title: Discriminative inhibitory control of cocaine seeking involves the prelimbic prefrontal cortex.
abstract: BACKGROUND
  Recent neuroimaging studies have shown that people with cocaine addiction retain some degree of control over drug craving that correlates with neural activity in the lateral prefrontal cortex (PFC). Here, we report similar findings in a rat model of inhibitory control of cocaine seeking.
  
  
  METHODS
  Rats actively responding for cocaine were trained to stop responding when presented with a discriminative stimulus that signaled lack of reinforcement. Rats were then tested for inhibitory control of cocaine seeking in novel behavioral contexts and in circumstances when cocaine seeking is particularly intense (e.g., following drug priming). The role of neuronal activity in different subregions of the PFC was assessed using local pharmacologic inactivation and c-Fos immunohistochemistry.
  
  
  RESULTS
  Rats progressively acquired the ability to stop cocaine seeking, even during drug intoxication and after a long history of cocaine self-administration. Inhibitory control of cocaine seeking was flexible, sufficiently strong to block cocaine-primed reinstatement, and selectively depended on increased neuronal activity within the prelimbic PFC, which is considered the rodent functional homolog of the human lateral PFC.
  
  
  CONCLUSIONS
  Parallel evidence in both animal models and humans indicate that recruitment of prefrontal inhibitory control of drug seeking is still functional after prolonged cocaine use. Preclinical investigation of the mechanisms underlying this capacity may contribute to designing new behavioral and/or pharmacologic strategies to promote its use for the prevention of relapse in addiction.
authors.affiliation: Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut des Maladies Neurodégénératives, Bordeaux, France.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mihindou
authors.forename: Karine
authors.initials: K
authors.lastname: Guillem
authors.forename: Sylvia
authors.initials: S
authors.lastname: Navailles
authors.forename: Caroline
authors.initials: C
authors.lastname: Vouillac
authors.forename: Serge H
authors.initials: SH
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D007266:Inhibition, Psychological; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine