title: N-acetylcysteine Facilitates Self-Imposed Abstinence After Escalation of Cocaine Intake.
abstract: N-acetylcysteine (NAC) has been suggested to prevent relapse to cocaine seeking. However, the psychological processes underlying its potential therapeutic benefit remain largely unknown.
  
  
  
  We investigated the hallmark features of addiction that were influenced by chronic NAC treatment in rats given extended access to cocaine: escalation, motivation, self-imposed abstinence in the face of punishment, or propensity to relapse. For this, Sprague Dawley rats were given access either to 1 hour (short access) or 6 hours (long access [LgA]) self-administration (SA) sessions until LgA rats displayed a robust escalation. Rats then received daily saline or NAC (60 mg/kg, intraperitoneal) treatment and were tested under a progressive ratio and several consecutive sessions in which lever presses were punished by mild electric foot shocks.
  
  
  
  NAC increased the sensitivity to punishment in LgA rats only, thereby promoting abstinence. Following the cessation of punishment, NAC-treated LgA rats failed to recover fully their prepunishment cocaine intake levels and resumed cocaine SA at a lower rate than short access and vehicle-treated LgA rats. However, NAC altered neither the escalation of SA nor the motivation for cocaine. At the neurobiological level, NAC reversed cocaine-induced decreases in the glutamate type 1 transporter observed in both the nucleus accumbens and the dorsolateral striatum. NAC also increased the expression of Zif268 in the nucleus accumbens and dorsolateral striatum of LgA rats.
  
  
  
  Our results indicate that NAC contributes to the restoration of control over cocaine SA following adverse consequences, an effect associated with plasticity mechanisms in both the ventral and dorsolateral striatum.
authors.affiliation: French Institute of Health and Medical Research, Avenir Team Psychobiology of Compulsive Disorders, Université de Poitiers, Poitiers, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Ducret
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Puaud
authors.affiliation: Service de Psychiatrie et Addictologie, Centre Hospitalier Universitaire de Fort-de-France, Martinique, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lacoste
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Aude
authors.initials: A
authors.lastname: Belin-Rauscent
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Maxime
authors.initials: M
authors.lastname: Fouyssac
authors.affiliation: French Institute of Health and Medical Research, Avenir Team Psychobiology of Compulsive Disorders, Université de Poitiers, Poitiers, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Dugast
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Murray
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Everitt
authors.affiliation: Service de Neurologie de l'Hôpital de Poitiers and Center for Clinical Investigation-French Institute of Health and Medical Research, Poitiers, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Houeto
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom. Electronic address: bdb26@cam.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Belin
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000534:rehabilitation; D003342:Corpus Striatum / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D004597:Electroshock; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism; D011678:Punishment; D051381:Rats; D012055:Reinforcement Schedule; D012646:Self Administration; D013997:Time Factors
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D027342:Excitatory Amino Acid Transporter 2; D003042:Cocaine; D000111:Acetylcysteine
keywords: Addiction; Cocaine; Compulsivity; Motivation; N-acetylcysteine; Zif268