Prolonged-access to cocaine induces distinct Homer2 DNA methylation, hydroxymethylation, and transcriptional profiles in the dorsomedial prefrontal cortex of Male Sprague-Dawley rats
| Autor: | Tod E. Kippin, Karen K. Szumlinski, Danay Baker-Andresen, Amanda E Carr, Jared R. Bagley, Timothy W. Bredy, Kyle L. Ploense, Xiang Li, Nick Woodward |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Messenger Self Administration Epigenesis Genetic Rats Sprague-Dawley chemistry.chemical_compound Substance Misuse 0302 clinical medicine Cocaine Dopamine Uptake Inhibitors Homer Scaffolding Proteins Gene expression Psychology Promoter Regions Genetic Prefrontal cortex DNA methylation Substance Abuse Self-administration Pharmacology and Pharmaceutical Sciences Epigenetics DNA Hydroxymethylation medicine.medical_specialty Drug Abuse (NIDA Only) mRNA Drug-Seeking Behavior Prefrontal Cortex Biology Homer2 Article Promoter Regions 03 medical and health sciences Cellular and Molecular Neuroscience Cocaine-Related Disorders Genetic Internal medicine Neuroplasticity medicine Genetics Animals RNA Messenger Pharmacology Messenger RNA Neurology & Neurosurgery Neurosciences DNA Methylation Rats Brain Disorders 030104 developmental biology Endocrinology Good Health and Well Being chemistry RNA Sprague-Dawley Transcriptome E1A-Associated p300 Protein 030217 neurology & neurosurgery DNA Epigenesis |
| Zdroj: | Ploense, KL; Li, X; Baker-Andresen, D; Carr, AE; Woodward, N; Bagley, J; et al.(2018). Prolonged-access to cocaine induces distinct Homer2 DNA methylation, hydroxymethylation, and transcriptional profiles in the dorsomedial prefrontal cortex of Male Sprague-Dawley rats.. Neuropharmacology, 143, 299-305. doi: 10.1016/j.neuropharm.2018.09.029. UC Santa Barbara: Retrieved from: http://www.escholarship.org/uc/item/2996w17f |
| Popis: | Repeated cocaine administration induces many long-term structural and molecular changes in the dorsal medial prefrontal cortex (dmPFC) and are known to underlie aspects of cocaine-seeking behavior. DNA methylation is a key long-lasting epigenetic determinant of gene expression and is implicated in neuroplasticity, however, the extent to which this epigenetic modification is involved in the neuroplasticity associated with drug addiction has received limited attention. Here, we examine the relation between DNA methylation and gene expression within the dorsal medial prefrontal cortex (dmPFC) following limited cocaine self-administration (1 h/day), prolonged cocaine self-administration (6 h/day), and saline self-administration (1 h/day). Rats were fitted with intravenous catheters and allowed to lever press for saline or cocaine (0.25 mg/kg/0.1 mL infusion) in the different access conditions for 20 days. Prolonged-access rats exhibited escalation in cocaine intake over the course of training, while limited-access rats did not escalate cocaine intake. Additionally, limited-access and prolonged-access rats exhibited unique Homer2 epigenetic profiles and mRNA expression. In prolonged-access rats, Homer2 mRNA levels in the dmPFC were increased, which was accompanied by decreased DNA methylation and p300 binding within the Homer2 promoter. Limited-access animals exhibited decreased DNA methylation, decreased DNA hydroxymethylation, and increased p300 binding within the Homer2 promoter. These data indicate that distinct epigenetic profiles are induced by limited-versus prolonged-access self-administration conditions that contribute to transcriptional profiles and lend support to the notion that covalent modification of DNA is implicated in addiction-like changes in cocaine-seeking behavior. |
| Databáze: | OpenAIRE |
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