Sedative effect of U-49900 (3,4-dichloro-N- (2-(diethylamino)cyclohexyl)-N-methyl-benzamide) in adult Zebrafish

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Abstract

BACKGROUND: U-49900 is a chemical analog of U-47700. Despite the growing abuse of synthetic opioids, including U-49900, its psychopharmacological and toxicological profiles remain poorly understood. The zebrafish (Danio rerio) is a promising model organism in neuroscience often used for the psychopharmacological evaluation of neurotropic drugs. OBJECTIVE: To evaluate the effects of U-49900 on the behavior of adult zebrafish in a new tank. MATERIALS AND METHODS: The effect of the test compound U-49900 at 1, 5, 10, and 25 mg/L concentrations (incubation for 20 minutes) on the behavior of adult zebrafish was assessed using the “new aquarium” test. U-49900 is 3.4-dichloro-N-(2-(diethylamino)cyclohexyl)-N-methylbenzamide and is considered an analog of the synthetic opioid U-47700, causing withdrawal in humans. RESULTS: The psychopharmacological profile of U-49900 at 1, 5, 10, and 25 mg/l concentrations (water immersion) in adult zebrafish was evaluated with the novel tank test. U-49900 at 25 mg/l for 20 min reduced the distance traveled and number of top entries in the novel tank test (p < 0.001 vs. control group), but unaltered other parameters. CONCLUSIONS: Overall, the sensitivity of zebrafish to synthetic non-fentanyl opioids such as U-49900 indicates the possibility of developing high-throughput screening platforms for finding effective therapies for pathological conditions caused by synthetic opioids.

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T. O. Kolesnikova

Sirius University of Science and Technology; Ural Federal University

Email: Philimontani@yandex.ru
ORCID iD: 0000-0002-5561-8583
SPIN-code: 8558-7887
Russian Federation, Sirius; Yekaterinburg

V. A. Shevyrin

Ural Federal University

Email: vadim.shevyrin@gmail.com
ORCID iD: 0000-0002-0369-0786
SPIN-code: 5899-6920

Cand. Sci. (Biology)

Russian Federation, Yekaterinburg

S. L. Khatsko

Ural Federal University

Email: hardscore@mail.ru
ORCID iD: 0000-0001-5921-6680
SPIN-code: 4973-7083
Russian Federation, Yekaterinburg

A. V. Kalueff

Sirius University of Science and Technology; Almazov National Medical Research Center

Author for correspondence.
Email: avkalueff@gmail.com
ORCID iD: 0000-0002-7525-1950
SPIN-code: 4134-0515

Dr. Sci. (Biology)

Russian Federation, 354340, Krasnodar Region, Sirius Federal Territory, Olimpiisky prospect, 1; Saint Petersburg

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