Victoria University of Wellington, New Zealand.
Victoria University of Wellington, New Zealand.
Pharmacol Biochem Behav. 2014 Jan;116:9-15. doi: 10.1016/j.pbb.2013.11.011. Epub 2013 Nov 16.
Drug discrimination studies have suggested that the subjective effects of low doses of (±)3,4-methylenedioxymethamphetamine (MDMA) are readily differentiated from those of d-amphetamine (AMPH) and that the discriminative stimulus properties are mediated by serotonergic and dopaminergic mechanisms, respectively. Previous studies, however, have primarily examined responses to doses that do not produce substantial increases in extracellular dopamine. The present study determined whether doses of MDMA that produce increases in synaptic dopamine would also produce subjective effects that were more like AMPH and were sensitive to pharmacological manipulation of D1-like receptors. A three-lever drug discrimination paradigm was used. Rats were trained to respond on different levers following saline, AMPH (0.5mg/kg, IP) or MDMA (1.5mg/kg, IP) injections. Generalization curves were generated for a range of different doses of both drugs and the effect of the D1-like antagonist, SCH23390 on the discriminative stimulus effects of different doses of MDMA was determined. Rats accurately discriminated MDMA, AMPH and saline. Low doses of MDMA produced almost exclusive responding on the MDMA lever but at doses of 3.0mg/kg MDMA or higher, responding shifted to the AMPH lever. The AMPH response produced by higher doses of MDMA was attenuated by pretreatment with SCH23390. The data suggest that low doses and higher doses of MDMA produce distinct discriminative stimuli. The shift to AMPH-like responding following administration of higher doses of MDMA, and the decrease in this response following administration of SCH23390 suggests a dopaminergic component to the subjective experience of MDMA at higher doses.
药物辨别研究表明，（±）3,4-亚甲二氧基甲基苯丙胺（MDMA）的低剂量的主观效应很容易与安非他命（AMPH）区分开来，其辨别刺激特性分别由血清素能和多巴胺能机制介导。然而，之前的研究主要检查了不会导致细胞外多巴胺大量增加的剂量的反应。本研究确定是否产生突触多巴胺增加的 MDMA 剂量也会产生更类似于 AMPH 的主观效应，并且对 D1 样受体的药理学操纵敏感。使用了三杆药物辨别范式。训练大鼠在盐水、AMPH（0.5mg/kg，IP）或 MDMA（1.5mg/kg，IP）注射后分别对不同的杠杆做出反应。为两种药物的一系列不同剂量生成了概括曲线，并确定了 D1 样拮抗剂 SCH23390 对不同剂量 MDMA 的辨别刺激作用的影响。大鼠准确地辨别了 MDMA、AMPH 和盐水。低剂量的 MDMA 几乎只产生 MDMA 杠杆上的反应，但在 3.0mg/kg 或更高剂量的 MDMA 时，反应转移到 AMPH 杠杆上。更高剂量的 MDMA 产生的 AMPH 反应被 SCH23390 预处理减弱。数据表明，低剂量和高剂量的 MDMA 产生不同的辨别刺激。在给予更高剂量的 MDMA 后，出现类似于 AMPH 的反应，以及在给予 SCH23390 后这种反应的减少，表明在更高剂量下 MDMA 的主观体验具有多巴胺能成分。
