Escalation of intravenous self-administration of methylone and mephedrone under extended access conditions.
Escalation of intravenous self-administration of methylone and mephedrone under extended access conditions.
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在扩大使用条件下增加静脉自我注射甲基酮和甲氧麻黄酮。
DOI：
10.1111/adb.12398
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发表时间：
2017
影响因子：
3.4
通讯作者：
Taffe,MichaelA
中科院分区：
文献类型：
--
作者：
Nguyen,JacquesD;Grant,Yanabel;Creehan,KevinM;Vandewater,SophiaA;Taffe,MichaelA
在美国，替代卡西酮的娱乐用途作为公共卫生问题继续增长。研究表明，扩大静脉（i. v.）可卡因和甲基苯丙胺等兴奋剂的自我给药导致药物摄入量相对于较短的获取时间而增加;然而，关于延长获取时间对甲基酮和4-甲基甲卡西酮（甲氧麻黄酮）等内毒素类兴奋剂自我给药的影响知之甚少。将雄性Wistar大鼠随机分配至短入路（ShA，2 h）和长入路（LgA，6 h）组，并使用固定比例1反应应急训练自我给予甲酮或甲氧麻黄酮（0.5 mg/kg/输注）。采用递增比例（PR）程序对甲基酮训练组进行评价，其中包括甲基酮（0.125-2.5 mg/kg/输注）、甲氧麻黄酮（0.125-2.5 mg/kg/输注）或甲基苯丙胺（MA; 0.01-0.5 mg/kg/输注）的剂量替代。对甲氧麻黄酮训练的大鼠进行了类似的PR评价，其中包括甲氧麻黄酮和MA。与ShA组相比，用LgA训练的大鼠在获得甲酮和甲氧麻黄酮期间获得更多的输注。在甲氧麻黄酮和MA PR测试中，接受过甲氧麻黄酮训练的LgA大鼠达到的断点显著高于所有其他组。与经甲酮训练的ShA大鼠相比，经甲酮训练的LgA大鼠的峰值有效剂量发生显著偏移，但总体疗效无变化。这些结果表明，甲氧麻黄酮的自我给药在LgA条件下以类似于传统兴奋剂的方式升级，而甲基酮6小时摄入量的升级并不伴随PR表现的差异。因此，甲氧麻黄酮代表了药物消费失调的更大风险。
The recreational use of substituted cathinones continues to grow as a public health concern in the United States. Studies have shown that extended access to intravenous (i.v.) self‐administration of stimulants, such as cocaine and methamphetamine, results in escalation of drug intake relative to shorter access; however, little is known about the impact of extended access on self‐administration of entactogen class stimulants such as methylone and 4‐methylmethcathinone (mephedrone). Male Wistar rats were randomly assigned to short‐access (ShA, 2‐ h) and long‐access (LgA, 6‐ h) groups and trained to self‐administer methylone or mephedrone (0.5 mg/kg/infusion) using a fixed‐ratio 1 response contingency. The methylone‐trained groups were evaluated on a progressive‐ratio (PR) procedure incorporating dose‐substitution of methylone (0.125–2.5 mg/kg/infusion), mephedrone (0.125–2.5 mg/kg/infusion) or methamphetamine (MA; 0.01–0.5 mg/kg/infusion). Mephedrone‐trained rats were similarly evaluated on a PR with mephedrone and MA. Rats trained with LgA to methylone and mephedrone earned more infusions during acquisition compared with ShA groups. Mephedrone‐trained LgA rats reached significantly higher breakpoints than all other groups in mephedrone and MA PR tests. Methylone‐trained LgA rats exhibited a rightward shift of the peak effective dose but no overall efficacy change compared with methylone‐trained ShA rats. These findings show that the self‐administration of mephedrone escalates under LgA conditions in a manner similar to traditional stimulants whereas escalation of 6 h intakes of methylone is not accompanied by differences in PR performance. Thus mephedrone represents the greater risk for dysregulated drug consumption.
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