Huang X, Nichols D E
Department of Pharmacology and Toxicology, Purdue University, School of Pharmacy and Pharmacal Sciences, West Lafayette, IN 47907.
Eur J Pharmacol. 1993 Jul 20;238(2-3):291-6. doi: 10.1016/0014-2999(93)90859-g.
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-HT2 receptor 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, MMAI, 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-HT2 receptor stimulation and dopamine efflux.
研究了5-羟色胺（5-HT）是否调节3,4-亚甲基二氧甲基苯丙胺（摇头丸，MDMA）诱导的多巴胺合成增加这一假设。给大鼠注射选择性5-HT2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（MMAI）、苯丙胺、MDMA，或苯丙胺与R-DOI或MMAI的组合，随后注射L-二羟基苯丙氨酸（DOPA）脱羧酶抑制剂3-羟基苄基肼（NSD-1015）。首次注射后45分钟处死大鼠，并测定纹状体DOPA含量。单独使用R-DOI、MMAI或苯丙胺不会增加DOPA的积累。然而，苯丙胺与MMAI或R-DOI的组合显著增加了DOPA的积累。多次注射R-DOI和苯丙胺的组合在处死一周后不会减少[3H]帕罗西汀结合位点。结果表明，MDMA增加多巴胺合成的作用既依赖于5-HT2受体刺激，也依赖于多巴胺外流。
