Roles of perirhinal and posterior piriform cortices in control and generation of seizures: a microinfusion study in rats exposed to soman.
Identification of critical receptors in seizure controlling brain regions may facilitate the development of more efficacious pharmacological therapies against nerve agent intoxication. In the present study, a number of drugs with anticonvulsant potency were microinfused into the perirhinal cortex (PRC) or posterior piriform cortex (PPC) in rats. The drugs used exert cholinergic antagonism (scopolamine), glutamatergic antagonism (ketamine, NBQX), both cholinergic and glutamatergic antagonism (procyclidine, caramiphen), or GABAergic agonism (muscimol). The results showed that in the PRC anticonvulsant efficacy against soman-induced seizures (subcutaneously administered) was achieved by procyclidine or NBQX, but not by ketamine, scopolamine, caramiphen, or muscimol (Experiment 1). Hence, both muscarinic and glutamatergic NMDA receptors had to be antagonized simultaneously or AMPA receptors alone, suggesting increased glutamatergic activation in the PRC before onset of seizures. In the PPC, anticonvulsant effects were assured by scopolamine or muscimol, but not by procyclidine, caramiphen, NBQX, or ketamine (Experiment 2). Thus, muscarinic and GABA(A) receptors appear to be the critical ones in the PPC. Microinfusion of soman into the PRC or PPC resulted in sustained seizure activity in the majority of the rats of both infusion categories. The rhinal structures encompassed in this study apparently have critical functions as both control and trigger sites for nerve agent-evoked seizures.
Myhrer
Trond
T
Norwegian Defence Research Establishment, Protection Division, Kjeller, Norway. trond.myhrer@ffi.no
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Siri
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Aas
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D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D018755:GABA Agonists / Q000009:adverse effects; D008297:Male; D018727:Muscarinic Antagonists / Q000009:adverse effects; D009118:Muscimol / Q000009:adverse effects; D011352:Procyclidine / Q000627:therapeutic use; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000009:adverse effects; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology*; D012999:Soman; D018709:Statistics, Nonparametric
D000927:Anticonvulsants; D018755:GABA Agonists; D018727:Muscarinic Antagonists; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D009118:Muscimol; D012999:Soman; D011352:Procyclidine; D012601:Scopolamine