The neuroprotective effect of tiagabine was investigated in global ischemia in gerbils. Two groups of the animals received 15 mg/kg of tiagabine 30 min before ischemia. In the first group, the temperature was controlled at 37 degrees C from time of injection to 1 h after ischemia. In the second group, the temperature was left uncontrolled to see the hypothermic effect of tiagabine. Microdialysis was performed in CA1 region of hippocampus in half of the animals in each group to assess the levels of glutamate and gamma-amino-butyric acid (GABA). Animal behavior was also tested in 28-day groups in a radial-arm maze. Histology was done 7 and 28 days after ischemia in CA1 region of hippocampus to assess early and delayed effect of drug. A significant suppression of glutamate was noted in both groups (P<0.01). Behavioral results showed that in the temperature-uncontrolled treatment group, animals significantly reduced their working memory errors as compared to the temperature-controlled treatment group. Histology revealed a significant neuroprotection (P<0.001) in the temperature-uncontrolled treatment group. In the temperature-controlled treatment group, however, neuroprotection was insignificant (P>0.05). A third group of animals received the same dose of tiagabine 3 h after ischemia. Temperature was not controlled in this group. The animals were sacrificed after 7 days so no behavior testing was carried out. Histology showed no neuroprotection in this group (P>0.05). These results show that tiagabine offers a significant neuroprotection in global ischemia in gerbils when given 30 min before ischemia but not when given 3 h after ischemia.