Acute effects of amitriptyline on adult zebrafish: Potential relevance to antidepressant drug screening and modeling human toxidromes / Demin K.A., Kolesnikova T.O., Khatsko S.L., Meshalkina D.A., Efimova E.V., Morzherin Y.Y., Kalueff A.V. // Neurotoxicology and Teratology. - 2017. - V. 62, l. . - P. 27-33.

ISSN:
08920362
Type:
Article
Abstract:
The need to develop novel antidepressants is an emerging problem in biomedicine. An aquatic vertebrate species, the zebrafish (Danio rerio) may serve as a useful in-vivo screen for CNS drugs, and displays high sensitivity to a wide range of antidepressants. Amitriptyline is a commonly used tricyclic antidepressant which acts primarily as a serotonin and noradrenaline reuptake inhibitor. Here, we characterize drug-induced behavioral and neurochemical responses in adult zebrafish following their acute exposure to amitriptyline. Overall, the drug at 1 and 5 mg/L significantly increased time spent in top and shortened the latency to enter it, thereby paralleling recent reports on zebrafish ‘serotonin toxicity-like behavior’ caused by various serotonergic agents. The 10 mg/L dose of the drug also significantly decreased top entries and maximal velocity and evoked overt ataxia, likely due to emerging non-specific toxic effects. Amitriptyline at 5 and 10 mg/L also dose-dependently increased serotonin turnover, but not noradrenaline levels, in zebrafish whole-brain samples. Overall, zebrafish high sensitivity to acute effects of amitriptyline can help improve our understanding of psychopharmacological profiles of this compound and the related CNS drugs, and contributes further to the development of aquatic experimental models of human toxidromes. © 2017 Elsevier Inc.
Author keywords:
Amitriptyline; Aquatic screening; Serotonin syndrome; Serotonin toxicity; Zebrafish
Index keywords:
нет данных
DOI:
10.1016/j.ntt.2017.04.002
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85019084876&doi=10.1016%2fj.ntt.2017.04.002&partnerID=40&md5=8046a97c06407cb89e3de50963d308f6
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Link https://www.scopus.com/inward/record.uri?eid=2-s2.0-85019084876&doi=10.1016%2fj.ntt.2017.04.002&partnerID=40&md5=8046a97c06407cb89e3de50963d308f6
Affiliations Ural Federal University, Ekaterinburg, Russian Federation; Institute of Translational Biomedicine (ITBM), St. Petersburg State University, St. Petersburg, Russian Federation; School of Pharmaceutical Sciences, Southwest University, Chongqing, China; Institutes of Chemical Technologies and Biological Sciences, Ural Federal University, Ekaterinburg, Russian Federation; Laboratory of Biological Psychiatry, ITBM, St. Petersburg State University, St. Petersburg, Russian Federation; ZENEREI Research Center, Slidell, LA, United States
Author Keywords Amitriptyline; Aquatic screening; Serotonin syndrome; Serotonin toxicity; Zebrafish
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Correspondence Address Kalueff, A.V.; School of Pharmaceutical Sciences, Southwest UniversityChina; email: avkalueff@gmail.com
Publisher Elsevier Inc.
CODEN NETEE
Language of Original Document English
Abbreviated Source Title Neurotoxicol. Teratol.
Source Scopus