Chronic haloperidol, but not clozapine, produces altered oral movements and increased extracellular glutamate in rats.
Chronic haloperidol, but not clozapine, produces altered oral movements and increased extracellular glutamate in rats.
复制标题
慢性氟哌啶醇（而不是氯氮平）会改变大鼠的口腔运动并增加细胞外谷氨酸。
DOI：
10.1016/0014-2999(94)90722-6
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发表时间：
1994
影响因子：
5
通讯作者：
Chapman,MA
中科院分区：
文献类型：
--
作者：
See,RE;Chapman,MA
在饮水中长期服用氟哌啶醇或氯氮平6个月的大鼠使用计算机视频分析系统监测口腔运动的变化。氟哌啶醇处理的动物表现出小幅度口腔运动的迟发性增加和1-2赫兹范围内口腔运动百分比的增加，同时如快速傅立叶分析所确定的那样，伴随着高频范围(>；6赫兹)口腔运动的减少。相比之下，氯氮平治疗的大鼠表现出中等幅度的口腔运动减少，但在不同频率的口腔运动分布上没有显著变化。分别于服药时和停药后3d，用脑内微透析法测定腹外侧纹状体细胞外γ-氨基丁酸和谷氨酸的浓度。在给药过程中，细胞外GABA和谷氨酸水平在组间没有显著差异。停药3天后，氟哌啶醇组大鼠血中谷氨酸水平显著升高。停药后，氯氮平治疗组大鼠的谷氨酸水平和两组大鼠的GABA水平均未见变化。这些结果证实了氯氮平在迟发性运动障碍动物模型中的非典型特征，并表明纹状体谷氨酸能功能的改变遵循典型的但不是非典型的抗精神病药物给药。
Rats administered chronic haloperidol or clozapine in their drinking water for 6 months were monitored for changes in oral movements using a computerized video analysis system. Haloperidol-treated animals exhibited late onset increases in small amplitude oral movements and an increase in the percentage of oral movements in the 1–2 Hz range, accompanied by a decrease in oral movements in the higher frequency range (> 6 Hz) as determined by fast fourier analysis. In contrast, clozapine-treated rats showed a decrease in medium-sized amplitude oral movements, but did not demonstrate significant changes in the distribution of oral movements across frequencies. Extracellular concentrations of γ-aminobutyric acid (GABA) and glutamate in the ventrolateral striatum were then assessed by intracranial microdialysis during oral drug administration and 3 days after drug withdrawal. Extracellular GABA and glutamate levels were not significantly different between groups during drug administration. However, 3 days after drug withdrawal, there was a significant increase in glutamate in the haloperidol-treated rats. No changes were noted for glutamate levels in clozapine-treated rats or for GABA levels in either group following withdrawal. These results confirm the atypical profile of clozapine in an animal model of tardive dyskinesia and suggest that alterations in striatal glutamatergic function follow typical, but not atypical, antipsychotic drug administration.