Delay discounting of the μ-opioid receptor agonist remifentanil in rhesus monkeys.
Delay discounting of the μ-opioid receptor agonist remifentanil in rhesus monkeys.
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DOI：
10.1097/fbp.0000000000000193
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发表时间：
2016-04
影响因子：
1.6
通讯作者：
France CP
中科院分区：
文献类型：
--
作者：
Maguire DR;Gerak LR;France CP
虽然冲动性增加（延迟折扣）是药物滥用的一个重要风险因素，但延迟对药物服用的影响相对较少受到关注。本研究检查了μ阿片受体激动剂瑞芬太尼在恒河猴（n=4）中对静脉内（i. v.）在并行选择程序下进行输注。通过改变一个杠杆上的可用剂量（0.001-0.32 μg/kg/输注），同时保持另一个杠杆上的可用剂量（0.1 μg/kg/输注）相同，确定瑞芬太尼的剂量效应曲线。当两种输注均立即递送时以及当固定剂量的递送延迟（15-180 s）时，测定剂量-效应曲线。当两种剂量的瑞芬太尼都被立即输送时，猴子选择了大剂量。延迟固定剂量的递送减少了该剂量的选择，并增加了立即可用的小剂量的选择。扩展以前的研究，这些结果表明，延迟选择两个剂量的μ阿片受体激动剂之间的影响是一致的双曲线折扣。延迟递送优选的药物（例如，大剂量药物）降低其有效性并增加小的立即可用剂量的有效性。这种延迟的影响，特别是对自我给药的影响，可能会助长药物滥用。
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 mu opioid receptor agonist remifentanil in rhesus monkeys (n=4) responding for intravenous (i.v.) 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 mu 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.