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.
Animals ; Behavior, Animal ; Female ; Hippocampus ; Humans ; Neurons ; Pentylenetetrazole ; Rats ; Rats, Wistar ; Receptors, Estrogen ; Salicylamides ; Seizures ; Tamoxifen

To study the different effects of soy extract on pentylenetetrazole (PTZ)-induced seizures in the presence and absence of ovarian hormones in rats, and the gender-dependent differences in the effects of phytoestrogens on behavior.

Objective: To investigate the effects of soy extract on pentylenetetrazol (PTZ)-induced seizures in ovariectomized (OVX) rats. Methods: Female Wistar rats were randomly divided into 4 groups (n=15 in each group) as follows: sham-operated, OVX, low-dose soy (LDS) and high-dose soy (HDS). The rats in each group were divided into two subgroups and received daily injection of a low dose of PTZ (40 mg/kg body weight, intraperitoneally, n=7 in each subgroup) for 14 d or a single injection of a high dose of PTZ (90 mg/kg body weight, intraperitoneally, n=8 in each subgroup). The rats of LDS and HDS groups were injected with 20 and 60 mg/kg body weight of soy extract intraperitoneally, respectively, just 30 min before each PTZ injection. The rats of the sham-operated and the OVX groups received saline instead of soy extract. After treatment, the rats were placed in a plexiglas cage and their behaviors were observed for 60 min. Results: The results of repeated injection of low dose of PTZ during 14 d showed that the seizure score of the rats of OVX group on days 3, 5, 8, 10, 11, 12, and 13 was lower than that of the sham-operated group (P<0.05 or P<0.01). However, the rats of both LDS and HDS groups had higher score compared with the OVX group on the mentioned days (P<0.05 or P<0.01). The results of a single injection of a high dose of PTZ showed a significant increase (P<0.01) in the generalized tonic-clonic seizure (GTCS), but not the minimal clonic seizure (MCS) in the OVX rats compared with the sham-operated rats. Treatment with both low and high doses of soy extract significantly decreased the GTCS and MCS latencies compared with the OVX group (P<0.01). Conclusion: Female hormones affect seizure severity induced by PTZ, and phytoestrogens of soy mimic this effects. However, more investigations need to be done in the future.