title: Bidirectional regulation over the development and expression of loss of control over cocaine intake by the anterior insula.
abstract: Increasing evidence suggests that the anterior insular cortex (AIC) plays a major role in cocaine addiction, being implicated in both impaired insight and associated decision-making and also craving and relapse. However, the nature of the involvement of the insula in the development and maintenance of cocaine addiction remains unknown, thereby limiting our understanding of its causal role in addiction. We therefore investigated whether pre- and post-training bilateral lesions of the AIC differentially influenced the development and the expression of the escalation of cocaine self-administration during extended access to the drug.
  
  
  
  In a series of experiments, Sprague Dawley rats received bilateral excitotoxic lesions of the AIC either prior to, or after 3 weeks of training under 12-h extended self-administration conditions, which are known to promote a robust escalation of intake. We also investigated the influence of AIC lesions on anxiety, as measured in an elevated plus maze and sensitivity to conditioned stimuli (CS)- or drug-induced reinstatement of an extinguished instrumental response.
  
  
  
  Whereas, post-escalation lesions of the AIC, as anticipated, restored control over cocaine intake and prevented drug-induced reinstatement, pre-training lesions resulted in a facilitation of the development of loss of control with no influence over the acquisition of cocaine self-administration or anxiety.
  
  
  
  AIC lesions differentially affect the development and maintenance of the loss of control over cocaine intake, suggesting that the nature of the contribution of cocaine-associated interoceptive mechanisms changes over the course of escalation and may represent an important component of addiction.
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Psychiatrie d'Adultes, Paris, France.|Inserm, CNRS, APHP, Institut du Cerveau et de la Moelle (ICM), Hôpital Pitié-Salpêtrière, Sorbonne Universités, UPMC Univ Paris 06, 75013, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Rotge
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Cocker
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Daniel
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
authors.forename: Aude
authors.initials: A
authors.lastname: Belin-Rauscent
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Everitt
authors.affiliation: Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK. bdb26@cam.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Belin
mesh_terms: D000818:Animals; D001007:Anxiety / Q000473:pathology / Q000523:psychology; D016739:Behavior, Addictive / Q000473:pathology* / Q000523:psychology; D002540:Cerebral Cortex / Q000473:pathology* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000473:pathology* / Q000523:psychology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
chemical_list: D003042:Cocaine
keywords: Addiction; Anterior insula; Cocaine; Escalation