Dopamine transporter blockade during adolescence increases adult dopamine function, impulsivity, and aggression.

Autor: Suri D; Department of Psychiatry, Columbia University, New York, NY, 10032, USA.; Department of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032, USA., Zanni G; Department of Psychiatry, Columbia University, New York, NY, 10032, USA.; Department of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032, USA., Mahadevia D; Department of Psychiatry, Columbia University, New York, NY, 10032, USA.; Department of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032, USA., Chuhma N; Department of Psychiatry, Columbia University, New York, NY, 10032, USA.; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, 10032, USA., Saha R; Department of Psychiatry, Columbia University, New York, NY, 10032, USA.; Department of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032, USA., Spivack S; Department of Psychiatry, Columbia University, New York, NY, 10032, USA.; Department of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032, USA., Pini N; Department of Psychiatry, Columbia University, New York, NY, 10032, USA.; Department of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032, USA., Stevens GS; Department of Psychiatry, Columbia University, New York, NY, 10032, USA.; Department of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032, USA., Ziolkowski-Blake A; Department of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032, USA., Simpson EH; Department of Psychiatry, Columbia University, New York, NY, 10032, USA.; Department of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032, USA., Balsam P; Department of Psychiatry, Columbia University, New York, NY, 10032, USA.; Department of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032, USA.; Department of Neuroscience and Behavior, Barnard College, Columbia University, New York, NY, 10032, USA., Rayport S; Department of Psychiatry, Columbia University, New York, NY, 10032, USA.; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, 10032, USA., Ansorge MS; Department of Psychiatry, Columbia University, New York, NY, 10032, USA. ma2362@cumc.columbia.edu.; Department of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032, USA. ma2362@cumc.columbia.edu.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2023 Aug; Vol. 28 (8), pp. 3512-3523. Date of Electronic Publication: 2023 Aug 02.
DOI: 10.1038/s41380-023-02194-w
Abstrakt: Sensitive developmental periods shape neural circuits and enable adaptation. However, they also engender vulnerability to factors that can perturb developmental trajectories. An understanding of sensitive period phenomena and mechanisms separate from sensory system development is still lacking, yet critical to understanding disease etiology and risk. The dopamine system is pivotal in controlling and shaping adolescent behaviors, and it undergoes heightened plasticity during that time, such that interference with dopamine signaling can have long-lasting behavioral consequences. Here we sought to gain mechanistic insight into this dopamine-sensitive period and its impact on behavior. In mice, dopamine transporter (DAT) blockade from postnatal (P) day 22 to 41 increases aggression and sensitivity to amphetamine (AMPH) behavioral stimulation in adulthood. Here, we refined this sensitive window to P32-41 and identified increased firing of dopaminergic neurons in vitro and in vivo as a neural correlate to altered adult behavior. Aggression can result from enhanced impulsivity and cognitive dysfunction, and dopamine regulates working memory and motivated behavior. Hence, we assessed these behavioral domains and found that P32-41 DAT blockade increases impulsivity but has no effect on cognition, working memory, or motivation in adulthood. Lastly, using optogenetics to drive dopamine neurons, we find that increased VTA but not SNc dopaminergic activity mimics the increase in impulsive behavior in the Go/NoGo task observed after adolescent DAT blockade. Together our data provide insight into the developmental origins of aggression and impulsivity that may ultimately improve diagnosis, prevention, and treatment strategies for related neuropsychiatric disorders.
(© 2023. The Author(s).)
Databáze: MEDLINE
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