REGULATION OF DELTA-FOSB AND FOSB-LIKE PROTEINS BY ELECTROCONVULSIVE SEIZURE AND COCAINE TREATMENTS

Previous work has shown that c-Fos and several Fos-like proteins or Fr as (Fos-related antigens) are induced acutely in brain in response to a wide variety of stimuli. In contrast, several stimuli induce apparen tly distinct Fos-like proteins, termed chronic Fras, after chronic adm inistration. We show that Delta FosB, a truncated splice Variant of Fo sB, responds like the other acute Fras: it is induced rapidly and tran siently in cerebral cortex after acute electroconvulsive seizure (ECS) and in striatum after acute cocaine but does not accumulate after chr onic ECS or cocaine treatment. Although the chronic Fras are immunoche mically related to Delta FosB, they can be distinguished from Delta Fo sB based on their temporal properties in that they are induced after c hronic ECS and cocaine treatments only. Moreover, the chronic Fras and Delta FosB can be distinguished by their migration patterns on one- a nd two-dimensional gel electrophoresis. The chronic Fras, therefore, a ppear to be novel FosB-related proteins. We also provide evidence that the chronic Eras heterodimerize primarily with Jun-D and Jun-B, as op posed to c-Jun. The possibility that AP-1 complexes containing the chr onic Fras function as negative regulators of AP-1 mediated transcripti on is discussed.