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Cocaine Administration and Its Withdrawal Enhance the Expression of Genes Encoding Histone-Modifying Enzymes and Histone Acetylation in the Rat Prefrontal Cortex
- Source :
- Neurotoxicity Research
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Chronic exposure to cocaine, craving, and relapse are attributed to long-lasting changes in gene expression arising through epigenetic and transcriptional mechanisms. Although several brain regions are involved in these processes, the prefrontal cortex seems to play a crucial role not only in motivation and decision-making but also in extinction and seeking behavior. In this study, we applied cocaine self-administration and extinction training procedures in rats with a yoked triad to determine differentially expressed genes in prefrontal cortex. Microarray analysis showed significant upregulation of several genes encoding histone modification enzymes during early extinction training. Subsequent real-time PCR testing of these genes following cocaine self-administration or early (third day) and late (tenth day) extinction revealed elevated levels of their transcripts. Interestingly, we found the enrichment of Brd1 messenger RNA in rats self-administering cocaine that lasted until extinction training during cocaine withdrawal with concomitant increased acetylation of H3K9 and H4K8. However, despite elevated levels of methyl- and demethyltransferase-encoded transcripts, no changes in global di- and tri-methylation of histone H3 at lysine 4, 9, 27, and 79 were observed. Surprisingly, at the end of extinction training (10 days of cocaine withdrawal), most of the analyzed genes in the rats actively and passively administering cocaine returned to the control level. Together, the alterations identified in the rat prefrontal cortex may suggest enhanced chromatin remodeling and transcriptional activity induced by early cocaine abstinence; however, to know whether they are beneficial or not for the extinction of drug-seeking behavior, further in vivo evaluation is required. Electronic supplementary material The online version of this article (doi:10.1007/s12640-017-9728-7) contains supplementary material, which is available to authorized users.
- Subjects :
- Male
0301 basic medicine
Time Factors
Self Administration
Craving
Microarray
Toxicology
Extinction, Psychological
Histones
0302 clinical medicine
Cocaine
Gene expression
Anesthetics, Local
Prefrontal cortex
Histone Acetyltransferases
biology
General Neuroscience
Acetylation
Histone-modifying enzymes
humanities
Histone
Original Article
medicine.symptom
medicine.medical_specialty
Drug-Seeking Behavior
Prefrontal Cortex
Nerve Tissue Proteins
Chromatin remodeling
Posttranslational histone modifications
Cocaine-Related Disorders
03 medical and health sciences
Histone H3
Internal medicine
medicine
Animals
RNA, Messenger
Epigenetics
Rats, Wistar
Histone-Lysine N-Methyltransferase
Extinction (psychology)
Cocaine self-administration
Rats
030104 developmental biology
Endocrinology
Gene Expression Regulation
biology.protein
Conditioning, Operant
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14763524 and 10298428
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Neurotoxicity Research
- Accession number :
- edsair.doi.dedup.....8dbb5bc2b09b1385f698538d3499570f