NA+, K+-ATPase activity in the brain of the rats with kainic acid-induced seizures: influence of lamotrigine.
Dinko Vitezić, Jasenka Mršić‐Pelčić, Gordana Župan, Miomira Vitezić, Đulijano Ljubičić, Ante Simonić
Abstract
Dinko Vitezić, Jasenka Mršić‐Pelčić, Gordana Župan, Miomira Vitezić, Đulijano Ljubičić, Ante Simonić
Abstract
OBJECTIVE: Kainic acid (KA) is used as an experimental agent which produces convulsions and neurotoxic lesions. Lamotrigine (LTG) is an antiepileptic drug, a glutamate release inhibitor, with action at the neuronal voltage-gated sodium channel. The aim of the present study was to investigate the Na+-K+-ATPase activity in the hippocampus and cortex of rats with KA-induced convulsions. Further, this study was also designed to investigate the influence of the LTG pre-treatment on the mentioned hippocampal and cortex changes. MATERIALS AND METHODS: The study was carried out on Hannover-Wistar rats. Na+, K+-ATPase activity from hippocampal and temporal cortex tissue was determined two hours after a single subcutaneous KA (8 mg/kg) injection as well as on the third or the fifth experimental day. LTG (30 mg/kg i.p.) was used one hour before KA application and during the next two or four consecutive days. All animals of KA and KA+LTG groups were observed during the first 2 hours after KA application and their behavior was noted. Only animals with characteristically KA-induced behavioral changes observed were used in the study. KA typical behavioral changes were confirmed with electroencephalography. RESULTS: After KA application, Na+, K+-ATPase activity was significantly inhibited. Na+-K+-ATPase activity inhibition in the hippocampus of the LTG pretreated rats on the fifth experimental day was statistically less pronounced than in KA treated rats. The LTG pretreatment showed also a protective effect on the Na+-K+-ATPase activity in the rats' brain cortex. CONCLUSION: KA systemic application induced Na+, K+- ATPase activity inhibition in the rat hippocampus and cortex and LTG pre-treatment showed a partially protective effect on the enzyme activity.
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OBJECTIVE: Kainic acid (KA) is used as an experimental agent which produces convulsions and neurotoxic lesions. Lamotrigine (LTG) is an antiepileptic drug, a glutamate release inhibitor, with action at the neuronal voltage-gated sodium channel. The aim of the present study was to investigate the Na+-K+-ATPase activity in the hippocampus and cortex of rats with KA-induced convulsions. Further, this study was also designed to investigate the influence of the LTG pre-treatment on the mentioned hippocampal and cortex changes. MATERIALS AND METHODS: The study was carried out on Hannover-Wistar rats. Na+, K+-ATPase activity from hippocampal and temporal cortex tissue was determined two hours after a single subcutaneous KA (8 mg/kg) injection as well as on the third or the fifth experimental day. LTG (30 mg/kg i.p.) was used one hour before KA application and during the next two or four consecutive days. All animals of KA and KA+LTG groups were observed during the first 2 hours after KA application and their behavior was noted. Only animals with characteristically KA-induced behavioral changes observed were used in the study. KA typical behavioral changes were confirmed with electroencephalography. RESULTS: After KA application, Na+, K+-ATPase activity was significantly inhibited. Na+-K+-ATPase activity inhibition in the hippocampus of the LTG pretreated rats on the fifth experimental day was statistically less pronounced than in KA treated rats. The LTG pretreatment showed also a protective effect on the Na+-K+-ATPase activity in the rats' brain cortex. CONCLUSION: KA systemic application induced Na+, K+- ATPase activity inhibition in the rat hippocampus and cortex and LTG pre-treatment showed a partially protective effect on the enzyme activity.
Key concepts: Kainic acid, Lamotrigine, Hippocampal formation, Hippocampus, Pharmacology, Epilepsy, Glutamate receptor, Anesthesia