A review of animal models of obsessive-compulsive disorder: a focus on developmental, immune, endocrine and behavioral models

Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition characterized by intrusive thoughts (obsessions) and/or repetitive behaviors (compulsions). Several models of OCD exist, many which employ behaviors such as over-grooming or hoarding as correlates for compulsive behaviors - often using a response to serotonergic agents as evidence for their validity. Recent discoveries in the genetics of OCD and the identification of aberrancies of glutamatergic, hormonal, and immune pathways in the OCD phenotype highlight a need to review existing of animal models of OCD. The focus of attention to these pathways may lead to possible new targets for drug discovery.In this review, the authors describe frameworks for animal models in OCD conceptualized as either biological (e.g., developmental, genetic, and endocrine pathways), or behavioral (e.g., repetitive grooming, and stereotypies). In addition, the authors give special attention to the emerging role of glutamate in OCD.While many animal models for OCD demonstrate pathologic repetitive behavior phenotypes, which are relieved by serotoninergic agents, animal models based on reversal learning, perseverative responding, and neurodevelopmental mechanisms represent robust new paradigms. Glutamatergic influences in these new animal models suggest that drug discovery using neuroprotective approaches may represent a new stage for pharmacologic developments in OCD.