Concentrations of MDPV in rat striatum correlate with the psychostimulant effect
Concentrations of MDPV in rat striatum correlate with the psychostimulant effect
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DOI：
10.1177/0269881115598415
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发表时间：
2015-11-01
影响因子：
4.1
通讯作者：
Escubedo, Elena
中科院分区：
文献类型：
--
作者：
Novellas, Judith;Lopez-Arnau, Raul;Escubedo, Elena
3，4-亚甲基二氧基吡喃丙酮或MDPV是一种合成的卡西酮，具有比可卡因更强的精神刺激特性。我们在给大鼠皮下给药后，对纹状体中的这种药物进行了量化。MDPV在给药后5分钟左右到达大脑，在20-25分钟后达到高峰。纹状体的消除半衰期(61分钟)与60分钟后精神刺激效应的降低有关。大约11%的给药剂量到达纹状体，考虑到均匀的脑分布，我们确定大约86%的血浆MDPV分布到大脑。MDPV诱导剂量依赖性的运动活动、饲养行为和刻板印象的增加，所有这些都被氟哌啶醇所阻止。随着时间的推移，运动活动或刻板印象与MDPV纹状体浓度之间的曲线图显示了因素之间的直接关系。在血浆中任何时候都没有检测到游离的MDPV代谢物，但用葡萄糖醛酸苷酶水解可以主要鉴定出三种代谢物，其中一种是首次在大鼠血浆中检测到的。目前的结果有助于证明MDPV主要通过多巴胺依赖的机制诱导多动。MDPV的行为效应和纹状体水平之间的良好相关性使我们得出结论，它的精神刺激作用主要是由于该物质在纹状体的分布。本研究提供了有关MDPV药代动力学的有用信息，并有助于利用动力学数据设计新的实验，以及更好地了解MDPV对人类的影响及其潜在的相互作用。
3,4-methylenedioxypyrovalerone or MDPV is a synthetic cathinone with psychostimulant properties more potent than cocaine. We quantified this drug in the striatum after subcutaneous administration to rats. MDPV reached the brain around 5 min after its administration and peaked at 20-25 min later. The elimination half-life in the striatum (61 min) correlates with the decrease in the psychostimulant effect after 60 min. Around 11% of the administered dose reached the striatum and, considering a homogeneous brain distribution, we determined that around 86% of the plasma MDPV is distributed to the brain. MDPV induced a dose-dependent increase in locomotor activity, rearing behaviour and stereotypies, all prevented by haloperidol. A plot of locomotor activity or stereotypies versus MDPV striatal concentrations over time showed a direct relationship between factors. No free MDPV metabolites were detected in plasma, at any time, but hydrolysis with glucuronidase allowed us to identify mainly three metabolites, one of them for the first time in rat plasma. The present results contribute to evidence that MDPV induces hyperlocomotion mainly through a dopamine-dependent mechanism. Good correlation between behavioural effects and striatal levels of MDPV leads us to conclude that its psychostimulant effect is mainly due to a striatal distribution of the substance. The present research provides useful information on the pharmacokinetics of MDPV, and can help design new experiments with kinetics data as well as provide a better understanding of the effects of MDPV in humans and its potential interactions.