Certain antidepressant medications exert effects on the serotonergic (5-HT) system but their mechanisms are still not well understood. Using extracellular ex vivo recording of spontaneous, epileptiform activity of neurons we determined changes in the reactivity of cortical and hippocampal slices to agonists of main subtypes 5-HT receptors, induced by repeated administration of the antidepressants. Repeated treatment with antidepressants enhances the 5-HT-mediated inhibition in both frontal cortex and hippocampal regions. Drugs administration induce opposite adaptive changes within 5-HT2 and 5-HT1A receptors in frontal cortex as well as in 5-HT1A and 5-HT4 receptors in the hippocampus. These effects may contribute to therapeutic effects of antidepressants administration.