Corticosteroids alter the 5-HT(1A) receptor-mediated response in CA1 hippocampal pyramidal cells.

The hippocampus, prolonged excessive corticosterone secretion, and the 5-hydroxytryptamine (5-HT) neurotransmitter system are implicated in the etiology and treatment of psychiatric disorders. Corticosterone regulates CA1 hippocampal physiology and the 5-HT(1A) receptor-effector pathway; however the effect of chronic stress levels of corticosterone is unknown. Bilateral adrenalectomy (ADX), adrenalectomy with high dose corticosterone replacement (HCT), or surgical sham (SHAM) treatments were for 2 weeks. Standard intracellular recording techniques were used in hippocampal slices to measure active and passive cellular properties and 5-HT(1A) receptor-mediated responses in CA1 pyramidal cells. The magnitude and half-decay time of the slow after-hyperpolarization (sAHP) were decreased and the membrane time constant (tau) was increased by HCT treatment. The E(max) and EC(50), but not the slope, of the concentration-response curve for 5-HT activation of the 5-HT(1A) receptor were reduced in cells recorded from HCT versus SHAM treated rats. The net effect of treatment with stress levels of corticosterone was to increase the excitability of the CA1 hippocampal pyramidal cell through changes in membrane properties and 5-HT(1A) receptor-mediated response.