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Modeling Restricted Repetitive Behavior in Animals

Allison Bechard and Mark Lewis

Restricted, repetitive behavior is one of the three diagnostic domains for autism spectrum disorders, and commonly observed in a number of other neurodevelopmental disorders. Despite its clinical significance, effective treatments for restricted, repetitive behavior are limited including few, if any, pharmacological interventions with demonstrated efficacy. This is in large measure due to the lack of knowledge of the pathophysiological mechanisms that mediate the development and expression of repetitive behaviors in autism spectrum disorders. Therefore, animal models, particularly those that encompass both lower order and higher order repetitive behaviors, could be particularly useful. Such models could identify various potential etiologies, characterize commonalities in pathophysiology, identify novel potential therapeutic targets, and guide the development and validation of novel treatments. We have organized existing models of restricted, repetitive behavior in animals into four different categories: repetitive behavior resulting from a specific CNS insult (e.g. genetic mutation); repetitive behavior induced by specific pharmacological agents (e.g. amphetamine); repetitive behavior consequent to confined or restricted housing (e.g. laboratory caging); and repetitive behavior associated with specific inbred mouse strains. We have reviewed the literature from each of these categories of animal models, and discuss their multiple etiologies in light of a potential shared common pathophysiology: alterations in cortical-basal ganglia circuitry. Our own work with deer mice as a model of restricted, repetitive behavior suggests reduced activity in the indirect pathway of the basal ganglia, and has identified novel potential therapeutic targets. Other promising models are emerging that can take full advantage of modern genetics and molecular neuroscience that can be used to elucidate the pathophysiology of restricted, repetitive behavior. However, much more work must be done in this area to uncover the mechanisms underlying restricted, repetitive behavior, a critical step in finding effective new treatments for individuals with autism spectrum disorders.