Marbre enterrant et Nestlet déchiquetage comme tests de répétitives, comportements compulsifs comme-chez les souris

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 condition that involves the exhibition of recurrent and unwanted behaviors in humans is obsessive-compulsive disorder (OCD). Behaviors that are highly characteristic of OCD include checking, counting, and excessive washing or grooming. OCD is a highly prevalent (affects 1-3% of the population) and debilitating psychiatric disorder¹. A large number of pharmacological and behavioral approaches have been used to treat OCD. Many of these fall short of providing long-term relief and relapse is common at the end of a treatment regimen^2,3. Another psychiatric condition that involves the expression repetitive behaviors is autism spectrum disorder (ASD). ASDs are characterized by deficits in communication and social interaction and repetitive, stereotyped behaviors to include spinning, rocking, finger flicking or flapping, and complex body movements. The Centers for Disease Control and Prevention has estimated that about 1 in 88 children are diagnosed with ASDs. Treatment options for this disorder are extremely limited in number and efficacy^4,5. The intensity and frequency of occurrence of repetitive behaviors in OCD and ASD can become great enough to displace most other normal behaviors and social interactions in patients with these conditions. In light of the prevalence and debilitating nature of psychiatric conditions characterized by repetitive behaviors, and considering the poor understanding of their causes and limited treatment options, the use of animal models to study these behaviors takes on added urgency.

A large number of animal models of repetitive behaviors as seen in OCD and ASDs have been developed over the past 30 years and numerous excellent reviews describing these models have been published^6-14. In general, these established models can be classified as genetic, pharmacological, neurodevelopmental and behavioral and most show good face, construct and predictive validity^6,7. We have used two behavioral models- marble burying and nestlet shredding- to assess repetitive behaviors in mice genetically depleted of serotonin^15,16. These methods have numerous advantages not the least of which are their ease of use, the accuracy with which the behaviors can be scored, the spontaneous exhibition of these behaviors in rodents, and their use in high-throughput screening of genetically modified mice for abnormal behavioral phenotypes. Furthermore, each test is carried out in standard and familiar rodent housing cages containing the same bedding used in subjects' home cages, minimizing the need for habituation of mice to novel testing chambers. Food and/or water restriction are not required to "motivate" mice to perform. The marble burying test takes advantage of the proclivity of mice to dig in natural settings (e.g. burrows, escape tunnels) and in standard cage bedding, and the nestlet shred test capitalizes on the fact that mice are nesting animals by nature that build nests for protection of themselves and their offspring against environmental conditions (e.g. sound, light, temperature). Using nonspecialized and commonly available rodent housing materials, the marble burying and nestlet shredding tasks are simple and powerful behavioral assays of repetitive, compulsive-like behaviors in mice.