Cyclosporine lowers seizure threshold in an experimental model of electroshock-induced seizures in Munich-Wistar rats.
We have developed a model of cyclosporin A (CsA) central nervous system toxicity in the Munich-Wistar rat in which CsA, 20 mg/kg/day i.p., produces significant EEG abnormalities and mortality. In the present study we used cohorts of Munich-Wistar rats to assess effects of CsA on the threshold for tonic-clonic electroshock-induced seizures. Rat cohorts were begun on cremephore, CsA-10 mg/kg/day, or CsA-20 mg/kg/day. On day 7 and day 14 of the dosing protocol, cohorts of animals were exposed to maximal electroshock (MES) using a minimal staircase method within each cohort. Multiple logistic regression models were used to determine differences between groups on the relative odds of producing a MES-induced seizure while controlling for other variables. Seizure threshold was significantly affected by shock amperage and body weight, but not by SUN, creatinine, bilirubin, sodium, potassium, weight loss or day the shock was delivered. The odds ratios of seizure induction in the CsA-treated groups versus placebo group were 1.91 for CsA-10 mg/kg/day and 3.63 for CsA 20-mg/kg/d, both statistically significant. These results suggest that cyclosporine lowers seizure threshold and probably increases susceptibility to seizures, the etiology of which may be multifactorial clinically.
Racusen
L C
LC
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
McCrindle
B W
BW
Christenson
M
M
Fivush
B
B
Fisher
R S
RS
D000818:Animals; D001663:Bilirubin / Q000097:blood; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000633:toxicity*; D004195:Disease Models, Animal; D004597:Electroshock; D008297:Male; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D012640:Seizures / Q000139:chemically induced*; D012964:Sodium / Q000097:blood
D003524:Cyclosporins; D012964:Sodium; D003404:Creatinine; D001663:Bilirubin; D011188:Potassium