Neuroleptics increase striatal catecholamine metabolites but not ascorbic acid in dialyzed perfusate

To determine the effects of dopamine receptor blockade upon oxidizable components of striatul extracellular fluid, high-performance liquid chromatography (HPLC) with electrochemical detection was used to assay levels of ascorbic acid, dihydroxyphenylacetic acid (DOPAC) homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) in perfusates obtained from unanesthetized rats following i.p. administration of haloperiodol (1.0 mg/kg) or clozapine (20 mg/kg). Striatal push-pull perfusion was performed by passing artificial CSF between two pulled glass micropipets, encapsulated by a hollow, semipermeable cellulose fiber, thereby limiting recovery to compounds under mw 5000. Samples were directly injected into a C-18 column at half-hour intervals before and after neuroleptic administration. Haloperidol administration resulted in increases in extracellular DOPAC and HVA while failing to alter 5-HIAA or ascorbic acid levels. Similar results were found with clozapine, except for a more variable individual response to the drug; clozapine also produced a small increase in 5-HIAA levels. Animals given a saline injection did not show increases in any of these compounds. These data confirm the involvement of extracellular dopamine metabolites in the electrochemical signal increases observed in vivo following dopamine receptor blockade and provide evidence that extracellular ascorbic acid in the striatum is insensitive to peripheral neuroleptic administration.

为了确定多巴胺受体阻断对纹状体细胞外液可氧化成分的影响，采用带有电化学检测的高效液相色谱法（HPLC）测定了在腹腔注射氟哌啶醇（1.0mg/kg）或氯氮平（20mg/kg）后，从未麻醉大鼠获得的灌流液中抗坏血酸、二羟基苯乙酸（DOPAC）、高香草酸（HVA）和5 - 羟基吲哚乙酸（5 - HIAA）的水平。纹状体推拉灌注是通过在两根拉制的玻璃微吸管之间通入人工脑脊液来进行的，这两根微吸管被一根中空的、半透性的纤维素纤维包裹，从而将回收限制在分子量小于5000的化合物。在给予神经安定药之前和之后，每隔半小时将样品直接注入C - 18柱。氟哌啶醇给药导致细胞外DOPAC和HVA增加，但未改变5 - HIAA或抗坏血酸水平。氯氮平也有类似结果，只是个体对药物的反应差异更大；氯氮平还使5 - HIAA水平略有增加。注射生理盐水的动物在这些化合物中没有任何一种出现增加。这些数据证实了细胞外多巴胺代谢产物参与了在体内观察到的多巴胺受体阻断后电化学信号的增加，并提供了证据表明纹状体中的细胞外抗坏血酸对外周神经安定药给药不敏感。