Ketanserin selectively blocks acute stress-induced changes in NGFI-A and mineralocorticoid receptor gene expression in hippocampal neurons

T Olsson, A Hakansson, J R Seckl

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Serotonin and glucocorticoids interact at the hippocampus to alter neuronal function. Serotonin and antidepressant drugs increase glucccorticoid receptor and mineralocorticoid receptor gene expression in hippocampal neurons over a few daps. The effects of serotonin are mediated via ketanserin-sensitive ''serotonin-2 type'' receptors and induction of cyclic A-MP, although the subsequent molecular mechanisms are unclear. Recently, we have shown that chronic environmental manipulations which induce glucocorticoid receptor gene expression in specific hippocampal subfields of the rat are associated with congruent induction of the transcription factor NGFI-A (zif268. krox24, egr-1) and repression of AP-2; both factors may bind to the glucocorticoid receptor gene promoter. However, any relationship between serotonin and these transcription factors is unknown. Here. we show that acute restraint stress, which causes serotonin release at the hippocampus, induces hipppocampal NGFI-A, but represses activator protein-2 and mineralocorticoid receptor gene expression within 90 min. These changes are sustained for 4 h, but not 12 h. Ketanserin attenuates the stress-induced rise in NGFI-A and fall in mineralocorticoid receptor gene expression, and partly also the fall in AP-2 messenger RNA expression.

These data suggest that restraint stress, acting via serotonin release and ketanserin-sensitive serotonin receptors, produces rapid, transient and specific changes in transcription factor gene expression in hippocampal neurons. Any link between these effects and the control of glucocorticoid and mineralocorticoid receptor expression with chronic serotonin or antidepressant treatment remains to be elucidated. Copyright (C) 1996 IBRO.

Original languageEnglish
Pages (from-to)441-448
Number of pages8
JournalNeuroscience
Volume76
Issue number2
Publication statusPublished - Jan 1997

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