Maguire David R, Li Jun-Xu, France Charles P
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
J Pharmacol Toxicol Methods. 2012 Nov-Dec;66(3):264-9. doi: 10.1016/j.vascn.2012.08.168. Epub 2012 Aug 27.
Impulsivity is a behavioral trait that is thought to contribute to a variety of disorders, including drug abuse. Efficient, sensitive procedures are needed for studying drug effects on impulsivity (e.g., delay discounting) in nonhumans.
Three monkeys responded under an operant choice procedure whereby responses on one lever resulted in immediate delivery of 0.15 ml of juice [Hawaiian Punch®] and responses on another lever resulted in delivery of 0.75 ml of juice, either immediately or after a delay (3.75-40 s). The delay to the larger reinforcer increased within-session across discrete blocks allowing for generation of delay-discounting functions within sessions.
Without delay, monkeys chose the larger reinforcer nearly exclusively. With increasing delay, monkeys progressively switched their choice from the larger to the smaller reinforcer in a delay-dependent manner. In 2 monkeys, acute administration of morphine (0.1 and 0.32 mg/kg) or ketamine (0.1 and 0.32 mg/kg) but not diazepam (0.1-1.0 mg/kg) dose-dependently shifted the delay-discounting functions to the left, indicating increased discounting. In one monkey, daily morphine treatment (0.32 mg/kg/day, 3-hour pretreatment) produced a rapid, sustained leftward shift in the delay-discounting function; the curve returned to the pre-drug position 6 days after discontinuation of treatment.
This delay discounting procedure is sensitive to both behavioral and pharmacological manipulations and appears to be particularly sensitive to chronic drug treatment and drug withdrawal. Given the importance of drug dependence and withdrawal in the initiation, maintenance of, and relapse to drug taking, this procedure should be useful to study one aspect of this process.
冲动是一种行为特征，被认为与包括药物滥用在内的多种疾病有关。需要高效、灵敏的程序来研究药物对非人类动物冲动性（如延迟折扣）的影响。
三只猴子在操作性选择程序下做出反应，按压一个杠杆会立即得到0.15毫升果汁[夏威夷宾治®]，按压另一个杠杆则会立即或延迟（3.75 - 40秒）后得到0.75毫升果汁。在整个实验过程中，较大强化物的延迟时间在不同的离散时间段内逐渐增加，从而能够在实验过程中生成延迟折扣函数。
在没有延迟的情况下，猴子几乎只选择较大的强化物。随着延迟时间的增加，猴子逐渐以延迟依赖的方式将选择从较大的强化物转向较小的强化物。在两只猴子中，急性注射吗啡（0.1和0.32毫克/千克）或氯胺酮（0.1和0.32毫克/千克），但不是地西泮（0.1 - 1.0毫克/千克），剂量依赖性地将延迟折扣函数向左移动，表明折扣增加。在一只猴子中，每日吗啡治疗（0.32毫克/千克/天，3小时预处理）使延迟折扣函数迅速、持续地向左移动；停药6天后，曲线恢复到用药前的位置。
这种延迟折扣程序对行为和药理学操作都很敏感，似乎对慢性药物治疗和药物戒断特别敏感。鉴于药物依赖和戒断在药物使用的起始、维持和复发中的重要性，该程序对于研究这一过程的一个方面应该是有用的。
