Effects of selective serotonin reuptake inhibitors on GABAergic inhibition in the hippocampus of normal and pilocarpine induced epileptic rats

Selective serotonin reuptake inhibitors (SSRIs) acting on the serotonin (5-HT) receptors may affect γ-aminobutyric acid (GABA)-ergic transmission. The role of 5-HT in the epileptic hippocampus remains controversial since 5-HT has both convulsive and anticonvulsive effects. We investigated the effects of fluoxetine, paroxetine and citalopram on the GABAergic transmission in the normal and pilocarpine-induced epileptic rat hippocampus using electroencephalogram (EEG), paired-pulse inhibition (PPI) and vesicular GABA transporter (VGAT) immunoreactivity. EEG showed spontaneous spike activities in normal rats treated with citalopram, fluoxetine, or paroxetine. PPIs were reduced in normal rats treated with citalopram or fluoxetine, and this reduction was especially prominent in normal rats treated with citalopram. PPIs were markedly reduced in the epileptic rats treated with citalopram, but not in the epileptic rats treated with paroxetine. Normal rats treated with citalopram or paroxetine showed a greater reduction in the relative density of VGAT immunoreactivity in the hippocampus than the normal control rats. Similarly, epileptic rats treated with citalopram or fluoxetine also showed a greater reduction in the relative density of VGAT immunoreactivity in the hippocampus than the epileptic control rats. These findings suggest that SSRI treatment has a slight influence on GABAergic transmission in the hippocampus. SSRI treatment may increase seizure susceptibility in the normal hippocampus and increase the frequency and intensity of seizures in the epileptic hippocampus. However, whether these differential effects result from a direct effect on GABAergic interneurons or via 5-HT subtype receptors remains to be elucidated.

Research Highlights
► In normal rats, EEG showed spontaneous spike activities following SSRI.
► In normal rats, paired pulse inhibition (PPI) was reduced following SSRI.
► In the epileptic rats, PPI was reduced following citalopram treatment.
► SSRI reduced VGAT expression in the hippocampus of normal and epileptic rats.
► These findings suggest that SSRI treatment influences GABAergic transmission.