Conditioned fear stimuli reinstate cocaine-induced conditioned place preference

Brain Res. 2001 Jul 20;908(1):86-92. doi: 10.1016/s0006-8993(01)02638-5.


These studies examined the ability of a conditioned stimulus previously paired with footshock to reinstate cocaine-induced conditioned place preference. Male rats were given either odor or tone in a paired (PRD group) or explicitly unpaired (random, RND group) manner with footshock. All rats were subsequently trained in a cocaine conditioned place preference (CPP) task. Cocaine CPP was demonstrated in all groups. After CPP extinction, presentation of the conditioned fear stimulus produced a greater degree of reinstatement in PRD rats compared to the RND group. This was true whether the conditioned stimulus was odor or tone, but when odor was used as the conditioned stimulus, the RND group also partially reinstated cocaine CPP. In rats trained with tone as the conditioned stimulus, presentation of the tone during the test for reinstatement produced robust reinstatement of cocaine CPP only in the PRD, but not RND, group. In contrast, a subsequent priming injection with cocaine reinstated cocaine CPP equally in both RND and PRD groups. These studies indicate for the first time that conditioned fear stimuli induce reinstatement of cocaine CPP, and suggest that stimuli associated with prior stress may produce relapse in humans.

Publication types

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

MeSH terms

  • Animals
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Central Nervous System / physiopathology
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / etiology*
  • Cocaine-Related Disorders / metabolism
  • Cocaine-Related Disorders / physiopathology
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Fear / drug effects
  • Fear / physiology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological / complications*
  • Stress, Physiological / metabolism
  • Stress, Physiological / physiopathology


  • Dopamine Uptake Inhibitors
  • Cocaine