Abstract | AIM: The changes of seizure susceptibility of transgenic mice overexpressing GABA transporter-1 (GAT-1) were studied to clarify the possible role of GABAergic transmission in epileptogenesis. METHODS: RESULTS: The percentages of occurrence of clonic seizures induced by PTZ 45 mg/kg, PIC 2.5 mg/kg, or KA 20 mg/kg in GAT-1 transgenic mice were 88.9 %, 100 %, and 83.3 % respectively, whereas those in control C57BL/6J mice were 42.9 %, 57.1 %, and 33.3 %. The percentages of occurrence of tonic seizures induced by PTZ 45 mg/kg, PIC 2.5 mg/kg, or KA 20 mg/kg in transgenic mice were 88.9 %, 100 %, and 83.3 % respectively, and whereas those in control mice were 28.6 %, 42.9 %, and 16.7 %. The latencies of both clonic and tonic seizures onset in transgenic mice were markedly shortened compared with those in control animals. The results indicated that GAT-1 transgenic mice showed increased susceptibility to seizures induced by the anti-GABAergic convulsive drugs (PTZ, PIC), as well as glutamic receptor agonist (KA). Ethyl nipecotate, inhibitor of GAT-1, inhibited PTZ-induced seizures in both GAT-1 transgenic and C57BL/6J mice. The incidence of seizures was decreased after the application of ethyl nipecotate, and the latencies to the onset of clonic or tonic seizures were also prolonged. CONCLUSION: The increase in seizure susceptibility of transgenic mice over-expressing GAT-1 is an evidence for involvement of GABAergic transmission in epileptogenesis, and this transgenic mouse might be a useful animal model for study on the role of GABAergic transmission in epileptogenesis.
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Authors | Wen-Juan Zhao, Ying-Hua Ma, Jian Fei, Zhen-Tong Mei, Li-He Guo |
Journal | Acta pharmacologica Sinica
(Acta Pharmacol Sin)
Vol. 24
Issue 10
Pg. 991-5
(Oct 2003)
ISSN: 1671-4083 [Print] United States |
PMID | 14531940
(Publication Type: Journal Article)
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Chemical References |
- Anticonvulsants
- Carrier Proteins
- GABA Plasma Membrane Transport Proteins
- Membrane Proteins
- Membrane Transport Proteins
- Nipecotic Acids
- Slc6a1 protein, mouse
- Picrotoxin
- nipecotic acid ethyl ester
- Kainic Acid
- Pentylenetetrazole
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Topics |
- Animals
- Animals, Genetically Modified
- Anticonvulsants
(pharmacology)
- Carrier Proteins
(genetics, metabolism)
- Disease Models, Animal
- Female
- GABA Plasma Membrane Transport Proteins
- Genetic Predisposition to Disease
- Kainic Acid
- Male
- Membrane Proteins
(genetics, metabolism)
- Membrane Transport Proteins
- Mice
- Mice, Inbred C57BL
- Nipecotic Acids
(pharmacology)
- Pentylenetetrazole
- Picrotoxin
- Seizures
(chemically induced, metabolism)
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