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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 2007
Externally publishedYes

Fingerprint

phenobarbital
Phenobarbital
seizures
Shock
Seizures
Dogs
dogs
Reaction Time
dosage
Rodentia
rodents
Logistic Models
Tonic-Clonic Epilepsy
drugs
electric current
Pharmaceutical Preparations
Cross-Over Studies
Canidae
animals
pretreatment

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

Cite this

Territo, P., Freise, K. J., Newhall, K., Barnhart, S. D., Peters, S. C., Engleking, D. R., ... 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

Development and validation of the maximal electro-shock seizure model in dogs. / Territo, Paul; Freise, K. J.; Newhall, K.; Barnhart, S. D.; Peters, S. C.; Engleking, D. R.; Burnett, T. J.; Abdul-Karim, B.; Shannon, H. E.

In: Journal of Veterinary Pharmacology and Therapeutics, Vol. 30, No. 6, 12.2007, p. 508-515.

Research output: Contribution to journalArticle

Territo, P, Freise, KJ, Newhall, K, Barnhart, SD, Peters, SC, Engleking, DR, Burnett, TJ, Abdul-Karim, B & Shannon, HE 2007, 'Development and validation of the maximal electro-shock seizure model in dogs', Journal of Veterinary Pharmacology and Therapeutics, vol. 30, no. 6, pp. 508-515. https://doi.org/10.1111/j.1365-2885.2007.00906.x
Territo, Paul ; Freise, K. J. ; Newhall, K. ; Barnhart, S. D. ; Peters, S. C. ; Engleking, D. R. ; Burnett, T. J. ; Abdul-Karim, B. ; Shannon, H. E. / Development and validation of the maximal electro-shock seizure model in dogs. In: Journal of Veterinary Pharmacology and Therapeutics. 2007 ; Vol. 30, No. 6. pp. 508-515.
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