NDLI: Protection Against Sarin-Induced Seizures in Rats by Direct Brain Microinjection of Scopolamine, Midazolam or MK-801

Content Provider	Springer Nature Link
Author	Skovira, Jacob W. McDough, John H. Shih, Tsung Ming
Copyright Year	2009
Abstract	Control of seizure activity is critical to survival and neuroprotection following nerve agent exposure. Extensive research has shown that three classes of drugs, muscarinic antagonists, benzodiazepines, and N-methyl-d-aspartate antagonists, are capable of moderating these seizures. This study began to map the neural areas in rat brain that respond to these three drug classes resulting in anticonvulsant effects. Drugs of each class (scopolamine, midazolam, MK-801) were evaluated for their ability to prevent sarin-induced seizures when injected into specific brain areas (lateral ventricle, anterior piriform cortex, basolateral amygdala, area tempestas). Animals were pretreated by microinjection with saline or a dose of drug from one of the three classes 30 min prior to receiving 150 μg/kg sarin, subcutaneously, followed by 2.0 mg/kg atropine methylnitrate, intramuscularly. Animals were then returned to their cages, where electroencephalographic activity was monitored for seizures. Anticonvulsant effective doses (ED$_{50}$) were determined using an up–down dosing procedure over successive animals. Scopolamine provided anticonvulsant effects in each area tested, while midazolam was effective in each area except the lateral ventricle. MK-801 was only effective at preventing seizures when injected into the basolateral amygdala or area tempestas. The results show a unique neuroanatomical and pharmacological specificity for control of nerve agent-induced seizures.
Starting Page	56
Ending Page	62
Page Count	7
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	40
Issue Number	1-2
e-ISSN	15591166
Language	English
Publisher	Humana Press Inc
Publisher Date	2009-08-19
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Sarin Seizures Microinjection Anticonvulsant Lateral ventricle Anterior piriform cortex Basolateral amygdala Area tempestas Neurology Neurosciences
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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