EFFECTS OF L-DOPA ON EXTRACELLULAR DOPAMINE IN STRIATUM OF NORMAL AND 6-HYDROXYDOPAMINE-TREATED RATS
EFFECTS OF L-DOPA ON EXTRACELLULAR DOPAMINE IN STRIATUM OF NORMAL AND 6-HYDROXYDOPAMINE-TREATED RATS
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DOI：
10.1016/0006-8993(90)91318-b
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发表时间：
1990-08-13
期刊：
影响因子：
2.9
通讯作者：
ZIGMOND, MJ
中科院分区：
文献类型：
--
作者：
ABERCROMBIE, ED;BONATZ, AE;ZIGMOND, MJ
在体微透析法观察了L-3，4-二羟基苯丙氨酸(L-DOPA)对完整纹状体和经儿茶酚胺能神经毒素6-羟基多巴胺(6-HDA)处理的大鼠纹状体细胞外液中多巴胺(DA)的影响。除非纹状体组织中DA含量降至对照组的20%以下，否则6-HDA对细胞外基础DA水平无明显影响。外周芳香氨基酸脱羧酶(AADC)抑制(RO4-4602，50 mg/kg I.P.)L-多巴酚丁胺(100 mg/kg，ip)。对照组大鼠纹状体细胞外多巴胺从37.+-升高。5至68。+-。11 pg/样品(n=7；根据透析探头的回收校正数值)。在双侧纹状体组织DA严重缺失(平均缺失87%；n=6)的动物中，L多巴使纹状体细胞外DA从8.+-升高。3至266。+-。每个样品60 pg。在单侧纹状体组织DA大量缺失(平均缺失96%；n=6)的动物中，L多巴治疗后损伤侧纹状体细胞外DA的增加幅度更大(从7.+-。4至245。+-。67 pg/样品)，而不是完整的一侧(从28。+-。11至61。+-。8pg/样品)。单侧DA耗竭的动物在L-多巴引流术后出现对侧旋转行为。除L多巴外，用高亲和力DA摄取抑制剂诺米芬新(5 mg/kg i.p；n=5)处理时，细胞外DA的增加接近DA耗竭纹状体的程度。
In vivo microdialysis was used to examine the effect of L-3,4-dihydroxyphenylalanine (L-DOPA) administration upon dopamine (DA) in extracellular fluid both in intact striatum and in striatum of rats treated with the catecholaminergic neurotoxin 6-hydroxydopamine (6-HDA). Basal extracellular levels of DA were not significantly altered by 6-HDA unless the DA content of striatal tissue was reduced to less than 20% of control. Peripheral aromatic amino acid decarboxylase (AADC) inhibition (RO4-4602, 50mg/kg i.p.) followed by L-DOPA treatment (100 mg/kg i.p.) elevated extracellular DA in striatum of control rats from 37 .+-. 5 to 68 .+-. 11 pg/sample (n = 7; values corrected for recovery of the dialysis probe). In animals with severe bilateral depletions of DA in striatal tissue (mean depletion 87%; n = 6) L-DOPA increased extracellular DA in striatum from 8 .+-. 3 to 266 .+-. 60 pg/sample. In animals with large unilateral depletions of DA in striatal tissue (mean depletion 96%; n = 6), the increase in extracellular DA in striatum after L-DOPA was greater on the lesion side (from 7 .+-. 4 to 245 .+-. 67 pg/sample) than on the intact side (from 28 .+-. 11 to 61 .+-. 8 pg/sample). Animals with unilateral DA depletions showed contralateral circling behavior after L-DOPA. Increases in extracellular DA approaching the magnitude of those occuring in DA-depleted striate were observed when intact animals were treated with nomifensine (5 mg/kg i.p.; n = 5), an inhibitor of high-affinity DA uptake, in addition to L-DOPA.