Baker L E, Virden T B, Miller M E, Sullivan C L
Department of Psychology, Western Michigan University, Kalamazoo 49008, USA.
Pharmacol Biochem Behav. 1997 Oct;58(2):505-16. doi: 10.1016/s0091-3057(97)00287-6.
The present study examined the discriminative stimulus effects of the MDMA optical isomers administered at different presession injection intervals. In the first experiment, male Sprague-Dawley rats were trained in a two-lever, food-reinforced operant procedure to discriminate either (+)-MDMA (1.25 mg/kg) or (-)-MDMA (3.50 mg kg) at either 20 or 90 min following injection. Animals administered (+)-MDMA or saline 90 min before training sessions failed to attain the discrimination criteria after 73 training sessions, whereas (-)-MDMA successfully established discriminative stimulus control at both the 20 min and the 90 min postinjection intervals. (+)-Amphetamine did not substitute for either isomer, although a significant amount of drug-appropriate responding occurred in animals trained to discriminate (+)-MDMA at 20 min and (-)-MDMA at 90 min. Sch 39166 partially reduced the discrimination of (+)-MDMA at 20 min and (-)-MDMA at 90 min, although this effect was not dose dependent. Sch 39166 had no effect on animals trained to discriminate (-)-MDMA at 20 min. Haloperidol did not alter the discrimination of (+)-MDMA at 20 min but partially reduced the discriminative stimulus control of (-)-MDMA at 20 min and (-)-MDMA at 90 min. Fenfluramine substituted for both isomers of MDMA. Pirenpirone completely blocked the discriminative stimulus effects of (-)-MDMA at 20 min, although (+)-MDMA at 20 min and (-)-MDMA at 90 min were only partly blocked. WAY 100,135 had little effect on drug-appropriate responding; however, the discrimination of (+)-MDMA at 20 min was partly reduced by this 5-HT1A antagonist. In a second experiment, rats trained to discriminate (+)-MDMA (1.5 mg/kg) or (-)-MDMA (3.0 mg/kg) from saline were administered substitution tests with both isomers 20, 60, 90 and 120 min after injection. Results confirmed those of the first experiment that (+)-MDMA appears to have a shorter duration of action than (-)-MDMA. These results are discussed in light of the training doses employed.
本研究考察了在不同注射前间隔时间给予摇头丸光学异构体的辨别刺激效应。在第一个实验中，雄性斯普拉格-道利大鼠在双杠杆、食物强化的操作性程序中接受训练，以辨别注射后20分钟或90分钟时的（+）-摇头丸（1.25毫克/千克）或（-）-摇头丸（3.50毫克/千克）。在训练前90分钟给予（+）-摇头丸或生理盐水的动物，在73次训练后未达到辨别标准，而（-）-摇头丸在注射后20分钟和90分钟时均成功建立了辨别刺激控制。（+）-苯丙胺不能替代任何一种异构体，尽管在训练辨别20分钟时的（+）-摇头丸和90分钟时（-）-摇头丸的动物中出现了大量与药物相符的反应。Sch 39166部分降低了20分钟时（+）-摇头丸和90分钟时（-）-摇头丸引起的辨别，尽管这种效应不依赖剂量。Sch 39166对训练辨别20分钟时（-）-摇头丸的动物没有影响。氟哌啶醇不改变20分钟时（+）-摇头丸引起的辨别，但部分降低了20分钟时（-）-摇头丸和90分钟时（-）-摇头丸的辨别刺激控制。芬氟拉明替代了摇头丸的两种异构体。哌仑西平完全阻断了20分钟时（-）-摇头丸的辨别刺激效应，尽管20分钟时的（+）-摇头丸和90分钟时的（-）-摇头丸仅被部分阻断。WAY 100,135对与药物相符的反应影响很小；然而，这种5-羟色胺1A拮抗剂部分降低了20分钟时（+）-摇头丸引起的辨别。在第二个实验中，训练辨别（+）-摇头丸（1.5毫克/千克）或（-）-摇头丸（3.0毫克/千克）与生理盐水的大鼠，在注射后20、60、90和120分钟接受两种异构体的替代试验。结果证实了第一个实验的结果，即（+）-摇头丸的作用持续时间似乎比（-）-摇头丸短。根据所采用的训练剂量对这些结果进行了讨论。
