Analysis of ecstasy (MDMA)-induced transcription

3，4-亚甲基二氧基甲基苯丙胺(MDMA，摇头丸)是一种流行的滥用药物。MDMA因其与经典致幻剂和兴奋剂的亲和力而被药理学归类为内源性致幻剂。口服单剂量的药物与人类的欣快感、自信心和感官意识的增强有关。已经提供了人类5-羟色胺(5-HT)系统神经毒性的证据。在大鼠中，一次注射MDMA会导致体温升高和形成活性氧物种。这些影响可能会导致MDMA相关的长期5-羟色胺耗竭，皮质对MDMA的生化效应非常敏感。有人提出，这些MDMA效应可能与大脑这一区域的分子变化有关。为了验证这些想法，我们利用了cDNA阵列分析，它可以提供对MDMA注射继发的分子变化的更全面的看法。我们的结果表明，受MDMA调控的基因编码属于信号通路、转录调节因子或异源代谢的蛋白质。我们的观察表明，皮质细胞通过调节几个基因的转录来对MDMA的急性给药做出反应，这些基因可能会导致大脑的长期变化。

3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular drug of abuse. MDMA is pharmacologically classified as an entactogen because of its affinities to classical hallucinogens and stimulants. Oral ingestion of a single dose of the drug is associated with euphoria, elevated self-confidence, and heightened sensory awareness in humans. Evidence for neurotoxicity in the human serotonin (5-HT) system has been provided. In rats, a single injection of MDMA induces hyperthermia and formation of reactive oxygen species. These effects may cause MDMA-associated, long-term 5-HT depletion, with the cortex being quite sensitive to the biochemical effects of MDMA. It has been suggested that these MDMA effects may be associated with molecular changes in this brain region. To test these ideas, we have made use of the cDNA array analysis, which can provide a more global view of the molecular changes secondary to MDMA injections. Our results show that the genes regulated by MDMA encode proteins that belong to signaling pathways, transcription regulators, or xenobiotic metabolism. Our observations indicate that cortical cells respond to the acute administration of MDMA by modulating transcription of several genes that might lead to long-term changes in the brain.