Effect of traumatic imagery on cerebrospinal fluid dopamine and serotonin metabolites in posttraumatic stress disorder

Geracioti, Thomas D.; Jefferson-Wilson, Lena; Baker, Dewleen G.; Dashevsky, Boris A.; Horn, Paul S.; Ekhator, Nosa N.

doi:10.1016/j.jpsychires.2013.01.023

Cited by 31 publications

(17 citation statements)

References 34 publications

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“…The modulation of various neurotransmitters observed with the predator exposure/psychosocial stress model is in concert with many of the neurotransmitter changes seen in human PTSD patients (Yehuda et al, 1992; Arora et al, 1993; Geracioti et al, 2001, 2013). Previous research has shown that stress blocks long-term potentiation (LTP) in the hippocampus as well as impairs hippocampal function (Kim and Diamond, 2002; Diamond et al, 2007).…”

Section: Discussionmentioning

confidence: 80%

Differential effects of sertraline in a predator exposure animal model of post-traumatic stress disorder

Wilson¹,

McLaughlin²,

Ebenezer³

et al. 2014

Front. Behav. Neurosci.

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Serotonin (5-HT), norepinephrine (NE), and other neurotransmitters are modulated in post-traumatic stress disorder (PTSD). In addition, pro-inflammatory cytokines (PIC) are elevated during the progression of the disorder. Currently, the only approved pharmacologic treatments for PTSD are the selective-serotonin reuptake inhibitors (SSRI) sertraline and paroxetine, but their efficacy in treating PTSD is marginal at best. In combat-related PTSD, SSRIs are of limited effectiveness. Thus, this study sought to analyze the effects of the SSRI sertraline on inflammation and neurotransmitter modulation via a predator exposure/psychosocial stress animal model of PTSD. We hypothesized that sertraline would diminish inflammatory components and increase 5-HT but might also affect levels of other neurotransmitters, particularly NE. PTSD-like effects were induced in male Sprague-Dawley rats (n = 6/group × 4 groups). The rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1 h on days 1 and 11 of a 31-day stress regimen. PTSD rats were also subjected to psychosocial stress via daily cage cohort changes. At the conclusion of the stress regimen, treatment group animals were injected intraperitoneally (i.p.) with sertraline HCl at 10 mg/kg for 7 consecutive days, while controls received i.p. vehicle. The animals were subsequently sacrificed on day 8. Sertraline attenuated inflammatory markers and normalized 5-HT levels in the central nervous system (CNS). In contrast, sertraline produced elevations in NE in the CNS and systemic circulation of SSRI treated PTSD and control groups. This increase in NE suggests SSRIs produce a heightened noradrenergic response, which might elevate anxiety in a clinical setting.

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Section: Discussionmentioning

confidence: 80%

Differential effects of sertraline in a predator exposure animal model of post-traumatic stress disorder

Wilson¹,

McLaughlin²,

Ebenezer³

et al. 2014

Front. Behav. Neurosci.

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“…The modulation of various neurotransmitters observed with the predator exposure/psychosocial stress model is in concert with many of the neurotransmitter changes seen in human PTSD patients [14], [18], [21], [24]. Previous research has shown that stress blocks hippocampal long-term potentiation (LTP) and impairs its function [33].…”

Section: Discussionmentioning

confidence: 96%

“…The dopamine metabolite homovanillic acid (HVA), often used as a diagnostic test for catecholamine-producing tumors of the adrenal glands, has also demonstrated aberrant levels in PTSD patients. Geracioti et al found HVA was significantly reduced in the CSF of combat-related PTSD patients immediately after viewing traumatic imagery [24]. Based on the previous research, the primary focus of this study was to determine how neurotransmitters were modulated in response to a predator exposure/psychosocial stress rodent model of pre-clinical PTSD.…”

