Synthetic cathinones and their rewarding and reinforcing effects in rodents.

Lucas R Watterson, M Foster Olive
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Abstract

Synthetic cathinones, colloquially referred to as "bath salts", are derivatives of the psychoactive alkaloid cathinone found in Catha edulis (Khat). Since the mid-to-late 2000's, 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 are MDPV ≥ methamphetamine > methylone. MDPV and methylone, as well as the "second generation" synthetic cathinones α-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.

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合成卡西酮及其对啮齿动物的奖赏和强化作用。
合成卡西酮,俗称 "浴盐",是在卡塔叶(Catha edulis)中发现的精神活性生物碱卡西酮的衍生物。自 2000 年代中后期以来,这些类似苯丙胺的精神兴奋剂因其药效强、成本低、易于购买和化学结构不断变化而在吸毒者中流行起来。随着其使用量的增加,关于其怪异和危险行为、对多个器官系统的毒性以及死亡的病例报告也越来越多。然而,有关这些药物滥用责任的科学信息却相对较少。最近,我们发表了几项研究,证明实验室啮齿类动物很容易通过静脉注射途径自行吸食 "第一代 "合成卡西酮类药物亚甲二氧基吡咯戊酮(MDPV)和甲酮,其模式与甲基苯丙胺类似。在累进比率强化计划下,这两种化合物的强化效果依次为 MDPV ≥ 甲基苯丙胺 > 甲酮。MDPV和甲酮,以及 "第二代 "合成卡西酮α-吡咯烷戊酮(α-PVP)和4-甲基乙卡西酮(4-MEC),也能按剂量增加大脑奖赏功能。总之,这些研究结果表明,合成卡西酮类药物具有很高的滥用和成瘾潜力,并强调今后有必要对这些新出现的滥用药物诱发神经毒性的程度和持续时间进行评估。
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Synthetic cathinones and their rewarding and reinforcing effects in rodents. Developing Attention: Behavioral and Brain Mechanisms.
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