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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 STATEMENT The 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.  相似文献   
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Menon  Aravind A.  Sahay  Sandeep  Braverman  Lewis E.  Farber  Harrison W. 《Lung》2019,197(6):761-768
Lung - Epoprostenol, a synthetic prostaglandin I2 (PGI2) analog, has been the mainstay of treatment for severe pulmonary arterial hypertension (PAH) for the last two decades. Treprostinil, another...  相似文献   
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Objective

To assess the association between occupational-related mechanical factors and the severity of radiographic peripheral and axial joint damage in patients with longstanding Psoriatic Arthritis (PsA).

Methods

Patients with longstanding PsA (disease duration≥10 years) were identified from a prospective longitudinal cohort. Using an occupation history questionnaire, patients were asked to report all paid employments since the age of 18. The key predictor variables included various occupational-related mechanical exposures. A job classification database was used to rate the level of exposure to various occupational physical activities. The outcomes were the extent of radiographic damage in the peripheral and axial joints, as measured by the modified Steinbrocker score (mSS), and the modified Stokes Ankylosing Spondylitis Spine Score (mSASSS). The association between the predictors and outcome variables was assessed by negative binomial regression models after adjusting for potential confounding variables.

Results

A total of 307 eligible patients were analyzed. In the multivariable analysis, exposure to prolonged repetitive hand movements (exp(β) 1.17 (95% 1.07, 1.28)) and occupations that required higher level of finger dexterity (exp(β) 1.27 (95% 1.09, 1.47)) were associated with a higher mSS. With regards to axial damage, none of the occupational exposures or workers abilities was associated with mSASSS.

Conclusion

High level of occupation-related mechanical stress is associated with increased radiographic peripheral joint damage among patients with longstanding PsA. This finding supports the potential role of micro-trauma in the pathogenesis of PsA.  相似文献   
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International Journal of Diabetes in Developing Countries - Studies on thyroid disorders in type 2 diabetes mellitus (DM) are fewer than those in type 1 diabetes, but data from different parts of...  相似文献   
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