Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been
implicated in the pathophysiology of depression and stress disorders.
Glucocorticoids, key regulators of stress response, have diverse effects on cellular
processes in the hippocampus. Beside non genomic pathways, glucocorticoids
effects are mediated through activation of the glucocorticoid receptor (GR), a
ligand activated transcriptional factor that belongs to the nuclear hormone receptor
superfamily. We analysed the GR protein level both, in the cytoplasmic and
nuclear compartments in Wistar rat hippocampus, exposed to 3 week social
isolation stress upon chronic fluoxetine treatment. Under chronic stress,
corticosterone level was decreased compared to the control and treatment with
fluoxetine did not change its level significantly in stressed animals. At the
molecular level, fluoxetine significantly decreased the level of nuclear GR protein
in the brain hippocampus of the chronically stressed rats. Fluoxetine reversed the
nuclear level of GR disrupted by chronic psychosocial isolation (CPSI), but it
failed to normalize HPA axis activity
