Reneman L, Habraken J B, Majoie C B, Booij J, den Heeten G J
Department of Nuclear Medicine (Graduate School of Neurosciences), Academic Medical Center, Amsterdam, The Netherlands.
AJNR Am J Neuroradiol. 2000 Jun-Jul;21(6):1001-7.
Abuse of the popular recreational drug "Ecstasy" (MDMA) has been linked to the occurrence of cerebrovascular accidents. It is known that MDMA alters brain serotonin (5-HT) concentrations and that brain postsynaptic 5-HT(2) receptors play a role in the regulation of brain microvasculature. Therefore, we used brain imaging to find out whether MDMA use predisposes one to cerebrovascular accidents by altering brain 5-HT neurotransmission.
The effects of MDMA use on brain cortical 5-HT(2A) receptor densities were studied using [(123)I]R91150 single-photon emission CT in 10 abstinent recent MDMA users, five former MDMA users, and 10 healthy control subjects. Furthermore, to examine whether changes in brain 5-HT(2A) receptor densities are associated with alterations in blood vessel volumes, we calculated relative cerebral blood volume maps from dynamic MR imaging sets in five MDMA users and six healthy control subjects.
An analysis of variance revealed that mean cortical [(123)I]R91150 binding ratios were significantly lower in recent MDMA users than in former MDMA users and control subjects. This finding suggests down-regulation of 5-HT(2) receptors caused by MDMA-induced 5-HT release. Furthermore, in MDMA users, low cortical 5-HT(2) receptor densities were significantly associated with low cerebral blood vessel volumes (implicating vasoconstriction) and high cortical 5-HT(2) receptor densities with high cerebral blood vessel volumes (implicating vasodilatation) in specific brain regions.
These findings suggest a relationship between the serotonergic system and an altered regulation of 5-HT(2) receptors in human MDMA users. MDMA users may therefore be at risk for cerebrovascular accidents resulting from alterations in the 5-HT neurotransmission system.
滥用流行的消遣性药物“摇头丸”(3,4-亚甲基二氧甲基苯丙胺,MDMA)与脑血管意外的发生有关。已知MDMA会改变脑内5-羟色胺(5-HT)浓度,且脑内突触后5-HT(2)受体在脑微血管系统调节中发挥作用。因此,我们采用脑成像技术来探究使用MDMA是否会通过改变脑内5-HT神经传递而使人易患脑血管意外。
使用[(123)I]R91150单光子发射计算机断层扫描技术,对10名近期已戒毒的MDMA使用者、5名既往MDMA使用者及10名健康对照者进行研究,以探讨使用MDMA对脑皮质5-HT(2A)受体密度的影响。此外,为了检验脑内5-HT(2A)受体密度的变化是否与血管容量改变相关,我们从5名MDMA使用者及6名健康对照者的动态磁共振成像数据集中计算出相对脑血容量图。
方差分析显示,近期MDMA使用者的平均皮质[(123)I]R91150结合率显著低于既往MDMA使用者及对照者。这一发现提示MDMA诱导的5-HT释放导致了5-HT(2)受体下调。此外,在MDMA使用者中,特定脑区皮质5-HT(2)受体密度低与脑血容量低(提示血管收缩)显著相关,而皮质5-HT(2)受体密度高与脑血容量高(提示血管扩张)显著相关。
这些发现提示了人类MDMA使用者中血清素能系统与5-HT(2)受体调节改变之间的关系。因此,MDMA使用者可能因5-HT神经传递系统改变而面临脑血管意外的风险。