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标题：Roles of γ-Aminobutyric AcidB (GABAB) and γ-Hydroxybutyric Acid Receptors in Hippocampal Long-Term Potentiation and Pathogenesis of Absence Seizures
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作者：Masahiro AIZAWA ; Yoshihisa ITO ; Hideomi FUKUDA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1997
卷号：20
期号：10
页码：1066-1070
DOI：10.1248/bpb.20.1066
出版社：The Pharmaceutical Society of Japan
摘要：Experiments were performed to examine the roles of γ-aminobutyric acid_B (GABA_B) and γ-hydroxybutyric acid (GHB) receptors in long-term potentiation (LTP) of the hippocampal CA1 region in vivo and in the genesis of the spike and wave discharges (SWDs) associated with absence seizures. When tetanic stimulation was delivered to the CA3 region, stable LTP was observed in the CA1 region in saline-treated mice. In mice treated with 5 mg/kg baclofen, the population spike amplitude was significantly potentiated by tetanic stimulation and the degree of potentiation was the same as that induced in saline controls. However, this potentiation decayed to the baseline level about 90 min after stimulation. The decay was reversed by pretreatment with 200 mg/kg P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35348), a selective GABA_B receptor antagonist. In mice treated with 50 mg/kg γ-butyrolactone (GBL), a prodrug of GHB, stable LTP was observed 90 min after tetanic stimulation and was greater than that in saline controls. GBL-induced potentiation of LTP was antagonized by 50 mg/kg NCS 382, a putative GHB receptor antagonist. Administration of baclofen (20 mg/kg) or GBL (70 mg/kg) induced absence-like seizures associated with 3-6 Hz SWDs, and CGP 35348 suppressed both baclofen- and GBL-induced SWDs. NCS 382 also attenuated SWDs induced by GBL and baclofen. These results suggest that baclofen and GHB have different effects on LTP in the CA1 region of the hippocampus in vivo, although they have a common mode of action on the thalamocortical functions related to the pathogenesis of absence seizures.
关键词：long-term potentiation;absence seizure;γ-aminobutyric acidB (GABAB) receptor;γ-hydroxybutyric acid (GHB) receptor