Fluoxetine normalizes the effects of prenatal maternal stress on depression- and anxiety-like behaviors in mouse dams and male offspring.
Maternal depression during pregnancy and the postpartum period (lactation) is a common debilitating condition affecting mother-fetus/-infant interactions, which can be a risk factor for cognitive and affective disorders in mothers and their children. Selective-serotonin-reuptake-inhibitor-(SSRI) pharmacotherapy is known as the first-line treatment of maternal depression. However, its use during pregnancy and lactation is a topic of concern. The present study aimed to investigate the effects of prenatal stress alone or in combination with fluoxetine (FLX) on hypothalamic-pituitary-adrenal axis (HPA) activity, anxiety-/depression-like behaviors in dams and in offspring. To do this, gestationally-stressed and non-stressed mouse dams were orally treated with FLX-(8/mg/kg/day) from gestational day 10 to lactation day 20. The behavioral outcomes of prenatal stress and FLX treatment in dams and male offspring were assessed using the sucrose preference, forced swim, zero maze, and light-dark box tests. Stress-induced corticosterone levels were also evaluated as indicative of abnormal HPA-axis function. Our findings indicated that maternal stress resulted in increased depression-like behavior and HPA axis hyperactivity in dams during pregnancy and lactation which were reversed by FLX. Furthermore, prenatal stress increased anxiety/depression-like behaviors and HPA-axis reactivity in male offspring. These effects were reversed by maternal FLX treatment. Developmental FLX exposure, without prenatal stress, did not have any adverse effects on the above measured parameters. Our results suggest that prenatal stress induces maternal depression-like behavior which affects the development of affective symptoms in male offspring, and that remediation of maternal depression-like behavior coincidences with the normalization of anxiety-and depression-like symptoms in male offspring.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Laboratory of Neuropsychopharmacology and Psychoneuroimmunology, Hayyan Research Institute, University of Tabriz, Tabriz, Iran. Electronic address: aa.salari@yahoo.com.
Ali-Akbar
AA
Salari
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Laleh
L
Fatehi-Gharehlar
Department of Anesthesiology, Division of Molecular Medicine, Cardiovascular Research Laboratories, University of California, Los Angeles, USA.
Negar
N
Motayagheni
Department of Cognitive Neuroscience, Centre for Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Judith R
JR
Homberg
D000818:Animals; D000831:Animals, Newborn; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology; D003345:Corticosterone / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D008425:Maternal Behavior / Q000187:drug effects / Q000502:physiology / Q000523:psychology; D051379:Mice; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000503:physiopathology; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000503:physiopathology
D003345:Corticosterone; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
Antidepressant; Corticosterone; HPA axis; Postpartum; Pregnancy; Prenatal stress