Analyzing cannabinoid-induced abnormal behavior in a zebrafish model.
Analyzing cannabinoid-induced abnormal behavior in a zebrafish model.
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DOI：
10.1371/journal.pone.0236606
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Yoshida KI
中科院分区：
文献类型：
--
作者：
Hasumi A;Maeda H;Yoshida KI
在这项研究中，我们研究了运动活动和重复的光和暗刺激的反应，以评估大麻素诱导的斑马鱼幼虫（Danio rerio）的异常行为，作为标准啮齿动物模型的替代。为了诱导所需的反应，我们使用了大麻二酚和WIN 55，212-2，两种主要的大麻素成分。使用重复的光和暗测试来评估药物暴露如何影响运动反应。在中度大麻二酚和WIN 55，212-2暴露后以及转移到未处理的水中后24小时，检查幼虫。我们发现，大麻二酚对自发活动没有产生剂量依赖性抑制作用，0.5和10 μg/mL的浓度都会降低运动速度和总运动距离。然而，观察到10 μg/mL大麻二酚减弱了暴露于黑暗的幼虫的反应。在淡水中24小时后，在对照组和大麻二酚处理组之间没有检测到差异。用0.5和1 μg/mL的WIN 55、212-2处理的鱼几乎没有活性，即使在黑暗中也是如此，而10 μg/mL的浓度诱导死亡。即使在WIN 55、212-2处理组中，在淡水中24小时的时间具有逆转大部分药物诱导的制动的作用。还评估了大麻二酚在初始暴露于WIN 55，212-2之后对大麻二酚的反应，因此发现用大麻二酚处理可以减弱WIN 55，212-2诱导的异常固定，而同等剂量的大麻二酚和WIN 55，212-2产生混合反应。总之，两种大麻素cannabidiol和WIN 55，212-2的行为效应似乎是比例依赖性的。重复光暗试验可作为一种较好的药物诱导行为的检测方法。
In this study, we investigated locomotor activity and responses to repeated light and dark stimuli to assess cannabinoid-induced abnormal behavior in zebrafish larvae (Danio rerio), as an alternative to standard rodent models. To induce the desired responses, we used cannabidiol and WIN55,212–2, two major cannabinoid components. A repeated light and dark test was used to assess how drug exposure influences locomotory responses. Larvae were examined after moderate cannabidiol and WIN55,212–2 exposure and at 24 h after transfer to untreated water. We found that cannabidiol did not produce a dose-dependent inhibitory effect on locomotor activity, with both 0.5 and 10 μg/mL concentrations reducing movement velocity and the total distance moved. However, 10 μg/mL cannabidiol was observed to attenuate the responses of larvae exposed to darkness. No differences were detected between the control and cannabidiol-treated groups after 24 h in fresh water. Fish treated with WIN55,212–2 at 0.5 and 1 μg/mL showed virtually no activity, even in darkness, whereas a concentration of 10 μg/mL induced mortality. A 24-h period in fresh water had the effect of reversing most of the drug-induced immobilization, even in the WIN55,212-2-treated groups. Larvae were also evaluated for their responses to cannabidiol subsequent to an initial exposure to WIN55,212–2, and it was accordingly found that treatment with cannabidiol could attenuate WIN55,212-2-induced abnormal immobilization, whereas equivalent doses of cannabidiol and WIN55,212–2 produced a mixed response. In conclusion, the behavioral effects of the two cannabinoids cannabidiol and WIN55,212–2 appear to be ratio dependent. Furthermore, the repeated light and dark test could serve as a suitable method for assaying drug-induced behavior.
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影响因子：
14.8
作者：
Bruni G;Rennekamp AJ;Velenich A;McCarroll M;Gendelev L;Fertsch E;Taylor J;Lakhani P;Lensen D;Evron T;Lorello PJ;Huang XP;Kolczewski S;Carey G;Caldarone BJ;Prinssen E;Roth BL;Keiser MJ;Peterson RT;Kokel D
通讯作者：
Kokel D
影响因子：
6.1
作者：
Farrell, Thomas C.;Cario, Clinton L.;Milanese, Chiara;Vogt, Andreas;Jeong, Jong-Hyeon;Burton, Edward A.
通讯作者：
Burton, Edward A.
影响因子：
4
作者：
McCarroll, Matthew N.;Gendelev, Leo;Keiser, Michael J.;Kokel, David
通讯作者：
Kokel, David
影响因子：
2.7
作者：
Ellis, L. D.;Berrue, F.;McDougall, J. J.
通讯作者：
McDougall, J. J.
影响因子：
3.8
作者：
Carty, Dennis R.;Thornton, Cammi;Willett, Kristine L.
通讯作者：
Willett, Kristine L.