Effects of chronic exposure of NG108-15 cells to morphine or ethanol on binding of nuclear factors to cAMP-response element.

The gel retardation assay with a single-stranded oligo-DNA of cAMP-response element (CRE) in a somatostatin promoter region was selected to examine the possibility of transcriptional regulation of cAMP-inducible genes by chronic morphine or ethanol treatment of NG108-15 cells. When the nuclear extracts from the cells treated with morphine (50 microM) or ethanol (100 mM) for several days were assayed, the amount of DNA-protein complex was decreased about 30-40% compared to that of the control. The decreased complex was recovered by 1-2 days after withdrawal of the drugs. Treatment of the cells with these drugs for 1 h did not change the amount of the DNA-protein complex. Thus, changes in CRE-binding proteins from the cells treated chronically with morphine or ethanol suggest that these drugs can modulate the expression of cAMP-inducible genes through which tolerance and dependence may develop.