Dysregulation of the serotonergic system and abnormalities of the hypothala
mic-pituitary-adrenal axis function have been implicated to be involved in
neuropsychiatric disorders, Serotonin-1A receptors have been shown to be su
ppressed by corticosteroid hormones in a variety of animal studies. This ef
fect may play a central role in the pathophysiology of depression. However,
little is known about the molecular mechanism underlying this suppressive
effect of corticosteroids, Here, we show by functional analysis of the prom
oter region of the rat serotonin-1A receptor gene that two NF-KB elements i
n the promoter contribute to induced transcription of the rat serotonin-1A
receptor gene. Furthermore, we show that corticosteroids repress this NF-KB
-mediated induction of transcription. Remarkably, we observed that only the
glucocorticoid receptor and not the mineralocorticoid receptor was able to
mediate this repressive effect of corticosteroids. We argue that negative
crosstalk between the glucocorticoid receptor and NF-KB may provide a basis
for the molecular mechanism underlying the negative action of corticostero
ids on serotonin signaling in the brain.