title: The pilocarpine model of temporal lobe epilepsy: Marked intrastrain differences in female Sprague-Dawley rats and the effect of estrous cycle.
abstract: Rat strains such as Sprague-Dawley (SD) or Wistar are widely used in epilepsy research, including popular models of temporal lobe epilepsy in which spontaneous recurrent seizures (SRS), hippocampal damage, and behavioral alterations develop after status epilepticus (SE). Such rats are randomly outbred, and outbred strains are known to be genetically heterogeneous populations with a high intrastrain variation. Intrastrain differences may be an important reason for discrepancies between studies from different laboratories, but the extent to which such differences affect the development of seizures, neurodegeneration, and psychopathology in post-SE models of epilepsy has received relatively little attention. In the present study, we induced SE by systemic administration of pilocarpine (following pretreatment with lithium) in SD rats from different breeders (Harlan, Charles River [CRL], Taconic) as well as different breeding locations of the same breeder (Harlan-Winkelmann [HW] in Germany vs. Harlan Laboratories [HL] in the Netherlands). Some experiments were also performed in Wistar rats. Pilocarpine was administered by a ramp-up dosing protocol that allows determining interindividual differences in susceptibility to the convulsant. Marked intrastrain differences in induction of SE and its long-term consequences were found. Sprague-Dawley rats from HW were significantly more sensitive to SE induction than all other SD substrains. The majority of SD rats from different vendors developed SRS after SE except SD rats from HL. The CRL-SD rats markedly differed in basal behavior and SE-induced behavioral alterations from other SD substrains. Susceptibility to pilocarpine was hardly affected by the estrous cycle. The marked intrastrain differences provide an interesting tool to study the impact of genetic and environmental factors on seizure susceptibility, epileptogenesis, and relationship between behavior and epilepsy and vice versa.
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Brandt
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Bankstahl
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Töllner
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Klee
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany. Electronic address: wolfgang.loescher@tiho-hannover.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Löscher
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003292:Convulsants; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced* / Q000473:pathology / Q000523:psychology; D030762:Estrous Cycle; D005260:Female; D006624:Hippocampus / Q000473:pathology; D007206:Individuality; D018020:Lithium Compounds / Q000494:pharmacology; D018721:Muscarinic Agonists; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012008:Recurrence; D013045:Species Specificity
chemical_list: D003292:Convulsants; D018020:Lithium Compounds; D018721:Muscarinic Agonists; D010862:Pilocarpine
keywords: Behavior; Hippocampal damage; Seizures; Sprague–Dawley; Status epilepticus; Wistar