Section: Introductionmentioning

confidence: 98%

Predator Exposure/Psychosocial Stress Animal Model of Post-Traumatic Stress Disorder Modulates Neurotransmitters in the Rat Hippocampus and Prefrontal Cortex

et al. 2014

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Post-Traumatic Stress Disorder (PTSD) can develop in response to a traumatic event involving a threat to life. To date, no diagnostic biomarkers have been identified for PTSD. Recent research points toward physiological abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis, sympathoadrenal medullary and immune system that may be implicated in the disorder. The modulation of neurotransmitters is another possible mechanism, but their role in the progression of PTSD is poorly understood. Low serotonin (5-HT) may be a factor, but it may not be the only neurotransmitter affected as modulation affects levels of other neurotransmitters. In this study, we hypothesized the predator exposure/psychosocial stress rodent model of PTSD may alter levels of 5-HT and other neurotransmitters in the rat hippocampus and prefrontal cortex (PFC). Male Sprague-Dawley rats were used in this experiment. We induced PTSD via a predator exposure/psychosocial stress model, whereby rats were placed in a cage with a cat for 1 hour on days 1 and 11 of the 31-day experiment. Rats also received psychosocial stress via daily cage cohort changes. On day 32, the rats were sacrificed and the brains dissected to remove the hippocampus and PFC. Norepinephrine (NE), 5-Hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), dopamine (DA), and 3,4-Dihydroxyphenylacetic acid (DOPAC), and 5-HT levels in the hippocampus and PFC were measured with high-performance liquid chromatography (HPLC). In the hippocampus, 5-HT and HVA were lower, while NE and DOPAC were higher, in the PTSD group vs. controls. In the PFC, only 5-HT was lower, while NE, DA, and DOPAC were higher, in the PTSD group vs. controls. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also examined and confirmed our findings. These results demonstrate that the predator exposure/psychosocial stress model of PTSD produces neurotransmitter changes similar to those seen in human patients and may cause a heightened noradrenergic response.

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“…Our findings showed that maternal PTSD reduced the dopamine levels in the offspring, in accordance with previous reports. Geracioti et al (2013) found that the acute decline in central nervous system homovanillic acid (HVA) concentrations is associated with laboratory-induced symptoms in patients with chronic PTSD. Another study showed that the nine-repeat allele in the 3' untranslated region variable number of tandem repeat (VNTR) of the SLC6A3 gene increases the risk of PTSD (Chang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic mechanism of maternal post-traumatic stress disorder in delayed rat offspring development: dysregulation of methylation and gene expression

X-G

Zhang

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Maternal post-traumatic stress disorder (PTSD) increases the risk of adverse neurodevelopmental outcomes in the child. Epigenetic alternations may play an essential role in the negative effects of PTSD. This study was aimed to investigate the possible epigenetic alterations of maternal PTSD, which underpins the developmental and behavioral impact. 24 pregnant Sprague-Dawley (SD) rats were randomly grouped into PTSD and control groups. Open-field tests (OFTs), elevated pull maze (EPM) assays, gene expression profile chip tests, and methylated DNA immunoprecipitation sequencing (MeDIPSeq) were performed on the offsprings 30 days after birth. The results 2 X.G. Zhang et al. Genetics and Molecular Research 15 (3): gmr.15039009 showed that PTSD offsprings had lower body weights and OFT scores than control offsprings. Enzyme-linked immunosorbent assays showed that serotonin receptor (5-HT) and dopamine levels were significantly lower in PTSD offsprings than in control offsprings. In contrast, corticosterone levels were higher in the PTSD group than in the control group. In a comparison of the PTSD group versus the control group, 4,160 significantly differentially methylated loci containing 30,657 CpGs were identified; 2,487 genes, including 13 dysmethylated genes, were validated by gene expression profiling, showing a negative correlation between methylation and gene expression (R = -0.617, P = 0.043). In conclusion, maternal PTSD could delay the physical and behavioral development of offsprings, and the underlying mechanism could contribute to changes in neurotransmitters and gene expression, owing to dysregulation of wholegenome methylation. These findings could support further clinical research on appropriate interventions for maternal PTSD to prevent methylation dysregulation and developmental retardation.

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Effect of traumatic imagery on cerebrospinal fluid dopamine and serotonin metabolites in posttraumatic stress disorder

Cited by 31 publications

References 34 publications

Differential effects of sertraline in a predator exposure animal model of post-traumatic stress disorder

Differential effects of sertraline in a predator exposure animal model of post-traumatic stress disorder

Predator Exposure/Psychosocial Stress Animal Model of Post-Traumatic Stress Disorder Modulates Neurotransmitters in the Rat Hippocampus and Prefrontal Cortex

Epigenetic mechanism of maternal post-traumatic stress disorder in delayed rat offspring development: dysregulation of methylation and gene expression

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