Different genes influence toluene- and ethanol-induced locomotor impairment in C. elegans
Different genes influence toluene- and ethanol-induced locomotor impairment in C. elegans
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DOI：
10.1016/j.drugalcdep.2011.08.030
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发表时间：
2012-04-01
影响因子：
4.2
通讯作者：
Bettinger, Jill C.
中科院分区：
文献类型：
--
作者：
Davies, Andrew G.;Friedberg, Ryan I.;Bettinger, Jill C.
背景：被滥用的挥发性溶剂甲苯与经典的中枢神经系统抑制剂如乙醇有许多行为效应。甲苯和乙醇之间的相似之处也已在体外电生理学中得到证实。总之，这些研究表明甲苯和乙醇可能至少部分地通过共同的机制起作用。方法：我们使用遗传模型，秀丽线虫，在一个简单的系统中检查甲苯对行为的影响，并使用已知改变了对其他中枢神经系统抑制剂的反应的突变菌株来检查这些基因在甲苯诱导的运动效应中的参与。结果：甲苯蒸气引起野生型蠕虫运动模式的改变，这与乙醇产生的明显不同。对乙醇或挥发性麻醉剂氟烷具有抗药性的SLO-1、RAB-3和UNC-基因突变株对甲苯没有抗药性。UNC-79基因的突变导致对乙醇、氟烷和甲苯的过敏，这表明这三种化合物的机制可能是趋同的。我们筛选并分离了两个突变，它们对甲苯的运动抑制效应产生抵抗力，但不会改变对乙醇的敏感性。结论：在线虫中，乙醇和甲苯具有不同的行为效应，并且在负责这些影响的基因方面重叠最少。这些发现表明，线虫模型系统提供了一种独特而灵敏的方法来描述经典中枢神经系统镇静剂和滥用挥发性吸入剂的神经化学效应的共性和差异。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
Background: The abused volatile solvent toluene shares many behavioral effects with classic central nervous system depressants such as ethanol. Similarities between toluene and ethanol have also been demonstrated using in vitro electrophysiology. Together, these studies suggest that toluene and ethanol may be acting, at least in part, via common mechanisms.Methods: We used the genetic model, Caenorhabditis elegans, to examine the behavioral effects of toluene in a simple system, and used mutant strains known to have altered responses to other CNS depressants to examine the involvement of those genes in the motor effects induced by toluene.Results: Toluene vapor brings about an altered pattern of locomotion in wild-type worms that is visibly distinct from that generated by ethanol. Mutants of the slo-1, rab-3 and unc-64 genes that are resistant to ethanol or the volatile anesthetic halothane show no resistance to toluene. A mutation in the unc-79 gene results in hypersensitivity to ethanol, halothane and toluene indicating a possible convergence of mechanisms of the three compounds. We screened for, and isolated, two mutations that generate resistance to the locomotor depressing effects of toluene and do not alter sensitivity to ethanol.Conclusions: In C. elegans, ethanol and toluene have distinct behavioral effects and minimal overlap in terms of the genes responsible for these effects. These findings demonstrate that the C. elegans model system provides a unique and sensitive means of delineating both the commonalities as well as the differences in the neurochemical effects of classical CNS depressants and abused volatile inhalants. (C) 2011 Elsevier Ireland Ltd. All rights reserved.