Gatch Michael B, Dolan Sean B, Forster Michael J
Center for Neuroscience Discovery, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107-2699, USA.
Psychopharmacology (Berl). 2017 Apr;234(8):1237-1245. doi: 10.1007/s00213-017-4562-4. Epub 2017 Feb 16.
Recent years have seen an increase in the recreational use of novel, synthetic psychoactive substances. There are little or no data on the abuse liability of many of the newer compounds.
The current study investigated the discriminative stimulus and locomotor effects of a series of synthetic analogs of cathinone: α-pyrrolidinopropiophenone (α-PPP), α-pyrrolidinohexiophenone (α-PHP), α-pyrrolidinopentiothiophenone (α-PVT), 3,4-methylenedioxybutiophenone (MDPBP), and ethylone.
Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine or methamphetamine from vehicle.
Each of the compounds produced an inverted-U dose-effect on locomotor activity. Maximal effects were similar among the test compounds, but potencies varied with relative potencies of MDPBP > α-PPP = α-PHP > ethylone > α-PVT. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine. α-PPP, α-PHP, and ethylone fully substituted for cocaine. α-PVT produced a maximum of 50% cocaine-appropriate responding, and MDPBP produced an inverted-U-shaped dose-effect curve with maximum effects of 67%.
These data provide initial evidence that these structurally similar, emerging novel psychoactive substances demonstrate potential for abuse and may be utilized for their stimulant-like effects, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of the classical psychostimulants cocaine and/or methamphetamine.
近年来,新型合成精神活性物质的娱乐性使用有所增加。关于许多较新化合物的滥用可能性,几乎没有数据。
本研究调查了一系列卡西酮合成类似物的辨别刺激和运动效应:α-吡咯烷丙苯酮(α-PPP)、α-吡咯烷己苯酮(α-PHP)、α-吡咯烷戊硫苯酮(α-PVT)、3,4-亚甲基二氧丁苯酮(MDPBP)和乙酮。
使用瑞士韦伯斯特小鼠在旷场试验中评估运动活性。在训练用于区分可卡因或甲基苯丙胺与赋形剂的斯普拉格-道利大鼠中评估辨别刺激效应。
每种化合物对运动活性均产生倒U型剂量效应。测试化合物之间的最大效应相似,但效力有所不同,相对效力为MDPBP > α-PPP = α-PHP > 乙酮 > α-PVT。每种测试化合物都能完全替代甲基苯丙胺的辨别刺激效应。α-PPP、α-PHP和乙酮能完全替代可卡因。α-PVT产生的可卡因样反应最多为50%,MDPBP产生倒U型剂量效应曲线,最大效应为67%。
这些数据提供了初步证据,表明这些结构相似的新型精神活性物质具有滥用潜力,鉴于它们能够刺激运动活性并替代经典精神兴奋剂可卡因和/或甲基苯丙胺的辨别刺激效应,可能因其类似兴奋剂的作用而被使用。