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 language | English (US) |
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Pages (from-to) | 77-91 |
Number of pages | 15 |
Journal | Psychopharmacology |
Volume | 198 |
Issue number | 1 |
DOIs | |
State | Published - May 2008 |
Keywords
- Abstinence
- Addiction
- Arc
- BDNF
- Extinction
- Relapse
- Self-administration
- c-fos
- zif/268