Incubation of methamphetamine and palatable food craving after punishment-induced abstinence

Neuropsychopharmacology. 2014 Jul;39(8):2008-16. doi: 10.1038/npp.2014.50. Epub 2014 Mar 3.


In a rat model of drug craving and relapse, cue-induced drug seeking progressively increases after withdrawal from methamphetamine and other drugs, a phenomenon termed 'incubation of drug craving'. However, current experimental procedures used to study incubation of drug craving do not incorporate negative consequences of drug use, which is a common factor promoting abstinence in humans. Here, we studied whether incubation of methamphetamine craving is observed after suppression of drug seeking by adverse consequences (punishment). We trained rats to self-administer methamphetamine or palatable food for 9 h per day for 14 days; reward delivery was paired with a tone-light cue. Subsequently, for one group within each reward type, 50% of the lever-presses were punished by mild footshock for 9-10 days, whereas for the other group lever-presses were not punished. Shock intensity was gradually increased over time. Next, we assessed cue-induced reward seeking in 1-h extinction sessions on withdrawal days 2 and 21. Response-contingent punishment suppressed extended-access methamphetamine or food self-administration; surprisingly, food-trained rats showed greater resistance to punishment than methamphetamine-trained rats. During the relapse tests, both punished and unpunished methamphetamine- and food-trained rats showed significantly higher cue-induced reward seeking on withdrawal day 21 than on day 2. These results demonstrate that incubation of both methamphetamine and food craving occur after punishment-induced suppression of methamphetamine or palatable food self-administration. Our procedure can be used to investigate mechanisms of relapse to drug and palatable food seeking under conditions that more closely approximate the human condition.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Craving / drug effects*
  • Cues
  • Drug-Seeking Behavior / drug effects*
  • Eating / psychology*
  • Electric Stimulation
  • Male
  • Methamphetamine / toxicity*
  • Punishment*
  • Rats
  • Rats, Sprague-Dawley
  • Reward*


  • Methamphetamine