From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive behavior

Autor: Morgane Besson, David Belin, D Howett, Jeffrey W. Dalley, Mickaël Puaud, Bianca Jupp, Trevor W. Robbins, Aude Belin-Rauscent, Stephen J. Sawiak, Daniele Caprioli, M-L Daniel, Colin McKenzie, Barry J. Everitt
Přispěvatelé: University of Cambridge [UK] (CAM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), National National Institute on Drug Abuse Intramural Research Program, National Institute of Health, Neurobiologie intégrative des Systèmes cholinergiques (NISC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), It was supported by an INSERM AVENIR grant and a FYSSEN foundation grant to DB. MLD was supported by a PhD fellowship from the Fondation pour la Recherche Médicale (FRM) and ABR was supported by a post-doctoral fellowship from the INSERM. BJE was supported by the United Kingdom Medical Research Council (MRC) Grant 9536855, This research was carried out within the Department of Psychology and the Department of Pharmacology of the University of Cambridge, as well as the INSERM AVENIR team Psychobiology of Compulsive Disorders of the University of Poitiers., Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Belin, D [0000-0002-7383-372X], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Serial reaction time
Obsessive-Compulsive Disorder
Neural substrate
[SDV]Life Sciences [q-bio]
Neuropsychological Tests
Choice Behavior
Developmental psychology
[SCCO]Cognitive science
0302 clinical medicine
5 - Choice serial reaction time task
MESH: Animals
Insular cortex
Cerebral Cortex
MESH: Neuropsychological Tests
Compulsivity
3. Good health
Psychiatry and Mental health
Schizophrenia
Compulsive behavior
animals
behavior
addictive
cerebral cortex
choice behavior
compulsive behavior
impulsive behavior
male
neuropsychological tests
obsessive-compulsive disorder
rats
reaction time
molecular biology
psychiatry and mental health
cellular and molecular neuroscience
Compulsive Behavior
MESH: Compulsive Behavior
MESH: Impulsive Behavior
medicine.symptom
Psychology
Impulsivity
Schedule induced polydipsia
MESH: Rats
MESH: Choice Behavior
03 medical and health sciences
Cellular and Molecular Neuroscience
MESH: Behavior
Addictive
Reaction Time
medicine
Animals
Molecular Biology
MESH: Obsessive-Compulsive Disorder
behavior
[SCCO.NEUR]Cognitive science/Neuroscience
addictive
medicine.disease
MESH: Cerebral Cortex
MESH: Male
Rats
MESH: Reaction Time
Behavior
Addictive
030104 developmental biology
Endophenotype
Impulsive Behavior
Neuroscience
Insula
030217 neurology & neurosurgery
Zdroj: Molecular Psychiatry
Molecular Psychiatry, Nature Publishing Group, 2016, 21 (4), pp.491-9. ⟨10.1038/mp.2015.140⟩
Molecular Psychiatry, 2016, 21 (4), pp.491-9. ⟨10.1038/mp.2015.140⟩
ISSN: 1359-4184
1476-5578
DOI: 10.1038/mp.2015.140⟩
Popis: International audience; Impulsivity is an endophenotype of vulnerability for compulsive behaviors. However, the neural mechanisms whereby impulsivity facilitates the development of compulsive disorders, such as addiction or obsessive compulsive disorder, remain unknown. We first investigated, in rats, anatomical and functional correlates of impulsivity in the anterior insular (AI) cortex by measuring both the thickness of, and cellular plasticity markers in, the AI with magnetic resonance imaging and in situ hybridization of the immediate early gene zif268, respectively. We then investigated the influence of bilateral AI cortex lesions on the high impulsivity trait, as measured in the five-choice serial reaction time task (5-CSRTT), and the associated propensity to develop compulsivity as measured by high drinking levels in a schedule-induced polydipsia procedure (SIP). We demonstrate that the AI cortex causally contributes to individual vulnerability to impulsive-compulsive behavior in rats. Motor impulsivity, as measured by premature responses in the 5-CSRTT, was shown to correlate with the thinness of the anterior region of the insular cortex, in which highly impulsive (HI) rats expressed lower zif268 mRNA levels. Lesions of AI reduced impulsive behavior in HI rats, which were also highly susceptible to develop compulsive behavior as measured in a SIP procedure. AI lesions also attenuated both the development and the expression of SIP. This study thus identifies the AI as a novel neural substrate of maladaptive impulse control mechanisms that may facilitate the development of compulsive disorders.
Databáze: OpenAIRE
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