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

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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.

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Acknowledgement

The authors thank Shannon Ghee and Anthony Carnell for excellent technical support. This research was supported by NIH P50 DA15369.

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  1. Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue BSB 403, Charleston, SC, 29245, USA

    M. C. Hearing, R. E. See & J. F. McGinty

  2. Department of Biostatistics, Bioinformatics, and Epidemiology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC, 29245, USA

    S. W. Miller

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  1. M. C. Hearing
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Correspondence to J. F. McGinty.

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Hearing, M.C., Miller, S.W., See, R.E. et al. Relapse to cocaine seeking increases activity-regulated gene expression differentially in the prefrontal cortex of abstinent rats. Psychopharmacology 198, 77–91 (2008). https://doi.org/10.1007/s00213-008-1090-2

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