Regional specific effects of clozapine and haloperidol on GABA and dopamine release in rat basal ganglia.
Regional specific effects of clozapine and haloperidol on GABA and dopamine release in rat basal ganglia.
复制标题
氯氮平和氟哌啶醇对大鼠基底神经节 GABA 和多巴胺释放的区域特异性影响。
DOI：
10.1016/0014-2999(90)90366-e
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发表时间：
1990
影响因子：
5
通讯作者：
Ungerstedt,U
中科院分区：
文献类型：
--
作者：
Drew,KL;O'Connor,WT;Kehr,J;Ungerstedt,U
在大鼠背外侧纹状体、纹状体底部（纹状体的腹侧区域）和苍白球中同时测量s.c.给予氟哌啶醇或氯氮平。在氟烷麻醉的大鼠中通过微透析测量释放。氯氮平（5.0 mg/kg）可增加纹状体底部GABA的释放，氟哌啶醇（0.5 mg/kg）可增加苍白球GABA的释放。相反，氯氮平（2.5-40 mg/kg）不能增加苍白球中GABA的释放，氟哌啶醇（0.1-2.0 mg/kg）不能增加眼底中GABA的释放。因此，氟哌啶醇和氯氮平通过其对纹状体基底和苍白球中GABA释放的影响而明显区分（两种药物均增加背外侧纹状体中的GABA释放）。多巴胺释放增加氟哌啶醇和氯氮平在纹状体的两个区域。然而，除了在纹状体底部，氯氮平诱导的多巴胺和GABA的增加平行发生，这两种药物释放多巴胺比GABA更有效。在灌注介质中加入1 μM河豚毒素可逆转药物诱导的GABA和多巴胺释放增加。这些数据表明：（1）氟哌啶醇和氯氮平对基底神经节GABA释放影响的区域差异可能与这些药物的独特临床特征相似;（2）低剂量氟哌啶醇和氯氮平后背外侧纹状体以及所有有效剂量氟哌啶醇后纹状体基底多巴胺释放增加可能独立于GABA能成分。
γ-Aminobutyric acid (GABA) and dopamine release were measured concomitantly in rat dorsolateral striatum, fundus striati (a ventral region of striatum) and globus pallidus following s.c. administration of haloperidol or clozapine. Release was measured by microdialysis in halothane-anesthetized rats. Clozapine (5.0 mg/kg) increased GABA release in the fundus striati and haloperidol (0.5 mg/kg) increased GABA release in the globus pallidus. In contrast, clozapine (2.5–40 mg/kg) failed to increase GABA release in the globus pallidus and haloperidol (0.1–2.0 mg/kg) failed to increase GABA release in the fundus. Thus, haloperidol and clozapine are clearly distinguished by their effects on GABA release in the fundus striati and globus pallidus (both drugs increased GABA release in the dorsolateral striatum). Dopamine release was increased by haloperidol and clozapine in the two regions of the striatum. However, except in the fundus striati where clozapine-induced inceases in dopamine and GABA occurred in parallel, both drugs were more potent in releasing dopamine than GABA. Drug-induced increases in GABA and dopamine release were reversed by addition of 1 μM tetrodotoxin to the perfusion medium. These data suggest that (1) regional differences in the effects of haloperidol and clozapine on GABA release in the basal ganglia may parallel the unique clinical profiles of these drugs; and (2) increases in dopamine release may occur independently of a GABAergic component in the dorsolateral striatum following low doses of haloperidol and clozapine and in the fundus striati following all effective doses of haloperidol.