Neuroadaptational changes in DNA binding of stimulatory protein-1 and nuclear factor-kB gene transcription factors during ethanol dependence

To define the molecular basis of ethanol dependence, the changes in gene transcription factor stimulatory protein-1 (SP1) and nuclear factor-kB (NF-kB) DNA binding activities were investigated in the rat cortex and hippocampus during ethanol treatment (15 days) and its withdrawal. It was found that both protracted ethanol treatment and its withdrawal (12, 24, or 72 h) had no effect on NF-kB DNA binding activity in the rat cortex and hippocampus. Time-course studies of the changes in SP1 DNA binding activity during ethanol withdrawal (0, 12, 24, and 72 h) after protracted ethanol exposure indicated that SP1 DNA binding in the rat cortex was significantly decreased at 0 h, and that it remained decreased at 12, 24, and 72 h of withdrawal. On the other hand, SP1 DNA binding activity did not change in the rat hippocampus during ethanol treatment but was significantly decreased at 12, 24, and 72 h of withdrawal. These results suggest the possibility that decreased SP1-dependent gene transcription in the rat cortex and hippocampus may be associated with the molecular mechanisms of ethanol dependence.