Effect of baclofen on alcohol and sucrose self-administration in rats.
Effect of baclofen on alcohol and sucrose self-administration in rats.
复制标题
巴氯芬对大鼠酒精和蔗糖自我给药的影响。
DOI：
10.1097/01.alc.0000071744.78580.78
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Woodward,DonaldJ
中科院分区：
文献类型：
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作者：
Anstrom,KristinK;Cromwell,HowardC;Markowski,Tania;Woodward,DonaldJ
背景：巴氯芬是一种γ -氨基丁酸B型激动剂，已被提议作为一种药物治疗剂用于治疗成瘾障碍，如酒精中毒。临床前研究证明巴氯芬对酒精摄入的影响提供了相互矛盾的结果。本研究的目的是确定巴氯芬预处理对乙醇和蔗糖增强应答的影响。方法：采用蔗糖褪色法，训练动物自行管理10%乙醇水溶液，按固定比例1进行强化。采用受试者内设计，研究了三种剂量的巴氯芬（1.8、3.2和5.6 mg/kg腹腔注射）对10%乙醇和2%蔗糖增强反应的影响。研究了剂量依赖性对反应和饮型微观结构的影响。结果：在固定比例为1的情况下，巴氯芬以类似的剂量依赖性方式降低了酒精和蔗糖强化的反应。在操作会话的初始阶段，当产生高度重复的反应模式时，可以看到剂量依赖性的反应衰减。对饮酒超微结构的进一步分析表明，巴氯芬通过延长自我启动的间隔时间改变了这些重复反应的模式。结论：全身给予巴氯芬以剂量依赖的方式减弱了酒精和蔗糖强化的反应。如果对蔗糖和酒精的强化效果和反应要求相匹配，那么巴氯芬对饮酒微观结构的反应和模式具有相似的效果。我们得出结论，支持乙醇和蔗糖自我给药行为的神经机制对γ -氨基丁酸B型调节很敏感。
Background:Baclofen, a γ‐aminobutyric acid type B agonist, has been proposed as a pharmacotherapeutic agent in the treatment of addictive disorders such as alcoholism. Preclinical studies documenting the effect of baclofen on alcohol intake have provided conflicting results. The goal of this study was to determine the effect of baclofen pretreatment on ethanol‐ and sucrose‐reinforced responding.Methods:Animals were trained to self‐administer a 10% ethanol in water solution on a fixed ratio 1 schedule of reinforcement by using the sucrose‐fade method. With a within‐subject design, the effect of three doses of baclofen (1.8, 3.2, and 5.6 mg/kg intraperitoneally) was examined on 10% ethanol‐ and 2% sucrose‐reinforced responding. Dose‐dependent effects on responding and on drinking‐pattern microstructure were examined.Results:Under a fixed ratio 1 schedule, baclofen reduced responding for alcohol and sucrose reinforcement in a similar, dose‐dependent manner. A dose‐dependent response attenuation was seen during the initial segment of an operant session when highly repetitive response patterns were generated. Further analysis of drinking ultrastructure revealed that baclofen altered the patterns of these repetitive responses by lengthening the self‐initiated intertrial intervals.Conclusions:Systemic baclofen administration attenuates responding for alcohol and sucrose reinforcement in a dose‐dependent manner. If the reinforcing efficacy and response requirement for sucrose and alcohol are matched, then baclofen has similar effects on responding and patterns of drinking microstructure. We conclude that the neural mechanisms that support both ethanol and sucrose self‐administration behavior are sensitive to γ‐aminobutyric acid type B modulation.