DISTRIBUTION OF FOS-RELATED AND JUN-RELATED PROTEINS AND ACTIVATOR PROTEIN-1 COMPOSITE FACTORS IN MOUSE-BRAIN INDUCED BY NEUROLEPTICS

The mechanisms by which the direct actions of neuroleptics ape transla ted into therapeutic effects are unknown. We immunocytochemically inve stigated the expression of Fos- and Jun-related proteins and examined activator protein-1 DNA-binding activity in ddY mouse brain 120 min af ter the administration of haloperidol (1 mg/kg), (-)-sulpiride (20 mg/ kg) and a selective dopamine D-1 receptor antagonist, SCH23390 (1 mg/k g). The densities of Fos-, FosB-, Fra-1-, Jun- and JunD-immunoreactive nuclei induced by haloperidol and sulpiride in the hippocampus, pirif orm cortex and accumbens nucleus were higher than those in the control groups. The same regions showed higher densities of FosB-, Fra-1- and JunD-immunoreactive nuclei induced by SCH23390 compared with the cont rol groups. We investigated further the activator protein-1 composite factors using super gel shift assays. These results suggested that ind uced Fos, FosB, Fra-1, Jun and JunD proteins constitute the activator protein-1 complex after the administration of haloperidol and sulpirid e. In contrast, FosB, Fra-1 and JunD appear to constitute the activato r protein-1 complex after the administration of SCH23390. Therefore, t he diversity of activator protein-1 composite factors suggests that va rious kinds of gene are induced to act by some neuroleptics. (C) 1998 IBRO. Published by Elsevier Science Ltd.