Relapse to cocaine seeking increases activity-regulated gene expression differentially in the prefrontal cortex of abstinent rats

M. C. Hearing, S. W. Miller, R. E. See, J. F. McGinty

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47 Scopus citations

Abstract

Rationale: Alterations in the activity of the prefrontal and orbitofrontal cortices of cocaine addicts have been linked with re-exposure to cocaine-associated stimuli. Objectives: Using an animal model of relapse to cocaine seeking, the present study investigated the expression patterns of four different activity-regulated genes within prefrontal cortical brain regions after 22 h or 15 days of abstinence during context-induced relapse. Materials and methods: Rats self-administered cocaine or received yoked-saline for 2 h/day for 10 days followed by 22 h or 2 weeks of abstinence when they were re-exposed to the self-administration chamber with or without levers available to press for 1 h. Brains were harvested and sections through the prefrontal cortex were processed for in situ hybridization using radioactive oligonucleotide probes encoding c-fos, zif/268, arc, and bdnf. Results: Re-exposure to the chamber in which rats previously self-administered cocaine but not saline, regardless of lever availability, increased the expression of all genes in the medial prefrontal and orbitofrontal cortices at both time points with one exception: bdnf mRNA was significantly increased in the medial prefrontal cortex at 22 h only if levers previously associated with cocaine delivery were available to press. Furthermore, re-exposure of rats to the chambers in which they received yoked saline enhanced both zif/268 and arc expression selectively in the orbitofrontal cortex after 15 days of abstinence. Conclusions: These results support convergent evidence that cocaine-induced changes in the prefrontal cortex are important in regulating drug seeking following abstinence and may provide additional insight into the molecular mechanisms involved in these processes.

Original languageEnglish (US)
Pages (from-to)77-91
Number of pages15
JournalPsychopharmacology
Volume198
Issue number1
DOIs
StatePublished - May 2008

Keywords

  • Abstinence
  • Addiction
  • Arc
  • BDNF
  • Extinction
  • Relapse
  • Self-administration
  • c-fos
  • zif/268

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