Panlilio L V, Goldberg S R, Gilman J P, Jufer R, Cone E J, Schindler C W
Preclinical Pharmacology Laboratory, Behavioral Pharmacology and Genetics Section, National Institute on Drug Abuse, Division of Intramural Research, Baltimore, MD 21224, USA.
Psychopharmacology (Berl). 1998 Jun;137(3):253-8. doi: 10.1007/s002130050618.
The goal of this study was to determine whether slowly infused, response-independent cocaine would reduce cocaine self-administration in an animal model of drug abuse. Seven male rhesus monkeys self-administered i.v. cocaine on a fixed-ratio 30 schedule (5-min time-out). With unit dose (0.056 mg/kg per infusion for one monkey and 0.032 mg/kg per infusion for the rest) and infusion volume (0.5 ml) held constant, the rate of delivery was manipulated (0.125, 0.1875, 0.375, 0.75 and 3 ml/min, with infusions lasting 240, 160, 80, 40, and 10 s, respectively). Response rates increased monotonically as a function of delivery rate. Responding for cocaine at the slowest delivery rate did not differ from saline. The effects of infusing additional cocaine (starting 30 min prior to the session) at this non-reinforcing rate (0.125 ml/min) were then determined. Delivery rate of the self-administered infusion was manipulated as before. Non-contingent cocaine significantly increased responding for cocaine (at the fastest delivery rate) and for saline. While non-contingent cocaine reduced responding for cocaine in two of the seven monkeys, it also significantly reduced responding in three monkeys that responded for food on the same schedule. Plasma levels of cocaine delivered at rates of 0.125 and 3 ml/min were compared in five other monkeys. While a higher peak was reached with the faster infusion, levels did not differ after 5 min. Thus, when an infusion became available (after the 5-min time-out) in the self-administration experiments, plasma levels should not have differed regardless of the delivery rate. These results suggest that a low-dose, slow-delivery treatment with cocaine might prime or reinstate drug seeking rather than decrease it.
本研究的目的是确定在药物滥用动物模型中，缓慢输注、与反应无关的可卡因是否会减少可卡因自我给药行为。七只雄性恒河猴按照固定比率30的时间表（5分钟超时）静脉注射可卡因。在单位剂量（一只猴子每次输注为0.056毫克/千克，其余猴子每次输注为0.032毫克/千克）和输注体积（0.5毫升）保持恒定的情况下，操纵给药速率（0.125、0.1875、0.375、0.75和3毫升/分钟，输注持续时间分别为240、160、80、40和10秒）。反应率随着给药速率单调增加。以最慢给药速率对可卡因的反应与对生理盐水的反应没有差异。然后确定以这种非强化速率（0.125毫升/分钟）输注额外可卡因（在实验开始前30分钟开始）的效果。自我给药输注的给药速率如前所述进行操纵。非条件性可卡因显著增加了对可卡因（在最快给药速率下）和对生理盐水的反应。虽然非条件性可卡因在七只猴子中的两只中减少了对可卡因的反应，但它也显著降低了三只按照相同时间表对食物有反应的猴子的反应。在另外五只猴子中比较了以0.125和3毫升/分钟的速率给药的可卡因的血浆水平。虽然较快输注达到了更高的峰值，但5分钟后水平没有差异。因此，在自我给药实验中，当输注可用时（在5分钟超时后），无论给药速率如何，血浆水平应该没有差异。这些结果表明，低剂量、缓慢给药的可卡因治疗可能会引发或恢复觅药行为，而不是减少它。
