4.7 Article

Reduced Motivation in Perinatal Fluoxetine-Treated Mice: A Hypodopaminergic Phenotype

期刊

JOURNAL OF NEUROSCIENCE
卷 41, 期 12, 页码 2723-2732

出版社

SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2608-20.2021

关键词

dopamine; fluoxetine; gestation; motivation; postnatal; serotonin

资金

  1. National Institute of Child Health and Human Development [R01 HD095966, R03 HD094978]

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Early life is a critical period where enhanced neural plasticity allows the developing brain to adapt to its environment. Exposure to fluoxetine in early postnatal period can lead to reduced effort-related motivation and blunted dopaminergic activation in reward tasks in adulthood. Administering bupropion in adulthood can rescue the reduction in motivation, highlighting the involvement of the dopaminergic system in this process.
Early life is a sensitive period, in which enhanced neural plasticity allows the developing brain to adapt to its environment. This plasticity can also be a risk factor in which maladaptive development can lead to long-lasting behavioral deficits. Here, we test how early-life exposure to the selective-serotonin-reuptake-inhibitor (SSRI), fluoxetine, affects motivation, and dopaminergic signaling in adulthood. We show for the first time that mice exposed to fluoxetine in the early postnatal period exhibit a reduction in effort-related motivation. These mice also show blunted responses to amphetamine and reduced dopaminergic activation in a sucrose reward task. Interestingly, we find that the reduction in motivation can be rescued in the adult by administering bupropion, a dopamine-norepinephrine reuptake inhibitor used as an antidepressant and a smoke cessation aid but not by fluoxetine. Taken together, our studies highlight the effects of early postnatal exposure of fluoxetine on motivation and demonstrate the involvement of the dopaminergic system in this process.

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