THE EFFECTS OF HALOPERIDOL AND CLOZAPINE ON EXTRACELLULAR GABA LEVELS IN THE PREFRONTAL CORTEX OF THE RAT - AN IN-VIVO MICRODIALYSIS STUDY
THE EFFECTS OF HALOPERIDOL AND CLOZAPINE ON EXTRACELLULAR GABA LEVELS IN THE PREFRONTAL CORTEX OF THE RAT - AN IN-VIVO MICRODIALYSIS STUDY
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DOI：
10.1093/cercor/4.1.69
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发表时间：
1994-01-01
期刊：
影响因子：
3.7
通讯作者：
DEUTCH, AY
中科院分区：
文献类型：
--
作者：
BOURDELAIS, AJ;DEUTCH, AY
最近的电生理学和药理学数据表明，多巴胺增强了前额叶皮层（PFC）中间神经元的活性，并诱导这些细胞释放GABA。我们使用在体微透析来研究两种多巴胺受体拮抗剂对清醒、自由活动大鼠前额叶皮层GABA释放的影响。去极化完成氯化钾或藜芦定的局部灌注显着增加细胞外GABA水平的RES。相反，TTX的局部灌注减少细胞外GABA水平的PFC，这些数据表明，细胞外GABA是部分来自神经元，和细胞外水平的抑制性氨基酸是冲动依赖性的。氟哌啶醇急性给药微弱但显著降低PFC细胞外GABA水平;未观察到氟哌啶醇对纹状体细胞外GABA水平的影响。非典型抗精神病药物氯氮平的全身管理显着降低细胞外GABA水平的PFC，但没有改变纹状体GABA水平。因此，释放GABA的中间神经元在RED抑制两种抗精神病药物。这些数据可能表明，不同的D-2样多巴胺受体定位于锥体和非锥体神经元在皮层。
Recent electrophysiological and pharmacological data indicate that dopamine enhances the activity of interneurons in the prefrontal cortex (PFC) and induces the release of GABA from these cells. We used in vivo microdialysis to examine the effects of two dopamine receptor antagonists on GABA release in the prefrontal cortex of awake, freely moving rats. Depolarization accomplished by local perfusion of potassium chloride or veratradine markedly increased extracellular GABA levels in the RES. In contrast, local perfusion of TTX reduced extracellular GABA levels in the PFC, These data indicate that extracellular GABA is derived in part from neurons, and that extracellular levels of the inhibitory amino acid are impulse dependent. The acute administration of haloperidol weakly but significantly decreased extracellular GABA levels in the PFC; no effect of haloperidol on striatal extracellular GABA levels was observed. Systemic administration of the atypical antipsychotic drug clozapine markedly reduced extracellular GABA levels in the PFC, but did not alter striatal GABA levels. Thus, release of GABA from interneurons in the RED is inhibited by two antipsychotic drugs. These data may suggest that different D-2-like dopamine receptors are localized to pyramidal and nonpyramidal neurons in the cortex.