MODULATION BY CHRONIC MORPHINE ADMINISTRATION OF SINGLE-STRANDED CAMPRESPONSE ELEMENT (SSCRE) BINDING-PROTEINS IN THE MOUSE CEREBELLUM

The development of opiate tolerance and dependence are thought to be a ssociated with gene expression. Our previous studies have shown that h e binding activity of nuclear factors to a single-stranded oligo-DNA c ontaining cAMP response element (ssCRE) is altered by long term treatm ent with morphine in cultured neuronal cells. In the present experimen ts, the effects of acute and chronic treatments with morphine on the b inding of nuclear proteins to single- and double-stranded oligo-DNAs o f the cAMP response element were studied in the mouse brains by using gel shift assay. The activity of single-stranded CRE binding proteins (ssCRE-BP) was decreased by chronic morphine treatment to about 40% of control in the cerebellum. The effect of chronic morphine treatment o n the binding activity persisted for at least 2 weeks after morphine w ithdrawal. The activity of double-stranded CRE binding proteins was al so detected in the cerebellum, but it was insensitive to the morphine treatment. The activity of ssCRE-BP was also decreased by acute morphi ne treatment in 5 h, but it returned to control level in 24 h. These d ata suggest that the change of ssCRE-BP can be involved in the develop ment of tolerance and dependence.