Evaluation of Neurotoxicity Potential in Rats: The Functional Observational Battery

Aurélie Boucard1, Anne‐Marie Bétat1, Roy Forster1, Alain Simonnard1, Guillaume Froget2

1 Centre International de Toxicologie (CIT), Evreux, France, 2 Porsolt & Partners Pharmacology, Boulogne‐Billancourt, France
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 10.12
DOI:  10.1002/0471141755.ph1012s51
Online Posting Date:  December, 2010
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Abstract

This unit describes the functional observational battery (FOB), a behavioral screening procedure commonly used in safety pharmacology and toxicology studies to assess potentially adverse effects of test agents on the central nervous system. The battery includes general observations and the determination of reactivity to various stimuli. Also presented is the severity score index for analyzing individual measurements and evaluations over a range of endpoints. The severity score index can be used to identify, quantify, and describe the effects of compounds on neurological, autonomic, and behavioral functions.Curr. Protoc. Pharmacol. 51:10.12.1-10.12.9. © 2010 by John Wiley & Sons, Inc.

Keywords: neurotoxicity; behavior; screening; safety pharmacology; toxicology; rat

     
 
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Table of Contents

  • Basic Protocol
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

 Basic Protocol
 Materials
  • Male or female rats (Sprague Dawley or Wistar), 6- to 8-weeks-old, body weight 130 to 180 g
  • Test compound
  • Vehicle (0.9% NaCl or any solution in which the test compound can be dissolved)
  • Electronic animal balance, accurate to 0.2 g (e.g., Mettler PM3000)
  • Polycarbonate cages (43.0 cm × 21.5 cm × 18.0 cm) containing autoclaved sawdust
  • Transparent polycarbonate arena (custom made; width: 43 cm, depth: 43 cm, height: 30 cm with an open top)
  • Microchip for animal identification (transponder; Réseaumatique, Bernay, France)
  • Absorbent paper towels
  • Light pen or a small flashlight
  • A clicker or another instrument producing a sound between 55 and 60 dB (D-Day Memorial, Caen, France)
  • Curved forceps for tail pinch response
  • Electronic digital rectal thermometer (e.g., Vedodigit, Artsana)
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Figures

  •  FigureFigure 10.12.1 Effect of clonidine on neurological, autonomic, and behavioral functions. Clonidine at both 1 and 5 mg/kg induces a severe impairment of the CNS functions 4 hr after dosing.
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Literature Cited

Literature Cited
    Baird, S., Catalano, P., Ryan, L., and Evans, J. 1997. Evaluation of effect profiles: Functional observational battery outcomes. Fundam. Appl. Toxicol. 40:37-51.
    Irwin, S. 1968. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioural and physiologic state of a mouse. Psychopharmacologia 13:222-257.
    Mattsson, J.L., Spencer, P.J., and Albee R.R. 1996. A performance standard for clinical and functional observational battery examinations of rats. J. Am. Coll. Toxicol. 15:239-254.
    Moser, V.C. 1992. Applications of neurobehavioral screening battery. J. Am. Coll. Toxicol. 10:661-669.
    Moser, V.C. 2000. Observational batteries in neurotoxicity testing. Int. J. Toxicol. 19:407-411.
    Moser, V.C., Becking, G.C., MacPhail, R.C., and Kulig, B.M. 1997. Workshop overview: The IPCS collaborative study on neurobehavioral screening methods. Fund. Appl. Toxicol. 35:143-151.
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