Comparison of cannabinoids with known analgesics using a novel high throughput zebrafish larval model of nociception
Comparison of cannabinoids with known analgesics using a novel high throughput zebrafish larval model of nociception
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DOI：
10.1016/j.bbr.2017.09.028
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发表时间：
2018-01-30
影响因子：
2.7
通讯作者：
McDougall, J. J.
中科院分区：
文献类型：
--
作者：
Ellis, L. D.;Berrue, F.;McDougall, J. J.
斑马鱼的成体和幼体都能对伤害性刺激产生伤害性反应，但利用幼体来测试新型止痛药还没有得到充分的探索。斑马鱼幼体是一种低成本、高通量的替代传统哺乳动物模型，用于在药物开发的初始阶段评估产品效果。在目前的研究中，描述了一种使用斑马鱼幼虫的新型伤害性感受模型。在从急性暴露于低水平的醋酸中恢复的过程中，幼虫表现出可能预示着伤害的行为的先天变化。为了评估这一模型在测试潜在止痛药方面的有效性，对三种已知的合成止痛药(布洛芬、对乙酰氨基酚和曲马多)以及三种天然产物(和厚朴酚、四氢大麻酚和大麻二酚)进行了评估。当比较每种化合物对醋酸回收率和控制活性的影响时，化合物之间既有相似之处，也有不同之处。最有趣的效应之一是大麻二酚，它似乎与AA暴露幼虫恢复期的活性变化相反，而对对照活性有名义上的影响。这似乎与目前证明大麻二酚伤害性的研究是一致的。在这里，我们提供了一个新的模型，将补充现有的斑马鱼模型，并将扩大斑马鱼幼虫用于研究伤害性和新的止痛药的潜在用途。
It has been established that both adult and larval zebrafish are capable of showing nociceptive responses to noxious stimuli; however, the use of larvae to test novel analgesics has not been fully explored. Zebrafish larvae represent a low-cost, high-throughput alternative to traditional mammalian models for the assessment of product efficacy during the initial stages of drug development. In the current study, a novel model of nociception using zebrafish larvae is described. During the recovery from an acute exposure to low levels of acetic acid, larvae display innate changes in behaviour that may be indicative of nociception. To assess the usefulness of this model for testing potential analgesics, three known synthetic pain medications were assessed (ibuprofen, acetaminophen and tramadol) along with three naturally occurring products (honokiol, tetrahydrocannabinol and cannabidiol). When the effect of each compound on both the acetic acid recovery and control activity was compared there appeared to be both similarities and differences between the compounds. One of the most interesting effects was found for cannabidiol which appeared to oppose the activity change during the recovery period of AA exposed larvae while having a nominal effect on control activity. This would appear to be in line with current research that has demonstrated the nociceptive properties of cannabidiol. Here we have provided a novel model that will complement existing zebrafish models and will expand on the potential use of zebrafish larvae for studying both nociception and new analgesics.