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-pro tein binding (ISDB), for investigating the distribution and changes of DNA binding activity of transcription factors in the brain. Using thi s method, we found that cAMP response element (CRE) binding activity w as decreased by chronic morphine treatment in specific regions includi ng the amygdala complex, thalamus, cerebral cortex and hypothalamus in mouse brain. This effect persisted for at least 14 days after the ces sation of morphine. These data suggest that chronic morphine treatment elicits a long-term change in cAMP-mediated gene expression in the br ain.