García-Osta Ana, Del Río Joaquín, Frechilla Diana
Department of Pharmacology, University of Navarra, School of Medicine, Aptdo. 177, 31080 Pamplona, Spain.
Brain Res Mol Brain Res. 2004 Jul 26;126(2):181-7. doi: 10.1016/j.molbrainres.2004.04.006.
A single administration of either 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") or p-chloroamphetamine (PCA) produced a rapid and marked reduction of serotonin (5-HT) content in rat frontal cortex and hippocampus. In the cortex of MDMA-treated rats, 5-HT levels returned to control values 48 h after drug administration. This recovery was correlated with an induction of CRE-binding activity and an enhanced expression of tryptophan hydroxylase (TPH) mRNA, the rate-limiting enzyme in 5-HT biosynthesis, suggesting that MDMA may up-regulate the TPH gene through a CREB-dependent mechanism. In the cortex of PCA-treated rats, neither a recovery of 5-HT levels nor changes in DNA-binding or TPH mRNA were found at the same time point. In the hippocampus of rats receiving either PCA or MDMA a decrease in TPH mRNA levels was found at all times, along with a reduced CRE-binding at the 8-h time point. The results show region-specific effects of MDMA. In the frontal cortex, the increased TPH expression suggests a compensatory response to MDMA-induced loss of serotonergic function.
单次给予3,4-亚甲基二氧甲基苯丙胺（摇头丸，MDMA）或对氯苯丙胺（PCA）均可使大鼠额叶皮质和海马体中的5-羟色胺（5-HT）含量迅速且显著降低。在接受MDMA治疗的大鼠皮质中，给药48小时后5-HT水平恢复至对照值。这种恢复与CRE结合活性的诱导以及色氨酸羟化酶（TPH）mRNA（5-HT生物合成中的限速酶）表达的增强相关，这表明MDMA可能通过CREB依赖机制上调TPH基因。在接受PCA治疗的大鼠皮质中，在同一时间点未发现5-HT水平恢复，也未发现DNA结合或TPH mRNA的变化。在接受PCA或MDMA的大鼠海马体中，始终发现TPH mRNA水平降低，同时在8小时时间点CRE结合减少。结果显示了MDMA的区域特异性作用。在额叶皮质中，TPH表达增加表明对MDMA诱导的5-羟色胺能功能丧失的一种代偿反应。
