See R E, Chapman M A
Department of Psychology, Washington State University, Pullman 99164-4820.
Eur J Pharmacol. 1994 Oct 3;263(3):269-76. doi: 10.1016/0014-2999(94)90722-6.
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 gamma-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.
给大鼠在饮用水中慢性给予氟哌啶醇或氯氮平6个月，使用计算机化视频分析系统监测其口腔运动的变化。接受氟哌啶醇治疗的动物表现出小幅度口腔运动的迟发性增加以及1-2赫兹范围内口腔运动百分比的增加，同时通过快速傅里叶分析确定高频范围（>6赫兹）内的口腔运动减少。相比之下，接受氯氮平治疗的大鼠中等幅度口腔运动减少，但在不同频率的口腔运动分布上未显示出显著变化。然后在口服给药期间和停药3天后，通过颅内微透析评估腹外侧纹状体中γ-氨基丁酸（GABA）和谷氨酸的细胞外浓度。给药期间各组之间细胞外GABA和谷氨酸水平无显著差异。然而，停药3天后，氟哌啶醇治疗的大鼠中谷氨酸有显著增加。停药后，氯氮平治疗的大鼠谷氨酸水平无变化，两组的GABA水平也无变化。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在典型抗精神病药物给药后出现，但非典型抗精神病药物给药后未出现。
