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恒河猴中μ-阿片受体激动剂瑞芬太尼的延迟折扣

Delay discounting of the μ-opioid receptor agonist remifentanil in rhesus monkeys.

作者信息

Maguire David R, Gerak Lisa R, France Charles P

机构信息

Departments of aPharmacology bPsychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

出版信息

Behav Pharmacol. 2016 Apr;27(2-3 Spec Issue):148-54. doi: 10.1097/FBP.0000000000000193.

Abstract

Although increased impulsivity (delay discounting) is an important risk factor for drug abuse, the impact of delay on drug taking has received relatively little attention. This study examined delay discounting of the μ-opioid receptor agonist remifentanil in rhesus monkeys (n=4) responding for intravenous infusions under a concurrent choice procedure. Dose-effect curves for remifentanil were determined by varying the dose available on one lever (0.001-0.32 μg/kg/infusion) while keeping the dose available on the other lever (0.1 μg/kg/infusion) the same. Dose-effect curves were determined when both infusions were delivered immediately and when delivery of the fixed dose was delayed (15-180 s). When both doses of remifentanil were delivered immediately, monkeys chose the large dose. Delaying delivery of the fixed dose reduced choice of that dose and increased choice of small immediately available doses. Extending previous studies, these results show that the effects of delay on choice between two doses of a μ-opioid receptor agonist are consistent with hyperbolic discounting. Delaying delivery of a preferred reinforcer (e.g. large dose of drug) reduces its effectiveness and increases the effectiveness of small immediately available doses. This effect of delay, particularly on drug self-administration, might contribute to drug abuse.

摘要

尽管冲动性增加(延迟折扣)是药物滥用的一个重要风险因素,但延迟对药物摄取的影响相对较少受到关注。本研究在恒河猴(n = 4)中,采用并发选择程序,对静脉输注进行反应时,检测了μ-阿片受体激动剂瑞芬太尼的延迟折扣。通过改变一个杠杆上可用的剂量(0.001 - 0.32μg/kg/输注),同时保持另一个杠杆上可用的剂量(0.1μg/kg/输注)不变,来确定瑞芬太尼的剂量效应曲线。当两种输注都立即进行时以及固定剂量的输注延迟(15 - 180秒)时,分别确定剂量效应曲线。当两种剂量的瑞芬太尼都立即输注时,猴子选择大剂量。延迟固定剂量的输注会减少对该剂量的选择,并增加对小的即时可用剂量的选择。扩展先前的研究,这些结果表明延迟对两种剂量的μ-阿片受体激动剂之间选择的影响与双曲线折扣一致。延迟递送偏好的强化物(例如大剂量药物)会降低其有效性,并增加小的即时可用剂量的有效性。这种延迟效应,特别是对药物自我给药的影响,可能导致药物滥用。

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