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

Abstract

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.

Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus

“…Rats were trained in the IA task and 24 h later were euthanized, and the bilateral hippocampus was quickly removed and prepared as previously described for high performance liquid chromatography (HPLC) determination of dopamine levels (38). The novelty group was exposed to a novelty 30 min before euthanasia.…”

“…Eight animals were divided in two groups: (i) For the control group, rats were trained in IA and 24 h later were euthanized for hippocampus dissection (n = 4), and (ii) for the novelty-exposed group, rats were trained in IA, 23.5 h later were exposed to the novelty, and 30 min later were euthanized for hippocampus dissection (n = 4). Both hippocampi were homogenized and prepared for determination of dopamine levels by HPLC (38).…”

“…The brain was removed, and the bilateral hippocampus was quickly dissected out in an iced surface and homogenized in 50 mM Tris·HCl, pH 7.4 (1/10, wt/vol). Afterward, samples were centrifuged at 2,400 × g for 20 min, and supernatants were filtered and then stored at -80°C until use (38).…”

Regulation of Adult Neurogenesis and Plasticity by (Early) Stress, Glucocorticoids, and Inflammation

“…Other neurotransmitter systems, such as the cannabinoids, opioids, nitric oxide, various neuropeptides, and gonadal steroids, may also contribute (e.g., see Galea 2008;Balu and Lucki 2009). Importantly, stress is well known to reduce the expression of several growth and neurotrophic factors, like BDNF, insulin-like growth factor 1 (IGF-1), nerve growth factor (NGF), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF), which can influence neurogenesis (e.g., see Schmidt and Duman 2007;Wilson et al 2014).…”

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

“…It is believed that alterations in the activity of the hypothalamuspituitary-adrenal (HPA) axis, which plays an essential role in the stress regulating system, are induced by severe stress stimulation in both animals and humans. Moreover, dysfunctional HPA axis activity is a well-characterized characteristic in PTSD (Baumeister et al, 2014;Wilson et al, 2014). The HPA axis secretes glucocorticoids to maintain biological homeostasis and adapt to chronic stress in response to stress (Wilson et al, 2014).…”