title: Anticonvulsant effects of damage to structures involved in seizure induction in rats exposed to soman.
abstract: In nerve agent research, it is assumed that the regions from which seizure activity is triggered may offer clues for the designing of effective anticonvulsive therapy. In the present study, selective brain lesions were made to identify critical cholinergic pathways and seizure controlling areas involved in the induction of epileptiform activity in rats challenged with soman. The results showed that rats with bilateral aspiration lesion of the seizure controlling substrate, area tempestas (AT) in the piriform cortex, displayed marked anticonvulsant effects, whereas such effects were not seen when substantia nigra was destroyed. Aspiration lesion of the medial septal area (MS) including the vertical limb of the diagonal band nucleus (DBN) caused increased latency to the onset of convulsions, whereas damage to the nucleus basalis magnocellularis (NBM), nucleus accumbens, or both MS and NBM did not cause anticonvulsant effects. Saporin lesion of MS, DBN (horizontal limb), or MS+DBN had no anticonvulsant effects, suggesting that aspiration lesion of MS disrupted pathways beyond cholinergic ones. Severe aphagia/adipsia and reduced body weight occurred in rats with lesions in the septal area. In separate sham operated rats, a strong positive correlation was found between body weight and latency to onset of convulsions in response to soman. Thus, weight loss and a relatively high dose of soman (1.6 x LD(50)) in this context may have masked potential anticonvulsant effects among some lesioned animals. It is inferred that MS and AT/piriform cortex occur as prime target areas for induction of seizures by soman.
authors.affiliation: Norwegian Defence Research Establishment, Protection Division, Kjeller, Norway. trond.myhrer@ffi.no
authors.forename: Trond
authors.initials: T
authors.lastname: Myhrer
authors.forename: Siri
authors.initials: S
authors.lastname: Enger
authors.forename: Pål
authors.initials: P
authors.lastname: Aas
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D001930:Brain Injuries / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D012999:Soman; D013997:Time Factors
chemical_list: D012999:Soman