title: Administration of the TrkB receptor agonist 7,8-dihydroxyflavone prevents traumatic stress-induced spatial memory deficits and changes in synaptic plasticity.
abstract: Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations and it is characterized by cognitive deficits that include impaired explicit memory. The neurobiological bases of such PTSD-associated memory alterations are yet to be elucidated and no satisfactory treatment for them exists. To address this issue, we first studied whether a single exposure of young adult rats (60 days) to immobilization on boards (IMO), a putative model of PTSD, produces long-term behavioral effects (2-8 days) similar to those found in PTSD patients. Subsequently, we investigated whether the administration of the TrkB agonist 7,8-dihydroxyflavone (DHF) 8 h after stress (therapeutic window) ameliorated the PTSD-like effect of IMO and the associated changes in synaptic plasticity. A single IMO exposure induced a spatial memory impairment similar to that found in other animal models of PTSD or in PTSD patients. IMO also increased spine density and long-term potentiation (LTP) in the CA3-CA1 pathway. Significantly, DHF reverted both spatial memory impairment and the increase in LTP, while it produced no effect in the controls. These data provide novel insights into the possible neurobiological substrate for explicit memory impairment in PTSD patients, supporting the idea that the activation of the BDNF/TrkB pathway fulfils a protective role after severe stress. Administration of DHF in the aftermath of a traumatic experience might be relevant to prevent its long-term consequences. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Unitat De Fisiologia Animal (Facultat De Biociències), Universitat Autònoma De Barcelona, 08193 Bellaterra, Barcelona, Spain.|Institut De Neurociències, Universitat Autonòma De Barcelona, 08193 Bellaterra, Barcelona, Spain.|Red De Trastornos Adictivos (RTA), Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Ancor
authors.initials: A
authors.lastname: Sanz-García
authors.affiliation: IkerBasque Research Professor, Biophysics Unit (Unidad De Biofísica CSIC-UPV/EHU), Leioa, Bizkaia, Spain.
authors.forename: Shira
authors.initials: S
authors.lastname: Knafo
authors.affiliation: Department of Psychobiology, Universidad Nacional De Educación a Distancia, Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Pereda-Pérez
authors.affiliation: Deparment of Molecular Neurobiology, Centro De Biología Molecular "Severo Ochoa," Consejo Superior De Investigaciones Científicas (CSIC)/Universidad Autónoma De Madrid, Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Esteban
authors.affiliation: Department of Psychobiology, Universidad Nacional De Educación a Distancia, Juan Del Rosal 10, Madrid, 28040, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Venero
authors.affiliation: Unitat De Fisiologia Animal (Facultat De Biociències), Universitat Autònoma De Barcelona, 08193 Bellaterra, Barcelona, Spain.|Institut De Neurociències, Universitat Autonòma De Barcelona, 08193 Bellaterra, Barcelona, Spain.|Red De Trastornos Adictivos (RTA), Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Armario
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D047309:Flavones / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000819:agonists* / Q000378:metabolism; D012149:Restraint, Physical; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D013313:Stress Disorders, Post-Traumatic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D046509:Tissue Culture Techniques
chemical_list: C485383:6,7-dihydroxyflavone; D047309:Flavones; D011619:Psychotropic Drugs; D020813:Receptor, trkB
keywords: 7,8-dihydroxyflavone; PTSD; TrkB; immobilization; spatial memory; synaptic plasticity