Towards the Neurobiology of Compulsive Rituals

G.G. de Haas

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)

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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 languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Utrecht University
Supervisors/Advisors
  • Adan, Roger, Primary supervisor
  • Kas, MJH, Co-supervisor
  • van der Plasse, G, Co-supervisor
Award date27 Sept 2012
Publisher
Print ISBNs978-90-8891-465-2
Publication statusPublished - 27 Sept 2012

Keywords

  • Econometric and Statistical Methods: General
  • Geneeskunde(GENK)
  • Medical sciences
  • Bescherming en bevordering van de menselijke gezondheid

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