Neurobiological evidence for hedonic allostasis associated with escalating cocaine use

Nat Neurosci. 2002 Jul;5(7):625-6. doi: 10.1038/nn872.


A paradoxical aspect of the transition to drug addiction is that drug users spend progressively more time and effort to obtain drug hedonic effects that continually decrease with repeated experience. According to the hedonic allostasis hypothesis, increased craving for and tolerance to the hedonic effects of drugs result from the same chronic alteration in the regulation of brain reward function (allostasis). Here we show in rats that repeated withdrawals from prolonged cocaine self-administration produces a persistent decrease in brain reward function that is highly correlated with escalation of cocaine intake and that reduces the hedonic impact of cocaine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / physiopathology*
  • Disease Models, Animal
  • Drug Administration Schedule
  • Drug Tolerance / physiology
  • Electric Stimulation
  • Electrodes, Implanted
  • Hypothalamus / drug effects
  • Hypothalamus / physiology
  • Male
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Regression Analysis
  • Reward
  • Self Administration
  • Sensory Thresholds / drug effects
  • Sensory Thresholds / physiology


  • Cocaine