Behavioral changes over time in post-traumatic stress disorder: Insights from a rat model of single prolonged stress

Wu, Zhuoyun; Tian, Qing; Li, Feng; Gao, Junqiao; Liu, Yan; Mao, Meng; Liu, Jing; Wang, Shuyan; Li, Genmao; Ge, Dongyu; Mao, Yingqiu; Zhang, Wei; Liu, Zhaolan; Song, Yuehan

doi:10.1016/j.beproc.2016.01.001

Cited by 30 publications

(17 citation statements)

References 43 publications

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“…Several previous studies have observed behavioral effects of SPS that persist for several weeks. Increased anxiodepressive behavior is seen shortly after SPS (Wu et al, ) and persists for at least 2–3 weeks (Ji et al, ; Khan & Liberzon, ; Lin, Tung, & Liu, ; Miao et al, ; Patki et al, ; Peng et al, ; Takahashi, Morinobu, Iwamoto, & Yamawaki, ), consistent with the increase in anxiety‐like behavioral changes observed here 1–2 weeks after stress. We found that elevated plus maze behavior and NSF returned to normal within 5 weeks of SPS in normal (wild type) rats.…”

Section: Discussionsupporting

confidence: 78%

New neurons restore structural and behavioral abnormalities in a rat model of PTSD

et al. 2019

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Post-traumatic stress disorder (PTSD) has been associated with anxiety, memory impairments, enhanced fear, and hippocampal volume loss, although the relationship between these changes remain unknown. Single-prolonged stress (SPS) is a model for PTSD combining three forms of stress (restraint, swim, and anesthesia) in a single session that results in prolonged behavioral effects. Using pharmacogenetic ablation of adult neurogenesis in rats, we investigated the role of new neurons in the hippocampus in the long-lasting structural and behavioral effects of SPS. Two weeks after SPS, stressed rats displayed increased anxiety-like behavior and decreased preference for objects in novel locations regardless of the presence or absence of new neurons. Chronic stress produced by daily restraint for 2 or 6 hours produced similar behavioral effects that were also independent of ongoing neurogenesis. At a longer recovery time point, one month after SPS, rats with intact neurogenesis had normalized, showing control levels of anxiety-like behavior. However, GFAP-TK rats, which lacked new neurons, continued to show elevated anxiety-like behavior and enhanced serum corticosterone response to anxiogenic experience. Volume loss in ventral CA1 paralleled increases in anxiety-like behavior, occurring in all rats exposed to SPS at the early time point and only rats lacking adult neurogenesis at the later time point. In chronic stress experiments, volume loss occurred broadly throughout the dentate gyrus and CA1 after 6-hour daily stress but was not apparent in any hippocampal subregion after 2-hr daily stress. No effect of SPS was seen on cell proliferation in the dentate gyrus, but the survival of young neurons born a week after stress was decreased. Together, these data suggest that new neurons are functionally important for recovery of normal behavior and hippocampal structure following a strong acute stress and point to the ventral CA1 region as a potential key mediator of stress-induced anxiety-like behavior.

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Section: Discussionsupporting

confidence: 78%

New neurons restore structural and behavioral abnormalities in a rat model of PTSD

et al. 2019

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“…When SPS rats reached adult stage, anxiety-like behavior previously evident at PND32 and 60 transformed into depression-like behavior at PND90. Previous evidence has suggested that SPS exposure during adulthood leads to significant anxiety- and depression-like behavior, and these negative effects discontinue about two weeks after the initial exposure (Wu, Tian et al 2016). On the other hand, early life stress, including prenatal and postnatal stress, is reported to cause long-lasting behavioral as well as morphological changes in brain regions that are the centers of emotional regulation, like hippocampus, amygdala, and prefrontal cortex (Wang and Schmidt 2016).…”

Section: Discussionmentioning

confidence: 99%

Behavioral and cognitive impact of early life stress: Insights from an animal model

Liu

Atrooz

Salvi

et al. 2017

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Background Children subjected to traumatic events during childhood are reported to exhibit behavioral and cognitive deficits later in life, often leading to post-traumatic stress disorder (PTSD) and major depression. Interestingly, some children continue to remain normal despite being exposed to the same risk factors. These trauma-related behavioral and cognitive profiles across different stages of life are not well understood. Animal studies can offer useful insights. Objective The goal of this study was to determine the impact of early life exposure to traumatic events on behavioral and cognitive profile in rats by tracking the behavior of each rat at different ages. Methods We utilized the single prolonged stress (SPS), a rodent model of PTSD, to study the effects of early life stress. Male Sprague-Dawley rats were exposed to SPS on post-natal day (PND) 25. Tests to assess anxiety- and depression-like behavior, as well as learning and memory function were performed at PND32, 60 and 90. Results Rats exposed to SPS exhibited both anxiety- and depression-like behavior at PND32. And, short-term (STM) but not long-term memory (LTM) was impaired. Rats exposed to SPS at PND60 exhibited anxiety- but not depression-like behavior. STM but not LTM was impaired. Rats exposed to SPS at PND90 exhibited fearful (as indicated by elevated plus maze test) but not an overall anxiety-like behavior (in light and dark test). These rats also displayed significant depression-like behavior with no changes in STM or LTM. Interestingly, when data was further analyzed, two subsets of PND90 rats exposed to SPS were identified, “suscep tible”: with depression-like behavior and “resilient”: without depression-like behavior. Importantly, while resilient group expressed early signs of anxiety- (at PND32 and PND60) and depression-like behavior (at PND32), these behavioral deficits were absent at PND90. On the other hand, susceptible PND90 rats exposed to SPS expressed later onset of anxiety-like behavior (at PND60), while depression-like phenotype was evident only later on at PND90. Conclusions Our findings suggest that early life stress caused co-occurrence of anxiety and depression-like behavior at PND32 (mimics human early-adolescent period). This co-occurrence was lost at PND60 with demonstration of anxiety- but not depression-like behavior. Later, depression but not anxiety-like behavior was observed at PND90. It seems that behavioral adaptations occur at the critical PND60 stage (mimics human late-adolescent period), where behavioral and cognitive switching occurs, thereby, expressing susceptible and resilient phenotypes.

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“…SPS rats demonstrate sleep abnormalities ( Vanderheyden et al, 2015 ) enhanced anxiety ( Han et al, 2014 ; Liu et al, 2016 ), arousal ( Khan and Liberzon, 2004 ), and fear learning ( Iwamoto et al, 2007 ; Keller et al, 2015b ) as well as impaired spatial and recognition memory, social interaction ( Kohda et al, 2007 ; Wen et al, 2016 ) and fear extinction ( Knox et al, 2012a ; Keller et al, 2015b ). Most changes are observed 7 days, but not 1 day, after exposure to the SPS procedure, suggesting that behavioral and cellular changes promoted by SPS are time-dependent ( Liberzon et al, 1999a ; Knox et al, 2016 ; Wu et al, 2016 ). Although it has been demonstrated that partial SPS does not generate extinction impairments ( Knox et al, 2012b ), the critical features of the SPS procedure for development of a PTSD-like phenotype remain unclear.…”

Section: Effects Of Sps On Behavior and The Brainmentioning

confidence: 97%

Using the Single Prolonged Stress Model to Examine the Pathophysiology of PTSD

2017

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The endurance of memories of emotionally arousing events serves the adaptive role of minimizing future exposure to danger and reinforcing rewarding behaviors. However, following a traumatic event, a subset of individuals suffers from persistent pathological symptoms such as those seen in posttraumatic stress disorder (PTSD). Despite the availability of pharmacological treatments and evidence-based cognitive behavioral therapy, a considerable number of PTSD patients do not respond to the treatment, or show partial remission and relapse of the symptoms. In controlled laboratory studies, PTSD patients show deficient ability to extinguish conditioned fear. Failure to extinguish learned fear could be responsible for the persistence of PTSD symptoms such as elevated anxiety, arousal, and avoidance. It may also explain the high non-response and dropout rates seen during treatment. Animal models are useful for understanding the pathophysiology of the disorder and the development of new treatments. This review examines studies in a rodent model of PTSD with the goal of identifying behavioral and physiological factors that predispose individuals to PTSD symptoms. Single prolonged stress (SPS) is a frequently used rat model of PTSD that involves exposure to several successive stressors. SPS rats show PTSD-like symptoms, including impaired extinction of conditioned fear. Since its development by the Liberzon lab in 1997, the SPS model has been referred to by more than 200 published papers. Here we consider the findings of these studies and unresolved questions that may be investigated using the model.

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Behavioral changes over time in post-traumatic stress disorder: Insights from a rat model of single prolonged stress

Cited by 30 publications

References 43 publications

New neurons restore structural and behavioral abnormalities in a rat model of PTSD

New neurons restore structural and behavioral abnormalities in a rat model of PTSD

Behavioral and cognitive impact of early life stress: Insights from an animal model

Using the Single Prolonged Stress Model to Examine the Pathophysiology of PTSD

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