Treatment of rats with antipsychotic drugs:: lack of an effect on brain N-acetyl aspartate levels
Treatment of rats with antipsychotic drugs:: lack of an effect on brain N-acetyl aspartate levels
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DOI：
10.1016/s0920-9964(02)00528-5
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发表时间：
2004-01-01
影响因子：
4.5
通讯作者：
Valenzuela, CF
中科院分区：
文献类型：
--
作者：
Bustillo, J;Wolff, C;Valenzuela, CF
背景资料：精神分裂症的质子磁共振波谱（H-1-MRS）研究表明，疾病或抗精神病药物对脑N-乙酰天冬氨酸（NAA）的影响，这是神经元活力的标志物。我们研究了抗精神病药物对大鼠几个脑区NAA的影响，据报道，在长期服药的精神分裂症患者中，NAA减少。研究方法：用氟哌啶醇（6 mg/kg/天）、氯氮平（70 mg/kg/天）和溶剂处理三组大鼠，每组9只，持续6周，然后处死。通过高效液相色谱法（HPLC）测定以下脑区的NAA浓度：皮质、纹状体、丘脑、海马和小脑。结果如下：NAA浓度的混合因子ANOVA显示药物组[ F（2，24）= 0.034; p = 0.966]或脑区相互作用组[ F（8，44）= 0.841; p = 0.572]无显著影响。皮层中NAA较高的区域存在显著的主效应[ F（4，21）= 6.104; p = 0.002]。结论：这些结果与典型和非典型抗精神病药物对大鼠脑中NAA影响的唯一其他研究一致。长期治疗的精神分裂症患者NAA较低，这可能不是抗精神病药物的简单作用。(C)2003 Elsevier Science B. V.保留所有权利。
Background: Proton magnetic resonance spectroscopy (H-1-MRS) studies of schizophrenia suggest an effect of the disease or of antipsychotic medications on brain N-acetyl aspartate (NAA), a marker of neuronal viability. We studied in the rat the effect of antipsychotic drugs on NAA in several brain regions where NAA reductions have been reported in chronically medicated patients with schizophrenia. Methods: Three groups of nine rats each were treated with haloperidol (6 mg/kg/day), clozapine (70 mg/kg/day) and vehicle for 6 weeks and were sacrificed. Concentrations of NAA were determined by high-performance liquid chromatography (HPLC) from the following brain regions: cortex, striatum, thalamus, hippocampus and cerebellum. Results: Mixed-factorial ANOVA of NAA concentrations revealed no significant effect of drug group [ F(2, 24) = 0.034; p = 0.966] or a group by brain region interaction [ F(8, 44) = 0.841; p = 0.572]. There was a significant main effect of region [ F(4, 2 1) = 6.104; p = 0.002] with higher NAA in the cortex. Conclusions: These results are consistent with the only other study of the effect of typical and atypical antipsychotic drugs on NAA in the rat brain. The well-documented lower NAA in chronically treated schizophrenia patients is probably not a simple effect of antipsychotic medications. (C) 2003 Elsevier Science B.V. All rights reserved.