Abercrombie E D, Bonatz A E, Zigmond M J
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
Brain Res. 1990 Aug 13;525(1):36-44. doi: 10.1016/0006-8993(90)91318-b.
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, 50 mg/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 occurring in DA-depleted striata 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.
采用体内微透析技术，研究左旋多巴（L-DOPA）给药对完整纹状体以及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。除非纹状体组织中的DA含量降至对照的20%以下，否则6-HDA不会显著改变DA的基础细胞外水平。外周芳香族氨基酸脱羧酶（AADC）抑制（RO4-4602，腹腔注射50mg/kg）后给予L-DOPA治疗（腹腔注射100mg/kg），可使对照大鼠纹状体中的细胞外DA从37±5pg/样本升高至68±11pg/样本（n=7；数值已校正透析探针回收率）。在纹状体组织中DA严重双侧耗竭的动物（平均耗竭87%；n=6）中，L-DOPA使纹状体中的细胞外DA从8±3pg/样本增加至266±60pg/样本。在纹状体组织中DA大量单侧耗竭的动物（平均耗竭96%；n=6）中，L-DOPA给药后，纹状体中细胞外DA的增加在损伤侧（从7±4pg/样本增加至245±67pg/样本）比在完整侧（从28±11pg/样本增加至61±8pg/样本）更大。单侧DA耗竭的动物在L-DOPA给药后出现对侧转圈行为。当完整动物除接受L-DOPA治疗外，还接受诺米芬辛（腹腔注射5mg/kg；n=5）——一种高亲和力DA摄取抑制剂治疗时，观察到细胞外DA的增加幅度接近DA耗竭纹状体中的增加幅度。
