Serial analysis of gene expression in the rat striatum following methamphetamine

用生理盐水或冰毒(40 mg/kg)处理动物，建立SAGE文库，2 h后处死动物。共有315个转录本在两个文库中差异表达(P&lt；0.05)，其中179个(56%)表达上调，136个(44%)表达下调。其中，CAATT增强子结合蛋白同源蛋白(CHOP)/GADD153(生长停滞和DNA损伤诱导基因153)被发现上调了约三倍。对CHOP下游基因(DOCS)表达的分析表明，冰毒诱导它们的表达显著增加。由于DOC1是碳酸氢酶(CA)的类似物，参与了二氧化碳和碳酸氢根离子之间的相互转化，因此我们还研究了冰毒对几种CA表达的影响。冰毒以一种时间依赖的方式显著上调了这些基因。这些结果表明，冰毒部分是通过药物诱导的生理过程的扰动而介导的，这些生理过程依赖于正常的pH和CO(2)动态平衡。

SAGE libraries were generated from animals treated with either saline or METH (40 mg/kg) and sacrificed 2 h later. A total of 315 transcripts were differentially expressed between the two libraries (P < 0.05), with 179 (56%) being upregulated and 136 (44%) being downregulated by the METH injection. Of these, CAATT enhancer-binding protein homologous protein (CHOP)/GADD153 (growth arrest- and DNA damage-inducible gene 153) was found to be upregulated by about threefold. Analysis of the expression of genes downstream of CHOP (DOCs) revealed significant METH-induced increases in their expression. Because DOC1 is an analog of carbonic anhydrase (CA) which is involved in the interconversion between carbon dioxide and the bicarbonate ion, we also measured the effects of METH on the expression of several CAs. These were significantly upregulated by METH in a time-dependent fashion. These results indicate that METH toxicity is mediated, in part, by drug-induced perturbations of physiological processes that are dependent on normal pH and CO(2) homeostasis.