Hope B T, Nye H E, Kelz M B, Self D W, Iadarola M J, Nakabeppu Y, Duman R S, Nestler E J
Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, Connecticut.
Neuron. 1994 Nov;13(5):1235-44. doi: 10.1016/0896-6273(94)90061-2.
Following chronic cocaine treatment, we have found a long-lasting increase in AP-1 binding in the rat nucleus accumbens and striatum, two important targets of the behavioral effects of cocaine. This increase develops gradually over several days and remains at 50% of maximal levels 7 days after the last cocaine exposure. Supershift experiments, along with one- and two-dimensional Western blots, indicate that this chronic AP-1 complex contains at least four Fos-related antigens (FRAs), some of which display delta FosB-like immunoreactivity, that are induced selectively by chronic, but not acute, cocaine treatment. The same chronic FRAs were also induced by several different types of chronic treatments in a region-specific manner in the brain. Thus, the chronic FRAs and associated chronic AP-1 complex could mediate some of the long-term changes in gene expression unique to the chronic-treated state as opposed to the acute-treated and normal states.
经过长期可卡因处理后，我们发现在大鼠伏隔核和纹状体中，AP-1结合出现了长期增加，这两个区域是可卡因行为效应的重要靶点。这种增加在数天内逐渐发展，并在最后一次接触可卡因7天后仍保持在最大水平的50%。超迁移实验以及一维和二维蛋白质印迹表明，这种慢性AP-1复合物至少包含四种Fos相关抗原（FRA），其中一些显示出δFosB样免疫反应性，这些抗原是由长期而非急性可卡因处理选择性诱导产生的。相同的慢性FRA也以区域特异性方式在大脑中由几种不同类型的慢性处理诱导产生。因此，慢性FRA和相关的慢性AP-1复合物可能介导了与急性处理和正常状态相比，慢性处理状态特有的一些基因表达的长期变化。
