title: Atomoxetine decreases vulnerability to develop compulsivity in high impulsive rats.
abstract: BACKGROUND
  The factors contributing to the development and severity of obsessive-compulsive spectrum disorders such as obsessive-compulsive disorder, Tourette's syndrome, pathological gambling, and addictions remain poorly understood, limiting the development of therapeutic and preventive strategies. Recent evidence indicates that impulse-control deficits may contribute to the severity of compulsivity in several of these disorders. This suggests that impulsivity may be a transnosological endophenotype of vulnerability to compulsivity. However, the precise nature of the link between impulsivity and compulsivity in anxiety-related compulsive disorders remains unknown.
  
  
  METHODS
  We investigated the relationship between impulsivity and the development of a compulsive behavior in rats, which captures the hallmarks of compulsivity as defined in the DSM-IV--namely, that it is maladaptive, excessive, repetitive, and anxiolytic.
  
  
  RESULTS
  We demonstrate that a high-impulsivity trait, as measured in the five-choice serial reaction time task, predicts an increased propensity to develop compulsivity as measured in a schedule-induced polydipsia procedure. Trait impulsivity and compulsivity were nonlinearly related. This impulsivity-compulsivity relationship was lost after the development of compulsivity or under chronic treatment with atomoxetine, a noradrenergic reuptake inhibitor used to treat attention-deficit/hyperactivity disorder. Atomoxetine treatment both decreased impulsivity and prevented the development of compulsivity in high-impulsive animals.
  
  
  CONCLUSIONS
  These observations provide insight into the reciprocal influence of impulsivity and compulsivity in compulsive disorders and suggest that atomoxetine may be a useful treatment for patients suffering from obsessive-compulsive spectrum disorders with high impulsivity.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1084-LNEC Experimental and Clinical Neurosciences Laboratory, Poitiers, France; Team Psychobiology of Compulsive Disorders, University of Poitiers, Poitiers, France; Service de Neurologie de l'Hôpital de Poitiers, Poitiers, France.
authors.forename: Solène
authors.initials: S
authors.lastname: Ansquer
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1084-LNEC Experimental and Clinical Neurosciences Laboratory, Poitiers, France; Team Psychobiology of Compulsive Disorders, University of Poitiers, Poitiers, France; INSERM European Associated Laboratory Psychobiology of Compulsive Habits, Cambridge, United Kingdom; INSERM CIC-0802, Poitiers, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Belin-Rauscent
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1084-LNEC Experimental and Clinical Neurosciences Laboratory, Poitiers, France; Team Psychobiology of Compulsive Disorders, University of Poitiers, Poitiers, France; INSERM European Associated Laboratory Psychobiology of Compulsive Habits, Cambridge, United Kingdom.
authors.forename: Emilie
authors.initials: E
authors.lastname: Dugast
authors.affiliation: Department of Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Théo
authors.initials: T
authors.lastname: Duran
authors.affiliation: Service de Neurologie de l'Hôpital de Poitiers, Poitiers, France; CNRS GDR 3557 "Institut de Psychiatrie", Poitiers, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Benatru
authors.affiliation: Hôpital Sainte Anne, Paris, France; Institut des Neurosciences de Grenoble-CR Inserm U.836; Université Joseph Fourier-Site Santé La Tronche-CHU Grenoble, Grenoble, France.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Mar
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1084-LNEC Experimental and Clinical Neurosciences Laboratory, Poitiers, France; Team Psychobiology of Compulsive Disorders, University of Poitiers, Poitiers, France; INSERM European Associated Laboratory Psychobiology of Compulsive Habits, Cambridge, United Kingdom; CNRS GDR 3557 "Institut de Psychiatrie", Poitiers, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Houeto
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1084-LNEC Experimental and Clinical Neurosciences Laboratory, Poitiers, France; Team Psychobiology of Compulsive Disorders, University of Poitiers, Poitiers, France; INSERM European Associated Laboratory Psychobiology of Compulsive Habits, Cambridge, United Kingdom; INSERM CIC-0802, Poitiers, France. Electronic address: bdb26@cam.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Belin
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D002755:Choice Behavior / Q000187:drug effects; D003192:Compulsive Behavior; D007175:Impulsive Behavior / Q000187:drug effects*; D008297:Male; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride
keywords: Atomoxetine; Tourette’s syndrome; compulsivity; five-choice serial reaction time task; impulsivity trait; obsessive-compulsive spectrum disorders; schedule-induced polydipsia