ΔFosB:: a molecular mediator of long-term neural and behavioral plasticity

Delta FosB, a member of the Fos family of transcription factors, is derived from the fosB gene via alternative splicing. Just as c-Fos and many other Fos family members are induced rapidly and transiently in specific brain regions in response to many types of acute perturbations, novel isoforms of Delta FosB accumulate in a region-specific manner in brain uniquely in response to many types of chronic perturbations, including repeated administration of drugs of abuse or of antidepressant or antipsychotic treatments. Importantly, once induced, these Delta FosB isoforms persist in brain for relatively long periods due to their extraordinary stability. Mice lacking the fosB gene show abnormal biochemical and behavioral responses to chronic administration of drugs of abuse or antidepressant treatments, consistent with an important role for Delta FosB in mediating long-term adaptations in the brain. More definitive evidence to support this hypothesis has recently been provided by inducible transgenic mice, wherein biochemical and behavioral changes, which mimic the chronic drug-treated state, are seen upon overexpression of Delta FosB in specific brain regions. This evolving work supports the view that Delta FosB functions as a type of 'molecular switch' that gradually converts acute responses into relatively stable adaptations that underlie long-term neural and behavioral plasticity to repeated stimuli. (C) 1999 Elsevier Science B.V. All rights reserved.