ABSTRACT
Introduction: Minocycline has anticonvulsant effects. Since some antiepileptic drugs increase the neurotransmitter GABA in the brain, the aim of this study is the effect of minocycline on gene expression of GABAA receptor in hippocampus and piriform brain areas on amygdale kindling acquisition in rat.
Methods: In this experimental study, three group [24 Wistar rats], after stereotaxic surgery and 1 week recovery period, received kindling stimulations[twice daily at 6 hours interval]. Group 1[n=8] did not receive daily kindling stimulations. Group 2 [n=8] received intraperitoneal saline [1ml/kg] and Group 3 [n=8] received intraperitoeneal minocycline [25 mg/kg] 60 min before kindling stimulation and respectively. Two hours after the last stimulation, animals' brains were removed and the changes of gene expression by ?2 subunit of GABAAreceptor in the hippocampus and piriform cortex were measured and compared with the control group. Data was analyzed using one-way ANOVA and Tukey post hoc tests [P<0/05].
Results: In Group 3 intraperitoneal administration of minocycline for 10 days reduced cumulative ADD significantly reduced in comparison with the control group [Group 2] [P<0.001]; also, it increased significantly the delay time of stage 4 [p<0.01] and stage 5 [p<0.001] of the seizures. In addition, the injection of minocycline before kindling stimulations removed the electrical stimulation induced an increase in mRNA of ?2 subunit of GABAA receptor in hippocampus and piriform cortex of amygdale kindling.
Conclusion: The results of this study showed that minocycline administration before electrical stimulation acts as an anticonvulsant, and this effect occurs via reducing GABAA receptors.
ABSTRACT
Background and purpose: Minocycline has got the anti-inflammatory and neuroprotective effects. Considering the interaction between cell death and seizure, and on the other hand, Kindling which increases expression NMDA receptors in brain, the aim of this study is to investigate the effect of minocycline on gene expression of NMDA receptor in hippocampus and piriform brain areas on amygdale kindling acquisition in rats.
Materials and Methods: In this experimental study, three animal groups of 24 Wistar rats received kindling stimulations [twice daily within 6 hours intervals] after being stereotaxic operated and taking one week recovery period. In first Group [n=8] animals did not received daily kindling stimulations. Animals of the second and the third Groups [n=8] respectively had been injected by saline [1ml/kg] and minocycline [25 mg/kg], 60 minutes before receiving kindling stimulations. Two hours after last stimulation animal's brains were removed and the changes of NR2A gene subunit of NMDA receptor in the hippocampus and piriform cortex were measured and compared relative to the control group. Datawere analyzed using ANOVA and Tukey post hoc tests at significant level of P<0/05.
Results: Intraperitoneal administration of minocycline before kindling stimulations prevented an increase in the mRNA of NR2A subunit of NMDA receptor in hippocampus and piriform cortex of amygdala kindling.
Conclusion: The results of this study have shown that minocycline administration before electrical stimulation has anticonvulsant effects which are applied through a decrease in expression of NMDA receptors.