Moore Eileen M, Serio Kristen M, Goldfarb Karen J, Stepanovska Sandra, Linsenbardt David N, Boehm Stephen L
Behavioral Neuroscience, Department of Psychology, Binghamton University -- SUNY, Binghamton, NY 13902-6000, United States.
Pharmacol Biochem Behav. 2007 Nov;88(1):105-13. doi: 10.1016/j.pbb.2007.07.011. Epub 2007 Jul 25.
GABA receptor systems have long been implicated in alcoholism, and GABAergic drugs have demonstrated efficacy in altering alcohol intake in some rodent models. The present study was designed to assess the effects of baclofen, muscimol, and gaboxadol (THIP) in a variation on a new mouse model of binge-like ethanol intake. Three hours into their dark cycle, male and female C57BL/6J mice were given access to a 20% unsweetened ethanol solution for 2 h each day, for four days. On day five, mice received varying doses of baclofen, muscimol or THIP and were allowed access to 20% ethanol for 60 min. Baclofen dose-dependently increased binge-like ethanol intake, while both muscimol and THIP reduced ethanol intake. Subsequent studies testing the effect of baclofen, muscimol and THIP on water intake using the same procedure revealed that whereas baclofen had no significant effect, muscimol and THIP both reduced the measure. These results add to the growing literature suggesting a role for GABA receptor systems in the modulation of ethanol intake. However, whereas the role of GABA(B) receptor systems seems selective in the modulation of binge-like ethanol intake, the role for GABA(A) receptor systems appears to also extend to general fluid intake.
长期以来，γ-氨基丁酸（GABA）受体系统一直被认为与酒精中毒有关，并且在一些啮齿动物模型中，GABA能药物已证明在改变酒精摄入量方面具有疗效。本研究旨在评估巴氯芬、蝇蕈醇和加波沙朵（THIP）在一种类似暴饮暴食样乙醇摄入的新小鼠模型变体中的作用。在它们黑暗周期的三小时，每天给雄性和雌性C57BL/6J小鼠提供20%的无糖乙醇溶液，持续2小时，共四天。在第五天，小鼠接受不同剂量的巴氯芬、蝇蕈醇或THIP，然后允许它们接触20%的乙醇60分钟。巴氯芬剂量依赖性地增加了类似暴饮暴食样的乙醇摄入量，而蝇蕈醇和THIP都减少了乙醇摄入量。随后使用相同程序测试巴氯芬、蝇蕈醇和THIP对水摄入量影响的研究表明，巴氯芬没有显著影响，而蝇蕈醇和THIP都减少了测量值。这些结果进一步丰富了相关文献，表明GABA受体系统在调节乙醇摄入中发挥作用。然而，虽然GABA(B)受体系统在调节类似暴饮暴食样乙醇摄入中的作用似乎具有选择性，但GABA(A)受体系统的作用似乎也扩展到一般液体摄入。
