Specific group II metabotropic glutamate receptor activation inhibits the development of kindled epilepsy in rats
Specific group II metabotropic glutamate receptor activation inhibits the development of kindled epilepsy in rats
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DOI：
10.1016/s0006-8993(97)01500-x
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发表时间：
1998-03-23
期刊：
影响因子：
2.9
通讯作者：
Bradford, HF
中科院分区：
文献类型：
--
作者：
Attwell, PJE;Koumentaki, A;Bradford, HF
测试了脑内给予II组代谢型谷氨酸受体激动剂2 R，4 R-APDC对杏仁核点燃发展和完全发展的第5期杏仁核点燃癫痫发作的影响。在8天的时间内，与对照动物相比，2 R，4 R-APDC（10 nmol，0.5 μ l）治疗动物的杏仁核点燃的发展显着延迟。在低剂量下，2 R，4 R-APDC（0.1 nmol）导致完全点燃动物的全身癫痫发作阈值增加42.5 +/- 26.6%。然而，随着给药剂量的增加，全身性癫痫发作阈值的变化不太明显，甚至可以观察到阈值的小幅降低（10 nmol时为-19.6 +/- 5.36%）。激动剂2 R，4 R-APDC抑制去极化诱导的皮质突触体释放[H-3] D-天冬氨酸，IC 50值为0.29 μ M。这种作用在1 μ M时最大，此后随剂量增加而降低。这些结果表明，选择性激活组II代谢型谷氨酸受体的激动剂，如2 R，4 R-APDC可能是治疗癫痫发作疾病的治疗潜力。(C)1998年Elsevier Science B.V.
The effects of intracerebral administration of the group II metabotropic glutamate receptor agonist, 2R,4R-APDC, were tested on both the development of amygdaloid kindling and on fully developed stage 5 amygdala kindled seizures. The development of amygdaloid kindling was significantly retarded in 2R,4R-APDC (10 nmol in 0.5 mu l) treated animals compared to control animals over a period of 8 days. At a low dose, 2R,4R-APDC (0.1 nmol) caused a 42.5 +/- 26.6% increase of the generalised seizure threshold in fully kindled animals. As higher doses were administered, however, the changes in generalised seizure threshold were less marked, and even a small decrease in the threshold was seen (-19.6 +/- 5.36% at 10 nmol). The agonist 2R,4R-APDC inhibited depolarization-induced release of [H-3]D-aspartate from cortical synaptosomes with an IC50 value of 0.29 mu M. This effect was maximal at 1 mu M, and decreased with dose thereafter. These findings suggest that the selective activation of the group II metabotropic glutamate receptors by agonists such as 2R,4R-APDC may be of therapeutic potential in the treatment of seizure disorders. (C) 1998 Elsevier Science B.V.