Vysokanov A, Flores-Hernandez J, Surmeier D J
Department of Physiology and Institute for Neuroscience, Northwestern University Medical School, Chicago, IL 60611, USA.
Neurosci Lett. 1998 Dec 24;258(3):179-82. doi: 10.1016/s0304-3940(98)00882-9.
The clinical efficacy of clozapine in treating schizophrenia may stem from its lack of receptor selectivity. If true, several clozapine-sensitive receptors may be co-expressed by neurons dysfunctional in schizophrenia. To test this hypothesis, neurons from the rat medial prefrontal cortex were acutely isolated and subjected to single cell RT-PCR analysis. The co-ordinated expression of five clozapine-sensitive receptors (D4, m1, 5-HT2a, 5-HT2c, 5-HT7) was examined in interneurons and pyramidal neurons. Profiling of GABAergic interneurons commonly revealed the co-expression of two or more clozapine-sensitive receptor mRNAs. Although co-expression of these receptors was less extensive in pyramidal neurons, it was also commonly found. These results suggest that clozapine's therapeutic effects may be mediated by antagonism of dopaminergic, cholinergic and serotoninergic signaling pathways at the single cell level.
氯氮平治疗精神分裂症的临床疗效可能源于其缺乏受体选择性。如果这一观点正确，那么精神分裂症中功能失调的神经元可能会共同表达几种对氯氮平敏感的受体。为了验证这一假设，从大鼠内侧前额叶皮质中急性分离出神经元，并进行单细胞逆转录聚合酶链反应（RT-PCR）分析。在中间神经元和锥体神经元中检测了五种对氯氮平敏感的受体（D4、m1、5-羟色胺2A、5-羟色胺2C、5-羟色胺7）的协同表达。对γ-氨基丁酸能中间神经元的分析通常显示两种或更多种对氯氮平敏感的受体mRNA的共同表达。虽然这些受体在锥体神经元中的共同表达范围较小，但也普遍存在。这些结果表明，氯氮平的治疗作用可能是通过在单细胞水平上拮抗多巴胺能、胆碱能和5-羟色胺能信号通路来介导的。
