Development and validation of the maximal electro-shock seizure model in dogs

P. R. Territo, K. J. Freise, K. Newhall, S. D. Barnhart, S. C. Peters, D. R. Engleking, T. J. Burnett, B. Abdul-Karim, H. E. Shannon

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4 Scopus citations

Abstract

The development and validation of the maximal electro-shock (MES) model using phenobarbital (Pb) as the positive control is described. This approach builds on previous work in rodent model systems, and has been adapted to dogs as a tool for pharmaceutical dose selection. Dogs, like rodents, exhibit generalized convulsions which manifest as progressive clinical signs in a dose (electrical current) dependent fashion. At the limit (300 mA, 200 msec) animals underwent clonic-tonic convulsions consistent with complete generalized (Grand Mal) seizures with a grade 3 clinical score (CS) and a menace response time of 98.5 ± 24.4 sec (n = 8). Pretreatment of animals with Pb at 3, 10, and 30 mg/kg, in a 4-by-4 complete block crossover design (Latin-Square), resulted in a dose-dependant reduction in CS and menace response time. Estimates of plasma Pb concentration taken prior to MES induction showed a similar dose-dependent reduction in CS and menace response time with concentration. Using a cumulative logistic regression model, a predicted 50% probability of a CS = 1 was approximately 11.4 mg/kg. In addition, plasma Pb concentrations predicted a 50% probability of a CS = 1 occurs at plasma Pb concentration of approximately 16.0 μg/mL. Combined these data suggest that MES is a useful model for evaluating generalized convulsions in canines and may provide a tool for dose selection of novel pharmaceutical compounds.

Original languageEnglish (US)
Pages (from-to)508-515
Number of pages8
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume30
Issue number6
DOIs
StatePublished - Dec 1 2007

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ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

Cite this

Territo, P. R., Freise, K. J., Newhall, K., Barnhart, S. D., Peters, S. C., Engleking, D. R., Burnett, T. J., Abdul-Karim, B., & Shannon, H. E. (2007). Development and validation of the maximal electro-shock seizure model in dogs. Journal of Veterinary Pharmacology and Therapeutics, 30(6), 508-515. https://doi.org/10.1111/j.1365-2885.2007.00906.x