Center for Drug Discovery, RTI International, 3040 Cornwallis Rd, Research Triangle Park, NC 27709, USA.
Center for Drug Discovery, RTI International, 3040 Cornwallis Rd, Research Triangle Park, NC 27709, USA.
Behav Brain Res. 2019 Dec 30;376:112211. doi: 10.1016/j.bbr.2019.112211. Epub 2019 Sep 4.
Synthetic cathinones are used for their stimulant-like properties. Stimulant-induced neurochemical changes are thought to occur at different times in different brain regions and neurotransmitter systems. This study sought to examine the behavioral and neurochemical effects of α-pyrrolidinopentiophenone (α-PVP) and mephedrone (4MMC) in female rats. Methods probed the chronology of effects of synthetic cathinone exposure. Female rats were trained to self-administer α-PVP, 4MMC, or saline. Drug exposure ceased after 7 days of autoshaping for half of each drug group; the other half self-administered for another 21 days. Amygdala, hippocampus, hypothalamus, PFC, striatum, and thalamus were extracted, and tissue was analyzed with electrochemical detection and liquid chromatography mass spectrometry. Responding was minimal during autoshaping; thus, most infusions were delivered noncontingently in the autoshaping phase. Rats acquired self-administration of α-PVP and 4MMC. Synthetic cathinone administration, and duration of exposure produced several effects on neurotransmitters. α-PVP primarily increased serotonin, 5-hydroxy-3-acetic acid (5-HIAA), norepinephrine, and glutamate in hypothalamus. In contrast, 4MMC decreased serotonin and 5-HIAA in several brain regions. Longer durations of exposure to both synthetic cathinones increased 5-HIAA, norepinephrine, and glutamate in multiple brain regions compared to the short exposure during autoshaping. Notably, both α-PVP and 4MMC produced minimal changes in dopamine levels, suggesting that the dopaminergic effects of these synthetic cathinones are transient. These alterations in neurotransmitter levels indicate that synthetic cathinone use may produce differential neurochemical changes during the transition from use to abuse.
合成卡西酮因其刺激作用而被使用。刺激诱导的神经化学变化被认为在不同的脑区和神经递质系统中发生在不同的时间。本研究旨在检测 α-吡咯戊基苯酮（α-PVP）和 4-甲基甲卡西酮（4MMC）在雌性大鼠中的行为和神经化学效应。方法探究了合成卡西酮暴露的效应的时间顺序。雌性大鼠被训练进行 α-PVP、4MMC 或盐水的自我给药。每组药物的一半在自我成型 7 天后停止药物暴露；另一半再自我给药 21 天。提取杏仁核、海马、下丘脑、PFC、纹状体和丘脑，并用电化学检测和液相色谱质谱法对组织进行分析。在自我成型阶段，反应很少；因此，大多数输注是非条件性的。大鼠获得了对 α-PVP 和 4MMC 的自我给药。合成卡西酮的给药和暴露时间对神经递质产生了多种影响。α-PVP 主要增加下丘脑的 5-羟色胺、5-羟乙酸（5-HIAA）、去甲肾上腺素和谷氨酸。相比之下，4MMC 减少了几个脑区的 5-羟色胺和 5-HIAA。与自我成型期间的短暴露相比，较长时间的暴露于两种合成卡西酮都会增加多个脑区的 5-HIAA、去甲肾上腺素和谷氨酸。值得注意的是，α-PVP 和 4MMC 对多巴胺水平的影响都很小，这表明这些合成卡西酮的多巴胺效应是短暂的。这些神经递质水平的变化表明，合成卡西酮的使用可能在从使用到滥用的转变过程中产生不同的神经化学变化。
