title: Large-Scale, Ion-Current-Based Proteomic Investigation of the Rat Striatal Proteome in a Model of Short- and Long-Term Cocaine Withdrawal.
abstract: Given the tremendous detriments of cocaine dependence, effective diagnosis and patient stratification are critical for successful intervention yet difficult to achieve due to the largely unknown molecular mechanisms involved. To obtain new insights into cocaine dependence and withdrawal, we employed a reproducible, reliable, and large-scale proteomics approach to investigate the striatal proteomes of rats (n = 40, 10 per group) subjected to chronic cocaine exposure, followed by either short- (WD1) or long- (WD22) term withdrawal. By implementing a surfactant-aided precipitation/on-pellet digestion procedure, a reproducible and sensitive nanoLC-Orbitrap MS analysis, and an optimized ion-current-based MS1 quantification pipeline, >2000 nonredundant proteins were quantified confidently without missing data in any replicate. Although cocaine was cleared from the body, 129/37 altered proteins were observed in WD1/WD22 that are implicated in several biological processes related closely to drug-induced neuroplasticity. Although many of these changes recapitulate the findings from independent studies reported over the last two decades, some novel insights were obtained and further validated by immunoassays. For example, significantly elevated striatal protein kinase C activity persisted over the 22 day cocaine withdrawal. Cofilin-1 activity was up-regulated in WD1 and down-regulated in WD22. These discoveries suggest potentially distinct structural plasticity after short- and long-term cocaine withdrawal. In addition, this study provides compelling evidence that blood vessel narrowing, a long-known effect of cocaine use, occurred after long-term but not short-term withdrawal. In summary, this work developed a well-optimized paradigm for ion-current-based quantitative proteomics in brain tissues and obtained novel insights into molecular alterations in the striatum following cocaine exposure and withdrawal.
authors.affiliation: New York State Center of Excellence in Bioinformatics & Life Sciences , Buffalo, New York 14203, United States.|Department of Biochemistry, School of Medicine and Biomedical Sciences, SUNY at Buffalo , Buffalo, New York 14214, United States.
authors.forename: Shichen
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Pharmaceutical Sciences, SUNY at Buffalo , Buffalo, New York 14214, United States.|New York State Center of Excellence in Bioinformatics & Life Sciences , Buffalo, New York 14203, United States.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutical Sciences, SUNY at Buffalo , Buffalo, New York 14214, United States.|New York State Center of Excellence in Bioinformatics & Life Sciences , Buffalo, New York 14203, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, SUNY at Buffalo , Buffalo, New York 14214, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Straubinger
authors.affiliation: Department of Psychology, SUNY at Buffalo , Buffalo, New York 14260, United States.|Research Institute on Addictions, SUNY at Buffalo , Buffalo, New York 14203, United States.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Suarez
authors.affiliation: New York State Center of Excellence in Bioinformatics & Life Sciences , Buffalo, New York 14203, United States.|Department of Biochemistry, School of Medicine and Biomedical Sciences, SUNY at Buffalo , Buffalo, New York 14214, United States.
authors.forename: Chengjian
authors.initials: C
authors.lastname: Tu
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology , Beijing 100850, China.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Psychology, SUNY at Buffalo , Buffalo, New York 14260, United States.|Research Institute on Addictions, SUNY at Buffalo , Buffalo, New York 14203, United States.
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Thompson
authors.affiliation: Department of Pharmaceutical Sciences, SUNY at Buffalo , Buffalo, New York 14214, United States.|New York State Center of Excellence in Bioinformatics & Life Sciences , Buffalo, New York 14203, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Qu
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders; D003342:Corpus Striatum / Q000737:chemistry*; D009473:Neuronal Plasticity / Q000187:drug effects; D020543:Proteome / Q000187:drug effects*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D013375:Substance Withdrawal Syndrome; D013997:Time Factors
chemical_list: D020543:Proteome; D003042:Cocaine
keywords: bottom-up proteomics; cocaine dependence; cocaine withdrawal; ion-current-based; neuroplasticity