Locomotor and reinforcing effects of pentedrone, pentylone and methylone in rats
Locomotor and reinforcing effects of pentedrone, pentylone and methylone in rats
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DOI：
10.1016/j.neuropharm.2017.09.002
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发表时间：
2018-05-15
影响因子：
4.7
通讯作者：
Taffe, Michael A.
中科院分区：
文献类型：
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作者：
Javadi-Paydar, Mehrak;Nguyen, Jacques D.;Taffe, Michael A.
可供使用者使用的合成卡西酮精神兴奋剂药物种类繁多，使了解健康风险的研究工作复杂化。第二代卡西酮喷替酮和戊酮通过3，4-亚甲二氧基结构基序（其将甲基苯丙胺与3，4-亚甲二氧基甲基苯丙胺区分开）彼此区分开，并且各自并入了包含在转运蛋白抑制剂卡西酮（3，4-亚甲二氧基吡咯戊酮（MDPV）、α-吡咯烷并苯甲酮（alpha-PVP））中但不包含在单胺释放剂（甲氧麻黄酮、甲酮）中的α-烷基链基序。在雄性和雌性Wistar大鼠中进行研究，使用植入式无线电遥测系统比较喷替酮、戊酮和甲酮的运动和体温调节作用。在接受过静脉内自我给药（IVSA）程序培训的雌性Wistar大鼠中评估了强化效应，并在固定比率1反应应急下进行了剂量替代（0.025-0.3 m/g/kg/inf）。将喷替酮、戊酮和甲酮的剂量-效应曲线与α-PVP和α-吡咯并己酮（α-PHP）的剂量-效应曲线进行对比。雄性和雌性大鼠腹腔注射戊酮（0.5-10.0 mg/kg）、喷替雄酮（0.5 - 10.0 mg/kg）或甲氧麻黄酮（0.5-10.0 mg/kg）后，观察到运动的剂量依赖性增加。最大运动效应在药物之间相似，但在喷替酮后持续时间最长。在喷替雄酮或戊酮给药后，两种性别的平均体温系统性变化均不超过0.5 ℃。在雄性大鼠中，在10.0 mg/kg甲基酮后观察到持续的体温过高（0.4-0.8 ℃）4小时。与甲酮相比，更多的喷替酮或戊酮输注是自我给药的，但这三种药物的效力都低于α-PVP或α-PHP。这些研究支持第二代卡西酮、戊酮和喷替酮的滥用倾向大于甲酮的推断。本文是题为“设计师药物和法律的高”特刊的一部分。'
The broad diversity of synthetic cathinone psychostimulant drugs that are available to users complicates research efforts to provide understanding of health risks. Second generation cathinones pentedrone and pentylone are distinguished from each other by the 3,4-methylenedioxy structural motif (which distinguishes methamphetamine from 3,4-methylenedioxymethamphetamine) and each incorporates the a-alkyl chain motif contained in the transporter-inhibitor cathinones (3,4-methylenedioxypyrovalerone (MDPV), alpha-pyrrolidinopentiophenone (alpha-PVP)) but not in the monoamine releasers (mephedrone, methylone). Studies were conducted in male and female Wistar rats to compare locomotor and thermoregulatory effects of pentedrone, pentylone and methylone using an implanted radiotelemetry system. Reinforcing effects were assessed in female Wistar rats trained in the intravenous selfadministration (IVSA) procedure and subjected to dose-substitution (0.025-0.3 m/gkg/inf) under a fixed-ratio 1 response contingency. Pentedrone, pentylone and methylone dose-effect curves were contrasted with those for alpha-PVP and alpha-pyrrohdmohexiophenone (alpha-PHP). Dose dependent increases in locomotion were observed after intraperitoneal injection of pentylone (0.5-10.0 mg/kg), pentedrone (0.5 -10.0 mg/kg) or mephedrone (0.5-10.0 mg/kg) in male and female rats. The maximum locomotor effect was similar across drugs but lasted longest after pentedrone. Mean body temperature did not vary systematically more than 0.5 degrees C after pentedrone or pentylone in either sex. A sustained hyperthermia (0.4-0.8 degrees C) was observed for four hours after 10.0 mg/kg methylone in male rats. More infusions of pentedrone or pentylone were self-administered compared with methylone, but all three were less potent than alpha-PVP or alpha-PHP. These studies support the inference that second generation cathinones pentylone and pentedrone have abuse liability greater than that of methylone.This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'