Analysis of ecstasy (MDMA)-induced transcriptional respo
Analysis of ecstasy (MDMA)-induced transcriptional respo
批准号:
6987718
负责人:
Jean Lud Cadet
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$0.0万
依托单位国家:
美国
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财政年份:
--
资助国家:
美国
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未结题
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至
中文摘要
3,4-亚甲基二氧甲基苯丙胺(MDMA,摇头丸)是一种普遍滥用的药物。MDMA在药理学上被归类为致幻剂,因为它与经典的致幻剂和兴奋剂有亲缘关系。口服一剂该药物可使人产生欣快感、增强自信心和增强感觉意识。人类5-羟色胺(5-HT)系统神经毒性的证据已经提供。在大鼠中,单次注射MDMA诱导高热和活性氧的形成。这些影响可能导致MDMA相关的长期5-羟色胺耗竭,而皮层对MDMA的生化作用相当敏感。有人认为,这些MDMA的影响可能与该大脑区域的分子变化有关。为了验证这些想法,我们使用了cDNA阵列分析,它可以提供一个更全面的MDMA注射后的分子变化视图。我们的研究结果表明,受MDMA调控的基因编码的蛋白质属于信号通路、转录调节因子或异种代谢。我们的观察表明,皮质细胞通过调节可能导致大脑长期变化的几个基因的转录对MDMA的急性给药作出反应。
英文摘要
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.
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海外基金