses of naltrexone, MPEP, or baclofen before the self-administration sessions, with saline injections on intervening days. Naltrexone produced a dose-dependent decrease in binge drinking, and the highest dose also significantly decreased operant self-administration of ethanol and sucrose. Both doses of baclofen significantly decreased binge alcohol consumption, but the higher dose also tended to decrease water intake. The highest dose of baclofen also significantly decreased operant self-administration of sucrose. MPEP (10mg/kg) significantly decreased binge alcohol consumption and sucrose self-administration. These results indicate that manipulation of the opioidergic, glutamatergic, and GABAergic systems significantly decreased binge drinking.