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.

3,4-二氯-N- [2-(二甲氨基)环己基] -N-甲基苯甲酰胺 (U-47700) 是一种选择性 μ-阿片受体激动剂，最初是作为一种前瞻性镇痛药物合成的。U-47700 的效力是吗啡的数倍，具有很高的滥用潜力，可能会导致临床神经毒性、欣快感、呼吸抑制和偶尔的死亡。U-47700 还会在人类和啮齿动物中引起镇痛、镇静和类似欣快的状态。尽管 U-47700 的使用和滥用越来越多，但其体内精神药理学和毒理学特征仍知之甚少。斑马鱼 ( Danio rerio) 正在迅速成为用于中枢神经系统 (CNS) 疾病建模和药物发现的流行水生模型生物。在这里，我们检查了 U-47700 对成年斑马鱼的急性（1、5、10、25 和 50 毫克/升，持续 20 分钟）和慢性（0.1、0.5 和 1 毫克/升，持续 14 天）的影响。总体而言，我们发现由急性引起的鱼明显镇静，以及由慢性药物治疗引起的具有抗焦虑样作用的过度运动。用 1 和 10 毫克/升 U-47700 进行急性治疗也导致大脑样本中可检测到这种药物，支持其通过血脑屏障的渗透性。总的来说，这些发现强调了 U-47700 在急性和慢性给药后的复杂的剂量和治疗依赖性 CNS 效应。我们的研究还支持斑马鱼对 U-47700 的高敏感性，