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 remain poorly understood. The zebrafish (Danio rerio) is rapidly becoming a popular aquatic model organism for 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 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. Collectively, these findings emphasize a complex dose- and treatment-dependent CNS profile 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 CNS effects evoked by novel synthetic opioid drugs.
|Журнал||Brain Research Bulletin|
|Состояние||Электронная публикация перед печатью - 26 ноя 2020|