In vivo potency and efficacy of the novel cathinone α-pyrrolidinopentiophenone and 3,4-methylenedioxypyrovalerone: self-administration and locomotor stimulation in male rats.
In vivo potency and efficacy of the novel cathinone α-pyrrolidinopentiophenone and 3,4-methylenedioxypyrovalerone: self-administration and locomotor stimulation in male rats.
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DOI：
10.1007/s00213-015-3944-8
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发表时间：
2015-08
影响因子：
3.4
通讯作者：
Taffe MA
中科院分区：
文献类型：
--
作者：
Aarde SM;Creehan KM;Vandewater SA;Dickerson TJ;Taffe MA
许多替代卡西酮药物已用于娱乐用途。这种多样性通常是对法律诉讼的回应； 3,4-亚甲基二氧基吡咯戊酮（MDPV；“浴盐”）在美国上市后，密切相关的药物 α-吡咯烷五苯酮（α-PVP；“flakka”）出现。直接比较 α-PVP 与 MDPV 的功效和效力。雄性 Wistar 大鼠组在固定比例 1 强化方案下接受静脉自我给药 (IVSA) α-PVP 或 MDPV 训练。检查另一组对非偶然施用 MDVP 或 α-PVP（1.0、5.6、10.0 mg/kg，腹腔注射）的运动和体温反应。获得 α-PVP（0.1 毫克/千克/输注）IVSA 导致药物摄入量低但一致，并且对药物配对杠杆具有出色的辨别力。固定比例 1 方案下的剂量替代（0.05-0.25 mg/kg/输注）已证实其效力与先前研究中的 MDPV 相似。与MDPV（0.05 mg/kg/输注）直接比较，接受α-PVP（0.05 mg/kg/输注）训练的大鼠对更多输注有反应，但在获得结束时表现出类似的药物杠杆歧视。然而，这些药物在渐进比例强化方案下的剂量反应（0.018-0.56 mg/kg/inf）功能反映了相同的功效和效力。腹膜内注射 1.0 mg/kg 后观察到对 MDPV 或 alpha-PVP 的峰值运动反应。剂量并持续约2小时。每种化合物的体温适度降低幅度相似（~0.75°C）。 MDPV 和 α-PVP 的效力和功效在多项检测中非常相似，预测 α-PVP 的滥用倾向将是显着的，并且与 MDPV 相似。
Numerous substituted cathinone drugs have appeared in recreational use. This variety is often a response to legal actions; the scheduling of 3,4-methylenedioxypyrovalerone (MDPV; “bath salts”) in the U.S.A. was followed by the appearance of the closely related drug α-pyrrolidinopentiophenone (alpha-PVP; “flakka”). To directly compare the efficacy and potency of alpha-PVP with that of MDPV. Groups of male Wistar rats were trained in the intravenous self-administration (IVSA) alpha-PVP or MDPV under a fixed-ratio 1 schedule of reinforcement. An additional group was examined for locomotor and body temperature responses to non-contingent administration of MDVP or alpha-PVP (1.0, 5.6, 10.0 mg/kg, i.p.). Acquisition of alpha-PVP (0.1 mg/kg/infusion) IVSA resulted in low, yet consistent drug intake and excellent discrimination for the drug-paired lever. Dose-substitution (0.05-0.25 mg/kg/infusion) under a fixed-ratio 1 schedule confirmed potency is similar to MDPV in prior studies. In direct comparison to MDPV (0.05 mg/kg/infusion), rats trained on alpha-PVP (0.05 mg/kg/infusion) responded for more infusions but demonstrated similar drug-lever discrimination by the end of acquisition. However, the dose-response (0.018-0.56 mg/kg/inf) functions of these drugs under a progressive-ratio schedule of reinforcement reflected identical efficacy and potency. Peak locomotor responses to MDPV or alpha-PVP were observed after the 1.0 mg/kg, i.p. dose and lasted ~2 hours. Modest body temperature decreases were of similar magnitude (~0.75°C) for each compound. The potency and efficacy of MDPV and alpha-PVP were very similar across multiple assays, predicting that the abuse liability of alpha-PVP will be significant and similar to that of MDPV.