Department of Pharmacodynamics, Medical University of Łódź, Łódź, Poland.
Central Scientific Laboratory, Medical University of Łódź, Łódź, Poland.
Pharmacol Rep. 2019 Dec;71(6):977-982. doi: 10.1016/j.pharep.2019.05.011. Epub 2019 May 19.
Synthetic cathinones (SCs) form one of the most prominent group of the New Psychoactive Substances. SCs enhance central dopaminergic and noradrenergic neurotransmission, and are used as substitutes for illicit psychostimulants, namely cocaine, amphetamine, and methamphetamine. Changes in the expression of immediate early genes (IEGs) in the striatum underlie the addictive potential of drugs of abuse belonging to distinct pharmacologic groups. This work was aimed to assess the impact of acute administration of the prominent SCs on the mRNA levels of IEGs in the mouse striatum.
Effects of 3,4-MDPV, 2,3-MDPV, α-PVP, PV8, PV9, methcathinone (MC) and 3-fluoromethcathinone (3-FMC) on the mRNA levels of ten IEGs, one and two hours after exposure, were measured in the mouse striatum using the quantitative RT-PCR technique.
All SCs used in the study produced increased mRNA levels of the following IEGs: Areg, c-fos, Csrnp1, Dusp1, Dusp14, Egr2, Egr4 and FosB. Additionally, the majority of SCs increased the expression of Homer1 and c-jun. The magnitude of observed changes varied by the drug, analyzed gene and, in many cases, by time after administration.
This study demonstrates that SCs increase the expression of IEGs in the mouse striatum, which may lead to a plethora of effects, as proteins encoded by the analyzed genes are involved in diverse actions, including an acute response to the drug and the neuroplasticity underlying the development of addiction.
合成卡西酮（SCs）构成了最突出的一类新型精神活性物质。SCs 增强了中枢多巴胺能和去甲肾上腺素能神经传递，被用作非法兴奋剂（如可卡因、安非他命和甲基苯丙胺）的替代品。纹状体中即刻早期基因（IEGs）表达的变化是具有不同药理作用的滥用药物成瘾潜力的基础。这项工作旨在评估急性给予突出的 SCs 对小鼠纹状体中 IEGs mRNA 水平的影响。
使用定量 RT-PCR 技术，在暴露后 1 小时和 2 小时，测量 3,4-MDPV、2,3-MDPV、α-PVP、PV8、PV9、甲卡西酮（MC）和 3-氟甲卡西酮（3-FMC）对十种 IEGs mRNA 水平的影响。
研究中使用的所有 SCs 均增加了以下 IEGs 的 mRNA 水平：Areg、c-fos、Csrnp1、Dusp1、Dusp14、Egr2、Egr4 和 FosB。此外，大多数 SCs 增加了 Homer1 和 c-jun 的表达。观察到的变化幅度因药物、分析基因以及给药后许多情况下的时间而异。
这项研究表明，SCs 增加了小鼠纹状体中 IEGs 的表达，这可能导致多种效应，因为分析基因编码的蛋白质参与了多种作用，包括对药物的急性反应和成瘾发展的神经可塑性。
