Kikumoto O, Okamoto Y, Hayakawa H, Yokota N, Kawai K, Motohashi N, Yamawaki S
Department of Neurology and Psychiatry, Hiroshima University School of Medicine, Japan.
Yakubutsu Seishin Kodo. 1993 Feb;13(1):39-42.
Effects of risperidone (RIS, 1 mg/kg) and haloperidol (HPD, 1 mg/kg) on catalepsy, and monoamine and GABA metabolism were examined in the rats. Catalepsy was evaluated by means of a horizontal bar method. The rats were sacrificed 3 h after orally administered HPD or RIS. Levels of monoamines and their metabolites determined by HPLC-ECD, and GABA levels were determined by a radioreceptor assay. The score of catalepsy was significantly low 120 min after administration of RIS as compared to HPD. In comparison to control, HPD treatment significantly increased DOPAC in the frontal cortex, thalamus + hypothalamus, and striatum, and HVA in the striatum. In RIS-treated rats, DOPAC and HVA were significantly increased in the striatum. Moreover, RIS increased 5-HIAA in the frontal cortex, hippocampus, thalamus + hypothalamus, mid brain, pons and striatum. The concentration of GABA was unchanged in all areas of the brain after treatment with HPD, but was significantly decreased in the pons in RIS-treated rats. The present results suggested that the effects of RIS on serotonin and GABA metabolism may be related to the cause of the low potency of RIS to induce catalepsy.
研究了利培酮(RIS,1毫克/千克)和氟哌啶醇(HPD,1毫克/千克)对大鼠僵住症以及单胺和GABA代谢的影响。采用水平杆法评估僵住症。在口服HPD或RIS 3小时后处死大鼠。通过高效液相色谱-电化学检测法测定单胺及其代谢产物的水平,通过放射受体分析法测定GABA水平。与HPD相比,给药120分钟后RIS组的僵住症评分显著降低。与对照组相比,HPD处理显著增加了额叶皮质、丘脑+下丘脑和纹状体中的3,4-二羟基苯乙酸(DOPAC)以及纹状体中的高香草酸(HVA)。在接受RIS治疗的大鼠中,纹状体中的DOPAC和HVA显著增加。此外,RIS增加了额叶皮质、海马体、丘脑+下丘脑、中脑、脑桥和纹状体中的5-羟吲哚乙酸(5-HIAA)。HPD处理后大脑所有区域的GABA浓度均未改变,但接受RIS治疗的大鼠脑桥中的GABA浓度显著降低。目前的结果表明,RIS对5-羟色胺和GABA代谢的影响可能与RIS诱导僵住症效力较低的原因有关。