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.