Cyclosporine lowers seizure threshold in an experimental model of electroshock-induced seizures in Munich-Wistar rats

Lorraine C Racusen, Brian W. McCrindle, Marie Christenson, Barbara A Fivush, Robert S. Fisher

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1021-1026
Number of pages6
JournalLife Sciences
Volume46
Issue number14
DOIs
StatePublished - 1990

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Electroshock
Cyclosporine
Wistar Rats
Rats
Seizures
Theoretical Models
Shock
Logistic Models
Odds Ratio
Neurology
Electroencephalography
Bilirubin
Toxicity
Logistics
Weight Loss
Creatinine
Potassium
Animals
Cohort Studies
Central Nervous System

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cyclosporine lowers seizure threshold in an experimental model of electroshock-induced seizures in Munich-Wistar rats. / Racusen, Lorraine C; McCrindle, Brian W.; Christenson, Marie; Fivush, Barbara A; Fisher, Robert S.

In: Life Sciences, Vol. 46, No. 14, 1990, p. 1021-1026.

Research output: Contribution to journalArticle

Racusen, Lorraine C ; McCrindle, Brian W. ; Christenson, Marie ; Fivush, Barbara A ; Fisher, Robert S. / Cyclosporine lowers seizure threshold in an experimental model of electroshock-induced seizures in Munich-Wistar rats. In: Life Sciences. 1990 ; Vol. 46, No. 14. pp. 1021-1026.
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