PCP(フェンシクリジン)投与により発現誘導される遺伝子cDNAのクローニング

为了阐明苯环利定（PCP）诱导人类精神分裂样精神病和实验动物行为异常的分子机制，我们采用差异筛选法从PCP处理的大鼠大脑皮层cDNA文库中筛选出一个PCP诱导的cDNA克隆，该克隆为谷氨酸脱氢酶（GDH）基因。在PCP给药后15 min，大脑皮层和小脑中GDH mRNA水平均显著升高。即使在蛋白质合成抑制剂放线菌酮（CHX）的存在下也观察到这种效果。与c-fos表达的短暂增加相反，GDH mRNA水平的升高持续长达8天。这些结果表明，GDH mRNA的诱导可能参与PCP所致精神病的病理过程，GDH可能是精神分裂症患者易感的候选基因之一。

To clarify the molecular mechanism of phencyclidine (PCP) -induced schizophreniform psychosis in humans and behavioral abnormalities in ex-perimental animals, we used differential screening of a cDNA library from rat cerebral cortex treated with PCP.We identified a PCP-induced cDNA clone as the gene coding glutamate dehydrogenase (GDH), an enzyme central to glutamate metabolism. GDH mRNA levels significantly increased as imrnediate-early as 15 min following PCP administration in both cerebral cortex and cerebellum. This effect was observed even in the presence of protein synthesis inhibitor, cycloheximide (CHX). In contrast to a transient increase of c-fos expression, the elevation of GDH mRNA level lasted long up to 8 days after PCP injection. These results suggest that GDH mRNA induction may be involved in the pathology of PCP-induced psychosis, and that GDH can be one of the candidate genes which are vulnerable in subjects with schizophrenia.