Relapse to cocaine-seeking increases activity-regulated gene expression differentially in the striatum and cerebral cortex of rats following short or long periods of abstinence.
One of the most insidious features of cocaine addiction is a high rate of relapse even after extended periods of abstinence. A wide variety of drug-associated stimuli, including the context in which a drug is taken, can gain incentive motivational properties that trigger drug desire and relapse to drug-seeking. Both animal and clinical studies suggest that extensive cocaine exposure may induce a transition from cortical to striatal control over decision-making as compulsive drug-seeking emerges. Using an animal model of relapse to cocaine-seeking, the present study investigated the expression patterns of three different activity-related genes (c-fos, zif/268, and arc) in cortical and striatal brain regions implicated in compulsive drug-seeking in order to determine the neuroadaptations that occur during context-induced relapse following brief or prolonged abstinence from cocaine self-administration. Re-exposure to the environment previously associated with cocaine self-administration following 22 h or 15 days of abstinence produced a significant increase in zif/268 and arc, but not c-fos mRNA, in the caudate-putamen and nucleus accumbens. With the exception of arc mRNA levels following 15 days of abstinence, all three genes were increased in the anterior cingulate cortex of animals with a cocaine history when they were re-exposed to the operant chamber. Additionally, c-fos, zif/268, and arc expression was differentially affected in the motor and sensory cortices at both timepoints. Together, these results support convergent evidence that drug-seeking induced by a cocaine-paired context changes the activity of corticostriatal circuits.
Hearing
M C
MC
Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue BSB 403, Charleston, SC 29425, USA.
See
R E
RE
McGinty
J F
JF
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D016739:Behavior, Addictive / Q000139:chemically induced / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013997:Time Factors
D003598:Cytoskeletal Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C092069:activity regulated cytoskeletal-associated protein; D003042:Cocaine