1 Inserm, UMR-S 1144, Paris-Descartes and Paris-Diderot University, Paris, France.
2 Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome and IRCCS Santa Lucia Foundation, Rome, Italy.
J Psychopharmacol. 2019 Mar;33(3):392-405. doi: 10.1177/0269881118822151. Epub 2019 Jan 15.
The substantial increase in use of 3,4-methylenedioxypyrovalerone (MDPV), a popular recreational synthetic cathinone, has raised legitimate questions about its behavioral consequences and abuse liability.
The aim of this study was to study MDPV-induced neurobehavioral effects in the rat, using different paradigms traditionally developed to study drug-attributed addictive properties.
Different patterns of intraperitoneal 3 mg/kg MDPV administration were investigated. Consequences on rat horizontal locomotion and behavior of acute, intermittent (once daily dosing over 10 days), and binge (three-time daily dosing for 3 days) MDPV administration as well as challenge after 10 day MDPV withdrawal were studied. The dopamine receptor-D1 antagonist, SCH23390, was bilaterally infused in the nucleus accumbens to determine the role of D1-receptors in MDPV-related effects on the associative memory recall using the conditioned place preference paradigm. In addition, in a separate experience using western blot, we investigated the effects of chronic MDPV administration (four injections during 24 h) on ΔFosB expression in the nucleus accumbens, caudate putamen, and prefrontal cortex.
Acute MDPV administration increased stereotypies and open arm entries in the elevated plus maze while SCH23390 abolished MDPV-induced enhancing effects on memory consolidation. Intermittent MDPV administration resulted in sensitization of MDPV-induced locomotor effects and tolerance during the following challenge. With binge MDPV administration, locomotor activity was not altered despite tolerance onset after challenge. SCH23390 abolished MDPV-induced conditioned place preference. Chronic MDPV administration induced ΔFosB accumulation in the nucleus accumbens, caudate putamen, and prefrontal cortex.
Our findings clearly show that MDPV produces profound behavioral alterations mediated by the activation of the dopaminergic system similarly to other amphetamines.
3,4-亚甲二氧基吡咯戊酮（MDPV）的使用量大幅增加，这种流行的消遣性合成苯丙胺类兴奋剂引起了人们对其行为后果和滥用倾向的合理关注。
本研究旨在使用传统用于研究药物成瘾特性的方法，研究 MDPV 对大鼠的神经行为影响。
研究了不同模式的 3 毫克/千克 MDPV 腹腔内给药。研究了急性、间歇性（10 天每日一次给药）和 binge（3 天每日三次给药）MDPV 给药对大鼠水平运动和行为的影响，以及 10 天 MDPV 戒断后的挑战。双侧 Accumbens 核中多巴胺受体 D1 拮抗剂 SCH23390 的输注，以确定 D1 受体在 MDPV 相关效应在条件性位置偏好范式中对联想记忆回忆的作用。此外，在使用 Western blot 的单独经验中，我们研究了慢性 MDPV 给药（24 小时内 4 次注射）对 Accumbens、尾状核和前额叶皮层中 ΔFosB 表达的影响。
急性 MDPV 给药增加了高架十字迷宫中的刻板行为和开放臂进入次数，而 SCH23390 消除了 MDPV 对记忆巩固的增强作用。间歇性 MDPV 给药导致 MDPV 诱导的运动效应的敏化和随后的挑战中的耐受性。在 binge MDPV 给药中，尽管在挑战后出现了耐受性，但运动活动没有改变。SCH23390 消除了 MDPV 诱导的条件性位置偏好。慢性 MDPV 给药导致 Accumbens、尾状核和前额叶皮层中 ΔFosB 的积累。
我们的研究结果清楚地表明，MDPV 通过激活多巴胺能系统产生深刻的行为改变，类似于其他安非他命类药物。
