Department of Cell and Systems Biology, University of Toronto Mississauga, Canada.
Department of Psychology, University of Toronto Mississauga, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jan 2;56:221-6. doi: 10.1016/j.pnpbp.2014.09.011. Epub 2014 Oct 5.
Chronic ethanol exposure paradigms have been successfully used in the past to induce behavioral and central nervous system related changes in zebrafish. However, it is currently unknown whether chronic ethanol exposure alters ethanol metabolism in adult zebrafish. In the current study we examine the effect of acute ethanol exposure on adult zebrafish behavioral responses, as well as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the liver. We then examine how two different chronic ethanol exposure paradigms (continuous and repeated ethanol exposure) alter behavioral responses and liver enzyme activity during a subsequent acute ethanol challenge. Acute ethanol exposure increased locomotor activity in a dose-dependent manner. ADH activity was shown to exhibit an inverted U-shaped curve and ALDH activity was decreased by ethanol exposure at all doses. During the acute ethanol challenge, animals that were continuously housed in ethanol exhibited a significantly reduced locomotor response and increased ADH activity, however, ALDH activity did not change. Zebrafish that were repeatedly exposed to ethanol demonstrated a small but significant attenuation of the locomotor response during the acute ethanol challenge but ADH and ALDH activity was similar to controls. Overall, we identified two different chronic ethanol exposure paradigms that differentially alter behavioral and physiological responses in zebrafish. We speculate that these two paradigms may allow dissociation of central nervous system-related and liver enzyme-dependent ethanol induced changes in zebrafish.
慢性乙醇暴露范式在过去已被成功用于诱导斑马鱼的行为和中枢神经系统相关变化。然而，目前尚不清楚慢性乙醇暴露是否会改变成年斑马鱼的乙醇代谢。在本研究中，我们研究了急性乙醇暴露对成年斑马鱼行为反应的影响，以及肝脏中乙醇脱氢酶（ADH）和醛脱氢酶（ALDH）的活性。然后，我们研究了两种不同的慢性乙醇暴露范式（连续和重复乙醇暴露）如何在随后的急性乙醇挑战中改变行为反应和肝脏酶活性。急性乙醇暴露以剂量依赖的方式增加了运动活性。ADH 活性表现出倒 U 形曲线，而 ALDH 活性在所有剂量下均被乙醇暴露所降低。在急性乙醇挑战期间，连续暴露于乙醇中的动物表现出运动反应显著降低和 ADH 活性增加，但 ALDH 活性没有变化。反复暴露于乙醇的斑马鱼在急性乙醇挑战期间表现出运动反应的微小但显著衰减，但 ADH 和 ALDH 活性与对照组相似。总体而言，我们确定了两种不同的慢性乙醇暴露范式，它们以不同的方式改变了斑马鱼的行为和生理反应。我们推测，这两种范式可能允许分离斑马鱼中枢神经系统相关和肝脏酶依赖性乙醇诱导变化。
