CORTICOSTERONE ALTERS 5-HT1A RECEPTOR-MEDIATED HYPERPOLARIZATION IN AREA CA1 HIPPOCAMPAL PYRAMIDAL NEURONS

The 5-hydroxytryptamine(1A) (5-HT1A) receptor in the CA1 region of the hippocampus is linked through a G protein to an inwardly rectifying p otassium conductance. Activation of the 5-HT1A receptor results in a m embrane hyperpolarization and decreases neuronal firing rate. The hipp ocampus contains a high concentration of the mineralocorticoid (MX) an d glucocorticoid (GX) corticosterone (CT) receptor subtypes. Some labo ratories have reported that CT modulates 5-HT1A receptor binding densi ty and mRNA levels in area CA1 of the hippocampus; however, others hav e reported no change. Previous electrophysiological studies have demon strated that acute (1 to 4 hour) MX activation in slices from adrenale ctomized (ADX) rats attenuates the 5-HT1A receptor-mediated hyperpolar ization, while acute MR + GX or GR activation alone did not alter the 5-HT1A response. Our results confirm that the 5-HT1A response was atte nuated 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 al ter the 5-HT1A response. Administration of high concentrations of CT i n vitro to neurons from chronically treated ADX rats decreased the mag nitude 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.