title: Increased impulsivity retards the transition to dorsolateral striatal dopamine control of cocaine seeking.
abstract: BACKGROUND
  Development of maladaptive drug-seeking habits occurs in conjunction with a ventral-to-dorsal striatal shift in dopaminergic control over behavior. Although these habits readily develop as drug use continues, high impulsivity predicts loss of control over drug seeking and taking. However, whether impulsivity facilitates the transition to dorsolateral striatum (DLS) dopamine-dependent cocaine-seeking habits or whether impulsivity and cocaine-induced intrastriatal shifts are additive processes is unknown.
  
  
  METHODS
  High- and low-impulsive rats identified in the five-choice serial reaction-time task were trained to self-administer cocaine (.25 mg/infusion) with infusions occurring in the presence of a cue-light conditioned stimulus. Dopamine transmission was blocked in the DLS after three stages of training: early, transition, and late-stage, by bilateral intracranial infusions of α-flupenthixol (0, 5, 10, or 15 μg/side) during 15-min cocaine-seeking test sessions in which each response was reinforced by a cocaine-associated conditioned stimulus presentation.
  
  
  RESULTS
  In early-stage tests, neither group was affected by DLS dopamine receptor blockade. In transition-stage tests, low-impulsive rats showed a significant dose-dependent reduction in cocaine seeking, whereas high-impulsive rats were still unaffected by α-flupenthixol infusions. In the final, late-stage seeking test, both groups showed dose-dependent sensitivity to dopamine receptor blockade.
  
  
  CONCLUSIONS
  The results demonstrate that high impulsivity is associated with a delayed transition to DLS-dopamine-dependent control over cocaine seeking. This suggests that, if impulsivity confers an increased propensity to addiction, it is not simply through a more rapid development of habits but instead through interacting corticostriatal and striato-striatal processes that result ultimately in maladaptive drug-seeking habits.
authors.affiliation: Department of Psychology, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, Cambridge, United Kingdom; INSERM European Associated Laboratory, Poitiers. Electronic address: jem98@cam.ac.uk.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Murray
authors.affiliation: Department of Psychology, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, Cambridge, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Dilleen
authors.affiliation: Institute of Neuroscience de la Timone, University of Aix-Marseille, Marseille, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Pelloux
authors.affiliation: Department of Psychology, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, Cambridge, United Kingdom.
authors.forename: Daina
authors.initials: D
authors.lastname: Economidou
authors.affiliation: Department of Psychology, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, Cambridge, United Kingdom; Department of Psychiatry, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Dalley
authors.affiliation: INSERM U1084-LNEC team Psychobiology of Compulsive Disorders, Universtié de Poitiers, Poitiers; INSERM European Associated Laboratory, Poitiers.
authors.forename: David
authors.initials: D
authors.lastname: Belin
authors.affiliation: Department of Psychology, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, Cambridge, United Kingdom; INSERM European Associated Laboratory, Poitiers.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Everitt
mesh_terms: D000818:Animals; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology*; D005475:Flupenthixol / Q000008:administration & dosage / Q000494:pharmacology; D007175:Impulsive Behavior / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D051381:Rats; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D018492:Dopamine Antagonists; D005475:Flupenthixol; D003042:Cocaine
keywords: Cocaine; dopamine; drug addiction; goal-directed; habitual; striatum