Persistent disruption of an established morphine conditioned place preference

J Neurosci. 2006 Mar 15;26(11):3010-20. doi: 10.1523/JNEUROSCI.4818-05.2006.


In human addicts, craving and relapse are frequently evoked by the recall of memories connected to a drug experience. Established memories can become labile if recalled and can then be disrupted by several interfering events and pharmacological treatments, including inhibition of protein synthesis. Thus, reactivation of mnemonic traces provides an opportunity for disrupting memories that contribute to pathological states. Here, we tested whether the memory of a drug experience can be weakened by inhibiting protein synthesis after the reactivation of its trace. We found that an established morphine conditioned place preference (mCPP) was persistently disrupted if protein synthesis was blocked by either anisomycin or cycloheximide after the representation of a conditioning session. Unlike other types of memories, an established mCPP did not become labile after contextual recall, but required the concomitant re-experience of both the conditioning context and the drug. An established mCPP was disrupted after the conditioning session if protein synthesis was blocked selectively in the hippocampus, basolateral amygdala, or nucleus accumbens but not in the ventral tegmental area. This disruption seems to be permanent, because the preference did not return after further conditioning. Thus, established memories induced by a drug of abuse can be persistently disrupted after reactivation of the conditioning experience.

Publication types

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

MeSH terms

  • Amnesia, Retrograde / chemically induced
  • Amnesia, Retrograde / metabolism
  • Amygdala / drug effects
  • Amygdala / metabolism
  • Amygdala / physiopathology
  • Animals
  • Anisomycin / administration & dosage
  • Anisomycin / pharmacology*
  • Association Learning / drug effects*
  • Association Learning / physiology
  • Conditioning, Classical / drug effects*
  • Conditioning, Classical / physiology
  • Cues
  • Cycloheximide / administration & dosage
  • Cycloheximide / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Learning
  • Male
  • Mental Recall / drug effects*
  • Mental Recall / physiology
  • Microinjections
  • Morphine / pharmacology*
  • Morphine / toxicity
  • Morphine Dependence / physiopathology
  • Morphine Dependence / psychology
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / physiology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiopathology
  • Organ Specificity
  • Protein Synthesis Inhibitors / administration & dosage
  • Protein Synthesis Inhibitors / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Reward
  • Spatial Behavior / drug effects*
  • Time Factors
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism
  • Ventral Tegmental Area / physiopathology


  • Nerve Tissue Proteins
  • Protein Synthesis Inhibitors
  • Anisomycin
  • Morphine
  • Cycloheximide