In the present study, the effects of tamoxifen on pentylenetetrazole (PTZ)-induced repeated seizures and hippocampal neuronal damage in ovariectomized rats were investigated. Thirty seven virgin female Wistar rats were divided to: (1) control, (2) sham-PTZ, (3) sham-PTZ-tamoxifen (sham-PTZ-T), (4) Ovariectomized -PTZ (OVX-PTZ) and (5) OVX-PTZ-tamoxifen (OVX-PTZ-T) groups. The animals of groups 3 and 5 were injected by tamoxifen (10 mg/kg) on 7 consecutive days. After 7 days of tamoxifen injection, they also were then injected by tamoxifen 30 min prior each PTZ injection. PTZ (40 mg/kg) was injected on 6 consecutive days and the animal behaviors were observed for 60 min. The histological methods were then used to determine dark neurons in hippocampus. A significant decrease in the seizure score was seen in OVX-PTZ group compared to Sham-PTZ. The animals of OVX-PTZ-T group had a significant higher seizure score compared to OVX-PTZ group. The dark neurons in DG of OVX group were lower than sham group (p<0.01). The numbers of dark neurons in CA1 area of OVX-PTZ-T group was higher than OVX-PTZ group (p<0.05) compared to control, the numbers of dark neurons in CA3 area showed a significant increase in Sham-PTZ and OVX-PTZ group (p<0.05 and p<0.01 respectively). Dark neurons in OVX-PTZ-T group were higher than OVX-PTZ group (p<0.05). It is concluded that pretreatment of the ovariectomized rats by tamoxifen increased PTZ-induced seizure score and dark neurons. It might be suggested that tamoxifen has agonistic effects for estrogen receptors to change the seizure severity.

Keywords: tamoxifen, seizure, dark neuron, rat, ovariectomized