Relapse to cocaine use persists following extinction of drug-primed craving

Neuropharmacology. 2019 Sep 1;155:185-193. doi: 10.1016/j.neuropharm.2019.05.036. Epub 2019 Jun 2.


Craving often precedes relapse into cocaine addiction. This explains why considerable research effort is being expended to try to develop anti-craving strategies for relapse prevention. Recently, we discovered using the classic reinstatement model of cocaine craving that the reinstating or priming effect of cocaine can be extinguished with repeated priming in rats - a phenomenon dubbed extinction of cocaine priming because it is thought to involve extinction of the conditioned interoceptive cues of the drug. Here we measured the effect of this extinction strategy on subsequent relapse-like behavior in rats (i.e., return to the pre-extinction pattern of cocaine self-administration once the drug is made again available after extinction). We found that extensive extinction of the conditioned priming effects of cocaine had no major impact on relapse-like behavior. This lack of effect occurred despite evidence for post-extinction loss of neuronal responses to cocaine priming in brain regions causally involved in cocaine reinstatement (i.e., the dorsomedial prefrontal cortex and the core of the nucleus accumbens). These findings suggest that the conditioned priming effects of cocaine can be dissociated from and are thus not essential for relapse-like behavior, and that extinction of these effects is unlikely to represent a viable approach to relapse prevention. Overall, these findings are in general agreement with previous neurobiological dissociation studies and with research on extinction of exteroceptive drug cues.

Keywords: Addiction; Cocaine; Prelimbic cortex; Relapse; Resistance to extinction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cocaine / administration & dosage*
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • Craving / drug effects*
  • Craving / physiology
  • Extinction, Psychological / drug effects*
  • Extinction, Psychological / physiology
  • Male
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / physiology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiology
  • Rats
  • Rats, Wistar
  • Recurrence
  • Self Administration


  • Cocaine