Abstract
The importance of catecholamines in post-traumatic stress disorder (PTSD) still needs to be explored. We aimed to evaluate epinephrine’s (EPI) causal role and molecular mechanism for the persistence of PTSD traumatic memories. Wild-type (WT) and EPI-deficient mice (phenylethanolamine-N-methyltransferase-knockout mice, Pnmt-KO) were induced with PTSD and behavioral tests were performed. Some Pnmt-KO mice were administered with EPI or vehicle. Catecholamines were quantified by HPLC-ED. Nr4a1, Nr4a2, and Nr4a3 mRNA expression were evaluated by real-time PCR in hippocampus samples. It was observed an increase in EPI and freezing behavior, and a decrease in open arm entries in the elevated plus-maze test and time spent in the light in the light–dark test in WT mice in the PTSD-induction group compared to control. After induction of PTSD, Pnmt-KO mice showed a decrease in freezing, as well as an increase in open arm entries and transitions between compartments compared to WT. After PTSD induction, Pnmt-KO mice administered with EPI showed an increase in freezing compared with the vehicle. On day 0 of PTSD induction, it was observed an increase in mRNA expression of Nr4a2 and Nr4a3 genes in the hippocampus of WT mice compared to control, contrary to Pnmt-KO mice. In conclusion, our data suggest that EPI may be involved in the persistence of traumatic memories in PTSD, possibly through enhancement of the expression of Nr4a2 and Nr4a3 genes in the hippocampus. Peripheral administration of EPI restored contextual traumatic memories in Pnmt-KO mice, which suggests a causal role for EPI. The persistence of contextual traumatic memories may contribute to anxiety-like behavior and resistance of traumatic memory extinction in this PTSD mice model.
Highlights
The autonomic nervous system mobilizes the body’s resources under stress and induces the ‘‘freeze, fight or flight’’ response, important for survival and adaptation in nature
To evaluate catecholamines levels in this post-traumatic stress disorder (PTSD) mice model, WT mice were put in metabolic cages
24-h urine volume was significantly increased in WT mice in the PTSD-induction group on day 7 when compared to day 2 and day 0, which was not observed in WT control mice (Figure 2D)
Summary
The autonomic nervous system mobilizes the body’s resources under stress and induces the ‘‘freeze, fight or flight’’ response, important for survival and adaptation in nature. Patients with PTSD usually have three major features: re-experience the stressful event, attempt to avoid reminders of the trauma, and a state of hyperarousal, such as increased hypervigilance and startle response (van der Kolk, 2000; Pole, 2007; Pitman et al, 2012; American Psychiatric Association, 2013; Yehuda et al, 2015). These symptoms are common after the traumatic event, they abnormally persist in individuals with PTSD. Patients with PTSD show deficits in the extinction of emotional memories and have persistent severe anxiety (Lissek et al, 2005; Inslicht et al, 2013)
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