INDUCTION OF A LONG-LASTING AP-1 COMPLEX COMPOSED OF ALTERED FOS-LIKEPROTEINS IN BRAIN BY CHRONIC COCAINE AND OTHER CHRONIC TREATMENTS

Following chronic cocaine treatment, we have found a long lasting incr ease in AP-1 binding in the rat nucleus accumbens and striatum, two im portant targets of the behavioral effects of cocaine. This increase de velops gradually over several days and remains at 50% of maximal level s 7 days after the last cocaine exposure. Supershift experiments, alon g with one and two-dimensional Western blots, indicate that this chron ic AP-1 complex contains at least four Fos-related antigens (FRAs), so me of which display Delta FosB-like immunoreactivity, that are induced selectively by chronic, but not acute, cocaine treatment. The same ch ronic FRAs were also induced by several different types of chronic tre atments in a region-specific manner in the brain. Thus, the chronic FR As 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.