Epinephrine May Contribute to the Persistence of Traumatic Memories in a Post-traumatic Stress Disorder Animal Model

Martinho, Raquel; Oliveira, Ana; Correia, Gabriela; Marques, Márcia Jonathas Guimarães; Seixas, Rafaela; Serrão, Paula; Moreira-Rodrigues, Mónica

doi:10.3389/fnmol.2020.588802

Cited by 15 publications

(40 citation statements)

References 92 publications

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“…We have shown in previous studies that mice deficient in AD (phenylethanolamine-N-methyltransferase-knockout, Pnmt-KO mice) have reduced contextual fear learning (Toth et al, 2013;Alves et al, 2016). Also, AD administered peripherally restored traumatic memories in Pnmt-KO mice (Martinho et al, 2020). In addition, catecholamines are increased in this PTSD mice model suggesting a causal role for AD in contributing to the persistence of contextual traumatic memories and anxiety-like behavior in PTSD (Martinho et al, 2020).…”

Section: Introductionmentioning

confidence: 65%

“…Also, AD administered peripherally restored traumatic memories in Pnmt-KO mice (Martinho et al, 2020). In addition, catecholamines are increased in this PTSD mice model suggesting a causal role for AD in contributing to the persistence of contextual traumatic memories and anxiety-like behavior in PTSD (Martinho et al, 2020).…”

Section: Introductionmentioning

confidence: 69%

“…PTSD mice model was performed as previously described (Li et al, 2006;Zhang et al, 2012;Verma et al, 2016;Martinho et al, 2020). In the two experimental protocols (Figures 1A,B), mice were exposed to an aversive procedure consisting of two training sessions (days 0 and 1).…”

Section: Ptsd Mice Modelmentioning

confidence: 99%

“…To study PTSD, several animal models have been developed using different types of traumatic events (Pynoos et al, 1996;Deslauriers et al, 2018). The PTSD animal model used in this study is based on the concept that foot shock exposure will trigger the pathophysiological process and the main symptomatology of PTSD in animals, including increased contextual traumatic memory and anxiety-like behavior (Li et al, 2006;Zhang et al, 2012;Martinho et al, 2020). In this model, the administration of multiple foot shocks has been confirmed to mimic the traumatic event (Li et al, 2006;Zhang et al, 2012;Verma et al, 2016;Martinho et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…The PTSD animal model used in this study is based on the concept that foot shock exposure will trigger the pathophysiological process and the main symptomatology of PTSD in animals, including increased contextual traumatic memory and anxiety-like behavior (Li et al, 2006;Zhang et al, 2012;Martinho et al, 2020). In this model, the administration of multiple foot shocks has been confirmed to mimic the traumatic event (Li et al, 2006;Zhang et al, 2012;Verma et al, 2016;Martinho et al, 2020). Also, contextual reminders in this animal model of PTSD seem to parallel the exposure to contextual cues present throughout an aversive stressful situation.…”

Section: Introductionmentioning

confidence: 99%

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Treatment With Nepicastat Decreases Contextual Traumatic Memories Persistence in Post-traumatic Stress Disorder

Martinho

Correia

Seixas

et al. 2021

Front. Mol. Neurosci.

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Post-traumatic stress disorder (PTSD) is a common anxiety mental disorder and can be manifested after exposure to a real or perceived life-threatening event. Increased noradrenaline and adrenaline in plasma and urine have been documented in PTSD. Dopamine-β-hydroxylase (DBH) catalyzes the conversion of dopamine to noradrenaline and consequently, DBH inhibition reduces catecholamines. Our aim was to evaluate if nepicastat treatment decreases PTSD signs in an animal model. Wild-type (129x1/SvJ) female mice were submitted to PTSD induction protocol. DBH-inhibitor nepicastat (30 mg/kg) or vehicle (0.2% HPMC) were administered once daily since day 0 until day 7 or 12. The percentage of freezing was calculated on days 0, 1, 2, and 7, and behavioral tests were performed. Quantification of nepicastat in plasma and DBH activity in the adrenal gland was evaluated. Catecholamines were quantified by HPLC with electrochemical detection. mRNA expression of Npas4 and Bdnf in hippocampus was evaluated by qPCR.Mice in the PTSD-group and treated with nepicastat showed a decrease in freezing, and an increase in the time spent and entries in open arms in elevated plus maze test. In mice treated with nepicastat, adrenal gland DBH activity was decreased, and catecholamines were also decreased in plasma and tissues. On day 7, in mice treated with nepicastat, there was an increase of Npas4 and Bdnf mRNA expression in the hippocampus.In conclusion, DBH inhibitor nepicastat has an effect consistent with a decrease in the persistence of traumatic memories and anxiety-like behavior in this PTSD mice model. The disruption of traumatic memories through interference with the formation, consolidation, retrieval, and/or expression processes may be important to decrease PTSD symptoms and signs. The increase in Npas4 and Bdnf mRNA expression in the hippocampus may be important to develop a weaker traumatic contextual memory after nepicastat treatment.

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Section: Introductionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 69%

Section: Ptsd Mice Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Treatment With Nepicastat Decreases Contextual Traumatic Memories Persistence in Post-traumatic Stress Disorder

Martinho

Correia

Seixas

et al. 2021

Front. Mol. Neurosci.

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Tanshinone IIA improves contextual fear‐ and anxiety‐like behaviors in mice via the CREB/BDNF/TrkB signaling pathway

Jiang

Wang

et al. 2022

Phytotherapy Research

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Posttraumatic stress disorder (PTSD) is one of the most common psychiatric diseases, which is characterized by the typical symptoms such as re‐experience, avoidance, and hyperarousal. However, there are few drugs for PTSD treatment. In this study, conditioned fear and single‐prolonged stress were employed to establish PTSD mouse model, and we investigated the effects of Tanshinone IIA (TanIIA), a natural product isolated from traditional Chinese herbal Salvia miltiorrhiza, as well as the underlying mechanisms in mice. The results showed that the double stress exposure induced obvious PTSD‐like symptoms, and TanIIA administration significantly decreased freezing time in contextual fear test and relieved anxiety‐like behavior in open field and elevated plus maze tests. Moreover, TanIIA increased the spine density and upregulated synaptic plasticity‐related proteins as well as activated CREB/BDNF/TrkB signaling pathway in the hippocampus. Blockage of CREB remarkably abolished the effects of TanIIA in PTSD model mice and reversed the upregulations of p‐CREB, BDNF, TrkB, and synaptic plasticity‐related protein induced by TanIIA. The molecular docking simulation indicated that TanIIA could interact with the CREB‐binding protein. These findings indicate that TanIIA ameliorates PTSD‐like behaviors in mice by activating the CREB/BDNF/TrkB pathway, which provides a basis for PTSD treatment.

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Leptin Attenuates Fear Memory by Inhibiting Astrocytic NLRP3 Inflammasome in Post-traumatic Stress Disorder Model

Gong

Wang

et al. 2022

Neurochem Res

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Epinephrine May Contribute to the Persistence of Traumatic Memories in a Post-traumatic Stress Disorder Animal Model

Cited by 15 publications

References 92 publications

Treatment With Nepicastat Decreases Contextual Traumatic Memories Persistence in Post-traumatic Stress Disorder

Treatment With Nepicastat Decreases Contextual Traumatic Memories Persistence in Post-traumatic Stress Disorder

Tanshinone IIA improves contextual fear‐ and anxiety‐like behaviors in mice via the CREB/BDNF/TrkB signaling pathway

Leptin Attenuates Fear Memory by Inhibiting Astrocytic NLRP3 Inflammasome in Post-traumatic Stress Disorder Model

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