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Characterization of the Brain Functional Architecture of Psychostimulant Withdrawal Using Single-Cell Whole-Brain Imaging

Kimbrough, Adam and Kallupi, Marsida and Smith, Lauren C. and Simpson, Sierra and Collazo, Andres and George, Olivier (2021) Characterization of the Brain Functional Architecture of Psychostimulant Withdrawal Using Single-Cell Whole-Brain Imaging. eNeuro, 8 (6). Art. No. ENEURO.0208-19.2021. ISSN 2373-2822. PMCID PMC8570684. doi:10.1523/ENEURO.0208-19.2021.

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Numerous brain regions have been identified as contributing to withdrawal behaviors, but it is unclear the way in which these brain regions as a whole lead to withdrawal. The search for a final common brain pathway that is involved in withdrawal remains elusive. To address this question, we implanted osmotic minipumps containing either saline, nicotine (24 mg/kg/d), cocaine (60 mg/kg/d), or methamphetamine (4 mg/kg/d) for one week in male C57BL/6J mice. After one week, the minipumps were removed and brains collected 8 h (saline, nicotine, and cocaine) or 12 h (methamphetamine) after removal. We then performed single-cell whole-brain imaging of neural activity during the withdrawal period when brains were collected. We used hierarchical clustering and graph theory to identify similarities and differences in brain functional architecture. Although methamphetamine and cocaine shared some network similarities, the main common neuroadaptation between these psychostimulant drugs was a dramatic decrease in modularity, with a shift from a cortical-driven to subcortical-driven network, including a decrease in total hub brain regions. These results demonstrate that psychostimulant withdrawal produces the drug-dependent remodeling of functional architecture of the brain and suggest that the decreased modularity of brain functional networks and not a specific set of brain regions may represent the final common pathway associated with withdrawal.

Item Type:Article
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URLURL TypeDescription CentralArticle Paper
Kimbrough, Adam0000-0001-9434-4987
Kallupi, Marsida0000-0002-8688-709X
Simpson, Sierra0000-0002-1352-0617
Collazo, Andres0000-0003-2274-7255
George, Olivier0000-0002-3700-5003
Alternate Title:Brain architecture of psychostimulant withdrawal
Additional Information:© 2021 Kimbrough et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Received May 31, 2019; accepted August 9, 2021; First published September 17, 2021. This work was supported by National Institutes of Health Grants DA044451, DA043799, DA047113, AA006420, AA020608, AA022977, AA027301, and AA007456; the Tobacco-Related Disease Research Program Grant 27IR-0047; Tobacco-Related Disease Research Program (grant no. T31KT1859); the 2021 Psychiatry Department Chair’s Excellence Fund to M.K.; the Pearson Center for Alcoholism and Addiction Research and the Preclinical Addiction Research Consortium at UCSD. Author contributions: A.K. and O.G. designed research; A.K., M.K., L.C.S., and A.C. performed research; A.K., L.C.S., and S.S. analyzed data; A.K. and O.G. wrote the paper. The authors declare no competing financial interests.
Funding AgencyGrant Number
California Tobacco-Related Disease Research Program27IR-0047
California Tobacco-Related Disease Research ProgramT31KT1859
Pearson Center for Alcoholism and Addiction ResearchUNSPECIFIED
University of California, San DiegoUNSPECIFIED
Subject Keywords:addiction; functional connectivity; graph theory; iDISCO; neural activity; withdrawal
Issue or Number:6
PubMed Central ID:PMC8570684
Record Number:CaltechAUTHORS:20190822-142447971
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Official Citation:Characterization of the Brain Functional Architecture of Psychostimulant Withdrawal Using Single-Cell Whole-Brain Imaging. Adam Kimbrough, Marsida Kallupi, Lauren C. Smith, Sierra Simpson, Andres Collazo, Olivier George. eNeuro 27 September 2021, 8 (6) ENEURO.0208-19.2021; DOI: 10.1523/ENEURO.0208-19.2021
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:98131
Deposited By: Tony Diaz
Deposited On:22 Aug 2019 21:35
Last Modified:08 Feb 2022 23:45

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