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3-氟甲基苯丙胺在啮齿类动物中具有强烈的精神运动、奖励和强化作用。

The potent psychomotor, rewarding and reinforcing properties of 3-fluoromethamphetamine in rodents.

机构信息

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.

出版信息

Addict Biol. 2020 Nov;25(6):e12846. doi: 10.1111/adb.12846. Epub 2019 Dec 4.

DOI:10.1111/adb.12846
PMID:31797481
Abstract

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.

摘要

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。

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