Research Center for Convergence Toxicology, Korea Institute of Toxicology, Daejeon, South Korea.
Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, Seoul, South Korea.
Addict Biol. 2020 Nov;25(6):e12846. doi: 10.1111/adb.12846. Epub 2019 Dec 4.
3-fluoromethamphetamine (3-FMA), a derivative of methamphetamine (METH), produces behavioral impairment and deficits in dopaminergic transmission in the striatum of mice. The abuse potential of 3-FMA has not been fully characterized. The aim of this study was to evaluate the effects of 3-FMA on locomotor activity as well as its rewarding and reinforcing properties in the conditioned place preference (CPP) and self-administration procedures. Intravenous (i.v.) administration of 3-FMA (0.5 and 1.0 mg/kg) significantly increased locomotor activity in a dose-dependent manner in rats. In the CPP procedure, intraperitoneal administration of 3-FMA (10 and 30 mg/kg) produced a significant alteration in place preference in mice. In the self-administration paradigms, 3-FMA showed drug-taking behavior at the dose of 0.1 mg/kg/infusion (i.v.) during 2 hr sessions under fixed ratio schedules and high breakpoints at the dose of 0.3 and 1.0 mg/kg/infusion (i.v.) during 6 hr sessions under progressive ratio schedule of reinforcement in rats. A priming injection of 3-FMA (0.4 mg/kg, i.v.), METH (0.2 mg/kg, i.v.), or cocaine (2.0 mg/kg, i.v.) reinstated 3-FMA-seeking behavior after an extinction period in 3-FMA-trained rats during 2 hr session. Taken together, these findings demonstrate robust psychomotor, rewarding and reinforcing properties of 3-FMA, which may underlie its potential for compulsive use in humans.
3-氟甲基苯丙胺(3-FMA)是苯丙胺(METH)的衍生物,可导致小鼠纹状体的行为障碍和多巴胺能传递缺陷。3-FMA 的滥用潜力尚未得到充分描述。本研究旨在评估 3-FMA 对运动活动的影响及其在条件性位置偏好(CPP)和自我给药程序中的奖赏和强化特性。静脉内(i.v.)给予 3-FMA(0.5 和 1.0 mg/kg)可显著增加大鼠的运动活动,呈剂量依赖性。在 CPP 程序中,腹腔内给予 3-FMA(10 和 30 mg/kg)可导致小鼠位置偏好发生显著改变。在自我给药范式中,3-FMA 在固定比率方案下以 0.1 mg/kg/剂量(i.v.)给药时表现出药物摄取行为,在强化递增比率方案下以 0.3 和 1.0 mg/kg/剂量(i.v.)给药时表现出高突破点在 6 小时会议中在大鼠中。3-FMA(0.4 mg/kg,i.v.)、METH(0.2 mg/kg,i.v.)或可卡因(2.0 mg/kg,i.v.)的引发注射在 3-FMA 训练大鼠的 2 小时会议期间在消退期后重新引发 3-FMA 寻求行为。总之,这些发现表明 3-FMA 具有强大的精神运动、奖赏和强化特性,这可能是其在人类中具有强迫性使用潜力的基础。