Osugi T, Aoki Y, Wang X B, Ikemoto M, Miki N
Department of Pharmacology I, Osaka University School of Medicine, Suita, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1994 Aug;14(4):185-93.
The development of drug tolerance and dependence are thought to be associated with gene expression. Our studies showed that the binding activity of nuclear factors to several DNA sequences is altered by long-term treatment with methamphetamine, cocaine and morphine: 1) the binding activity of AP-1 increased markedly in the mouse brain after administration of methamphetamine and cocaine, 2) CRE-binding activity was decreased by chronic morphine treatment in the amygdala complex, cerebral cortex and hypothalamus of the mouse brain, and 3) the binding activity of single-stranded CRE binding proteins was decreased by chronic morphine treatment in the mouse cerebellum. These data suggest that the changes of DNA binding proteins can be involved in the development of drug tolerance and dependence.
药物耐受性和依赖性的发展被认为与基因表达有关。我们的研究表明，长期使用甲基苯丙胺、可卡因和吗啡会改变核因子与多个DNA序列的结合活性：1）在给予甲基苯丙胺和可卡因后，小鼠脑中AP-1的结合活性显著增加；2）慢性吗啡处理可降低小鼠脑杏仁核复合体、大脑皮层和下丘脑的CRE结合活性；3）慢性吗啡处理可降低小鼠小脑单链CRE结合蛋白的结合活性。这些数据表明，DNA结合蛋白的变化可能参与了药物耐受性和依赖性的发展。
