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Exercise and Fluoxetine Treatment During Adolescence Protect Against Early Life Stress-Induced Behavioral Abnormalities in Adult Rats Publisher Pubmed



Zolfaghari FS1 ; Pirri F2 ; Gauvin E3 ; Peeri M1 ; Amiri S2
Authors
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Authors Affiliations
  1. 1. Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
  2. 2. Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada

Source: Pharmacology Biochemistry and Behavior Published:2021


Abstract

Depression is a psychiatric disorder with several comorbidities that has a complicated pathophysiology. Multiple mechanisms such as abnormal hypothalamic-pituitary adrenal (HPA) axis activity, neurotransmission (namely serotonin), and immune-inflammatory responses are involved in the pathophysiology of disease. In this study, we hypothesized that applying exercise (running wheel (RW) and treadmill (TM)) or fluoxetine (FLX) during adolescence could protect adult rats against the negative impact of early-life stress. To do this, we applied maternal separation stress (MS) to neonatal rats from postnatal day (PND) 2 to 14 and at PND 28, rats were divided into 8 experimental groups and were subjected to TM or RW or FLX treatment. After four weeks of physical activity or FLX treatment, at PND 64, behaviors were assessed by applying forced swimming test, sucrose preference test, open-field test, and elevated plus maze test. Serum cortiscosterone (CORT) levels and expression of genes associated with inflammatory factors (Il1β, Hmgb1, and Il6) and serotonergic systems (5-ht2c and 5-ht3a) were studies in the hippocampus (HIPP) and prefrontal cortex (PFC). Our results revealed that RW and FLX treatment during adolescence are capable of attenuating MS-induced depressive- and anxiety-like disorders in adult male rats. These effects were accompanied by the normalization of both serum CORT and the expression of genes in the HIPP and PFC. TM exercise in adolescence showed anxiolytic effects but failed to produce antidepressant-like effects. Results of this study suggest that voluntary physical activity during adolescence can reduce the negative effects of early-life stress through different mechanisms. © 2021 Elsevier Inc.
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