Individual Differences in the Relative Reinforcing Effects of 3,4-Methylenedioxypyrovalerone under Fixed and Progressive Ratio Schedules of Reinforcement in Rats
Individual Differences in the Relative Reinforcing Effects of 3,4-Methylenedioxypyrovalerone under Fixed and Progressive Ratio Schedules of Reinforcement in Rats
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DOI：
10.1124/jpet.116.239376
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发表时间：
2017-04-01
影响因子：
3.5
通讯作者：
Collins, Gregory T.
中科院分区：
文献类型：
--
作者：
Gannon, Brenda M.;Galindo, Kayla I.;Collins, Gregory T.
娱乐使用特制毒品，包括合成卡西诺酮(浴盐)，与高度滥用和毒性有关，并对公众健康构成日益严重的威胁。3，4-亚甲基二氧基吡喃丙酮(MDPV)是一种类似可卡因的单胺摄取抑制剂，也是应用最广泛和滥用最多的合成卡西酮之一。本研究使用雄性SD大鼠直接比较：(1)固定比率(FR)1强化计划下对MDPV和可卡因的反应获得；(2)FR5计划下MDPV和可卡因的全量-反应曲线；(3)累进比率(PR)强化计划。MDPV和可卡因的自身给药以类似的速度获得，并且由类似百分比的大鼠获得。与可卡因相比，MDPV在维持应答(PR；最终比率完成)方面的效力类似于10倍，类似于3倍。与可卡因不同的是，在大鼠中观察到的可卡因几乎没有变异性，相对于其他有相同病史的大鼠(低应答者)，MDPV的FR5剂量-反应曲线相对于其他有相同病史的大鼠(低应答者)，在一组大鼠(高反应者)中类似地向上移动了3倍。与低反应性大鼠相比，高反应性大鼠在FR5计划下也自我注射更多的可卡因，在公关强化计划下获得显著更多的MDPV、可卡因和甲基苯丙胺。除了作为一种明显比可卡因或甲基苯丙胺更有效的增强剂外，MDPV在大鼠身上建立持久表型的能力似乎也是独一无二的，其特征是异常高的药物摄入量。尽管这种高反应性表型背后的因素尚不清楚，但它们可能与人类吸毒行为的个体差异有关。
The recreational use of designer drugs, including synthetic cathinones (bath salts), is associated with high levels of abuse and toxicity, and represents a growing threat to public health. 3,4-Methylenedioxypyrovalerone (MDPV) is a cocaine-like monoamine uptake inhibitor, and one of the most widely available and abused synthetic cathinones. The present study used male Sprague-Dawley rats to directly compare: (1) the acquisition of responding for MDPV and cocaine under a fixed ratio (FR) 1 schedule of reinforcement; (2) full dose-response curves for MDPV and cocaine under a FR5 schedule; and (3) progressive ratio (PR) schedules of reinforcement. Selfadministration of MDPV and cocaine was acquired at comparable rates, and by a similar percentage of rats. Compared with cocaine, MDPV was similar to 10-fold more potent and similar to 3-fold more effective at maintaining responding (PR; final ratio completed). Unlike cocaine, for which little variability was observed among rats, the FR5 dose-response curve for MDPV was shifted similar to 3-fold upward for a subset of rats (high-responders) relative to other rats with identical histories (low-responders). Compared with low-responding rats, high responders also self-administered more cocaine under the FR5 schedule, and earned significantly more MDPV, cocaine, and methamphetamine under a PR schedule of reinforcement. In addition to functioning as a significantly more effective reinforcer than either cocaine or methamphetamine, MDPV also appears to be unique in its capacity to establish an enduring phenotype in rats, characterized by unusually high levels of drug intake. Although the factors underlying this high-responder phenotype are unclear, they might be related to individual differences in human drug-taking behavior.