Neurobehavioral Screening in Rodents

Virginia C. Moser1

1 null, Apex, North Carolina
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 11.2
DOI:  10.1002/0471140856.tx1102s06
Online Posting Date:  May, 2001
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Abstract

Neurobehavioral evaluations are an important component of screening for neurotoxicological effects. A neurobehavioral test battery is chosen to assess a variety of endpoints, including autonomic, neuromuscular, sensory, and excitability functions. Such a battery includes observation of gait and posture, reactivity and arousal, gait and postural characteristics, involuntary/abnormal motor movements, clinical signs and manipulation of neurological reflexes and reactions and neuromuscular activity and postural reactions. Finally, the battery includes assessment of sensory responses.

     
 
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Table of Contents

  • Observational Assessments
  • Basic Protocol 1: Observation of Spontaneous Activity Levels
  • Basic Protocol 2: Observation of Reactivity and Arousal
  • Basic Protocol 3: Observation of Gait and Postural Characteristics
  • Basic Protocol 4: Observation of Involuntary/Abnormal Motor Movements
  • Basic Protocol 5: Observation of Clinical Signs
  • Manipulative Tests
  • Basic Protocol 6: Assessment of Neurological Reflexes/Reactions
  • Basic Protocol 7: Neuromuscular Tests and Assessment of Postural Reactions
  • Basic Protocol 8: Assessment of Sensory Responses
  • Commentary
  • Tables
     
 
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Materials

Basic Protocol 1: Observation of Spontaneous Activity Levels

  Materials
  • Subject animals
  • Home cage
  • Open field
  • Silent laboratory counter

Basic Protocol 2: Observation of Reactivity and Arousal

  Materials
  • Subject animals
  • Home cage
  • Open field

Basic Protocol 3: Observation of Gait and Postural Characteristics

  Materials
  • Subject animals
  • Open field

Basic Protocol 4: Observation of Involuntary/Abnormal Motor Movements

  Materials
  • Subject animals
  • Open field or home cage

Basic Protocol 5: Observation of Clinical Signs

  Materials
  • Subject animal
  • Open field

Basic Protocol 6: Assessment of Neurological Reflexes/Reactions

  Materials
  • Subject animal
  • Narrow‐beam light source: e.g., pocket‐size flashlight (penlight) or otoscope
  • A fine object such as a thin wire

Basic Protocol 7: Neuromuscular Tests and Assessment of Postural Reactions

  Materials
  • Subject animals
  • Strain gauge with attached wire‐mesh or T bar
  • Paint or ink
  • Paper
  • Measuring stick or ruler

Basic Protocol 8: Assessment of Sensory Responses

  Materials
  • Subject animals
  • Odorant
  • Blunt object (e.g., pen or pencil, brush, wire)
  • Metal clicker or other sound device
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Figures

