title: A single episode of juvenile status epilepticus reduces the threshold to adult seizures in a stimulus-specific way.
abstract: We have previously reported that an episode of pentylenetetrazole (PTZ)-induced status epilepticus (SE) in immature rats induces a long-term increase in cholinergic excitation assessed in the adult brain in vitro. In this in vivo work, we tested the responsiveness of adult SE-conditioned rats to pilocarpine and PTZ, two convulsants with different mechanisms of action. Postnatal day (P) 20 Sprague-Dawley juvenile rats were conditioned by an episode of PTZ-induced SE (i.e. a stage 5 seizure of ≥ 20 min, SE-rats). These and their untreated littermates serving as controls (seizure-naïve, SN) were challenged between P60 and P70 with subconvulsive doses of pilocarpine or PTZ, until the manifestation of a stage 5 seizure; results were also analyzed according to gender. Pilocarpine (250 mg/kg) provoked convulsive behavior in 67% of SE-rats vs 13% of SN-rats (p=0.001); of those, 38% of SE-rats vs 4% of SN-rats reached stage 5 (p=0.008); no gender differences were detected. PTZ provoked up to stage 4 seizures at 20 and 30 mg/kg and stage 5 seizures at 50mg/kg in both groups without difference. Nevertheless, stage 5 seizures lasted significantly longer in SE-rats vs SN-rats (p=0.007) and some gender differences were detected. These results show that a juvenile PTZ-induced SE increases the long-term sensitivity to a muscarinic convulsant but not to a non-cholinergic agent, suggesting a stimulus-specific decrease of the adult seizure threshold. They thus raise the possibility that adult subjects with an immature SE history may be particularly sensitive threshold-wise to stimuli that activate cholinergic mechanisms.
authors.affiliation: Laboratory of Animal & Human Physiology, Department of Biological Applications and Technology, Faculty of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Kouis
authors.affiliation: Laboratory of Animal & Human Physiology, Department of Biological Applications and Technology, Faculty of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Mikroulis
authors.affiliation: Laboratory of Animal & Human Physiology, Department of Biological Applications and Technology, Faculty of Health Sciences, University of Ioannina, 45110 Ioannina, Greece. Electronic address: cpsarrop@uoi.gr.
authors.forename: Caterina
authors.initials: C
authors.lastname: Psarropoulou
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D008297:Male; D018721:Muscarinic Agonists / Q000633:toxicity; D010433:Pentylenetetrazole / Q000633:toxicity; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D003292:Convulsants; D018721:Muscarinic Agonists; D010862:Pilocarpine; D010433:Pentylenetetrazole
keywords: GABA(A) channel blocker; Generalized seizures; Immature brain; Muscarinic receptors; Pentylenetetrazole; Pilocarpine