METHAMPHETAMINE NEUROTOXICITY AND STRIATAL GLUTAMATE RELEASE - COMPARISON TO 3,4-METHYLENEDIOXYMETHAMPHETAMINE
METHAMPHETAMINE NEUROTOXICITY AND STRIATAL GLUTAMATE RELEASE - COMPARISON TO 3,4-METHYLENEDIOXYMETHAMPHETAMINE
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DOI：
10.1016/0006-8993(92)90713-j
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发表时间：
1992-05-29
期刊：
影响因子：
2.9
通讯作者：
YAMAMOTO, BK
中科院分区：
文献类型：
--
作者：
NASH, JF;YAMAMOTO, BK
在清醒、自由活动的大鼠中，使用体内微透析研究了重复给予甲基苯丙胺（MA）、3，4-亚甲二氧基甲基苯丙胺（MDMA）或溶剂对细胞外谷氨酸（GLU）、天冬氨酸、牛磺酸、多巴胺（DA）及其代谢产物3，4-二羟基苯乙酸（DOPAC）浓度的影响。MA（7.5 mg/kg，i.p.）每2小时给药一次，共注射3次，增加了前内侧纹状体中GLU的细胞外浓度。相比之下，溶媒和MDMA（9.2和13.8 mg/kg）均未增加重复给药后的GLU外排。MA和MDMA均增加纹状体中DA的细胞外浓度。然而，与MA组相比，MDMA给药动物中DA的累积增加显著更大。MA、MDMA和溶剂重复给药后7天，测定纹状体中DA、5-羟色胺（5-HT）及其代谢产物的浓度。MA，而不是MDMA或车辆，降低纹状体中DA的浓度。相反，MDMA（13.8 mg/kg）降低了5-HT的浓度，而MA、MDMA（9.2 mg/kg）和溶剂对纹状体5-HT含量没有影响。这些数据表明，MA重复给药产生的长期（7天）DA神经毒性部分由GLU细胞外浓度延迟增加介导。与此相反，重复给予MDMA，剂量产生长期（7天）的纹状体5-HT含量耗尽，没有影响GLU流出纹状体。
The effect of repeated administration of either methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA) or vehicle on the extracellular concentrations of glutamate (GLU), aspartate, taurine, dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), was studied in awake, freely moving rats using in vivo microdialysis. MA (7.5 mg/kg, i.p.) administered every 2 h for a total of 3 injections, increased the extracellular concentration of GLU in the anteromedial striatum. By contrast, neither vehicle nor MDMA (9.2 and 13.8 mg/kg) increased GLU efflux following repeated administration. Both MA and MDMA increased the extracellular concentration of DA in the striatum. However, the cumulative increase in DA was significantly greater in the MDMA treated animals as compared to the MA group. The concentrations of DA, serotonin (5-HT) and their metabolites were determined in the striatum 7 days following the repeated administration of MA, MDMA and vehicle. MA, but not MDMA or vehicle, decreased the concentration of DA in the striatum. Conversely, MDMA (13.8 mg/kg) decreased the concentration of 5-HT, whereas MA, MDMA (9.2 mg/kg) and vehicle had no effect on striatal 5-HT content. These data are suggestive that the long-term (7 day) DA neurotoxicity produced by the repeated administration of MA is mediated, in part, by a delayed increase in extracellular concentrations of GLU. In contrast, repeated administration of MDMA, at a dose which produced a long-term (7 day) depletion of striatal 5-HT content, had no effect on GLU efflux in the striatum.