Abstract

This study tested whether imipramine reverses adaptive modifications in the function of hippocampal 5-HT 1A and 5-HT 4 receptors induced by repetitive administration of corticosterone. Rats received corticosterone for 1 or 3 weeks or imipramine for 2 weeks. The fourth experimental group was treated with corticosterone for 3 weeks and additionally with imipramine, beginning on the eighth day of corticosterone administration. Hippocampal slices were prepared 48 h after the last drug administration. 5-HT 1A and 5-HT 4 receptor-mediated effects on CA1 population spike amplitude were measured. While repeated corticosterone attenuated the inhibitory effect of 5-HT 1A receptor activation by 8-OH-DPAT and enhanced the excitatory effect of 5-HT 4 receptor activation by zacopride, imipramine treatment of naïve rats resulted in opposite changes. In the corticosterone plus imipramine group, the effect of 8-OH-DPAT and zacopride were not different from control, indicating that corticosterone-induced adaptive changes in the reactivity of 5-HT 1A and 5-HT 4 receptors were reversed by imipramine treatment.

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