Gene expression changes in the medial prefrontal cortex and nucleus accumbens following abstinence from cocaine self-administration

BMC Neuroscience

Research Article

Kent E Vrana¹  Melinda E Lull¹  Willard M Freeman²  David CS Roberts³  Drake Morgan⁴  Kruti M Patel⁵  Robert M Brucklacher⁵ 

[1] Department of Pharmacology, Penn State College of Medicine, 17033, Hershey, PA, USA;Department of Pharmacology, Penn State College of Medicine, 17033, Hershey, PA, USA;Functional Genomics Facility, Penn State College of Medicine, 17033, Hershey, PA, USA;Department of Physiology & Pharmacology, Wake Forest University School of Medicine, 27157, Winston-Salem, NC, USA;Department of Psychiatry, University of Florida, 32611, Gainesville, FL, USA;Functional Genomics Facility, Penn State College of Medicine, 17033, Hershey, PA, USA;

关键词: Cocaine;    Synaptic Plasticity;    Gene Expression Change;    Medial Prefrontal Cortex;    Cocaine Abuse;   

DOI  :  10.1186/1471-2202-11-29

 received in 2009-09-23, accepted in 2010-02-26,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMany studies of cocaine-responsive gene expression have focused on changes occurring during cocaine exposure, but few studies have examined the persistence of these changes with cocaine abstinence. Persistent changes in gene expression, as well as alterations induced during abstinence may underlie long-lasting drug craving and relapse liability.ResultsWhole-genome expression analysis was conducted on a rat cocaine binge-abstinence model that has previously been demonstrated to engender increased drug seeking and taking with abstinence. Gene expression changes in two mesolimbic terminal fields (mPFC and NAc) were identified in a comparison of cocaine-naïve rats with rats after 10 days of cocaine self-administration followed by 1, 10, or 100 days of enforced abstinence (n = 6-11 per group). A total of 1,461 genes in the mPFC and 414 genes in the NAc were altered between at least two time points (ANOVA, p < 0.05; ± 1.4 fold-change). These genes can be subdivided into: 1) changes with cocaine self-administration that do not persist into periods of abstinence, 2) changes with cocaine self-administration that persist with abstinence, 3) and those not changed with cocaine self-administration, but changed during enforced abstinence. qPCR analysis was conducted to confirm gene expression changes observed in the microarray analysis.ConclusionsTogether, these changes help to illuminate processes and networks involved in abstinence-induced behaviors, including synaptic plasticity, MAPK signaling, and TNF signaling.

【 授权许可】

CC BY   
© Freeman et al; licensee BioMed Central Ltd. 2010