title: Preclinical validation of a novel cocaine exposure therapy for relapse prevention.
abstract: BACKGROUND
  Cocaine not only induces intense rewarding sensations but also craving for more cocaine, particularly during abstinence, an effect that contributes, together with other factors, to relapse. Here we sought to prevent this effect by extinguishing the conditioned interoceptive cues of cocaine that are thought to be acquired during repeated cocaine use.
  
  
  METHODS
  Cocaine-induced craving was studied in rats using the well-validated model of drug-primed reinstatement of cocaine seeking. To extinguish the conditioned interoceptive effects of cocaine, rats received daily repeated cocaine priming in the absence of drug reinforcement.
  
  
  RESULTS
  Cocaine-primed reinstatement of cocaine seeking dramatically decreased with repeated cocaine priming regardless of the testing dose and even following a history of extended access to cocaine self-administration. The extinction of cocaine-primed reinstatement of cocaine seeking was enduring, generalized to stress-another major trigger of drug craving and relapse-and was context-dependent.
  
  
  CONCLUSIONS
  These findings clearly show that it is feasible to prevent the ability of cocaine and stress to induce cocaine seeking using an approach designed to extinguish the drug's conditioned interoceptive cues. Although this preclinical extinction approach has limitations that need to be overcome in future research (i.e., its context-dependency), it may nevertheless represent a promising basis for the development of a novel exposure therapy against cocaine relapse.
authors.affiliation: Institut des Maladies Neurodégénératives, Université de Bordeaux, Bordeaux, France.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mihindou
authors.forename: Caroline
authors.initials: C
authors.lastname: Vouillac
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.forename: Serge H
authors.initials: SH
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000517:prevention & control*; D003042:Cocaine / Q000008:administration & dosage / Q000627:therapeutic use*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000517:prevention & control*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004558:Electric Stimulation / Q000379:methods; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D055502:Secondary Prevention; D012646:Self Administration / Q000379:methods / Q000523:psychology; D013315:Stress, Psychological / Q000523:psychology
chemical_list: D003042:Cocaine