Evaluation of Hippocampal Allostatic Load-Associated Factors in Animal Models of Post-Traumatic Stress Disorder: Relevance to Human PTSD
Dennis Kelley
March 2, 2022 DOI: 10.31390/gradschool_dissertations.5761 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study |
|---|---|
| Population | Rats |
| Intervention | experimental 5-HT2A agonist |
| Topics | PTSD |
| Keywords | Allostatic load Hippocampus Stressor Hippocampal formation Allostasis Chronic stress Clinical psychology |
| Citations | 1 |
| Key points | Mitochondrial dysfunction in the hippocampus is associated with PTSD-like behaviors and allostatic load factors in rats. |
Abstract
Post-traumatic stress disorder (PTSD) is associated with elevated allostatic load, nearly double the risk for metabolic syndrome, reduced hippocampal volume, and contextual memory processing deficits. Emerging evidence suggests that these stress effects may predispose individuals to the development of PTSD, and there is a known relationship between chronic stress and metabolic dysfunction. In this work, we utilized two rat models of PTSD to explore these connections. We used an acute predator odor stressor to investigate the relationship between PTSD-like behaviors and mitochondrial dysfunction in the hippocampus of rats, and we observed that conditioned place avoidance was associated with reduced mitochondrial spare capacity and ROS production. In a separate multiple stressor + chronic psychosocial stress model, we observed increased cholesterol, triglycerides, and ROS production, fundamental allostatic load factors, in the hippocampus. In the same model, we also tested an experimental 5-HT2A agonist and known psychoplastogen and observed that it reduced ROS production in the cortex and hippocampus and normalized gene expression overlapping with human PTSD. Here, we show an association between mitochondrial dysfunction in the brain, the development of PTSD-like behaviors, and the induction of known allostatic load factors in the rat hippocampus after predator exposure + chronic psychosocial stress. Together these data support emerging models that suggest metabolic and allostatic characteristics of PTSD are related to functional changes in the hippocampus.
Comparable studies
Other preclinical and animal studies on PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Pharmahuasca and DMT Rescue ROS Production and Differentially Expressed Genes Observed after Predator and Psychosocial Stress: Relevance to Human PTSD. Rats exposed to a 30-day stress regimen | 2022 | Preclinical animal study with in vitro assays | |
| Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells. Mice | 2024 | Experimental animal study | |
| Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors Male and female mice | 2024 | Experimental study | |
| Molecular signatures of astrocytes and microglia maladaptive responses to acute stress are rescued by a single administration of ketamine in a rodent model of PTSD. Rats | 2024 | Animal study | |
| Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder. Male rats | 2024 | Preclinical study |
Citations in the library
Cites 50
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- Active interoceptive inference and the emotional brain Philosophical transactions of the Royal Society of London. Series B, Biological sciences October 11, 2016
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
and 45 more in the library