Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys.
Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys.
复制标题
雄性恒河猴中肌肉内甲基苯丙胺的歧视性刺激作用与血浆甲基苯丙胺水平之间的关系。
DOI：
10.1016/j.pbb.2015.12.001
复制
发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Poklis JL
中科院分区：
文献类型：
--
作者：
Banks ML;Smith DA;Kisor DF;Poklis JL
甲基苯丙胺是一种全球滥用的药物，它代谢为苯丙胺，也会产生与滥用有关的行为影响。然而，甲基苯丙胺代谢为苯丙胺在甲基苯丙胺滥用相关主观效应中的作用尚不清楚。本临床前研究旨在确定1）血浆甲基苯丙胺水平与甲基苯丙胺辨别刺激效应之间的关系和2）甲基苯丙胺代谢物苯丙胺在恒河猴中甲基苯丙胺辨别刺激效应中的作用。成年雄性恒河猴（n=3）进行了培训，以区分0.18毫克/公斤肌内（+）-甲基苯丙胺盐水中的两个关键的食物强化的歧视程序。测定盐水、（+）-甲基苯丙胺（0.032-0.32 mg/kg）和（+）-苯丙胺（0.032-0.32 mg/kg）辨别刺激效应的时间过程。在相同的猴子中进行平行的药代动力学研究，以确定甲基苯丙胺给药后的血浆甲基苯丙胺和苯丙胺水平以及苯丙胺给药后的苯丙胺水平，以与辨别程序中的行为相关。甲基苯丙胺和苯丙胺均产生完全的、≥ 90%的甲基苯丙胺样辨别刺激效应。安非他明显示一个轻微的，但显着的，更长的时间比甲基苯丙胺的歧视程序的行动。甲基苯丙胺和苯丙胺的行为影响有关的甲基苯丙胺和苯丙胺的血浆水平的顺时针滞后环表明急性耐受性已发展到歧视性的刺激效果。此外，甲基苯丙胺给药后的苯丙胺水平不存在时，甲基苯丙胺的刺激效果最大，甲基苯丙胺的歧视性刺激效果返回到盐水样水平时达到峰值。总体而言，这些结果表明甲基苯丙胺代谢物苯丙胺不会导致甲基苯丙胺滥用相关的主观影响。
Methamphetamine is a globally abused drug that is metabolized to amphetamine, which also produces abuse-related behavioral effects. However, the contributing role of methamphetamine metabolism to amphetamine in methamphetamine's abuse-related subjective effects is unknown. This preclinical study was designed to determine 1) the relationship between plasma methamphetamine levels and methamphetamine discriminative stimulus effects and 2) the contribution of the methamphetamine metabolite amphetamine in the discriminative stimulus effects of methamphetamine in rhesus monkeys. Adult male rhesus monkeys (n=3) were trained to discriminate 0.18 mg/kg intramuscular (+)-methamphetamine from saline in a two-key food-reinforced discrimination procedure. Time course of saline, (+)-methamphetamine (0.032-0.32 mg/kg), and (+)-amphetamine (0.032-0.32 mg/kg) discriminative stimulus effects were determined. Parallel pharmacokinetic studies were conducted in the same monkeys to determine plasma methamphetamine and amphetamine levels after methamphetamine administration and amphetamine levels after amphetamine administration for correlation with behavior in the discrimination procedure. Both methamphetamine and amphetamine produced full, ≥90%, methamphetamine-like discriminative stimulus effects. Amphetamine displayed a slightly, but significantly, longer duration of action than methamphetamine in the discrimination procedure. Both methamphetamine and amphetamine behavioral effects were related to methamphetamine and amphetamine plasma levels by a clockwise hysteresis loop indicating acute tolerance had developed to the discriminative stimulus effects. Furthermore, amphetamine levels after methamphetamine administration were absent when methamphetamine stimulus effects were greatest and peaked when methamphetamine discriminative stimulus effects returned to saline-like levels. Overall, these results demonstrate the methamphetamine metabolite amphetamine does not contribute to methamphetamine's abuse-related subjective effects.