Videos

Literature Cited

Literature Cited
   Creason, J.P. 1989. Data evaluation and statistical analysis of functional observational battery data using a linear models approach. J. Am. Coll. Toxicol. 8:157‐169.
   Daughtrey, W.C., Gill, M.W., Pritts, I.M., Douglas, J.F., Kneiss, J.J., and Andrews, L.S. 1997. Neurotoxicological evaluation of methyl tertiary‐butyl ether in rats. J. Appl. Toxicol. 17:S57‐S64.
   Edwards, P.M. and Parker, V.H. 1977. A simple, sensitive and objective method for early assessment of acrylamide neuropathy in rats. Toxicol. Appl. Pharmacol. 40:589‐591.
   Ehrich, M., Shell, L., Rozum, M., and Jortner, B.S. 1993. Short‐term clinical and neuropathologic effects of cholinesterase inhibitors in rats. J. Am. Coll. Toxicol. 12:55‐68.
   Gad, S.C. 1982. A neuromuscular screen for use in industrial toxicology. J. Toxicol. Environ. Health 9:691‐704.
   Gad, S.C. 1989. Statistical analysis of screening studies in toxicology with special emphasis on neurotoxicology. J. Am. Coll. Toxicol. 8:171‐183.
   Gill, M.W., Burleigh‐Flayer, H.D., Strother, D.E., Masten, L.W., McKee, R.H., Tyler, T.R., and Gardiner, T.H. 1995. Isopropanol: Acute vapor inhalation neurotoxicity study in rats. J. Appl. Toxicol. 15:77‐84.
   Haggerty, G.C. 1989. Development of tier I neurobehavioral testing capabilities for incorporation into pivotal rodent safety assessment studies. J. Am. Coll. Toxicol. 8:53‐69.
   Haggerty, G.C. and Brown, G. 1996. Neurobehavioral profile of subcutaneously administered MK‐801 in the rat. Neurotoxicology 17:913‐921.
   LeBel, C.P. and Foss, J.A. 1996. Use of rodent neurotoxicity screening battery in the preclinical safety assessment of recombinant‐methionyl human brain‐derived neurotrophic factor. Neurotoxicology 17:851‐863.
   MacPhail, R.C., Peele, D.B., and Crofton, K.M. 1989. Motor activity and screening for neurotoxicity. J. Am. Coll. Toxicol. 8:117‐125.
   McDaniel, K.L. and Moser, V.C. 1993. Utility of a neurobehavioral screening battery for differentiating the effects of two pyrethroids, permethrin and cypermethrin. Neurotoxicol. Teratol. 15:71‐83.
   Meyer, O.A., Tilson, H.A., Byrd, W.C., and Riley, M.T.A. 1979. A method for the routine assessment of fore‐ and hindlimb grip strength of rats and mice. Neurobehav. Toxicol. 1:233‐236.
   Moser, V.C. 1991. Applications of a neurobehavioral screening battery. J. Am. Coll. Toxicol. 10:661‐669.
   Moser, V.C. 1996. Rat strain‐ and gender‐related differences in neurobehavioral screening: Acute trimethyl tin neurotoxicity. J. Toxicol. Environ. Health 47:567‐586.
   Moser, V.C. (ed.) 1997. Neurobehavioral screening methods. A report of the International Programme on Chemical Safety's Collaborative Study on Neurobehavioral Screening Methods. Neurotoxicology Vol. 18
   Moser, V.C. and Ross, J.F. 1996. Training Film and Reference Manual for a Functional Observational Battery. U.S. Environmental Protection Agency and the American Industrial Health Council, Washington, D.C.
   Moser, V.C., McCormick, J.P., Creason, J.P., and MacPhail, R.C. 1988. Comparison of chlordimeform and carbaryl using a functional observational battery. Fund. Appl. Toxicol. 11:189‐206.
   Moser, V.C., McDaniel, K.L., and Phillips, P.M. 1991. Rat strain and stock comparisons using a functional observational battery: Baseline values and effects of amitraz. Toxicol. Appl. Pharmacol. 108:267‐283.
   Moser, V.C., Anthony, D.C., Sette, W.F., and MacPhail, R.C. 1992. Comparison of subchronic neurotoxicity of 2‐hydroxyethyl acrylate and acrylamide in rats. Fundam. Appl. Toxicol. 18:343‐352.
   O'Donoghue, J.L. 1989. Screening for neurotoxicity using a neurologically based examination and neuropathology. J. Am. Coll. Toxicol. 8:97‐116.
   O'Donoghue, J.L. 1996. Clinical neurologic indices of toxicity in animals. Environ. Health Perspect. 104:323‐330.
   O'Keeffe, R.T. and Lifshitz, K. 1989. Nonhuman primates in neurotoxicity screening and neurobehavioral toxicity studies. J. Am. Coll. Toxicol. 8:127‐140.
   Reiter, L.W. and MacPhail, R.C. 1979. Motor activity: A survey of methods with potential use in toxicity testing. Neurobehav. Toxicol. 1:53‐66.
   Schaeppi, U. and Fitzgerald, R.E. 1989. Practical procedure of testing for neurotoxicity. J. Am. Coll. Toxicol. 8:29‐34.
   Sette, W.F. 1989. Adoption of new guidelines and data requirements for more extensive neurotoxicity testing under FIFRA. Toxicol. Ind. Health 5:181‐194.
   Tegeris, J.S. and Balster, R.L. 1994. A comparison of the acute behavioral effects of alkylbenzenes using a functional observational battery in mice. Fundam. Appl. Toxicol. 22:240‐250.
   Tilson, H.A. and Moser, V.C. 1992. Comparison of screening approaches. Neurotoxicology 13:1‐14.
Key References
   Gad, 1982; Haggerty, 1989; McDaniel, and Moser, 1993; Moser et al., 1988; O'Donoghue, 1989, 1996. See above.
  These references describe specific FOB protocols.
   Irwin, S. 1968. Comprehensive observational assessment: Ia. A systemic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia (Berl.) 13:222‐257.
  The first description of a full observational battery
   Moser and Ross, 1996. See above.
  Training video and manual intended to help achieve consistency in neurobehavioral screening.
   Reiter and MacPhail, 1979. See above.
  A description and comparison of automated motor activity devices.
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