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Brain-wide functional architecture remodeling by alcohol dependence and abstinence

Kimbrough, Adam ; Lurie, Daniel J. ; Collazo, Andres ; Kreifeldt, Max ; Sidhu, Harpreet ; Macedo, Giovana Camila ; D’Esposito, Mark ; Contet, Candice ; George, Olivier

Proceedings of the National Academy of Sciences - PNAS, 2020-01, Vol.117 (4), p.2149-2159 [Periódico revisado por pares]

United States: National Academy of Sciences

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  • Título:
    Brain-wide functional architecture remodeling by alcohol dependence and abstinence
  • Autor: Kimbrough, Adam ; Lurie, Daniel J. ; Collazo, Andres ; Kreifeldt, Max ; Sidhu, Harpreet ; Macedo, Giovana Camila ; D’Esposito, Mark ; Contet, Candice ; George, Olivier
  • Assuntos: Abuse ; Alcohol use ; Alcohols ; Amygdala ; Animal models ; Architecture ; Biological Sciences ; Biomarkers ; Brain ; Brain architecture ; Brain research ; Dependence ; Drinking behavior ; Drug abuse ; Drug dependence ; Mesencephalon ; Modularity ; Modules ; Neostriatum ; Neuroimaging ; PNAS Plus ; Social problems ; Target recognition ; Thalamus
  • É parte de: Proceedings of the National Academy of Sciences - PNAS, 2020-01, Vol.117 (4), p.2149-2159
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Edited by Huda Akil, University of Michigan, Ann Arbor, MI, and approved December 16, 2019 (received for review June 10, 2019)
    Author contributions: A.K. and O.G. designed research; A.K., A.C., M.K., H.S., G.C.M., and C.C. performed research; D.J.L. and M.D. contributed new reagents/analytic tools; A.K., D.J.L., M.D., and C.C. analyzed data; and A.K. and O.G. wrote the paper.
  • Descrição: Alcohol abuse and alcohol dependence are key factors in the development of alcohol use disorder, which is a pervasive societal problem with substantial economic, medical, and psychiatric consequences. Although our understanding of the neurocircuitry that underlies alcohol use has improved, novel brain regions that are involved in alcohol use and novel biomarkers of alcohol use need to be identified. The present study used a single-cell whole-brain imaging approach to 1) assess whether abstinence from alcohol in an animal model of alcohol dependence alters the functional architecture of brain activity and modularity, 2) validate our current knowledge of the neurocircuitry of alcohol abstinence, and 3) discover brain regions that may be involved in alcohol use. Alcohol abstinence resulted in the whole-brain reorganization of functional architecture in mice and a pronounced decrease in modularity that was not observed in nondependent moderate drinkers. Structuring of the alcohol abstinence network revealed three major brain modules: 1) extended amygdala module, 2) midbrain striatal module, and 3) cortico-hippocampo-thalamic module, reminiscent of the three-stage theory. Many hub brain regions that control this network were identified, including several that have been previously overlooked in alcohol research. These results identify brain targets for future research and demonstrate that alcohol use and dependence remodel brain-wide functional architecture to decrease modularity. Further studies are needed to determine whether the changes in coactivation and modularity that are associated with alcohol abstinence are causal features of alcohol dependence or a consequence of excessive drinking and alcohol exposure.
  • Editor: United States: National Academy of Sciences
  • Idioma: Inglês
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