Assessment of social behavior, corticosterone secretion, and oxytocin involvement in an animal model of posttraumatic stress disorder: possible association with vulnerability to traumatic stress

• Grant number: 18/06053-2
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): December 01, 2018
• Effective date (End): July 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Deborah Suchecki
• Grantee: Paula Agostina Zoe Sumaran Ortega
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Approximately 20 to 30% of individuals exposed to traumatic events develop posttraumatic stress disorder (PTSD), strongly suggesting the existence of inherent resilience and vulnerability factors. PTSD patients exhibit dysfunctional secretion of oxytocin (OT) and cortisol. Contextual fear conditioning (CMC)-based animal models of this disorder induce persistent behavioral responses, which present individual variability, allowing the study of vulnerability and resilience factors to traumatic stress. The aim of this study is to further characterize the model, by assessing social behavior, corticosterone (CORT) and OT secretion in male Wistar rats submitted to a CMC-based traumatic stress protocol. On day 0, both Stress (STR, n=65) and Control (CTL, n=10) groups will freely explore a novel context for 2 min, after which rats in the STR group will receive a 2 mA, 1 s footshock. Fifteen days later, both groups will be re-exposed to the same context for quantification of freezing time. On day 22, rats will be submitted to the three-chamber social investigation test, in which a caged, novel social stimulus and a novel object will be presented. On day 24, rats will be submitted to the social interaction test, in which both tested and target rat will be allowed to freely interact with each other. Thirty minutes after the end of the test, animals will be euthanized, and brain and blood will be collected. To control for the effects of previous manipulation on social behavior and neurobiological measurements, one Unmanipulated Tested (UT) group (N=10) and one Unmanipulated Non-tested (UNT) group (N=10) will be included in the protocol. Rats in the STR group will be divided between Affected and Unaffected groups based on the assessment of their behavioral profile, which considers as the "normal" behavioral expression the range between the average ± 1 SD of the data from the CTL and UT groups. Hypothalamic OT and plasma OT and CORT levels will be determined by ELISA commercial kits. To assess whether activation of the oxytocinergic system reverts alterations in social behavior caused by traumatic stress, thirty STR and 20 CTL rats will be submitted to the same procedures described, but 10 min before the social interaction test half of the animals will be treated with a single dose of carbetocin acetate (6,4 mg/kg), while the other half will receive an equivalent volume of saline. For both experiments, differences between groups will be verified by ANOVA, and if necessary, Newman-Keuls post hoc test will be used. The significance level will be set at p<0,05.