Repeated haloperidol administration changes basal release of striatal dopamine and subsequent response to haloperidol challenge
Repeated haloperidol administration changes basal release of striatal dopamine and subsequent response to haloperidol challenge
复制标题
重复给予氟哌啶醇会改变纹状体多巴胺的基础释放以及随后对氟哌啶醇激发的反应
DOI：
10.1016/0006-8993(89)90387-9
复制
发表时间：
1989
期刊：
影响因子：
2.9
通讯作者：
Jau
中科院分区：
文献类型：
--
作者：
Wanqin Zhang;H. A. Tilson;Michal K. Stachowiak;Jau
使用微透析探针研究了急性或重复施用氟哌啶醇对清醒大鼠纹状体释放多巴胺（DA）和高香草酸（HVA）的影响。单次注射氟哌啶醇（1 mg/kg，腹腔注射）可产生灌注液中 DA 和 HVA 的时间依赖性增加。对用 300 mg/kg 水合氯醛腹腔注射麻醉的大鼠进行的比较研究发现麻醉减少了 DA 的基础释放，但不减少 HVA，并显着阻止氟哌啶醇诱导的 DA 增加，而氟哌啶醇诱导的 HVA 增加不受影响。对清醒大鼠进行的研究发现，每天重复注射 21 次氟哌啶醇会增加 DA 的基础释放，但不会增加 HVA。随后用氟哌啶醇进行攻击表明，长期给药的大鼠对氟哌啶醇诱导的 DA 释放的反应性显着降低，但 HVA 没有显着降低。这些数据表明，反复接触氟哌啶醇会导致细胞外 DA 释放补偿性增加。这些代偿性变化可能与重复给药后精神安定药的治疗效果增加或锥体外系副作用有关，值得进一步研究。
The effects of acute or repeated administration of haloperidol on release of dopamine (DA) and homovanillic acid (HVA) from striata of awake rats were studied using a microdialysis probe. A single injection of haloperidol (1 mg/kg, i.p.) produced a time-dependent increase in DA and HVA in the perfusate. Comparative studies in rats anesthetized with 300 mg/kg of chloral hydrate given i.p. found that anesthesia decreased the basal release of DA, but not HVA, and significantly blocked haloperidol-induced increases in DA, while haloperidol-induced increases in HVA were not affected. Studies done in awake rats found that 21 repeated daily injections of haloperidol increased the basal release of DA, but not HVA. Subsequent challenge with haloperidol indicated a significant decrease in responsiveness to haloperidol-induced release of DA, but not HVA, in chronically dosed rats. These data suggest that repeated exposure to haloperidol causes a compensatory increase in extracellular DA release. That these compensatory changes may be associated with the increased therapeutic efficacy or extrapyramidal side effects of neuroleptics following repeated dosing warrants further study.