Duloxetine prevents the effects of prenatal stress on depressive-like and anxiety-like behavior and hippocampal expression of pro-inflammatory cytokines in adult male offspring rats |
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| Affiliation: | 1. College of Humanities and Social Sciences, Applied Psychology, China Medical University, PR China;2. Department of Psychiatry, the First Affiliated Hospital of China Medical University, PR China;3. Essential Qualities Oriented Education College, Liaoning Finance Vocational College, PR China;1. Laboratório de Neurociências, Unidade Acadêmica em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil;2. Laboratório de Fisiopatologia Clínica e Experimental, Universidade do Sul de Santa Catarina, Tubarão, SC, Brazil;3. Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA;4. Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA;5. Neuroscience Graduate Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA;1. Department of Exercise Rehabilitation & Welfare, Gachon University, Incheon, Republic of Korea;2. Department of Molecular Medicine and TIDRC, School of Medicine, Ewha Womans University, Seoul, Republic of Korea;3. Department of Physical Education, Dankook University, Cheonan-si, Chungnam-do 330-951, Republic of Korea;1. Urmia University of Medical Sciences, School of Medicine, Department of Physiology, Urmia, Iran;2. Urmia University of Medical Sciences, Neurophysiology Research Center, Urmia, Iran;3. Urmia University of Medical Sciences, Faculty of Medicine, Department of Anatomical Sciences, Urmia, Iran;4. Urmia University of Medical Sciences, Cellular and Molecular Research Center, Urmia, Iran;1. Department of Social Medicine, College of Public Health, Xinjiang Medical University, Urumqi 830011, China;2. Department of Occupational Health and Environmental Health, College of Public Health, Xinjiang Medical University, Urumqi 830011, China;3. Department of Occupational Health and Environmental Health, College of Public Health, College of Medical, Nantong University, Jiangsu 226000, China;4. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong;1. Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran;2. Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran;3. Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran;4. Physiology Research Center, Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran |
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| Abstract: | Stress during pregnancy may cause neurodevelopmental and psychiatric disorders. However, the mechanisms are largely unknown. Currently, pro-inflammatory cytokines have been identified as a risk factor for depression and anxiety disorder. Unfortunately, there is very little research on the long-term effects of prenatal stress on the neuroinflammatory system of offspring. Moreover, the relationship between antidepressant treatment and cytokines in the central nervous system, especially in the hippocampus, an important emotion modulation center, is unclear. Therefore, the aim of this study was to determine the effects of prenatal chronic mild stress during development on affective-like behaviors and hippocampal cytokines in adult offspring, and to verify whether antidepressant (duloxetine) administration from early adulthood could prevent the harmful consequences. To do so, prenatally stressed and non-stressed Sprague-Dawley rats were treated with either duloxetine (10 mg/kg/day) or vehicle from postnatal day 60 for 21 days. Adult offspring were divided into four groups: 1) prenatal stress + duloxetine treatment, 2) prenatal stress + vehicle, 3) duloxetine treatment alone, and 4) vehicle alone. Adult offspring were assessed for anxiety-like behavior using the open field test and depression-like behavior using the forced swim test. Brains were analyzed for pro-inflammatory cytokine markers in the hippocampus via real-time PCR. Results demonstrate that prenatal stress-induced anxiety- and depression-like behaviors are associated with an increase in hippocampal inflammatory mediators, and duloxetine administration prevents the increased hippocampal pro-inflammatory cytokine interleukin-6 and anxiety- and depression-like behavior in prenatally stressed adult offspring. This research provides important evidence on the long-term effect of PNS exposure during development in a model of maternal adversity to study the pathogenesis of depression and its therapeutic interventions. |
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| Keywords: | Prenatal stress Pro-inflammatory cytokines Duloxetine Anxiety Depression |
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