Mineralocorticoid hormones suppress serotonin-induced hyperpolarization of rat hippocampal CA1 neurons

Pyramidal neurons in the rat CA 1 hippocampal area contain intracellular mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) to which the adrenal hormone corticosterone can bind with differential affinity. The pyramidal neurons also have high amounts of 5-HT1a receptors, which mediate a membrane hyperpolarization. With intracellular recording in vitro, we found that selective occupation of MRs suppresses the 5-HT-induced hyperpolarization of CA 1 pyramidal neurons. The suppression of 5-HT responses was observed 1-4 hr after a brief (20-min) application of the steroids. Binding properties of the 5-HT1a receptor were not significantly affected by in vitro steroid application. Furthermore, responses to the GABA(B) agonist baclofen were not changed after treatment with MR ligands, implying that the K+ conductance to which both GABA(B) and 5-HT1a receptors are linked is also no target for the steroid action. The MR-mediated effect on 5-HT responsiveness potentially enhances cellular activity. Because activation of GRs was previously found to suppress norepinephrine-induced excitability in the same neurons, the data support the concept that cellular homeostasis in the hippocampus is under control of corticosterone via coordinative, antagonistic MR- and GR-mediated events.