Schmitt Andrea, Zink Mathias, Petroianu Georg, May Brigitte, Braus Dieter F, Henn Fritz A
Central Institute of Mental Health, PO Box 122120, D-68072 Mannheim, Germany.
Neurosci Lett. 2003 Aug 21;347(2):81-4. doi: 10.1016/s0304-3940(03)00653-0.
Post-mortem studies in schizophrenic patients revealed alterations in glutamate transporter gene expression. The question concerning a possible influence of chronic antipsychotic treatment on these gene expressions, however, remained open. In this study, 11 rats per group were treated with either haloperidol (1.5 mg/kg per day) or clozapine (45 mg/kg per day) over a period of 6 months in doses comparable to clinic application. Gene expression of glial glutamate transporter EAAT2 and the predominantly neuronal glutamate transporter EAAT3 were examined by in situ hybridization. Clozapine significantly downregulated EAAT2 in hippocampal CA1 and parietal cortex and EAAT3 in the cingulate cortex compared to the expression upon haloperidol treatment and controls. Additionally, clozapine decreased EAAT2 in temporal, cingulate and frontal cortex and downregulated EAAT3 in cingulate and infralimbic cortex, striatum and hippocampal CA1 and CA2 compared to controls. Haloperidol downregulated EAAT2 in cingulate and frontal cortex and reduced EAAT3 in nucleus accumbens, infralimbic cortex and hippocampal CA2. We hypothesize that glutamate transporter downregulation by neuroleptics increases glutamatergic action at the postsynaptic neuron and thereby may be related to beneficial antipsychotic effects and side effects.
对精神分裂症患者的尸检研究显示谷氨酸转运体基因表达存在改变。然而，关于慢性抗精神病药物治疗对这些基因表达可能产生的影响这一问题仍未解决。在本研究中，每组11只大鼠接受为期6个月的氟哌啶醇（每天1.5毫克/千克）或氯氮平（每天45毫克/千克）治疗，剂量与临床应用相当。通过原位杂交检测胶质谷氨酸转运体EAAT2和主要神经元谷氨酸转运体EAAT3的基因表达。与氟哌啶醇治疗组和对照组的表达相比，氯氮平显著下调了海马CA1区和顶叶皮质中的EAAT2以及扣带回皮质中的EAAT3。此外，与对照组相比，氯氮平降低了颞叶、扣带回和额叶皮质中的EAAT2，并下调了扣带回和边缘下皮质、纹状体以及海马CA1区和CA2区中的EAAT3。氟哌啶醇下调了扣带回和额叶皮质中的EAAT2，并降低了伏隔核、边缘下皮质和海马CA2区中的EAAT3。我们推测，抗精神病药物导致的谷氨酸转运体下调会增加突触后神经元处的谷氨酸能作用，因此可能与抗精神病药物的有益作用和副作用有关。
