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Synthetic Cathinones and Their Rewarding and Reinforcing Effects in Rodents

机译:合成卡他酮及其在啮齿动物中的奖励和补强作用

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Synthetic cathinones, colloquially referred to as “bath salts,” are derivatives of the psychoactive alkaloid cathinone found inCatha edulis(Khat). Since the mid-to-late 2000s, these amphetamine-like psychostimulants have gained popularity amongst drug users due to their potency, low cost, ease of procurement, and constantly evolving chemical structures. Concomitant with their increased use is the emergence of a growing collection of case reports of bizarre and dangerous behaviors, toxicity to numerous organ systems, and death. However, scientific information regarding the abuse liability of these drugs has been relatively slower to materialize. Recently we have published several studies demonstrating that laboratory rodents will readily self-administer the “first generation” synthetic cathinones methylenedioxypyrovalerone (MDPV) and methylone via the intravenous route, in patterns similar to those of methamphetamine. Under progressive ratio schedules of reinforcement, the rank order of reinforcing efficacy of these compounds is MDPV ≥ methamphetamine > methylone. MDPV and methylone, as well as the “second generation” synthetic cathinonesα-pyrrolidinovalerophenone (α-PVP) and 4-methylethcathinone (4-MEC), also dose-dependently increase brain reward function. Collectively, these findings indicate that synthetic cathinones have a high abuse and addiction potential and underscore the need for future assessment of the extent and duration of neurotoxicity induced by these emerging drugs of abuse.
机译:合成的卡西酮,俗称“沐浴盐”,是可食的Catha edulis(Khat)中的精神活性生物碱卡西酮的衍生物。自2000年代中后期以来,这些类苯丙胺类兴奋剂因其效价高,成本低,易于购买以及化学结构不断发展而在吸毒者中广受欢迎。随着使用量的增加,出现了越来越多的有关奇异和危险行为,对许多器官系统的毒性以及死亡的病例报告。但是,有关这些药物滥用责任的科学信息的实现相对较慢。最近,我们发表了几项研究,证明实验室啮齿动物可以通过静脉内途径以与甲基苯丙胺相似的方式轻易地自行施用“第一代”合成卡西酮亚甲基二氧基吡咯烷酮(MDPV)和甲酮。在增强的逐步配比方案下,这些化合物的增强功效的等级顺序为MDPV≥甲基苯丙胺>甲酮。 MDPV和甲酮,以及“第二代”人工合成的卡西酮α-吡咯烷基戊二苯甲酮(α-PVP)和4-甲基乙卡西酮(4-MEC)也剂量依赖性地增加了大脑的奖励功能。总的来说,这些发现表明合成的卡西酮具有很高的滥用和成瘾潜力,并强调了今后需要评估这些新兴滥用药物引起的神经毒性的程度和持续时间。

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