Relapse to cocaine seeking increases activity-regulated gene expression differentially in the prefrontal cortex of abstinent rats.
BACKGROUND
Alterations in the activity of the prefrontal and orbitofrontal cortices of cocaine addicts have been linked with re-exposure to cocaine-associated stimuli.


OBJECTIVE
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.


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.
Hearing
M C
MC
Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue BSB 403, Charleston, SC 29245, USA.
Miller
S W
SW
See
R E
RE
McGinty
J F
JF
D000818:Animals; D001345:Autoradiography; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D051766:Early Growth Response Protein 1 / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D016762:Genes, fos / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000523:psychology*
D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein