A role for the mineralocorticoid receptor in a rapid and transient suppression of hippocampal 5-HT1A receptor mRNA by corticosterone.
The interaction between corticosterone and hippocampal 5-HT1A receptor mRNA expression was investigated in male rats. Two days after adrenalectomy, 5-HT1A receptor mRNA was increased in the granule cell layer of the dentate gyrus. Injection of corticosterone led to a significant dose-dependent and transient suppression of 5-HT1A receptor mRNA. The effect of a low dose of corticosterone (50 micrograms/kg) could be blocked by RU 28318, a specific mineralocorticoid receptor antagonist, but not by RU 38486, a glucocorticoid antagonist. The effect of a higher dose of corticosterone (300 micrograms/kg) could be partially blocked by RU 28318, whereas there was no additional effect of RU 38486. These results point to a stringent regulation of hippocampal 5-HT1A receptors by corticosterone that is predominantly mediated by the mineralocorticoid receptor.
Meijer
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Leiden/Amsterdam Center for Drug Research, Sylvius Laboratories, The Netherlands.
de Kloet
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D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000096:biosynthesis*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011985:Receptors, Serotonin; D013148:Spironolactone; D015735:Mifepristone; C041006:RU 28318; D003345:Corticosterone