Exp Neurobiol.  2013 Jun;22(2):116-123. 10.5607/en.2013.22.2.116.

Tamoxifen Mimics the Effects of Endogenous Ovarian Hormones on Repeated Seizures Induced by Pentylenetetrazole in Rats

Affiliations
  • 1Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 91779-48564, Iran.
  • 2Neurocognitive Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 91779-48564, Iran.
  • 3Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 91779-48564, Iran. EbrahimzadehBA@mums.ac.ir

Abstract

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.

Keyword

tamoxifen; seizure; dark neuron; rat; ovariectomized

MeSH Terms

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