Desole M S, Miele M, Enrico P, Esposito G, Fresu L, De Natale G, Miele E
Institute of Pharmacology, University of Sassari, Italy.
Eur J Pharmacol. 1992 Aug 14;219(1):67-74. doi: 10.1016/0014-2999(92)90581-n.
Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid and dehydroascorbic acid (DHAA) were measured by HPLC in the striatum of rats whose fronto-parietal cortex had been unilaterally ablated after a single injection of apomorphine (1 mg/kg s.c.), scopolamine (0.6 mg/kg s.c.) or L-glutamate (500 mg/kg i.p.). Unilateral cortical ablation decreased striatal levels of glutamate in both striata ipsilateral (35%) and contralateral (17-25%) to the lesion. Apomorphine and scopolamine significantly increased (+94 and +122%, respectively) the DHAA/ascorbic acid ratio in the striata ipsilateral to the lesion in unoperated and sham-operated rats (+72 and +34%, respectively), but both drugs failed to increase it in ablated rats. L-Glutamate significantly increased the DHAA/ascorbic acid ratio in unoperated (+53%) and ablated rats (+37%). The increase in sham-operated rats (+34%) did not reach statistical significance. Apomorphine and scopolamine significantly decreased the DOPAC/DA ratio in the striata ipsilateral to the lesion of unoperated, sham-operated and ablated rats. The decrease in the DOPAC/DA ratio induced by apomorphine and scopolamine was greater in ablated rats than in sham-operated rats. L-Glutamate induced only minor changes in striatal DA and DOPAC levels. We conclude that the apomorphine- and scopolamine-induced increase in ascorbic acid oxidation in the striatum requires intact cortico-striatal glutamatergic pathways. Cortical ablation potentiates the apomorphine- and scopolamine-induced inhibition of striatal DA turnover.
在单次注射阿扑吗啡（1毫克/千克，皮下注射）、东莨菪碱（0.6毫克/千克，皮下注射）或L-谷氨酸（500毫克/千克，腹腔注射）后，对大鼠单侧额顶叶皮层进行切除，然后通过高效液相色谱法（HPLC）测量其纹状体中多巴胺（DA）、3,4-二羟基苯乙酸（DOPAC）、抗坏血酸和脱氢抗坏血酸（DHAA）的水平。单侧皮层切除使损伤同侧（35%）和对侧（17 - 25%）纹状体中的谷氨酸水平降低。在未手术和假手术大鼠中，阿扑吗啡和东莨菪碱使损伤同侧纹状体中的DHAA/抗坏血酸比值显著升高（分别为+94%和+122%），在假手术大鼠中也有升高（分别为+72%和+34%），但在切除皮层的大鼠中这两种药物均未能使其升高。L-谷氨酸使未手术大鼠（+53%）和切除皮层的大鼠（+37%）中的DHAA/抗坏血酸比值显著升高。假手术大鼠中的升高（+34%）未达到统计学意义。阿扑吗啡和东莨菪碱使未手术、假手术和切除皮层大鼠损伤同侧纹状体中的DOPAC/DA比值显著降低。阿扑吗啡和东莨菪碱诱导的DOPAC/DA比值降低在切除皮层的大鼠中比在假手术大鼠中更大。L-谷氨酸仅引起纹状体中DA和DOPAC水平的微小变化。我们得出结论，阿扑吗啡和东莨菪碱诱导的纹状体中抗坏血酸氧化增加需要完整的皮质 - 纹状体谷氨酸能通路。皮层切除增强了阿扑吗啡和东莨菪碱诱导的对纹状体DA周转的抑制作用。
