Transcriptomics of Environmental Enrichment Reveals a Role for Retinoic Acid Signaling in Addiction.

Autor: Zhang Y; Center for Addiction Research, The University of Texas Medical Branch, GalvestonTX, USA; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, GalvestonTX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, GalvestonTX, USA., Kong F; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, GalvestonTX, USA; Biomedical Informatics Program, The University of Texas Medical Branch, GalvestonTX, USA., Crofton EJ; Center for Addiction Research, The University of Texas Medical Branch, GalvestonTX, USA; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, GalvestonTX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, GalvestonTX, USA., Dragosljvich SN; Center for Addiction Research, The University of Texas Medical Branch, GalvestonTX, USA; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, GalvestonTX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, GalvestonTX, USA., Sinha M; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, GalvestonTX, USA; Biomedical Informatics Program, The University of Texas Medical Branch, GalvestonTX, USA; Sealy Center for Molecular Medicine, Institute for Translational Science, The University of Texas Medical Branch, GalvestonTX, USA., Li D; Center for Addiction Research, The University of Texas Medical Branch, GalvestonTX, USA; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, GalvestonTX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, GalvestonTX, USA., Fan X; Center for Addiction Research, The University of Texas Medical Branch, GalvestonTX, USA; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, GalvestonTX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, GalvestonTX, USA., Koshy S; Center for Addiction Research, The University of Texas Medical Branch, GalvestonTX, USA; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, GalvestonTX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, GalvestonTX, USA., Hommel JD; Center for Addiction Research, The University of Texas Medical Branch, GalvestonTX, USA; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, GalvestonTX, USA., Spratt HM; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, GalvestonTX, USA; Biomedical Informatics Program, The University of Texas Medical Branch, GalvestonTX, USA; Sealy Center for Molecular Medicine, Institute for Translational Science, The University of Texas Medical Branch, GalvestonTX, USA; Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, GalvestonTX, USA., Luxon BA; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, GalvestonTX, USA; Biomedical Informatics Program, The University of Texas Medical Branch, GalvestonTX, USA; Sealy Center for Molecular Medicine, Institute for Translational Science, The University of Texas Medical Branch, GalvestonTX, USA., Green TA; Center for Addiction Research, The University of Texas Medical Branch, GalvestonTX, USA; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, GalvestonTX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, GalvestonTX, USA.
Jazyk: angličtina
Zdroj: Frontiers in molecular neuroscience [Front Mol Neurosci] 2016 Nov 16; Vol. 9, pp. 119. Date of Electronic Publication: 2016 Nov 16 (Print Publication: 2016).
DOI: 10.3389/fnmol.2016.00119
Abstrakt: There exists much variability in susceptibility/resilience to addiction in humans. The environmental enrichment paradigm is a rat model of resilience to addiction-like behavior, and understanding the molecular mechanisms underlying this protective phenotype may lead to novel targets for pharmacotherapeutics to treat cocaine addiction. We investigated the differential regulation of transcript levels using RNA sequencing of the rat nucleus accumbens after environmental enrichment/isolation and cocaine/saline self-administration. Ingenuity Pathways Analysis and Gene Set Enrichment Analysis of 14,309 transcripts demonstrated that many biofunctions and pathways were differentially regulated. New functional pathways were also identified for cocaine modulation (e.g., Rho GTPase signaling) and environmental enrichment (e.g., signaling of EIF2, mTOR, ephrin). However, one novel pathway stood out above the others, the retinoic acid (RA) signaling pathway. The RA signaling pathway was identified as one likely mediator of the protective enrichment addiction phenotype, an interesting result given that nine RA signaling-related genes are expressed selectively and at high levels in the nucleus accumbens shell (NAcSh). Subsequent knockdown of Cyp26b1 (an RA degradation enzyme) in the NAcSh of rats confirmed this role by increasing cocaine self-administration as well as cocaine seeking. These results provide a comprehensive account of enrichment effects on the transcriptome and identify RA signaling as a contributing factor for cocaine addiction.
Databáze: MEDLINE