Brain and Behaviour Lab, School of Pharmacy and Biomedical Sciences, University of Portsmouth, UK.
Brain and Behaviour Lab, School of Pharmacy and Biomedical Sciences, University of Portsmouth, UK.
Pharmacol Biochem Behav. 2020 Dec;199:173066. doi: 10.1016/j.pbb.2020.173066. Epub 2020 Oct 31.
There has been rapid growth in the use of larval zebrafish as a complementary vertebrate model for drug discovery, abuse liability and pharmacological toxicology, resulting in a huge increase in zebrafish facilities worldwide. However, many research groups working with zebrafish do not typically report the pH of husbandry conditions in methodologies, nor are the pH of drug treatments reported in many research articles. This unknown factor can be a major contributor in the differential effects of drug treatments. Therefore, as a case study, we tested the impact of altering pH of several drugs of abuse and assessed locomotor changes associated with a single drug concentration delivered at different pHs. We found that a change of a single pH unit, within the pH ranges commonly used in zebrafish husbandry, was enough to alter locomotor activity at a fixed drug concentration. Many pharmacological agents are dependent on environmental factors, such as pH, to determine bioavailability. Efficaciousness for many classes of drug is dependent on their ionization state in which shifts towards uncharged species can influence the easy of a drug crossing biological membranes. Thus, we urge users to report pH in husbandry methods and drug treatments to improve replicability and inter-study comparisons.
在药物发现、滥用倾向和药理学毒理学方面，幼体斑马鱼作为一种补充的脊椎动物模型得到了广泛应用，其使用呈快速增长趋势，这导致了全球范围内斑马鱼设施的大量增加。然而，许多使用斑马鱼的研究小组在方法中通常没有报告养殖条件的 pH 值，也没有在许多研究文章中报告药物处理的 pH 值。这个未知因素可能是药物处理差异效应的一个主要因素。因此，作为一个案例研究，我们测试了改变几种滥用药物的 pH 值的影响，并评估了在不同 pH 值下以单一药物浓度给药时与运动变化相关的影响。我们发现，在斑马鱼养殖中常用的 pH 范围内，单一 pH 值的变化足以改变在固定药物浓度下的运动活性。许多药理学药物依赖于环境因素，如 pH 值，来确定生物利用度。许多类别的药物的有效性取决于其离解状态，其中向非带电物质的转变会影响药物穿过生物膜的难易程度。因此，我们敦促用户报告养殖方法和药物处理中的 pH 值，以提高可重复性和研究间的可比性。
