Drug-induced reinstatement to heroin and cocaine seeking: a rodent model of relapse in polydrug use

Exp Clin Psychopharmacol. 2001 Aug;9(3):297-306. doi: 10.1037//1064-1297.9.3.297.


The authors investigated several features of polydrug use in rats. Heroin and cocaine were self-administered following responses on different levers, with only 1 drug and 1 lever available on alternate days of training. Four doses of each drug (heroin: 25, 50, 100, and 200 microg/kg/infusion; cocaine: 0.25, 0.5, 1, and 2 mg/kg/infusion) were tested, and each rat was exposed to a single dose combination. Rats readily developed drug-specific and dose-related responding. During extinction, rats displayed a significant bias for responding on the cocaine- associated lever. Priming injections of either cocaine (20 mg/kg) or heroin (0.25 mg/kg) reinstated responding that was selective for the lever previously associated with each drug. These results suggest that in this type of polydrug use, drugs have the capacity to activate drug-seeking behavior selectively oriented toward stimuli previously associated with their administration.

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 / pharmacology
  • Cocaine-Related Disorders / psychology*
  • Conditioning, Operant / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Extinction, Psychological
  • Heroin / administration & dosage
  • Heroin / pharmacology
  • Heroin Dependence / psychology*
  • Infusions, Intravenous
  • Male
  • Narcotics / administration & dosage
  • Narcotics / pharmacology
  • Rats
  • Rats, Long-Evans
  • Recurrence
  • Self Administration


  • Narcotics
  • Heroin
  • Cocaine