Lamas X, Negus S S, Hall E, Mello N K
Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, Belmont, MA 02178, USA.
Psychopharmacology (Berl). 1995 Oct;121(3):331-8. doi: 10.1007/BF02246072.
The relationship between the discriminative stimulus effects and plasma pharmacokinetics of cocaine was evaluated in six rhesus monkeys trained to discriminate cocaine (0.4 mg/kg, IM) from saline under a FR30 schedule of food presentation. The same monkeys were tested in two procedures. In a cumulative dosing procedure, five cumulative doses of cocaine (0.013-1.3 mg/kg) were administered and discriminative stimulus effects were evaluated 10 min after the administration of each dose. Cocaine plasma concentrations were measured in separate sessions using the same doses and interdose intervals. In a single dosing procedure, the time-courses of the discriminative stimulus effects and plasma concentrations of cocaine were assessed after the administration of cocaine (0.4 mg/kg). A close correspondence between cocaine's discriminative stimulus effects and plasma concentrations was obtained in both procedures. Cocaine was virtually undetectable in plasma at doses that produced saline-appropriate responding (0.013 and 0.04 mg/kg), whereas increasing plasma concentrations were measured at doses that produced primarily cocaine-appropriate responding (0.13 mg/kg or higher). The time-course of the discriminative stimulus effects of cocaine was characterized by a rapid onset (within 1-3 min post-cocaine) and offset (within 20-60 min post-cocaine). Peak plasma levels were obtained at 10 min post-cocaine. No differences in plasma concentrations were found 10 min after the administration of a cumulative versus a single dose of cocaine 0.4 mg/kg (mean, 75.8 and 74.0 ng/ml, respectively). Cocaine plasma concentrations lasted longer than its discriminative stimulus effects. The results of the present study confirm that the cumulative dosing procedure used yields plasma concentrations of cocaine that are similar to the concentrations obtained after single cocaine dosing.
在六只恒河猴中评估了可卡因的辨别性刺激效应与血浆药代动力学之间的关系，这些猴子经过训练，在食物呈现的FR30程序下区分可卡因（0.4毫克/千克，肌肉注射）和生理盐水。同样的猴子在两个程序中接受测试。在累积给药程序中，给予五个累积剂量的可卡因（0.013 - 1.3毫克/千克），并在每次给药后10分钟评估辨别性刺激效应。使用相同剂量和给药间隔在单独的实验中测量可卡因血浆浓度。在单次给药程序中，给予可卡因（0.4毫克/千克）后评估辨别性刺激效应和可卡因血浆浓度的时间进程。在两个程序中都获得了可卡因的辨别性刺激效应与血浆浓度之间的密切对应关系。在产生与生理盐水反应相当的剂量（0.013和0.04毫克/千克）下，血浆中几乎检测不到可卡因，而在产生主要与可卡因反应相当的剂量（0.13毫克/千克或更高）下，测量到血浆浓度升高。可卡因辨别性刺激效应的时间进程特点是起效迅速（可卡因给药后1 - 3分钟内）和消退迅速（可卡因给药后20 - 60分钟内）。可卡因给药后10分钟达到血浆峰值水平。给予0.4毫克/千克累积剂量与单次剂量可卡因10分钟后，血浆浓度没有差异（平均值分别为75.8和74.0纳克/毫升）。可卡因血浆浓度持续的时间比其辨别性刺激效应更长。本研究结果证实，所使用的累积给药程序产生的可卡因血浆浓度与单次可卡因给药后获得的浓度相似。
