| Autor: |
Lauren M. Reynolds, Giovanni Hernandez, Del MacGowan, Christina Popescu, Dominique Nouel, Santiago Cuesta, Samuel Burke, Katherine E. Savell, Janet Zhao, Jose Maria Restrepo-Lozano, Michel Giroux, Sonia Israel, Taylor Orsini, Susan He, Michael Wodzinski, Radu G. Avramescu, Matthew Pokinko, Julia G. Epelbaum, Zhipeng Niu, Andrea Harée Pantoja-Urbán, Louis-Éric Trudeau, Bryan Kolb, Jeremy J. Day, Cecilia Flores |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-22 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-39665-1 |
| Popis: |
Abstract 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full text from SpringerLink