Opposite effects of antidepressants and corticosterone on the sensitivity of hippocampal CA1 neurons to 5-HT1A and 5-HT4 receptor activation

Using extracellular and intracellular ex vivo recording techniques we studi ed changes in the reactivity of hippocampal pyramidal CA1 neurons to seroto nin (5-HT) and to the 5-HT1A- and 5-HT4 receptor agonists (+/-)-2-dipropyla mino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT) and z acopride, respectively, evoked by repeated electroconvulsive shock (ECS), i mipramine and corticosterone treatments. Rats were subjected to ECS for 1 o r 10 days, treated with imipramine for 1, 7, 14 or 21 days (10 mg/kg p.o., twice daily) and with corticosterone for 7 days (10 mg/kg s.c., twice daily ). Hippocampal slices were prepared 2 days after the last treatment. Activa tion of 5-HT1A receptors decreased the amplitude of population spikes evoke d by stimulation of the Schaffer/collateral-commissural pathway and hyperpo larized CA1 cells. Activation of 5-HT4 receptors increased the population s pike amplitude and decreased the amplitude of slow afterhyperpolarization. Both repeated ECS and imipramine enhanced the effects related to 5-HT1A rec eptor activation and attenuated the effects of 5-HT, receptor activation. T he action of imipramine was significant after a 7-day treatment and reached a maximum after lit daily applications, remaining at the same level in a g roup of animals treated for 21 days. Repeated corticosterone attenuated the inhibitory effect of 5-HT and 8-OH-DPAT on the population spike amplitude and enhanced the increase in population spike amplitude induced by zacoprid e. These findings indicate that antidepressant treatments and repeated cort icosterone have opposite effects on hippocampal responsiveness to 5-HT1A an d 5-HT4 receptor activation. In consequence, antidepressants enhance, where as corticosterone reduces the 5-HT-mediated inhibition of hippocampal CA1 c ells, which may be relevant to the antidepressant and pro-depressant effect s of either treatment, respectively.