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摇头丸(MDMA)使用者的记忆功能与5-羟色胺转运体启动子基因多态性

Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users.

作者信息

Reneman Liesbeth, Schilt T, de Win Maartje M, Booij Jan, Schmand Ben, van den Brink Wim, Bakker Onno

机构信息

Graduate School of Neurosciences, Department of Radiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

出版信息

J Psychopharmacol. 2006 May;20(3):389-99. doi: 10.1177/0269881106063266.

Abstract

Although 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the long-term consequences of MDMA-induced 5-HT neurotoxic lesions on functions in which 5-HT is involved, such as cognitive function. Because 5-HT transporters play a key element in the regulation of synaptic 5-HT transmission it may be important to control for the potential covariance effect of a polymorphism in the 5-HT transporter promoter gene region (5-HTTLPR) when studying the effects of MDMA as well as cognitive functioning. The aim of the study was to investigate the effects of moderate and heavy MDMA use on cognitive function, as well as the effects of long-term abstention from MDMA, in subjects genotyped for 5-HTTLPR. A second aim of the study was to determine whether these effects differ for females and males. Fifteen moderate MDMA users (<55 lifetime tablets), 22 heavy MDMA+ users (>55 lifetime tablets), 16 ex-MDMA+ users (last tablet > 1 year ago) and 13 controls were compared on a battery of neuropsychological tests. DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods.A significant group effect was observed only on memory function tasks (p = 0.04) but not on reaction times (p = 0.61) or attention/executive functioning (p = 0.59). Heavy and ex-MDMA+ users performed significantly poorer on memory tasks than controls. In contrast, no evidence of memory impairment was observed in moderate MDMA users. No significant effect of 5-HTTLPR or gender was observed. While the use of MDMA in quantities that may be considered "moderate" is not associated with impaired memory functioning, heavy use of MDMA use may lead to long lasting memory impairments. No effect of 5-HTTLPR or gender on memory function or MDMA use was observed.

摘要

尽管3,4-亚甲基二氧甲基苯丙胺(摇头丸)已被证明会损害动物乃至可能人类的脑血清素(5-羟色胺,5-HT)神经元,但对于摇头丸诱导的5-HT神经毒性损伤对5-HT所涉及功能(如认知功能)的长期影响却知之甚少。由于5-HT转运体在突触5-HT传递调节中起关键作用,因此在研究摇头丸的影响以及认知功能时,控制5-HT转运体启动子基因区域(5-HTTLPR)多态性的潜在协方差效应可能很重要。本研究的目的是调查5-HTTLPR基因分型受试者中,适度和大量使用摇头丸对认知功能的影响,以及长期戒除摇头丸的影响。该研究的第二个目的是确定这些影响在女性和男性中是否存在差异。对15名适度摇头丸使用者(终生服用量<55片)、22名大量摇头丸使用者(终生服用量>55片)、16名曾经使用过摇头丸的人(最后一次服药>1年前)和13名对照组人员进行了一系列神经心理学测试。使用标准聚合酶链反应方法对来自外周核血细胞的DNA进行5-HTTLPR基因分型。仅在记忆功能任务上观察到显著的组效应(p = 0.04),而在反应时间(p = 0.61)或注意力/执行功能(p = 0.59)上未观察到显著组效应。大量和曾经使用过摇头丸的人在记忆任务上的表现明显比对照组差。相比之下,在适度摇头丸使用者中未观察到记忆损害的证据。未观察到5-HTTLPR或性别的显著影响。虽然使用可能被视为“适度”数量的摇头丸与记忆功能受损无关,但大量使用摇头丸可能会导致长期的记忆损害。未观察到5-HTTLPR或性别对记忆功能或摇头丸使用的影响。

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