Li Feng, Du Han, Wu Bo, Wei Jiayun, Qiao Yanling, Lai Miaojun, Zhou Wenhua, Shen Haowei, Wang Youmei, Xu Peng, Di Bin
School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Beijing, China.
Addict Biol. 2022 May;27(3):e13171. doi: 10.1111/adb.13171.
2-Fluorodeschloroketamine (2-FDCK) as a substitute for ketamine has emerged among drug abusers in recent years. However, 2-FDCK has not been controlled or regulated in many countries, which may be partly related to the lack of evidence on its abuse potential. In this study, we evaluated the abuse potential of 2-FDCK via the tests of the conditioned place preference (CPP), locomotor sensitization, drug self-administration and drug discrimination using ketamine as a reference. 2-FDCK induced significant CPP at a minimum dose of 3 mg/kg in mice, an effect comparable with that of ketamine (3 mg/kg). Acute injections of 2-FDCK or ketamine at 30 mg/kg enhanced locomotor activity. Repeated treatments with this dose of 2-FDCK and ketamine induced locomotor sensitization after withdrawal. 2-FDCK readily induced self-administration with 0.5 mg/kg/infusion, the same dose for ketamine, and induced the highest seeking response at 1 mg/kg. Drug discrimination test showed that 2-FDCK dose-dependently substitute for ketamine with comparable ED to ketamine in substitution testing. Taken together, these results strongly suggested that 2-FDCK has an abuse potential comparable with ketamine.
2-氟去氯胺酮（2-FDCK）作为氯胺酮的替代品近年来在药物滥用者中出现。然而，2-FDCK在许多国家尚未受到管控，这可能部分与缺乏关于其滥用潜力的证据有关。在本研究中，我们以氯胺酮作为参照，通过条件性位置偏爱（CPP）、运动敏化、药物自我给药和药物辨别试验评估了2-FDCK的滥用潜力。2-FDCK在小鼠中最低剂量为3毫克/千克时可诱导显著的CPP，这一效应与氯胺酮（3毫克/千克）相当。以30毫克/千克急性注射2-FDCK或氯胺酮可增强运动活性。用该剂量的2-FDCK和氯胺酮重复给药后停药可诱导运动敏化。2-FDCK以0.5毫克/千克/输注的剂量很容易诱导自我给药，这与氯胺酮的剂量相同，并且在1毫克/千克时诱导出最高的觅药反应。药物辨别试验表明，在替代试验中，2-FDCK以与氯胺酮相当的半数有效剂量（ED）剂量依赖性地替代氯胺酮。综上所述，这些结果强烈表明2-FDCK具有与氯胺酮相当的滥用潜力。
