Disruption of the FK506 Binding Protein 5 and Glucocorticoid Receptor Protein Complex with an Intravenous Therapeutic Peptide Decreases Fear-like Freezing Behavior in an Animal Model of Post-traumatic Stress Disorder

Post-traumatic Stress Disorder (PTSD) is a debilitating mental health disorder provoked in response to a wide range of traumatic events where patients experience recurrent physical and psychological stress responses to specific stimuli. The morbidity of this disease is poorly improved through available therapies, and management remains a challenge. Our lab has established that a protein complex, formed between the Glucocorticoid Receptor (GR) and FK506 Binding Protein 5 (FKBP51), is elevated in PTSD patients and in a classically fear-conditioned mouse model of PTSD. Our lab created and tested the effects of a small interfering peptide (TAT-GRpep) to disrupt the FKBP51-GR complex and reduce behavioural and molecular effects of PTSD in an animal model. We found a significant reduction in freezing behaviour following direct amygdala and intraperitoneal injections. The current project assessed the viability and function of TAT-GRpep following a single intravenous injection to significantly reduce fear-like freezing behaviour in fear-conditioned mice.M.Sc