The effect of tiagabine on physical development and neurological reflexes and their relationship with the γ-aminobutyric acid switch in the rat cerebral cortex during developmental stages.

In the present study, we focused on γ-aminobutyric acid (GABA) signaling through the γ-aminobutyric acid transporter (GAT) in the developing rat cerebral cortex. Tiagabine was used as a GAT inhibitor. The offspring received injections from birth until postnatal day 21 intraperitoneally. Physical development and neurological reflexes were assessed daily. Tiagabine did not influence body weight, the onset and completion of incisor eruption, or the time to appearance of cliff avoidance. However, the onset and completion of eye opening, ear unfolding, and fur growth occurred earlier in treated pups. Further, the slanted board test and righting reflex showed accelerated development (i.e. decreased time to criterion) when compared with the control group. To determine whether the obtained effects are related to the GABA switch, we examined the protein and mRNA expression of the K(+)-Cl(-) cotransporter KCC2 using western blotting and RT-PCR, respectively. Downregulation of KCC2 mRNA and protein levels was observed when GAT was inhibited. The results may indicate a role of GAT in the neurobehavioral changes that accompany the developmental switch in GABA function.