Pretzel Camilla W, Borba João V, Resmim Cássio M, De Abreu Murilo S, Kalueff Allan V, Fontana Barbara D, Canzian Julia, Rosemberg Denis B
Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Pharmacol Biochem Behav. 2024 Dec;245:173892. doi: 10.1016/j.pbb.2024.173892. Epub 2024 Oct 8.
Anxiety can be a protective emotion when animals face aversive conditions, but is commonly associated with various neuropsychiatric disorders when pathologically exacerbated. Drug repurposing has emerged as a valuable strategy based on utilizing the existing pharmaceuticals for new therapeutic purposes. Ketamine, traditionally used as an anesthetic, acts as a non-competitive antagonist of the glutamate N-methyl-d-aspartate (NMDA) receptor, and shows potential anxiolytic and antidepressant effects at subanesthetic doses. However, the influence of ketamine on multiple behavioral domains in vertebrates is not completely understood. Here, we evaluated the potential modulatory effect of ketamine on the spatio-temporal exploratory dynamics and homebase-related behaviors in adult zebrafish using the open field test (OFT). Animals were exposed to subanesthetic concentrations of ketamine (0, 2, 20, and 40 mg/L) for 20 min and their locomotion-, exploration- and homebase-related behaviors were assessed in a single 30-min trial. Our data revealed that acute ketamine (20 and 40 mg/L) induced hyperlocomotion, as verified by the increased total distance traveled. All concentrations tested elicited circling behavior, a stereotyped-like response which gradually reduced across the periods of test. We also observed modulatory effects of ketamine on the spatio-temporal exploratory pattern, in which the reduced thigmotaxis and homebase activity, associated with the increased average length of trips, suggest anxiolytic-like effects. Collectively, our findings support the modulatory effects of ketamine on the spatio-temporal exploratory activity, and corroborate the utility of homebase-related measurements to evaluate the behavioral dynamics in zebrafish models.
当动物面临厌恶条件时，焦虑可以是一种保护情绪，但在病理上加剧时通常与各种神经精神疾病相关。药物重新利用已成为一种基于将现有药物用于新治疗目的的有价值策略。氯胺酮传统上用作麻醉剂，它作为谷氨酸N-甲基-D-天冬氨酸（NMDA）受体的非竞争性拮抗剂，在亚麻醉剂量下显示出潜在的抗焦虑和抗抑郁作用。然而，氯胺酮对脊椎动物多个行为领域的影响尚未完全了解。在这里，我们使用旷场试验（OFT）评估了氯胺酮对成年斑马鱼时空探索动态和与家基相关行为的潜在调节作用。将动物暴露于亚麻醉浓度的氯胺酮（0、2、20和40mg/L）20分钟，并在单次30分钟试验中评估它们的运动、探索和与家基相关的行为。我们的数据显示，急性氯胺酮（20和40mg/L）诱导了运动亢进，这通过总游动距离的增加得到证实。所有测试浓度均引发了转圈行为，这是一种刻板样反应，在测试期间逐渐减少。我们还观察到氯胺酮对时空探索模式的调节作用，其中与平均游动长度增加相关的触觉回避和家基活动减少表明有抗焦虑样作用。总的来说，我们的研究结果支持氯胺酮对时空探索活动的调节作用，并证实了与家基相关测量在评估斑马鱼模型行为动态中的实用性。
