Reduced Motivation in Perinatal Fluoxetine-Treated Mice: A Hypodopaminergic Phenotype
| Autor: | John F. Smiley, Francisco X. Castellanos, K. Yaragudri Vinod, Lindsay C. Laughlin, Edenia C. Menezes, Andrea Balla, André Corvelo, Cátia M. Teixeira, Henry Sershen, Relish Shah, Catarina Cunha |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Mice 129 Strain Dopamine Microdialysis 03 medical and health sciences Mice 0302 clinical medicine Internal medicine Fluoxetine Neuroplasticity Medicine Animals Amphetamine Research Articles 030304 developmental biology Bupropion 0303 health sciences Motivation business.industry General Neuroscience Dopaminergic Mice Inbred C57BL Endocrinology Phenotype Animals Newborn Antidepressant Female business Reuptake inhibitor 030217 neurology & neurosurgery Locomotion Selective Serotonin Reuptake Inhibitors medicine.drug |
| Zdroj: | J Neurosci |
| Popis: | 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.SIGNIFICANCE STATEMENTThe developmental period is characterized by enhanced plasticity. During this period, environmental factors have the potential to lead to enduring behavioral changes. Here, we show that exposure to the SSRI fluoxetine during a restricted period in early life leads to a reduction in adult motivation. We further show that this reduction is associated with decreased dopaminergic responsivity. Finally, we show that motivational deficits induced by early-life fluoxetine exposure can be rescued by adult administration of bupropion but not by fluoxetine. |
| Databáze: | OpenAIRE |
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