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.
Original language | English |
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Qualification | Doctor of Philosophy |
Awarding Institution |
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Supervisors/Advisors |
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Award date | 27 Sept 2012 |
Publisher | |
Print ISBNs | 978-90-8891-465-2 |
Publication status | Published - 27 Sept 2012 |
Keywords
- Econometric and Statistical Methods: General
- Geneeskunde(GENK)
- Medical sciences
- Bescherming en bevordering van de menselijke gezondheid