Pharmacological control of seizure activity following nerve agent exposure is critical in reducing neuropathology and improving survival in casualties. Three classes of drugs, anticholinergics, benzodiazepines and excitatory amino acid (EAA) antagonists, have been shown to be effective at moderating nerve agent-induced seizures. However, little is known about which brain structures are involved in producing the anticonvulsant response. This study evaluated drugs from each class, injected directly into one of three specific brain structures, the perirhinal cortex, the entorhinal cortex, or the mediodorsal thalamus, for their ability to modulate seizures induced by the nerve agent soman. The drugs evaluated were the anticholinergic scopolamine, the benzodiazepine midazolam, and the EAA antagonist MK-801. For each drug treatment in each brain area, anticonvulsant ED₅₀ values were calculated using an up-down dosing procedure over successive animals. There was no statistical difference in the anticonvulsant ED₅₀ values for scopolamine and MK-801 in the perirhinal and entorhinal cortices. MK-801 pretreatment in the mediodorsal thalamus had a significantly lower anticonvulsant ED₅₀ value than any other treatment/injection site combination. Midazolam required significantly higher doses than scopolamine and MK-801 in the perirhinal and entorhinal cortices to produce an anticonvulsant response and was ineffective in the mediodorsal thalamus. These findings support the contention that specific neuroanatomical pathways are activated during nerve agentinduced seizures and that the discrete brain structures involved have unique pharmacological thresholds for producing an anticonvulsant response. This study is also the first to show the involvement of the mediodorsal thalamus in the control of nerve agent-induced seizures.

中文翻译：

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涉及梭曼诱发的癫痫发作的大脑结构的神经药理学特异性。

暴露于神经毒剂后癫痫发作活动的药理控制对于减少神经病理学和提高伤亡生存率至关重要。已经显示出三类药物，抗胆碱能药，苯二氮卓类药物和兴奋性氨基酸（EAA）拮抗剂可有效减轻神经药引起的癫痫发作。然而，对于哪种大脑结构参与产生抗惊厥反应知之甚少。这项研究评估了直接注射到三种特定的大脑结构之一的神经周围皮层，内嗅皮层或中间嗅觉丘脑中的每种药物的调制神经药梭曼诱发的癫痫发作的能力。评估的药物是抗胆碱能东pol碱，苯二氮卓咪达唑仑和EAA拮抗剂MK-801。对于每个大脑区域的每种药物治疗，使用连续给药动物的上下给药程序计算抗惊厥ED 50值。东pol碱和内嗅皮质的东pol碱和MK-801的抗惊厥ED₅₀值无统计学差异。在中腹部丘脑中进行的MK-801预处理的抗惊厥ED₅₀值明显低于其他任何治疗/注射部位组合。咪达唑仑在皮层和内层皮层中需要比东pol碱和MK-801更高的剂量才能产生抗惊厥反应，并且在中下丘脑中无效。这些发现支持以下论点：特定的神经解剖通路在神经药诱发的癫痫发作中被激活，并且所涉及的离散脑结构具有产生抗惊厥反应的独特药理学阈值。