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MDPV“高反应”大鼠在固定比率强化程序下自我给药的羟考酮也比“低反应”大鼠多。

MDPV "high-responder" rats also self-administer more oxycodone than their "low-responder" counterparts under a fixed ratio schedule of reinforcement.

机构信息

Department of Pharmaceutical Sciences, Mercer University College of Pharmacy, Atlanta, GA, 30341, USA.

Department of Pharmacology, Toxicology & Neuroscience; and the Louisiana Addiction Research Center, Louisiana State University Health Sciences Center - Shreveport, LA, 71103, Shreveport, USA.

出版信息

Psychopharmacology (Berl). 2021 Apr;238(4):1183-1192. doi: 10.1007/s00213-021-05764-4. Epub 2021 Jan 23.

Abstract

RATIONALE

Oxycodone is one of the most commonly prescribed and most frequently abused opioid analgesics, yet little is known regarding individual vulnerabilities to oxycodone abuse. The synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) has been shown to produce a "high-responder" phenotype characterized by increased drug intake and responding during periods of signaled drug unavailability (e.g., during post-infusion timeouts) in ~ 40% of male Sprague-Dawley rats. This phenotype also transfers to other psychostimulants (e.g., cocaine and methamphetamine), but it is unknown whether this phenotype transfers to other (non-stimulant) drugs of abuse.

OBJECTIVES

The present study aimed to (1) reestablish the "high-responder" phenotype in male Sprague-Dawley rats (n = 11) that acquired self-administration of MDPV (0.032 mg/kg/inf) on a fixed ratio 1 (FR1) schedule of reinforcement and (2) compare full dose-response curves for MDPV and oxycodone self-administration under an FR5 schedule of reinforcement.

RESULTS

MDPV was ~ 3-fold more potent at maintaining peak levels of behavior and resulted in greater overall drug intake than oxycodone. High levels of timeout responding were noted in a subset of rats that acquired MDPV self-administration ("high-responders", n = 5), and the FR5 dose-response curve for MDPV was shifted upward for these rats relative to their "low-responder" (n = 6) counterparts. "High-responders" also self-administered more infusions of oxycodone under an FR5 schedule of reinforcement than "low-responders"; however, this was not coupled with increased levels of timeout responding.

CONCLUSIONS

The present data suggest that a subset of individuals with a history of using synthetic cathinones may be particularly vulnerable to the abuse of oxycodone.

摘要

理由

羟考酮是最常开处方和最常滥用的阿片类镇痛药之一,但人们对羟考酮滥用的个体易感性知之甚少。合成卡西酮 3,4-亚甲基二氧吡咯戊酮(MDPV)已被证明可产生“高反应者”表型,其特征是在信号药物不可用时(例如,在输注后超时期间)增加药物摄入和反应,在约 40%的雄性 Sprague-Dawley 大鼠中。这种表型也转移到其他精神兴奋剂(例如可卡因和甲基苯丙胺),但尚不清楚这种表型是否转移到其他(非兴奋剂)滥用药物。

目的

本研究旨在(1)在雄性 Sprague-Dawley 大鼠(n = 11)中重新建立 MDPV(0.032 mg/kg/inf)固定比率 1(FR1)强化方案下自我给药的“高反应者”表型,(2)比较 FR5 强化方案下 MDPV 和羟考酮自我给药的全剂量反应曲线。

结果

MDPV 维持行为高峰水平的效力约为羟考酮的 3 倍,导致总药物摄入量更大。在一组获得 MDPV 自我给药的大鼠中(“高反应者”,n = 5),注意到超时反应水平较高,并且这些大鼠的 MDPV FR5 剂量反应曲线相对于其“低反应者”(n = 6)对照向上移动。“高反应者”在 FR5 强化方案下自我给药的羟考酮剂量也多于“低反应者”;然而,这并没有伴随着超时反应水平的增加。

结论

本研究数据表明,有滥用合成卡西酮史的个体亚群可能特别容易滥用羟考酮。

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