Effects of Oxytocin on Fear Memory and Neuroinflammation in a Rodent Model of Posttraumatic Stress Disorder

Abstract

Posttraumatic stress disorder (PTSD) is a trauma-induced mental disorder characterized by fear extinction abnormalities, which involve biological dysfunctions among fear circuit areas in the brain. Oxytocin (OXT) is a neuropeptide that regulates sexual reproduction and social interaction and has recently earned specific attention due to its role in adjusting neurobiological and behavioral correlates of PTSD; however, the mechanism by which this is achieved remains unclear. The present study aimed to examine whether the effects of OXT on traumatic stress-induced abnormalities of fear extinction (specifically induced by single prolonged stress (SPS), an animal model of PTSD) are associated with pro-inflammatory cytokines. Seven days after SPS, rats received intranasal OXT 40 min before a cue-dependent Pavlovian fear conditioning-extinction test in which rats’ freezing degree was used to reflect the outcome of fear extinction. We also measured mRNA expression of IL-1β, IFN-γ, and TNF-α in the medial prefrontal cortex (mPFC), hippocampus, and amygdala at the end of the study, together with plasma oxytocin, corticosterone, IL-1β, IFN-γ, and TNF-α, to reflect the central and peripheral changes of stress-related hormones and cytokines after SPS. Our results suggested that intranasal OXT effectively amends the SPS-impaired behavior of fear extinction retrieval. Moreover, it neurochemically reverses the SPS increase in pro-inflammatory cytokines; thus, IL-1β and IFN-γ can be further blocked by the OXT antagonist atosiban (ASB) in the hippocampus. Peripheral profiles revealed a similar response pattern to SPS of OXT and corticosterone (CORT), and the SPS-induced increase in plasma levels of IL-1β and TNF-α could be reduced by OXT. The present study suggests potential therapeutic effects of OXT in both behavioral and neuroinflammatory profiles of PTSD.

IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier

“…We confirmed that ligature-induced periodontal inflammation significantly increased the IL-1β expression levels in the hippocampus through serum IL-6. The mRNA expression level upregulated by ligature is a 1.5-fold change compared with the control, consistent with previous data showing that posttraumatic stress disorder increased IL-1β expression approximately 1.5-fold, which is connected with neurodegenerative disorder [ 45 ]. Sustained increased levels from periodontal inflammation may cause neurodegenerative diseases such as AD.…”

Fear response-based prediction for stress susceptibility to PTSD-like phenotypes

“…Consistent with previous observation [ 7 , 21 – 24 ], the acute traumatic stress did not affect fear conditioning or extinction learning, leading to comparable freezing responses between stressed and unstressed mice (Fig. 1 b and e).…”

Fear response-based prediction for stress susceptibility to PTSD-like phenotypes

“…Consistent with previous reports [7,[22][23][24][25], the acute traumatic stress did not affect fear conditioning or extinction learning, leading to comparable freezing responses between stressed and unstressed mice ( Fig. 1B and E).…”