ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
From Memory Impairment to Posttraumatic Stress Disorder-Like Phenotypes: The Critical Role of an Unpredictable Second Traumatic Experience.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Post-Traumatic Stress Disorder and Alcohol Consumption: Biological Mechanisms of Stress Resilience to Subsequent Alcohol Consumption.Alcohol research : current reviews · 2026Review
- Unpredictable stress boosts perceptual learning and alters glucocorticoid and norepinephrine receptors in rats' dorsal hippocampus.Translational psychiatry · 2025Article
- Predator odor stress produces sex- and subpopulation-specific increases in alcohol drinking, anxiety-like behavior, and lateral hypothalamic Crh expression.Neuropharmacology · 2025Article
- Neurogenesis-dependent remodeling of hippocampal circuits reduces PTSD-like behaviors in adult mice.Molecular psychiatry · 2024Article
- Methyl-CpG binding protein 2 expression is associated with symptom severity in patients with PTSD in a sex-dependent manner.Translational psychiatry · 2023Article
- Neurocognitive effects of stress: a metaparadigm perspective.Molecular psychiatry · 2023Review
- Glucocorticoid-Responsive Tissue Plasminogen Activator (tPA) and Its Inhibitor Plasminogen Activator Inhibitor-1 (PAI-1): Relevance in Stress-Related Psychiatric Disorders.International journal of molecular sciences · 2023Review
- Protective effects and mechanisms of the Erzhi formula on glucocorticoid induced primary cortical neuron injury.Frontiers in pharmacology · 2023Article
- Sex and context differences in the effects of trauma on comorbid alcohol use and post-traumatic stress phenotypes in actively drinking rats.Journal of neuroscience research · 2021Article
- Photobiomodulation prevents PTSD-like memory impairments in rats.Molecular psychiatry · 2021Article
- PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory.Molecular psychiatry · 2021Article
- Importance of sex and trauma context on circulating cytokines and amygdalar GABAergic signaling in a comorbid model of posttraumatic stress and alcohol use disorders.Molecular psychiatry · 2021Article
- Is PTSD-Phenotype Associated with HPA-Axis Sensitivity? Feedback Inhibition and Other Modulating Factors of Glucocorticoid Signaling Dynamics.International journal of molecular sciences · 2021Article
- Predicting susceptibility and resilience in an animal model of post-traumatic stress disorder (PTSD).Translational psychiatry · 2020Article
- Corticosterone administration targeting a hypo-reactive HPA axis rescues a socially-avoidant phenotype in scarcity-adversity reared rats.Developmental cognitive neuroscience · 2019Article
- Animal models of PTSD: a challenge to be met.Molecular psychiatry · 2019Review
- Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus.Frontiers in molecular neuroscience · 2019Article
- Data-driven criteria to assess fear remission and phenotypic variability of extinction in rats.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Article
- A reminder before extinction strengthens episodic memory via reconsolidation but fails to disrupt generalized threat responses.Scientific reports · 2017Article
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4 authors.
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Abstract
Arousal and stress critically regulate memory formation and retention. Increasing levels of stress produce an inverted U-shaped effect on cognitive performance, including the retention of explicit memories, and experiencing a severe stress during a traumatic event may lead to posttraumatic stress disorder (PTSD). The molecular mechanisms underlying the impairing effect of a severe stress on memory and the key contribution of traumatic experiences toward the development of PTSD are still unknown. Here, using increasing footshock intensities in an inhibitory avoidance paradigm, we reproduced the inverted U-shaped curve of memory performance in rats. We then show that the inverted U profile of memory performance correlates with an inverted U profile of corticosterone level in the circulation and of brain-derived neurotrophic factor, phosphorylated tropomyosin-receptor kinase B, and methyl CpG binding protein in the dorsal hippocampus. Furthermore, training with the highest footshock intensity (traumatic experience) led to a significant elevation of hippocampal glucocorticoid receptors. Exposure to an unpredictable, but not to a predictable, highly stressful reminder shock after a first traumatic experience resulted in PTSD-like phenotypes, including increased memory of the trauma, high anxiety, threat generalization, and resistance to extinction. Systemic corticosterone injection immediately after the traumatic experience, but not 3 d later, was sufficient to produce PTSD-like phenotypes. We suggest that, although after a first traumatic experience a suppression of the corticosterone-dependent response protects against the development of an anxiety disorder, experiencing more than one trauma (multiple hits) is a critical contributor to the etiology of PTSD.
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