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Gene coexpression patterns predict opiate-induced brain-state transitions.
Brynildsen, Julia K; Mace, Kyla D; Cornblath, Eli J; Weidler, Carmen; Pasqualetti, Fabio; Bassett, Danielle S; Blendy, Julie A.
Afiliación
  • Brynildsen JK; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Mace KD; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Cornblath EJ; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104.
  • Weidler C; Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104.
  • Pasqualetti F; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104.
  • Bassett DS; Department of Electrical & Systems Engineering, University of Pennsylvania, Philadelphia, PA 19104.
  • Blendy JA; Department of Physics & Astronomy, University of Pennsylvania, Philadelphia, PA 19104.
Proc Natl Acad Sci U S A ; 117(32): 19556-19565, 2020 08 11.
Article en En | MEDLINE | ID: mdl-32694207
Opioid addiction is a chronic, relapsing disorder associated with persistent changes in brain plasticity. Reconfiguration of neuronal connectivity may explain heightened abuse liability in individuals with a history of chronic drug exposure. To characterize network-level changes in neuronal activity induced by chronic opiate exposure, we compared FOS expression in mice that are morphine-naïve, morphine-dependent, or have undergone 4 wk of withdrawal from chronic morphine exposure, relative to saline-exposed controls. Pairwise interregional correlations in FOS expression data were used to construct network models that reveal a persistent reduction in connectivity strength following opiate dependence. Further, we demonstrate that basal gene expression patterns are predictive of changes in FOS correlation networks in the morphine-dependent state. Finally, we determine that regions of the hippocampus, striatum, and midbrain are most influential in driving transitions between opiate-naïve and opiate-dependent brain states using a control theoretic approach. This study provides a framework for predicting the influence of specific therapeutic interventions on the state of the opiate-dependent brain.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Dependencia de Morfina / Red Nerviosa Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Dependencia de Morfina / Red Nerviosa Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos