Measurement of Rodent Stereotyped Behavior

Ann E. Kelley1

1 University of Wisconsin Medical School, Madison, Wisconsin
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 8.8
DOI:  10.1002/0471142301.ns0808s04
Online Posting Date:  May, 2001
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Abstract

This unit presents a quantitative, observational method for the assessment of rodent stereotyped behavior which consists of motor responses that are repetitive, invariant, and seemingly without purpose or goal. The most classic behavioral pattern that is characteristic of stereotypy is that elicited by high doses of stimulants, such as cocaine and amphetamine, in rats, although it can also occur in response to other drugs or neurotoxic treatments affecting the basal ganglia. An observational time-sampling procedure is described in which animals are observed and rated by an experimenter, who is blind to treatment, at regular time points over the course of a behavioral testing period. The frequency of different behaviors is measured by scoring the presence or absence of a given behavior during predetermined time bins. The apparatus and test procedures are described, and a comprehensive list of commonly observed behaviors that may appear as stereotyped is provided. In addition to being ideally suited to the measurement of stereotypy, the protocol can be adapted to sampling many forms of spontaneous behaviors, including locomotion, rearing, grooming, eating, and drinking. Samples of behavioral checklists and scoring sheets are also provided.

     
 
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Table of Contents

  • Basic Protocol
  • Commentary
  • Bibliography
  • Figures
  • Tables
     
 
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Materials

 Basic Protocol
 Materials
  • Rats
  • Observational test cages: clear polycarbonate or suitable transparent material, with dimensions (in cm) ~47 (l) × 26 (w) × 20 (h)—with wire tops and bottoms (optional) to facilitate expression of gnawing or licking behaviors (top can be flat, or indented to accommodate food and water bottle)
  • Behavioral scoring sheets (for prototype see Fig. 8.8.1) and data summary sheets (for prototype see Fig. 8.8.2) or keyboard/computer-based data recording system, if available
     FigureFigure 8.8.1 Prototype of a behavioral scoring sheet.
     FigureFigure 8.8.2 Prototype of a data summary sheet.
  • Video camera, VCR, and monitor (optional)
  • Equipment for treatments of interest (e.g., systemic injections or intracranial infusions)
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Figures

  •  FigureFigure 8.8.1 Prototype of a behavioral scoring sheet.
  •  FigureFigure 8.8.2 Prototype of a data summary sheet.
  •  FigureFigure 8.8.3 Antagonism of the expression of amphetamine-induced orofacial stereotypy by NMDA receptor antagonists within the ventrolateral striatum. In this study, rats were pretreated with either the noncompetitive antagonist MK-801 or the competitive blocker AP-5. Immediately following this infusion, all rats were given a microinfusion of 20 µg amphetamine into the striatum. Testing was carried out over a 30-min session in which animals were observed for 1 min every 5 min. The double asterisks signify p < 0.01, compared with saline. From Delfs and Kelley, 1994.
  •  FigureFigure 8.8.4 Example of a time-course study of stereotypy. Different doses of serotonin (5-HT) were infused into the ventrolateral striatum. In this experiment, behaviors were observed over 4.5 hr and animals were rated every 10 min. The raw data from 3 time bins were summed into 30-min time bins to obtain the time-course data shown on the right. The total scores over the entire test session are shown on the left. Administration of 5-HT was designated as time zero. The asterisks signify p < 0.05 compared with saline. From Yeghiayan and Kelley, 1995.
  •  FigureFigure 8.8.5 Example of behavioral data from a study in which 20 µg of amphetamine was microinjected into the ventrolateral striatum of the rat. Shown are mean scores totaled over a 30-min session in which 1-min observations were taken every 5 min, as described in the Basic Protocol. “Combined oral” is a composite score of licking, biting and gnawing. Single asterisks signify p < 0.05; double asterisks signify p < 0.01, and triple asterisks signify p < 0.001, compared with saline. From Kelley et al., 1988.

