Saadat Kathryn S, Elliott J Martin, Colado M Isabel, Green A Richard
Neuropharmacology Research Group, Leicester School of Pharmacy, De Montfort University, UK.
J Psychopharmacol. 2006 Mar;20(2):264-71. doi: 10.1177/0269881106058022.
When mice are exposed to harmless objects such as marbles in their cage they bury them, a behaviour sometimes known as defensive burying. We investigated the effect of an acute dose of MDMA (èecstasy') and other psychoactive drugs on marble burying and also examined the effect of a prior neurotoxic dose of MDMA or p-chloroamphetamine (PCA) on burying. Acute administration of MDMA produced dose-dependent inhibition of marble burying (EC50: 7.6 micro mol/kg). Other drugs that enhance monoamine function also produced dose-dependent inhibition: methamphetamine PCA paroxetine MDMA GBR 12909 methylphenidate. None of these drugs altered locomotor activity at a dose that inhibited burying. A prior neurotoxic dose of MDMA, which decreased striatal dopamine content by 60%, but left striatal 5-HT content unaltered, did not alter spontaneous marble burying 18 or 40 days later. However, a neurotoxic dose of PCA which decreased striatal dopamine by 60% and striatal 5-HT by 70% attenuated marble burying 28 days later. Overall, these data suggest that MDMA, primarily by acutely increasing 5-HT function, acts like several anxiolytic drugs in this behavioural model. Long-term loss of cerebral 5-HT content also produced a similar effect. Since this change was observed only after 28 days, it is probably due to an adaptive response in the brain.
当小鼠在笼子里接触到无害物体，如弹珠时，它们会把弹珠埋起来，这种行为有时被称为防御性埋匿。我们研究了急性剂量的摇头丸（MDMA，“摇头丸”）和其他精神活性药物对弹珠埋匿行为的影响，还考察了先前给予神经毒性剂量的MDMA或对氯苯丙胺（PCA）对埋匿行为的影响。急性给予MDMA会产生剂量依赖性的弹珠埋匿抑制作用（半数有效浓度：7.6微摩尔/千克）。其他增强单胺功能的药物也会产生剂量依赖性抑制作用：甲基苯丙胺、PCA、帕罗西汀、MDMA、GBR 12909、哌醋甲酯。这些药物在抑制埋匿行为的剂量下均未改变运动活性。先前给予神经毒性剂量的MDMA使纹状体多巴胺含量降低了60%，但纹状体5-羟色胺（5-HT）含量未变，在18天或40天后并未改变自发的弹珠埋匿行为。然而，给予神经毒性剂量的PCA使纹状体多巴胺含量降低了60%，纹状体5-HT含量降低了70%，28天后减弱了弹珠埋匿行为。总体而言，这些数据表明，MDMA主要通过急性增加5-HT功能，在这个行为模型中其作用类似于几种抗焦虑药物。大脑5-HT含量的长期丧失也产生了类似的效果。由于这种变化仅在28天后才观察到，这可能是大脑中的一种适应性反应。
