title: Effects of moderate treadmill exercise and fluoxetine on behavioural and cognitive deficits, hypothalamic-pituitary-adrenal axis dysfunction and alternations in hippocampal BDNF and mRNA expression of apoptosis - related proteins in a rat model of post-traumatic stress disorder.
abstract: Post-traumatic stress disorder (PTSD) is a condition that develops after an individual has experienced a major trauma. Currently, selective serotonin reuptake inhibitors (SSRIs) like fluoxetine are the first-line choice in PTSD drug treatment but their moderate response rates and side effects indicate an urgent need for the development of new treatment. Physical activity is known to improve symptoms of certain neuropsychiatric disorders. The present study investigated the effects of moderate treadmill exercise, the antidepressant fluoxetine and the combined treatment on behavioural deficits, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. We also examined alternations in hippocampal brain-derived neurotrophic factor (BDNF) and mRNA expression of apoptosis - related proteins in a rat model of PTSD: the single prolonged stress (SPS) model. Rats were exposed to SPS (restraint for 2h, forced swimming for 20min and ether anaesthesia) and were then kept undisturbed for 14days. After that, SPS rats were subjected to chronic treatment with fluoxetine (10mg/kg/day, for 4weeks), moderate treadmill running (4weeks, 5day per week) and the combined treatment (fluoxetine plus treadmill exercise), followed by behavioural, biochemical and apoptosis markers assessments. SPS rats exhibited increased anxiety levels in the elevated plus maze and light/dark box, impaired fear conditioning and extinction in inhibitory avoidance (IA) task, impaired spatial memory in a recognition location memory task and enhanced negative feedback on the HPA axis following a dexamethasone suppression test. SPS rats also showed reduced hippocampal BDNF and enhanced apoptosis. Moderate treadmill exercise, fluoxetine and the combined treatment alleviated the SPS-induced alterations in terms of anxiety levels, HPA axis inhibition, IA conditioning and extinction, hippocampal BDNF and apoptosis markers. Furthermore, the combined treatment was more effective than fluoxetine alone, but in most tests, the effects of the combined treatment were similar to those of exercise alone, suggesting that exercise is the main factor in the beneficial effects of the combined therapy in PTSD patients.
authors.affiliation: Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Sakineh
authors.initials: S
authors.lastname: Shafia
authors.affiliation: Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Abbas Ali
authors.initials: AA
authors.lastname: Vafaei
authors.affiliation: Department of Neurology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Seyed Afshin
authors.initials: SA
authors.lastname: Samaei
authors.affiliation: Laboratory of Endocrine Research, Research Center of Physiology and Department of Biochemistry, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Bandegi
authors.affiliation: Department of Immunology, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Rafiei
authors.affiliation: Department of Immunology, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Valadan
authors.affiliation: Department of Immunology, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hosseini-Khah
authors.affiliation: Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Raziyeh
authors.initials: R
authors.lastname: Mohammadkhani
authors.affiliation: Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Electronic address: Rashidy-pour@semums.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Rashidy-Pour
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000378:metabolism; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Anxiety profile; Apoptosis; BDNF; Cognition; Fear extinction; Fluoxetine; Moderate exercise; Post-traumatic stress disorder; Single prolonged stress