Amphetamine disrupts dopamine axon growth in adolescence by a sex-specific mechanism in mice.

Autor: Reynolds LM; Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada.; Douglas Mental Health University Institute, Montréal, QC, Canada.; Plasticité du Cerveau CNRS UMR8249, École supérieure de physique et de chimie industrielles de la Ville de Paris (ESPCI Paris), Paris, France., Hernandez G; Douglas Mental Health University Institute, Montréal, QC, Canada., MacGowan D; Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada.; Douglas Mental Health University Institute, Montréal, QC, Canada., Popescu C; Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada.; Douglas Mental Health University Institute, Montréal, QC, Canada., Nouel D; Douglas Mental Health University Institute, Montréal, QC, Canada., Cuesta S; Douglas Mental Health University Institute, Montréal, QC, Canada.; Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA., Burke S; CNS Research Group, Department of Pharmacology and Physiology, Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada., Savell KE; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA., Zhao J; Douglas Mental Health University Institute, Montréal, QC, Canada., Restrepo-Lozano JM; Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada.; Douglas Mental Health University Institute, Montréal, QC, Canada., Giroux M; Douglas Mental Health University Institute, Montréal, QC, Canada., Israel S; Douglas Mental Health University Institute, Montréal, QC, Canada., Orsini T; Douglas Mental Health University Institute, Montréal, QC, Canada., He S; Douglas Mental Health University Institute, Montréal, QC, Canada., Wodzinski M; Douglas Mental Health University Institute, Montréal, QC, Canada., Avramescu RG; Douglas Mental Health University Institute, Montréal, QC, Canada., Pokinko M; Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada.; Douglas Mental Health University Institute, Montréal, QC, Canada., Epelbaum JG; Douglas Mental Health University Institute, Montréal, QC, Canada., Niu Z; Douglas Mental Health University Institute, Montréal, QC, Canada., Pantoja-Urbán AH; Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada.; Douglas Mental Health University Institute, Montréal, QC, Canada., Trudeau LÉ; CNS Research Group, Department of Pharmacology and Physiology, Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada., Kolb B; Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, Canada., Day JJ; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA., Flores C; Douglas Mental Health University Institute, Montréal, QC, Canada. cecilia.flores@mcgill.ca.; Department of Psychiatry and Department of Neurology and Neurosurgery, McGill University, Montréal, Canada. cecilia.flores@mcgill.ca.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jul 07; Vol. 14 (1), pp. 4035. Date of Electronic Publication: 2023 Jul 07.
DOI: 10.1038/s41467-023-39665-1
Abstrakt: Initiating drug use during adolescence increases the risk of developing addiction or other psychopathologies later in life, with long-term outcomes varying according to sex and exact timing of use. The cellular and molecular underpinnings explaining this differential sensitivity to detrimental drug effects remain unexplained. The Netrin-1/DCC guidance cue system segregates cortical and limbic dopamine pathways in adolescence. Here we show that amphetamine, by dysregulating Netrin-1/DCC signaling, triggers ectopic growth of mesolimbic dopamine axons to the prefrontal cortex, only in early-adolescent male mice, underlying a male-specific vulnerability to enduring cognitive deficits. In adolescent females, compensatory changes in Netrin-1 protect against the deleterious consequences of amphetamine on dopamine connectivity and cognitive outcomes. Netrin-1/DCC signaling functions as a molecular switch which can be differentially regulated by the same drug experience as function of an individual's sex and adolescent age, and lead to divergent long-term outcomes associated with vulnerable or resilient phenotypes.
(© 2023. The Author(s).)
Databáze: MEDLINE
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