Decrease In Cre Binding-Activity By Chronic Morphine Administration In Mouse-Brain

RECENT studies have suggested that opiate addiction is associated with transcriptional changes. We developed a novel method, in situ DNA-protein binding (ISDB), for investigating the distribution and changes of DNA binding activity of transcription factors in the brain. Using this method, we found that cAMP response element (CRE) binding activity was decreased by chronic morphine treatment in specific regions including the amygdala complex, thalamus, cerebral cortex and hypothalamus in mouse brain. This effect persisted for at least 14 days after the cessation of morphine. These data suggest that chronic morphine treatment elicits a long-term change in cAMP-mediated gene expression in the brain.