5-HT2 receptor-mediated potentiation of dopamine synthesis and central serotonergic deficits.
5-HT2 receptor-mediated potentiation of dopamine synthesis and central serotonergic deficits.
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5-HT2 受体介导的多巴胺合成增强和中枢血清素能缺陷。
DOI：
10.1016/0014-2999(93)90859-g
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发表时间：
1993
影响因子：
5
通讯作者：
Nichols,DE
中科院分区：
文献类型：
--
作者：
Huang,X;Nichols,DE
对5-羟色胺（5-HT）调节3，4-亚甲二氧基甲基苯丙胺（MDMA）诱导的多巴胺合成增加的假设进行了检验。用选择性5-HT 2受体激动剂（R）-1-（2，5-二甲氧基-4-碘苯基）-2-氨基丙烷（R-DOI）、选择性5-羟色胺释放剂5-甲氧基-6-甲基-2-氨基茚满（MMAI）、苯丙胺、MDMA或苯丙胺和R-DOI或MMAI的组合，随后用L-二羟基苯丙氨酸（DOPA）脱羧酶抑制剂3-羟基苄肼（NSD-1015）处理大鼠。首次注射后45分钟处死大鼠，测定纹状体多巴。单独使用R-DOI、NMAI或安非他明不会增加多巴的蓄积。然而，苯丙胺与MMAI或R-DOI的组合显著增加了多巴的积累。多次剂量的R-DOI和安非他明组合在杀死后一周没有减少[3 H]帕罗西汀结合位点。结果表明，MDMA的促多巴胺合成作用既依赖于5-HT_2受体的兴奋，又依赖于多巴胺的外排。
The hypothesis was tested that serotonin (5-HT) modulates 3,4-methylenedioxymethamphetamine (MDMA)-induced increase in dopamine synthesis. Rats were treated with the selective 5-HT2receptor agonist (R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (R-DOI), the selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan (MMAI), amphetamine, MDMA, or a combination of amphetamine and R-DOI or MMAI, followed by the L-dihydroxyphenylalanine (DOPA) decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD-1015). Rats were killed 45 min after the first injection and striatal DOPA was determined. R-DOI, NMAI, or amphetamine alone did not increase DOPA accumulation. However, combination of amphetamine with either MMAI or R-DOI significantly increased DOPA accumulation. Multiple doses of the R-DOI and amphetamine combination did not decrease [3H]paroxetine binding sites at one week after killing. The results indicate that the dopamine synthesis increasing effect of MDMA depends both on 5-HT2receptor stimulation and dopamine efflux.