Kirkby R D, Forbes R A, Subramaniam S
Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA.
Epilepsy Res. 1996 Jun;24(2):79-90. doi: 10.1016/0920-1211(96)00003-4.
We assessed the effects of N(omega)-nitro-L-arginine-methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), on behavioral and electrographic seizures elicited in mice by convulsant doses of kainate. In Expt. 1, L-NAME dose-dependently potentiated the convulsant effects of kainate (44 mg/kg s.c.), transforming long-latency clonic convulsions into short-latency fits of wild-running, and increased the incidence of kainate-induced mortality. The proconvulsant effects of L-NAME (5 mg/kg i.p.) did not reflect shortened latency to kainate-induced epileptiform afterdischarge recorded via electrodes chronically implanted into the hippocampus, amygdala, frontal cortex or mesencephalic reticular formation (Expt. 2). We also observed a dramatic uncoupling of behavioral and electrographic seizures in mice treated with L-NAME 30 min prior to kainate: 4/6 mice treated with L-NAME failed to express afterdischarge from any of the sites assessed during fits of wild-running. The proconvulsant effects of L-NAME were dependent on the route of administration of kainate, as the inhibitor of NOS failed to alter behavioral (clonic) or electrographic seizures elicited by intrahippocampal kainate (1 nmol, Expt. 3) yet shortened latency to fits of wild-running following i.c.v. kainate (1 nmol, Expt. 4) and reduced the dose of systemic kainate required for either clonic convulsions or wild-running (Expt. 5). The observations that L-NAME potentiates kainate-induced wild-running but not necessarily clonus suggest the involvement of tectopontine mechanisms.
我们评估了一氧化氮合酶（NOS）抑制剂N（ω）-硝基-L-精氨酸甲酯（L-NAME）对惊厥剂量的海藻酸诱发的小鼠行为性和脑电图癫痫发作的影响。在实验1中，L-NAME剂量依赖性地增强了海藻酸（44 mg/kg皮下注射）的惊厥作用，将长潜伏期阵挛性惊厥转变为短潜伏期的狂奔发作，并增加了海藻酸诱导的死亡率。L-NAME（5 mg/kg腹腔注射）的促惊厥作用并未反映出通过长期植入海马、杏仁核、额叶皮质或中脑网状结构的电极记录的海藻酸诱发的癫痫样后放电潜伏期缩短（实验2）。我们还观察到在给予海藻酸前30分钟用L-NAME处理的小鼠中，行为性和脑电图癫痫发作出现了显著的分离：4/6接受L-NAME处理的小鼠在狂奔发作期间未能从任何评估部位表达后放电。L-NAME的促惊厥作用取决于海藻酸的给药途径，因为NOS抑制剂未能改变海马内注射海藻酸（1 nmol，实验3）诱发的行为性（阵挛性）或脑电图癫痫发作，但缩短了脑室内注射海藻酸（1 nmol，实验4）后狂奔发作的潜伏期，并降低了全身性海藻酸诱发阵挛性惊厥或狂奔发作所需的剂量（实验5）。L-NAME增强海藻酸诱导的狂奔发作但不一定增强阵挛这一观察结果提示顶盖脑桥机制的参与。
