Psychopharmacological characterization of an emerging drug of abuse, a synthetic opioid U-47700, in adult zebrafish.

Autor: Kolesnikova TO; Ural Federal University, Ekaterinburg, Russia; Institute of Experimental Medicine, Almazov National Medical Research Center, Ministry of Healthcare of Russian Federation, St. Petersburg, Russia; Laboratory of Biological Psychiatry, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia., Shevyrin VA; Ural Federal University, Ekaterinburg, Russia., Eltsov OS; Ural Federal University, Ekaterinburg, Russia., Khatsko SL; Ural Federal University, Ekaterinburg, Russia., Demin KA; Institute of Experimental Medicine, Almazov National Medical Research Center, Ministry of Healthcare of Russian Federation, St. Petersburg, Russia; Laboratory of Biological Psychiatry, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia., Galstyan DS; Granov Scientific Research Center of Radiology and Surgical Technologies, Ministry of Healthcare of Russian Federation, St. Petersburg, Russia., de Abreu MS; Bioscience Institute, University of Passo Fundo, Passo Fundo, Brazil; Laboratory of Cell and Molecular Biology and Neurobiology, Moscow Institute of Physics and Technology, Dolgoprudny, Russia., Kalueff AV; School of Pharmacy, Southwest University, Chongqing, China; Laboratory of Petrochemistry, Ural Federal University, Ekaterinburg, Russia. Electronic address: avkalueff@gmail.com.
Jazyk: angličtina
Zdroj: Brain research bulletin [Brain Res Bull] 2021 Feb; Vol. 167, pp. 48-55. Date of Electronic Publication: 2020 Nov 26.
DOI: 10.1016/j.brainresbull.2020.11.017
Abstrakt: 3,4-Dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) is a selective μ-opioid receptor agonist originally synthesized as a prospective analgesic drug. Several times more potent than morphine, U-47700 has high abuse potential and may cause clinical neurotoxicity, euphoria, respiratory depression and occasional mortality. U-47700 also evokes analgesia, sedation and euphoria-like states in both humans and rodents. Despite the growing use and abuse of U-47700, its psychopharmacological and toxicological profiles in vivo remain poorly understood. The zebrafish (Danio rerio) is rapidly becoming a popular aquatic model organism for central nervous system (CNS) disease modeling and drug discovery. Here, we examine acute (1, 5, 10, 25 and 50 mg/L for 20-min) and chronic (0.1, 0.5 and 1 mg/L for 14 days) effects of U-47700 in adult zebrafish. Overall, we found overt sedation evoked in fish by acute, and hyperlocomotion with an anxiolytic-like action by chronic, drug treatments. Acute treatment with 1 and 10 mg/L U-47700 also resulted in detectable amounts of this drug in the brain samples, supporting its permeability through the blood-brain barrier. Collectively, these findings emphasize complex dose- and treatment-dependent CNS effects of U-47700 following its acute and chronic administration. Our study also supports high sensitivity of zebrafish to U-47700, and suggests these aquatic models as promising in-vivo screens for probing potential CNS effects evoked by novel synthetic opioid drugs.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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