Chen A C, Gurling H M
Molecular Psychiatry Laboratory, Department of Psychiatry and Behavioural Science, University College London Medical School, 46 Cleveland Street, London W1P 6DB, UK.
Brain Res Mol Brain Res. 1999 May 7;68(1-2):14-21. doi: 10.1016/s0169-328x(99)00037-6.
Glutamate receptor function has been hypothesized as an important factor in both the aetiology and treatment of schizophrenia. We have used a multiprobe oligonucleotide solution hybridization (MOSH) technique to examine the regulation of gene expression of the GluR1-7, KA1, and KA2 glutamate receptor subunits in the left rat brain following treatment with the optical isomers of flupenthixol at a dose of 0.2 mg kg-1 day-1 over a period of 4, 12, 24 weeks in order to understand how specific glutamate receptor genes are involved in the treatment of schizophrenia. The GluR2/3 and GluR6/7 subunit immunoreactivity in the right brain following 4 and 24 weeks of drug treatment was also examined by Western blotting. Neither trans- nor cis-flupenthixol was found to alter the gene expression of any of the 9 non-NMDA glutamate receptor subunits. On the other hand, we found a nearly two-fold increase in gene expression of the D2 dopamine receptor in specific brain regions. These results suggest that non-NMDA types of glutamate receptor subunits, in contrast to NMDA receptors, are less likely to have a role in the action of antipsychotic drugs.
谷氨酸受体功能被认为是精神分裂症病因学和治疗中的一个重要因素。我们使用了多探针寡核苷酸溶液杂交（MOSH）技术，以了解特定谷氨酸受体基因如何参与精神分裂症的治疗，研究在12周、24周内，以0.2mg/kg/天的剂量用氟哌噻吨的旋光异构体处理大鼠后，大鼠左脑GluR1-7、KA1和KA2谷氨酸受体亚基的基因表达调控情况。还通过蛋白质免疫印迹法检测了药物治疗4周和24周后右脑GluR2/3和GluR6/7亚基的免疫反应性。未发现反式或顺式氟哌噻吨改变9种非NMDA谷氨酸受体亚基中任何一种的基因表达。另一方面，我们发现特定脑区中D2多巴胺受体的基因表达增加了近两倍。这些结果表明，与NMDA受体相比，非NMDA型谷氨酸受体亚基在抗精神病药物作用中发挥作用的可能性较小。
