DEXAMETHASONE ATTENUATES KAINATE-INDUCED AP-1 ACTIVATION IN RAT-BRAIN

The goal of this investigation was to determine if administration of t he synthetic glucocorticoid dexamethasone modulates rat brain AP-1 DNA binding activity. Treatment with the selective excitatory amino acid agonist kainate was used to activate AP-1 formation. Kainate (12 mg/kg ) administration induced a biphasic activation of AP-1 in rat cerebral cortex and hippocampus with maximal levels observed at 1.5 h and 4.5 h and lower levels at 3 h and 6 h. Kainate also induced biphasic incre ases in the concentrations of some of the AP-1 constituent proteins (i mmediate early gene protein products), with initial increases of c-Jun , Fos, and Jun B occurring at 1.5 h and secondary larger increases at 4.5 h, but the level of Jun D was not altered by kainate treatment. Pr etreatment with dexamethasone (1 mg/kg) reduced AP-1 activity at both 1.5 h and 4.5 h after kainate administration in both brain regions. De xamethasone pretreatment did not modify the concentrations of the AP-1 constituent proteins obtained after kainate administration except for a reduction of Jun B levels 1.5 h after kainate. These results demons trate that elevated glucocorticoid levels reduce the stimulation by ka inate of AP-1 activity in rat cortex and hippocampus without causing c orresponding decreases in the levels of immediate early gene proteins. Binding of the activated glucocorticoid receptor to c-Jun or Fos is l ikely to contribute to the decreased AP-1 DNA binding activity followi ng dexamethasone treatment.