Incubation of cocaine craving after withdrawal: a review of preclinical data

Neuropharmacology. 2004:47 Suppl 1:214-26. doi: 10.1016/j.neuropharm.2004.06.027.


Using a rat model of drug craving and relapse, we recently found that cocaine seeking induced by re-exposure to drug-associated cues progressively increases over the first 2 months after withdrawal from cocaine self-administration, suggesting that drug craving incubates over time [Nature 412 (2001) 141]. Here, we summarize data from studies that further characterized this incubation phenomenon and briefly discuss its implications for drug addiction. The main findings of our ongoing research are: 1. Incubation of cocaine craving is long-lasting, but not permanent: cocaine seeking induced by exposure to cocaine cues remains elevated for up to 3 months of withdrawal, but decreases after 6 months. 2. Incubation of reward craving is not drug specific: sucrose seeking induced by re-exposure to the reward cues also increases after withdrawal, but for a time period that is shorter than that of cocaine. 3. Incubation of cocaine craving is not evident after acute re-exposure to cocaine itself: cocaine seeking induced by cocaine priming injections remains essentially unchanged over the first 6 months of withdrawal. 4. Incubation of cocaine craving after withdrawal is associated with increases in the levels of brain-derived neurotrophic factor (BDNF) in mesolimbic dopamine areas.

Publication types

  • Review

MeSH terms

  • Amphetamine-Related Disorders / psychology
  • Animals
  • Brain / pathology
  • Brain Chemistry / genetics
  • Brain Chemistry / physiology
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cocaine-Related Disorders / metabolism
  • Cocaine-Related Disorders / pathology
  • Cocaine-Related Disorders / psychology*
  • Cues
  • Dopamine / physiology
  • Generalization, Psychological
  • Methamphetamine
  • Neuropeptides / biosynthesis
  • Neuropeptides / genetics
  • Rats
  • Recurrence
  • Substance Withdrawal Syndrome / metabolism
  • Substance Withdrawal Syndrome / pathology
  • Substance Withdrawal Syndrome / psychology*


  • Brain-Derived Neurotrophic Factor
  • Neuropeptides
  • Methamphetamine
  • Dopamine