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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Representative Results
  • Discussion
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

Disease, head injury, genetic modifications, and treatment of mice with drugs can have profound effects on behavior. Utilizing well-characterized and validated approaches such as marble burying and nestlet shredding, compulsive-like behaviors can be documented accurately in mice as models of human obsessive-compulsive disorder and autism spectrum disorder.

Abstract

Tvangslidelse (OCD) og autismespekterforstyrrelser (ASD) er alvorlige og ødeleggende psykiatriske tilstander og hver utgjør et betydelig folkehelseproblem, særlig hos barn. Begge disse forholdene er fremhevet av gjentatte uttrykk for meningsløse atferd. Personer med OCD ofte vise kontroll, hyppig håndvask, og telling. Barn med ASDer også engasjere seg i repeterende tapping, arm eller hånd flagrende, og rocking. Denne oppførselen kan variere mye i intensitet og hyppighet av uttrykk. Mer intense former for repeterende atferd kan også føre til skade (for eksempel overdreven grooming, håndvask, og selvstimulering). Disse atferd er derfor svært forstyrrende og normal sosial diskurs vanskelig. Behandlingstilbud for repeterende atferd i OCD og ASDs er noe begrenset, og det er stor interesse for å utvikle mer effektive behandlingsformer for hver tilstand. Mange dyremodeller for evaluating tvangslignende atferd har blitt utviklet over de siste tre tiårene. Kanskje de dyremodeller med størst gyldighet og brukervennlighet er det marmor nedgraving test og nestlet shredding test. Begge testene dra nytte av det faktum at målet oppførsel oppstår spontant i mus. I marmor nedgraving test, er 20 klinkekuler kledd på overflaten av rent sengetøy. Antallet kuler begravd i en 30 min økt er scoret av etterforskere blinde til behandling eller status av fagene. I nestlet rivetesten, er en nestlet består av utgnidd bomullsfiber var veid på forhånd og plasseres på toppen av buret bedding og mengden av den resterende nestlet intakt etter 30 min testsesjon blir bestemt. I dag beskriver vi protokoller for og vise filmen dokumentasjon av marmor nedgraving og nestlet shredding. Begge testene er enkelt og nøyaktig scoret og hver er følsomme for små endringer i uttrykket av tvangslignende atferd som følge av genetisk manipulations, sykdom, eller hodeskade.

Introduction

Mouse models of human behaviors, and particularly psychiatric disorders, constitute important and essential experimental approaches to the study of disease mechanisms and to the development of new therapies. Many psychiatric illnesses remain extremely difficult to model in animals (e.g. schizophrenia). However, animals exhibit a large number of natural and distinctive behaviors that can readily be linked to similar behaviors in humans. Movement or locomotor activity is one example of a behavior in animals that has a counterpart in humans. Rodents often engage in a variety of repetitive behaviors and examples include grooming or digging. One psychiatric c....

Protocol

All protocols using animals were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocols were approved by the Institutional Care and Use Committee of Wayne State University (Permit Number A3310-01).

1. Preparation of Cages for Marble Burying and Nestlet Shredding

  1. Use standard polycarbonate rat cages (26 cm x 48 cm x 20 cm) with fitted filter-top covers for the marble b.......

Representative Results

A primary advantage of the marble burying and nestlet shredding tests is the fact that each depends on natural and spontaneous behaviors of mice that can be quantified after test completion, allowing a single investigator to set up an experiment and then remain outside of the testing room until sessions end. A critical component of the marble burying test is the careful removal of the subject from the cage after testing. Mice typically attempt to avoid capture and, in the process, can dislodge or move marbles that were p.......

Discussion

The marble burying and nestlet shredding tests are good examples of behavioral methods for studying repetitive and compulsive-like behaviors in mice. Both tests show excellent face, construct and predictive validity for the human disorders they model6-11. These repetitive behaviors are natural and spontaneous in rodents and their frequency and intensity can vary after genetic modifications, as shown presently, or after head injury and treatment of subjects with drugs. The value of these two tests derives from .......

Acknowledgements

This work was supported by grants from the Department of Veterans Affairs and the National Institutes of Health.

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Materials

NameCompanyCatalog NumberComments
Glass toy marbleslocal toy storeN/Aassorted styles, colors, clear, and opaque
NestletsAncareNES3600
N10 series mouse cageAncareN10HTstandard rodent cage with wire top
R20 series rat cageAncareR20standard rodent cage with wire top
Bed-o'CobsThe Andersons8Bstandard rodent bulk bedding, 1/8 in

References

  1. Chamberlain, S. R., Blackwell, A. D., Fineberg, N. A., Robbins, T. W., Sahakian, B. J. The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers. Neurosci. Biobehav. Rev. 29, 399-419 (2005).
  2. McGuire, J. F., Lewin, A. B., Horng, B., Murphy....

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Marble BuryingNestlet ShreddingRepetitive BehaviorsCompulsive like BehaviorsObsessive compulsive Disorder OCDAutism Spectrum Disorders ASDAnimal ModelsMice

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