Research for the Involvement of Noradrenergic System in the Seizures of Epileptic El Mice

为了阐明去甲肾上腺素能系统在癫痫小鼠癫痫发作中的作用，我们测试了不同药物的抗惊厥作用。我们还对受刺激和未受刺激的E1小鼠及其母系ddy小鼠的全脑和局部脑中去甲肾上腺素(NA)、多巴胺(DA)和环磷酸腺苷(CAMP)的肾上腺素能受体进行了定量测定。结果如下：1)脑内的脑能系统似乎对癫痫发作有抑制作用。这种抑制作用可能是通过激活α_1和α_2肾上腺素能受体来实现的。2)纹状体和小脑的α_1肾上腺素能受体上调，大脑皮层、海马区和脑干中的α_2肾上腺素能受体在受刺激和未受刺激的情况下均可观察到。4)从癫痫发作后NA翻转和NA含量随时间变化的结果可以看出，海马区NA能神经元功能亢进，纹状体NA能神经元功能亢进。因此，中枢神经系统抑制癫痫发作的方式因脑区不同而不同，这种差异可能与E1小鼠的癫痫敏感性密切相关。5)在受刺激的E1小鼠大脑皮层中，c-AMP含量降低。癫痫发作后，除海马区外，其余脑区c-AMP含量均升高。

To elucidate the role of noradrenergic system in the seizures of epileptic E1 mice, we tested the anticonvulsant effects of various drugs. We also quantitated adrenergic receptors, noradrenaline (NA), dopamine (DA) and cyclic-AMP (cAMP).in the whole brains and regional brains of the stimulated and unstimulated E1 mice, and their maternal ddY mice. Obtained results are as followings;1) NAergic system in the brains of E1 mice seemed to play a inhibitory bole on the seizures of the E1 mice. This inhibition seemed to be mediated by activations of alpha_1 - and alpha_2- adrenoceptors.2) Up-regulations of alpha_1-adrenoceptors in the striatum and cerebellum, alpha_2-adrenoceptors in the cerebral cortex, hippocampus and brainstem were observed in the stimulated and unstimulated E1 mice.3) Decreases of NA contents were observed in the striatum, hippocampus and frontal cortex of the stimulated E1 mice. These decrebtses became to be observed when mice were getting seizure susceptibility.4) From the results of NA turnover and time-dependent change of NA contents after seizures, hyperfunction of NAergic neurons in the hippocampus and hyperfunction of those in the striatum were suggested. Therefore, the manner of inhibition for seizured by NA- ergic system was different by brain regions, and this difference may be closely related the seizure susceptibility of the E1 mice.5) In the cerebral cortex of the stimulated E1 mice, c-AMP concentrations were decreased. After seizures, c-AMP contents increased in all of the brain regions except for hippocampus.