Coordinative Mineralocorticoid and Glucocorticoid Receptor-Mediated Control of Responses to Serotonin in Rat Hippocampus

In a previous study we showed that selective occupation of the mineralocorticoid receptor (MR) in hippocampal slices from adrenalectomized (ADX) rats attenuates the membrane hyperpolarization and resistance decrease induced in CA1 pyramidal neurons by serotonin (5HT). In the present study we established responses to 5HT in the hippocampal slice when not only MRs but also glucocorticoid receptors (GRs) were occupied, using either a combination of selective MR and GR ligands or different concentrations of the endogenous mixed agonist corticosterone. We observed that the GR agonist RU 28362 blocks the attenuating action of the MR agonist aldosterone on responses to 3, 10 and 30-mu-M 5HT; RU 28362 by itself did not affect 5HT responses. If a low concentration of the mixed agonist corticosterone (0.5 nM, close to the Kd for the MR) was continuously perfused in vitro, 5HT responses were steadily depressed with a delay of 2 h, while high levels of corticosterone (5 nM, around Kd for GR) only temporarily reduced 5HT responses. Finally, 5HT responses in slices from sham-operated rats (with relatively high plasma corticosterone levels) were similar to the responses obtained in slices from ADX rats. These data suggest that the previously reported MR-mediated attenuation of 5HT responses may be limited to conditions of low adrenocortical activity or pathophysiological conditions where the balance of MR- and GR-mediated effects is disturbed.