Videos

Literature Cited

 Literature Cited
    Albin, R.L., Young, A.B., and Penney, J.B. 1995. The functional anatomy of disorders of the basal ganglia. Trends Neurosci. 18:63-64.
    Aldridge, J.W., Berridge, K.C., Herman, M., and Zimmer, L. 1993. Neuronal coding of serial order: Syntax of grooming in the neostriatum. Psychol. Sci. 4:391-395.
    Arnt, J. 1985. Antistereotypic effects of dopamine D-1 and D-2 antagonists after intrastriatal injection in rats: Pharmacological and regional specificity. Naunyn-Schmiedeberg's Arch. Pharmacol. 330:97-104.
    Baldessarini, R.J. and Tarsy, D. 1980. Dopamine and the pathophysiology of dyskinesias induced by antipsychotic drugs. Annu. Rev. Neurosci. 3:23-41.
    Berridge, K.C., Fentress, J.C. and Parr, H. 1987. Natural syntax rules control action sequences. Behav. Brain Res. 23:59-68.
    Carlsson, A. 1978. Antipsychotic drugs, neurotransmitters, and schizophrenia. Am. J. Psychiatry 135:164-173.
    Cools, A.R. and Van Rossum, J.M. 1970. Caudate dopamine and stereotyped behaviour of cats. Archiv. Int. Pharmacodyn. 187:163-173.
    Cooper, S.J. and Dourish, C.T. 1990. Neurobiology of Stereotyped Behavior. Clarendon Press, Oxford.
    Costall, B., Naylor, R.J., and Olley, J.E. 1972. Stereotypic and anti-cataleptic activities of amphetamine after intracerebral injections. Eur. J. Pharmacol. 18:83-94.
    Creese, I. and Iversen, S.D. 1973. Blockage of amphetamine-induced motor stimulation and stereotypy in the adult rat following neonatal treatment with 6-hydroxydopamine. Brain Res. 55:369-382.
    Creese, I. and Iversen, S.D. 1975. The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res. 83:419-436.
    Creese, I., Burt, D.R. and Snyder, S.H. 1976. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481-483.
    Cromwell, H.C. and Berridge, K.C. 1996. Implementation of action sequences by a neostriatal site: A lesion mapping study of grooming syntax. J. Neurosci. 16:3444-3458.
    Delfs, J.M. and Kelley, A.E. 1990. The role of D-1 and D-2 dopamine receptors in oral stereotypy induced by dopaminergic stimulation of the ventrolateral striatum. Neuroscience 39:59-67.
    Delfs, J.M. and Kelley, A.E. 1994. Excitatory amino acid receptors mediate the orofacial stereotypy elicited by dopaminergic stimulation of the ventrolateral striatum. Neuroscience 60:85-95.
    Ernst, A.M. 1967. Mode of action of apomorphine and dexamphetamine in gnawing compulsion in rats. Psychopharmacologia 10:316-323.
    Fog, R. 1972. On stereotypy and catalepsy: Studies on the effect of amphetamines and neuroleptics in rats. Acta Neurol. Scand. Suppl. 50:3-66.
    Fog, R. and Pakkenberg, H. 1970. Lesions in corpus striatum and cortex of rat brains and the effect on pharmacologically induced stereotyped, aggressive and cataleptic behavior. Psychopharmacologia (Berl.) 18:346-356.
    Fog, R. and Pakkenberg, H. 1971. Behavioral effects of dopamine and p-hydroxyamphetamine injected into corpus striatum of rats. Exp. Neurol. 31:75-86.
    Fray, P.J., Sahakian, B.J., Robbins, T.W., Koob, G.F., and Iversen, S.D. 1980. An observational method for quantifying the behavioural effects of dopamine agonists: Contrasting effects of d-amphetamine and apomorphine. Psychopharmacology 69:253-259.
    Frith, C.D. and Done, D.J. 1990. Stereotyped behavior in madness and health. In Neurobiology of Stereotyped Behavior. (S.J. Cooper and C.T. Dourish, eds.) pp. 232-269. Clarendon Press, Oxford.
