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題名 | Effects of Acute Clozapine Administration on Local Cerebral Glucose Utilization in Rats=單次給予Clozapine對大白鼠腦局部葡萄糖代謝的影響 |
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作者 | 蔡世仁; 黃銀河; 黃慧貞; | 書刊名 | 臺灣精神醫學 |
卷期 | 12:2 1998.06[民87.06] |
頁次 | 頁58-65 |
分類號 | 418.21 |
關鍵詞 | 腦局部葡萄糖代謝率; 大白鼠; Clozapine; Haloperidol; Local cerebral glucose utilization; Rats; |
語文 | 英文(English) |
中文摘要 | 目的︰Clozapine較傳統抗精神藥物在治療負性症狀上較有療效且引起較少的錐體外徑副作用。4Clozapine的治療機轉至今仍未清楚,本實驗利用去氧葡萄糖方法來研究Clozapine 對腦部神經核的影響。方法︰四組大白鼠分別單次給予0.1N HCL鹽水、Clozapine 10 mg/kg、Clozapine 40 mg/kg或Haloperidol 0.5 mg/kg腹腔注射。在注射藥物15分鐘後測量腦局部葡萄糖代謝率。結果︰本研究分析Clozapine及Haloperidol注射後在38個腦區腦局部葡萄糖代謝率的改變。低劑量的Clozapine較對照組在大部份腦區有代謝減少但未達顯著差異。高劑量的Clozapine較對照組在11個腦區有顯著的減少腦局部葡萄糖代謝率。Haloperidol組與對照組則無顯著差異。結論︰在高劑量組腦局部葡萄糖代謝率普遍的降低與正子掃描造影在接受Clozapine病人的研究結果相似,此降低的原因可能與Clozapine的腎上腺素受體,膽胺受體或血清促進素受體的拮抗作用有關。在受影響的神經核中,伏核,外側中隔核及視丘內背側核可能與Clozapine的治療效果有關。此外,在黑質網狀系統中也有兩個神經核受影響,此結果與病患的正子掃描造影結果相似,表示雖然Clozapine少引起錐體外徑副作用,但仍會對此系統有影響。 |
英文摘要 | Objective: This study used the autoradiographic [�釮] 2-deoxyglucose method to investigate the effects of acute clozapine administration on local cerebral glucose utilization (LCGU). Methods: Four groups of rats received intraperitoneal injections of either saline (control group), clozapine 10 mg/kg, clozapine 40 mg/kg or haloperidol 0.5 mg/kg. The [�釮]2-deoxyglucose method was used to measure LCGU in 38 different cerebral structures at 15 min after injection. Results: In most of the 38 structures, LCGU tended to decrease after low dose (10 mg/kg) clozapine administration. Clozapine administration at the higher dose (40 mg/kg) produced a generalized reduction of LCGU compared to the control group, with significant change in 11 regions, including the substantia nigra pars reticulata, the subthalamic nucleus and the shell part of the nucleus accumbens. LCGU in rats that received haloperidol was not significantly different from the control group. Conclusion: The reduction of LCGU after 40 mg/kg clozapine treatment in this study is similar to reported following clozapine treatment in humans as measured by positron emission tomography. Among the nuclei affected by clozapine treatment, the nucleus accumbens, the lateral septal nucleus and the mediodorsal nucleus of the thalamus are most likely to be related to its therapeutic effects because of the association of these areas with the etiology of schizophrenia. In addition, two nuclei of the nigrostriatal system also showed metabolic reduction with clozapine. This finding suggests that the relatively low incidence of extrapyramidal side effects in clozapine treatment compared to other typical antipsychotic medications may be due to its special effects on the nigrostriatal system. |
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