Role of the NMDA receptor and nitric oxide in memory reconsolidation of cocaine-induced conditioned place preference in mice

Yossef Itzhak

Research output: Chapter in Book/Report/Conference proceedingConference contribution

47 Scopus citations


Classical pavlovian conditioning has a major role in the development and persistence of drug addiction. Appetitive conditioning by drug reward, as measured by the conditioned place preference (CPP) paradigm, is an exemplar of classical pavlovian conditioning. Aversive conditioning by footshock involves learning and memory processes similar to those involved in appetitive conditioning. Studies on fear conditioning have shown that long-term fear memory can be extinguished by disruption of reconsolidation of specific memories associated with the fear response. Hence disruption of memory reconsolidation may hold promise for the extinction of maladaptive conditioned behavior. In the present study the effects of the NMDA receptor antagonist, MK-801, and the nNOS inhibitor 7-nitroindazole (7-NI) on memory reconsolidation of cocaine-induced CPP in mice were investigated. We report that, following the acquisition of cocaine CPP, a single acute administration of either MK-801 or 7-NI immediately after retrieval of place preference extinguished subsequent place preference. Moreover, a priming dose of cocaine did not reinstate place preference in the drug-treated groups compared to controls. Male nNOS knockout (KO) mice acquired short-lived cocaine CPP compared to wild-type (WT) mice. A single acute administration of the NO-donor molsidomine to nNOS KO mice immediately after retrieval of CPP prolonged the expression of place preference compared to controls that received saline, suggesting partial strengthening of memory reconsolidation. Taken together, these findings support the role of the NMDAR/NO signaling pathway in memory reconsolidation of cocaine CPP, and suggest that disruption of this pathway during memory reconsolidation may afford resistance to drug-seeking behavior.

Original languageEnglish (US)
Title of host publicationDrug Addiction
Subtitle of host publicationResearch Frontiers and Treatment Advances
PublisherBlackwell Publishing Inc.
Number of pages8
ISBN (Print)9781573317184
StatePublished - Oct 2008

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • Cocaine
  • Extinction
  • Memory reconsolidation
  • Nitric oxide
  • NMDA receptor
  • nNOS knockout mice

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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