Riva M A, Tascedda F, Lovati E, Racagni G
Di.Bi.T. San Raffaele Scientific Institute, Milan, Italy.
Brain Res Mol Brain Res. 1997 Oct 15;50(1-2):136-42. doi: 10.1016/s0169-328x(97)00175-7.
Based on anatomical and biochemical observations a role of glutamate in schizophrenia has been postulated. In the present work we have investigated the gene expression for two families of NMDA receptor subunits (NR-1 and NR-2) following acute and chronic treatment with typical (haloperidol) and atypical (clozapine) antipsychotic drug (APD) in rats. A single injection of the two drugs elicited a significant increase in the mRNA levels of NR-2B in the nucleus accumbens, whereas only haloperidol was able to elevate NR-2A and NR-2B in the hippocampus. Following a 21 day treatment, significant differences in the regulatory pattern of NMDA-R subunits were observed. Haloperidol increased their mRNA levels in striatum whereas clozapine, consistent with its relatively weaker influence on nigro-striatal dopamine function, did not change the expression of NR subunits in this region. Both APD's were able to decrease the expression of NR-2 subunits in the hypothalamus, but only clozapine was capable of reducing NR-2C in frontal cortex and accumbens. The regulation of NMDA-R subunits in specific brain regions may represent a novel and important mechanism through which APD's exert some of their effects on brain function.
基于解剖学和生物化学观察结果，已推测谷氨酸在精神分裂症中发挥作用。在本研究中，我们研究了大鼠经典型（氟哌啶醇）和非典型（氯氮平）抗精神病药物（APD）急性和慢性治疗后，两类NMDA受体亚基（NR-1和NR-2）的基因表达情况。单次注射这两种药物均可使伏隔核中NR-2B的mRNA水平显著升高，而仅氟哌啶醇能够提高海马体中NR-2A和NR-2B的水平。经过21天的治疗后，观察到NMDA-R亚基的调节模式存在显著差异。氟哌啶醇可增加纹状体中它们的mRNA水平，而氯氮平由于对黑质-纹状体多巴胺功能的影响相对较弱，并未改变该区域NR亚基的表达。两种APD均可降低下丘脑NR-2亚基的表达，但只有氯氮平能够降低额叶皮质和伏隔核中NR-2C的表达。特定脑区中NMDA-R亚基的调节可能代表了一种新的重要机制，通过该机制APD对脑功能发挥某些作用。
