Nov 25, 2019

Central norepinephrine transmission is required for stress-induced repetitive behavior in two rodent models of obsessive-compulsive disorder

BioRxiv : the Preprint Server for Biology
Daniel LustbergDavid Weinshenker

Abstract

Rationale: Obsessive-compulsive disorder (OCD) is characterized by repetitive behaviors exacerbated by stress. Many OCD patients do not respond to available pharmacotherapies, but neurosurgical ablation of the anterior cingulate cortex (ACC) can provide symptomatic relief. Although the ACC receives noradrenergic innervation and expresses adrenergic receptors (ARs), the involvement of norepinephrine (NE) in OCD has not been investigated. Objective: To determine the effects of genetic or pharmacological disruption of NE neurotransmission on marble burying (MB) and nestlet shredding (NS) in two animal models of OCD. Methods: We assessed NE-deficient ( Dbh -/- ) mice and NE-competent ( Dbh +/- ) controls in MB and NS tasks. We also measured the effects of anti-adrenergic drugs on NS and MB in control mice and the effects of pharmacological restoration of central NE in Dbh -/- mice. Finally, we compared c-fos induction in the locus coeruleus (LC) and ACC of Dbh -/- and control mice following both tasks. Results: Dbh -/- mice virtually lacked MB and NS behaviors seen in control mice but did not differ in the elevated zero maze (EZM) model of general anxiety-like behavior. Pharmacological restoration of central NE synthesis in Dbh -/-...Continue Reading

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Mentioned in this Paper

c-fos Genes
SLC6A4
Obsessive-Compulsive Disorder
Evaluation
Nerve Supply
Structure of Locus Ceruleus
Erythema Elevatum Diutinum
FOS
Norepinephrine
DBH

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