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尼古丁对斑马鱼的抗焦虑作用。

Anxiolytic effects of nicotine in zebrafish.

作者信息

Levin Edward D, Bencan Zachary, Cerutti Daniel T

机构信息

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.

出版信息

Physiol Behav. 2007 Jan 30;90(1):54-8. doi: 10.1016/j.physbeh.2006.08.026. Epub 2006 Oct 13.

Abstract

Anxiolytic effects of nicotine have been documented in studies with rodents and humans. Understanding the neural basis of nicotine-induced anxiolysis can help both with developing better aids for smoking cessation as well as with the potential development of novel nicotinic ligands for treating anxiety. Complementary non-mammalian models may be useful for determining the molecular bases of nicotine effects on neurobehavioral function. The current project examined whether a zebrafish model of anxiety would be sensitive to nicotine. When zebrafish are placed in a novel environment, they dive to the bottom of the tank. In the wild, diving could help to escape predation. We tested the anxiolytic effect of nicotine on the novelty-elicited diving response and subsequent habituation. Zebrafish placed in a novel tank spent the majority of time at the bottom third of the tank during the first minute of a 5-min session and then show a gradual decrease in time spent at the tank bottom. Nicotine treatment at 100 mg/l for 3 min by immersion before testing caused a significant decrease in diving throughout the session, while 50 mg/l was effective during the first minute when the greatest bottom dwelling was seen in controls. Nicotine effects were reversed by the nicotinic antagonist mecamylamine given together with nicotine, but not when administered shortly before the test session after prior nicotine dosing. This implies that the effect of nicotine on diving was due to net stimulation at nicotinic receptors, an effect that is blocked by mecamylamine; and that once invoked, this effect is no longer dependent on continuing activation of nicotinic receptors. The effect of nicotine on diving did not seem to be the result of a general disorientation of the fish. The 100 mg/ml nicotine dose was shown in our earlier study to significantly improve spatial-discrimination learning in zebrafish. Nicotine-induced anxiolytic effects can be modeled in the zebrafish. This preparation will help in the investigation of the molecular bases of this effect.

摘要

尼古丁的抗焦虑作用已在啮齿动物和人类研究中得到证实。了解尼古丁诱导抗焦虑作用的神经基础,有助于开发更好的戒烟辅助工具,以及开发用于治疗焦虑的新型烟碱配体。互补的非哺乳动物模型可能有助于确定尼古丁对神经行为功能影响的分子基础。当前项目研究了焦虑斑马鱼模型是否对尼古丁敏感。当斑马鱼被置于新环境中时,它们会潜入水箱底部。在自然环境中,潜入水底有助于逃避捕食。我们测试了尼古丁对新奇引发的潜水反应及随后习惯化的抗焦虑作用。置于新水箱中的斑马鱼在5分钟测试期的第一分钟大部分时间都待在水箱底部三分之一处,然后在水箱底部停留的时间逐渐减少。在测试前通过浸泡给予100mg/l尼古丁处理3分钟,会导致整个测试期内潜水显著减少,而50mg/l在第一分钟有效,此时对照组中待在水箱底部的时间最长。尼古丁与烟碱拮抗剂美加明一起给予时,其作用会被逆转,但在先前给予尼古丁后测试前不久给予美加明则不会。这意味着尼古丁对潜水的作用是由于烟碱受体的净刺激,这种作用被美加明阻断;而且一旦产生这种作用,就不再依赖于烟碱受体的持续激活。尼古丁对潜水的作用似乎不是鱼普遍迷失方向的结果。我们早期的研究表明,100mg/ml的尼古丁剂量能显著改善斑马鱼的空间辨别学习能力。尼古丁诱导的抗焦虑作用可以在斑马鱼中建模。这种制剂将有助于研究这种作用的分子基础。

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