Department of Pharmacology and Neuroscience Program, Tulane Neurophenotyping Platform, Zebrafish Neuroscience Research Consortium, Tulane University Medical School,1430 Tulane Ave., New Orleans, LA 70112, USA
Neurotoxicol Teratol. 2011 Nov-Dec;33(6):658-67. doi: 10.1016/j.ntt.2011.05.011. Epub 2011 Jun 13.
Ketamine is a non-competitive glutamatergic antagonist used to induce sedation and analgesia. In sub-anesthetic doses, it induces hyperlocomotion, impairs memory and evokes stereotypic circling in rodents. Zebrafish (Danio rerio) emerged as a promising new animal model to screen the effects of psychotropic compounds. Here, we investigated the effects of sub-anesthetic doses of ketamine on anxiety, locomotion, habituation and social behavior of adult zebrafish. Acute 20-min exposure to 20 and 40 mg/L (but not 2 mg/L) of ketamine reduced anxiety, impaired intra-session habituation, evoked circular swimming and disrupted zebrafish shoaling. Additionally, ketamine reduced whole-body cortisol levels and elevated brain c-fos expression in zebrafish. Our findings demonstrate the sensitivity of zebrafish to behavioral and physiological effects of sub-anesthetic doses of ketamine, further supporting the utility of this species as a model for neuropharmacological research, including testing ketamine and related drugs.
氯胺酮是一种非竞争性的谷氨酸能拮抗剂，用于诱导镇静和镇痛。在亚麻醉剂量下，它会引起过度运动、损害记忆并在啮齿动物中引起刻板的旋转。斑马鱼（Danio rerio）作为一种有前途的新型动物模型，可用于筛选精神药物化合物的作用。在这里，我们研究了亚麻醉剂量的氯胺酮对成年斑马鱼焦虑、运动、习惯化和社交行为的影响。急性 20 分钟接触 20 和 40 mg/L（但不是 2 mg/L）的氯胺酮可降低焦虑、损害单次内习惯化、诱发圆形游泳并破坏斑马鱼的聚集。此外，氯胺酮降低了斑马鱼的全身皮质醇水平并增加了大脑 c-fos 的表达。我们的发现表明斑马鱼对亚麻醉剂量的氯胺酮的行为和生理效应敏感，进一步支持该物种作为神经药理学研究模型的实用性，包括测试氯胺酮和相关药物。
