title: Induction of audiogenic seizures in imipenem/cilastatin-treated rats.
abstract: We investigated the effect of intense audiogenic stimulation (AGS) on rats treated with the antibiotic imipenem and dipeptidase inhibitor cilastatin (Imi/Cil). Under pentobarbital anesthesia (40 mg/kg) adult male Wistar rats were implanted with electrodes and cannulas were placed in the right lateral ventricle. Animals were divided into the following groups: (1) vehicle, (2) Imi/Cil 10 microg/10 microg, (3) Imi/Cil 25 microg/25 microg, (4) vehicle+AGS, (5) Imi/Cil 10 microg/10 microg +AGS, and (6) Imi/Cil 25 microg/25 microg +AGS. Imi/Cil was administered intracerebroventricularly in 5 microl of physiological saline. AGS (100+/-3 dB, 60 seconds) was applied at 15-minute intervals after the injection. Imi/Cil-induced seizures (twitching, forelimb clonus, headnodding, rearing, and clonic convulsions) and Imi/Cil-audio-induced seizures (wild running, clonic and tonic convulsions) were scored according to appropriate rating scales. Imi/Cil provoked convulsions dose-dependently. Each behavioral seizure response had a characteristic EEG correlate. AGS by itself did not provoke seizures in untreated rats. Sound stimulation in Imi/Cil-injected rats elicited typical audiogenic seizures, which were induced during five AGS tests (75 minutes postinjection). In most cases audiogenic seizures were not associated with epileptiform activity in the EEG, indicating that spreading of seizures did not involve the cortex. Since Imi/Cil-induced and Imi/Cil-audio-induced seizures differed behaviorally and electroencephalographically, it is suggested that different neural pathways are responsible for these two types of seizures: neuronal networks in the cortex are involved in Imi/Cil-induced seizures, whereas audiogenic seizures use networks residing primarily in the brainstem.
authors.affiliation: Institute of Physiology, School of Medicine, University of Belgrade, Visegradska 26/II, 11000 Belgrade, Serbia. zdragana@afrodita.rcub.bg.ac.yu
authors.forename: Dragana
authors.initials: D
authors.lastname: Zivanovic
authors.forename: Olivera
authors.initials: O
authors.lastname: Stanojlovic
authors.forename: Jelena
authors.initials: J
authors.lastname: Stojanovic
authors.forename: Veselinka
authors.initials: V
authors.lastname: Susic
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D015377:Cilastatin / Q000633:toxicity*; D004150:Dipeptidases / Q000633:toxicity*; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000187:drug effects*; D015378:Imipenem / Q000633:toxicity*; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D012815:Signal Processing, Computer-Assisted
chemical_list: D000900:Anti-Bacterial Agents; D015377:Cilastatin; D015378:Imipenem; D004150:Dipeptidases; C038937:dipeptidase