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

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.

Keywords

zebrafish / U-49900 / synthetic opioids / behavior / sedative effect

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