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.