title: Convergent transcriptomics and proteomics of environmental enrichment and cocaine identifies novel therapeutic strategies for addiction.
abstract: Transcriptomic and proteomic approaches have separately proven effective at identifying novel mechanisms affecting addiction-related behavior; however, it is difficult to prioritize the many promising leads from each approach. A convergent secondary analysis of proteomic and transcriptomic results can glean additional information to help prioritize promising leads. The current study is a secondary analysis of the convergence of recently published separate transcriptomic and proteomic analyses of nucleus accumbens (NAc) tissue from rats subjected to environmental enrichment vs. isolation and cocaine self-administration vs. saline. Multiple bioinformatics approaches (e.g. Gene Ontology (GO) analysis, Ingenuity Pathway Analysis (IPA), and Gene Set Enrichment Analysis (GSEA)) were used to interrogate these rich data sets. Although there was little correspondence between mRNA vs. protein at the individual target level, good correspondence was found at the level of gene/protein sets, particularly for the environmental enrichment manipulation. These data identify gene sets where there is a positive relationship between changes in mRNA and protein (e.g. glycolysis, ATP synthesis, translation elongation factor activity, etc.) and gene sets where there is an inverse relationship (e.g. ribosomes, Rho GTPase signaling, protein ubiquitination, etc.). Overall environmental enrichment produced better correspondence than cocaine self-administration. The individual targets contributing to mRNA and protein effects were largely not overlapping. As a whole, these results confirm that robust transcriptomic and proteomic data sets can provide similar results at the gene/protein set level even when there is little correspondence at the individual target level and little overlap in the targets contributing to the effects.
authors.affiliation: Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX, USA; Dept. of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX, USA; Dept. of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Crofton
authors.affiliation: Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX, USA; Dept. of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Fan
authors.affiliation: Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX, USA; Dept. of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Dingge
authors.initials: D
authors.lastname: Li
authors.affiliation: Dept. of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Fanping
authors.initials: F
authors.lastname: Kong
authors.affiliation: Sealy Center for Molecular Medicine, Institute for Translational Science, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Mala
authors.initials: M
authors.lastname: Sinha
authors.affiliation: Dept. of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Molecular Medicine, Institute for Translational Science, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Luxon
authors.affiliation: Dept. of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA; Sealy Center for Molecular Medicine, Institute for Translational Science, The University of Texas Medical Branch, Galveston, TX, USA; Dept. of Preventative Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Spratt
authors.affiliation: Dept. of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Cheryl F
authors.initials: CF
authors.lastname: Lichti
authors.affiliation: Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX, USA; Dept. of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX, USA; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX, USA. Electronic address: tom.green@utmb.edu.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Green
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000628:therapy*; D019295:Computational Biology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004777:Environment; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D020543:Proteome; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D012934:Social Isolation; D059467:Transcriptome
chemical_list: D018765:Dopamine Uptake Inhibitors; D020543:Proteome; D012333:RNA, Messenger; D003042:Cocaine
keywords: addiction; cocaine; environmental enrichment; proteomics; self-administration; transcriptomics