Corticosterone alters 5-HT1A receptor-mediated hyperpolarization in area CA1 hippocampal pyramidal neurons

The 5-hydroxytryptamine1A (5-HT1A) receptor in the CA1 region of the hippocampus is linked through a G protein to an inwardly rectifying potassium conductance. Activation of the 5-HT1A receptor results in a membrane hyperpolarization and decreases neuronal firing rate. The hippocampus contains a high concentration of the mineralocorticoid (MR) and glucocorticoid (GR) corticosterone (CT) receptor subtypes. Some laboratories have reported that CT modulates 5-HT1A receptor binding density and mRNA levels in area CA1 of the hippocampus; however, others have reported no change. Previous electrophysiological studies have demonstrated that acute (1 to 4 hour) MR activation in slices from adrenalectomized (ADX) rats attenuates the 5-HT1A receptor-mediated hyperpolarization, while acute MR+ GR or GR activation alone did not alter the 5-HT1A response. Our results confirm that the 5-HT1A response was attenuated 2 to 8 hours following MR activation. However, we found that GR activation alone decreased the potency, but not the maximal response to 5-HT. Chronic (2-week) treatment with basal levels of CT did not alter the 5-HT1A response. Administration of high concentrations of CT in vitro to neurons from chronically treated ADX rats decreased the magnitude of the 5-HT1A receptor-mediated hyperpolarization. We conclude that the 5-HT1A receptor-effector system in CA1 hippocampal pyramidal neurons is modulated by CT in a dose- and time-dependent manner.