Towards the Neurobiology of Compulsive Rituals

Abstract

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder characterized by lengthy rituals of increased and repetitive non-functional behavior. Cortico-striatal circuitry and genetic components have been implicated in the pathogenesis of OCD; however, systematic animal studies are necessary to show their functional relationship to disease phenotype. This study shows behavioral, neurochemical and pharmacological homology of OCD rituals in the A/J inbred mouse strain. In contrast to the C57BL/6J genetic background strain, A/J mice showed increased and repetitive non-functional behaviors during scheduled feeding. Sub-chronic treatment with a broad range of clinically effective and ineffective compounds for OCD provided strong predictive validity for this OCD-like behavior in mice. A/J mice also expressed cognitive inflexibility, an OCD characteristic, in a set-shifting task. Moreover, the compulsive phenotype was rescued by wireless deep brain stimulation of the lateral-ventral orbital frontal cortex (OFC), demonstrating the functional importance of targeted OFC neuronal signaling in OCD treatment.