    Fuxe, K. and Ungerstedt, U. 1970. Histochemical, biochemical and functional studies on central monoamine neurons after acute and chronic amphetamine administration. In Amphetamines and Related Compounds. (E. Costa and S. Garattini, eds.) pp. 257-288. Raven Press, New York.
    Kelly, P.H., Seviour, P.W., and Iversen, S.D. 1975. Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res. 94:507-522.
    Kelley, A.E., Winnock, M., and Stinus, L. 1985. Amphetamine, apomorphine and investigatory behavior in the rat: Analysis of the structure and pattern of responses. Psychopharmacology 88:66-74.
    Kelley, A.E., Lang, C.G., and Gauthier, A.M. 1988. Induction of oral stereotypy following amphetamine microinjection into a discrete subregion of the striatum. Psychopharmacology 95:556-559.
    Lyon, M. and Robbins, T.W. 1975. The action of central nervous system stimulant drugs: A general theory concerning amphetamine effects. In Current Developments in Psychopharmacology. (W.B. Essman and L. Valzelli, eds.) pp. 80-163. Spectrum Publications, New York.
    Neisewander, J.L., Ong, A., and McGonigle, P. 1995. Anatomical localization of SKF-38393-induced behaviors in rats using the irreversible monoamine receptor antagonist EEDQ. Synapse 19:134-143.
    Randrup, A. and Munkvad, I. 1967. Stereotyped activities produced by amphetamine in several animal species and man. Psychopharmacologia (Berl.) 11:300-310.
    Randrup, A. and Munkvad, I. 1970. Biochemical, anatomical and psychological investigations of sterotyped behavior induced by amphetamines. In Amphetamines and Related Compounds. (E. Costa and S. Garattini, eds.) pp. 695- 713. Raven Press, New York.
    Randrup, A. and Munkvad, I. 1974. Pharmacology and physiology of stereotyped behavior. J. Psychiatr. Res. 11:1-10.
    Robbins, T.W. and De Weid, D. 1991. Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats: A.M. Ernst. Psychopharmacologia (Berl.) 10:316-323 (1967). Psychopharmacology 103:285-286.
    Rosenthal, R. and Rosnow, R.L. 1991. Essentials of Behavioral Research: Methods and Data Analysis. McGraw-Hill, New York.
    Schiorring, E. 1979. An open field study of stereotyped locomotor activity in amphetamine-treated rats. Psychopharmacology 66:281-287.
    Seeman, P., Chau-Wong, M., Tedesco, J., and Wong, K. 1975. Brain receptors for antipsychotic drugs and dopamine: Direct binding assays. Proc. Nat. Acad. Sci. U.S.A. 72:4376-4380.
    Siegel, S. 1956. Nonparametric statistics for the behavioral sciences. McGraw-Hill, New York.
    Teitelbaum, P., Pellis, S.M., and DeVietti, T.L. 1990. Disintegration into stereotypy induced by drugs or brain damage: A microdescriptive behavioural analysis. In Neurobiology of Stereotyped Behaviour. (S.J. Cooper and C.T. Dourish, eds.) pp 169- 199. Clarendon Press, Oxford.
    Waddington, J.L. 1990. Spontaneous orofacial movements induced in rodents by very long-term neuroleptic drug administration: Phenomenology, pathophysiology and putative relationship to tardive dyskinesia. Psychopharmacology 101:431-447.
    Yeghiayan, S.K. and Kelley, A.E. 1995. Serotonergic stimulation of the ventrolateral striatum induces orofacial stereotypy. Pharmacol. Biochem. Behav. 52:493-501.
 Key Reference
    Cooper and Dourish, 1990. See above.

An extensive review of the theoretical aspects of analysis of stereotypy.

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