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E1小鼠癫痫发作中的作用，我们测试了各种药物的抗惊厥作用。我们还定量了刺激和未刺激的E1小鼠及其母体ddY小鼠的全脑和局部脑中的肾上腺素能受体、去甲肾上腺素（NA）、多巴胺（DA）和环腺苷酸（cAMP）。结果表明：（1）E1小鼠脑内NA能系统对E1小鼠癫痫发作起抑制作用。（2）纹状体和小脑的α_1-肾上腺素能受体、大脑皮层、海马和脑干的α_2-肾上腺素能受体在刺激和未刺激的E1小鼠中表达上调;（3）纹状体、海马和额叶皮质的NA含量在刺激后均降低。（4）癫痫发作后海马和纹状体的NA能神经元功能亢进，海马和纹状体的NA能神经元的含量随时间的变化而变化，海马和纹状体的NA能神经元功能亢进。因此，NA能系统对癫痫发作的抑制方式因脑区而异，这种差异可能与E1小鼠癫痫发作的易感性密切相关。5）在受刺激的E1小鼠大脑皮层，c-AMP浓度降低。癫痫发作后，除海马外，其余脑区cAMP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.