N-acetylcysteine reduces extinction responding and induces enduring reductions in cue- and heroin-induced drug-seeking

Biol Psychiatry. 2008 Feb 1;63(3):338-40. doi: 10.1016/j.biopsych.2007.06.008. Epub 2007 Aug 24.


Background: Previous studies show that the acute administration of N-acetylcysteine (NAC) inhibits the desire for cocaine in addicts and cocaine-seeking in animals.

Methods: Rats were trained to self-administer heroin, and the reinstatement model of drug seeking was used to determine whether chronic NAC treatment inhibited heroin-seeking.

Results: Daily NAC administration inhibited cue- and heroin-induced seeking. Moreover, repeated NAC administration during extinction training reduced extinction-responding and inhibited cue- and heroin-induced reinstatement for up to 40 days after discontinuing daily NAC injection.

Conclusions: These data show that daily NAC inhibits heroin-induced reinstatement and produces an enduring reduction in cue- and heroin-induced drug seeking for over 1 month after the last injection of NAC. Both the inhibitory effect of NAC on the reinstatement of heroin-seeking and the ability of NAC to reduce extinction-responding support clinical evaluation of repeated NAC administration to decrease in drug-seeking in heroin addicts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Animals
  • Behavior, Animal / drug effects
  • Cues*
  • Disease Models, Animal
  • Drug Interactions
  • Extinction, Psychological / drug effects*
  • Free Radical Scavengers / pharmacology*
  • Heroin / administration & dosage*
  • Heroin Dependence / drug therapy*
  • Heroin Dependence / psychology
  • Male
  • Narcotics / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors


  • Free Radical Scavengers
  • Narcotics
  • Heroin
  • Acetylcysteine