POTENTIATION OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE-INDUCED DOPAMINE RELEASE AND SEROTONIN NEUROTOXICITY BY 5-HT2 RECEPTOR AGONISTS
POTENTIATION OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE-INDUCED DOPAMINE RELEASE AND SEROTONIN NEUROTOXICITY BY 5-HT2 RECEPTOR AGONISTS
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DOI：
10.1016/0014-2999(94)90669-6
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发表时间：
1994-11-03
影响因子：
5
通讯作者：
NASH, JF
中科院分区：
文献类型：
--
作者：
GUDELSKY, GA;YAMAMOTO, BK;NASH, JF
研究了5-HT2受体激动剂1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）和5-甲氧基- n， n -二甲基色胺（5-MeODMT）对3,4-亚甲基二氧基甲基苯丙胺（MDMA）诱导的纹状体多巴胺释放和5-HT消耗的影响。通过体内微透析评估，在DOI （2 mg/kg, ip.）或5-MeODMT （15 mg/kg, ip.）处理的大鼠中，mdma诱导的纹状体中多巴胺细胞外浓度的增加显著增强。DOI和5-MeODMT都不能单独改变纹状体中多巴胺的细胞外浓度。单次给予MDMA (10 mg/kg, sc) 7天后，纹状体5-羟色胺浓度下降，但不显著。然而，在DOI和MDMA联合治疗7天后，纹状体5-羟色胺浓度明显低于单独使用MDMA或用载药处理的对照组。我们得出结论，5-HT2受体的激活是细胞外多巴胺急性增加的重要决定因素，因此，MDMA产生的脑5-HT的长期消耗。
The effects of the 5-HT2 receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminoproane (DOI) and 5-methoxy-N,N-dimethyrtryptamine (5-MeODMT) on 3,4-methylenedioxymethamphetamine (MDMA)-induced dopamine release and 5-HT depletion in the striatum were studied. The MDMA-induced increase in the extracellular concentration of dopamine in the striatum was enhanced significantly in rats treated with either DOI (2 mg/kg, ip.) or 5-MeODMT (15 mg/kg, ip.), as assessed using in vivo microdialysis. Neither DOI nor 5-MeODMT alone altered the extracellular concentration of dopamine in the striatum. The striatal concentration of 5-HT was decreased, but not significantly, 7 days following a single administration of MDMA (10 mg/kg, sc.). However, 7 days following the concomitant treatment with DOI and MDMA the striatal concentration of 5-HT was significantly less than that in rats treated with MDMA alone or the vehicle-treated controls. It is concluded that activation of 5-HT2 receptors is an important determinant of the acute increase in extracellular dopamine and, consequently, the long-term depletion of brain 5-HT produced by MDMA.