PTSD and stress sensitisation: A tale of brain and body Part 2: Animal models

Stam, Rianne

doi:10.1016/j.neubiorev.2007.01.001

Cited by 103 publications

(84 citation statements)

References 187 publications

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“…PTSD is characterized in part by symptoms of hyperarousal resulting from a non-associative general sensitization process (Dunsmoor and Paz, 2015;Pitman et al, 2012;Stam, 2007). Also, heightened heart rate reactivity to startling stimuli (loud tones) and larger skin conductance response to novel stimuli have been observed in PTSD patients (Pitman et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Also, heightened heart rate reactivity to startling stimuli (loud tones) and larger skin conductance response to novel stimuli have been observed in PTSD patients (Pitman et al, 2012). In animal models, exaggerated acoustic startle response and reduced locomotor activity in a novel environment have been used as measures of hyperarousal after exposure to traumatic stressors (Hendriksen et al, 2010;Kinn Rød et al, 2012;Stam, 2007;van Dijken et al, 1992;Wang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, IFS procedure produces a reduction in the activity in unknown environments 7 days after exposure to the shock (Daviu et al, 2010;Hendriksen et al, 2010;van Dijken et al, 1993;van Dijken et al, 1992). This effect of IFS has been considered an index of hypervigilance similar to the hyperarousal observed in PTSD patients (Pitman et al, 2012;Stam, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Ronzoni

Arco

Mora

et al. 2016

Psychoneuroendocrinology

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SummaryIncreased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats previously exposed to traumatic stress showing inconsistent results. The aim of this study was to investigate the effects of an inescapable foot shock (IFS) procedure 1) on reactivity to novelty in an open-field (as an index of hyperarousal), and 2) on noradrenaline release in the amygdala during an acute stress. To test the role of noradrenaline in amygdala, we also investigated the effects of microinjections of propranolol, a β-adrenoreceptor antagonist, and clenbuterol, a β-adrenoreceptor agonist, into the amygdala of IFS and control animals. Finally, we evaluated the expression of mRNA levels of β-adrenoreceptors (β1 and β2) in the amygdala, the hippocampus and the prefrontal cortex. Male Wistar rats (3 months) were stereotaxically implanted with bilateral guide cannulae. After recovering from surgery, animals were exposed to IFS (10 shocks, 0.86 mA, and 6 seconds per shock) and seven days later either microdialysis or microinjections were performed in amygdala. Animals exposed to IFS showed a reduced locomotion compared to IFS modified the mRNA expression of β1 and β2 adrenoreceptors in the prefrontal cortex and the hippocampus. These results suggest that an increased noradrenergic activity in the amygdala contributes to the expression of hyperarousal in an animal model of PTSD.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Ronzoni

Arco

Mora

et al. 2016

Psychoneuroendocrinology

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“…An increasing number of animal models based on stress interventions have been shown to effectively mimic a variety of psychopathological alterations (Willner, 2005;Renthal et al, 2007;Stam, 2007;Ilin and Richter-Levin, 2009). In both animals and humans, excessive and/or enduring stress has been found to cause structural and neurochemical alterations in several brain structures, especially in the hippocampus (Lupien et al, 1998;Sheline et al, 1999;McEwen, 2000;Pham et al, 2003;Bisaz et al, 2011), the prefrontal cortex (Drevets et al, 1997;Rajkowska, 2000;Holmes and Wellman, 2009) and the amygdala (Sandi et al, 2008;Mitra et al, 2009;Roozendaal et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

Castro

Diessler

Varea

et al. 2012

Psychoneuroendocrinology

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Summary Emerging evidence indicates that certain behavioral traits, such as anxiety, are associated with the development of depression-like behaviors after exposure to chronic stress. However, single traits do not explain the wide variability in vulnerability to stress observed in outbred populations. We hypothesized that a combination of behavioral traits might provide a better characterization of an individual's vulnerability to prolonged stress. Here, we sought to determine whether the characterization of relevant behavioral traits in rats could aid in identifying individuals with different vulnerabilities to developing stress-induced depressionlike behavioral alterations. We also investigated whether behavioral traits would be related to the development of alterations in the hypothalamic-pituitary-adrenal axis and in brain activityas measured through phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) -in response to an acute stressor following either sub-chronic (2 weeks) or chronic (4 weeks) unpredictable stress (CUS). Sprague-Dawley rats were characterized using a battery of behavioral tasks, and three principal traits were identified: anxiety, exploration and activity. When combined, the first two traits were found to explain the variability in the stress responses. Our findings confirm the increased risk of animals with high anxiety developing certain depression-like behaviors (e.g., increased floating time in the forced swim test) when progressively exposed to stress. In contrast, the behavioral profile based on combined low anxiety and low exploration was resistant to alterations related to social behaviors, while the high anxiety and low exploration profile displayed a particularly vulnerable pattern of physiological and neurobiological responses after sub-chronic stress exposure. Our findings indicate important differences in

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“…Thus, the hypothesis behind this project was that giving a combination of a β-adrenergic antagonist plus a glucocorticoid receptor antagonist immediately after a traumatic experience might decrease the strength of the abnormally enhanced fear-provoking memories, and reduce PTSD-like symptoms that emerge over time. To test this hypothesis, we proposed using a published rat model of PTSD, acute massed footshock (MFS) (Stam, 2007), and then employ a battery of tests designed to assess PTSD-like behavioral changes in rats, including social withdrawal on the social interaction test, generalized anxiety and stress-sensitization on the elevated plus-maze, enhanced fear conditioning, and attenuated extinction of cue-conditioned fear. One reason that we initially selected the MFS model was that the acute temporal nature of this stressor made it amenable to testing acute drug treatment in the immediate post-stress period.…”

Section: Project W81xwh-08-1-0202 (Cdmrp Ptsd Concept Award Pt073760)mentioning

confidence: 99%

Post-Stress Combined Administration of Beta-Receptor and Glucocorticoid Antagonists as a Novel Preventive Treatment in an Animal Model of PTSD

Morilak¹

2010

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY) SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)US ARMY MEDICAL RESEARCH AND MATERIEL COMMAND SPONSOR/MONITOR'S REPORTFORT DETRICK, MD 21702-5012 NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release; distribution unlimited SUPPLEMENTARY NOTES14. Many PTSD symptoms reflect pathologically enhanced memory of traumatic stress. Stress-induced secretion of brain norepinephrine and glucocorticoids (GC) activate β-receptors and GC-receptors in the amygdala, enhancing consolidation of emotional memories. We hypothesized that giving a β-antagonist plus a GC-antagonist immediately after stress might decrease the strength of those associations, and prevent the emergence of PTSD. The goals of this work were to 1) validate a reliable model of PTSD amenable to testing acute drug treatment; 2) establish a reliable and valid test battery of PTSD-like behaviors in rats, including fear conditioning and extinction; and 3) test the combined drug treatment using the established model. Although we developed a reliable test battery for PTSD-like behavior, it proved more challenging to establish a consistent, reliable and valid model inducing PTSD-like behaviors. The proposed massed footshock model, derived from the literature, failed to affect the most relevant behavioral measures, and confounded fear conditioning. A modified Single Prolonged Stress model, also from the literature, was more promising but had only modest effects. Early results using a new combined Chronic + Acute Prolonged Stress (CAPS) model, incorporating both chronic and acute features of stress often associated with PTSD, were very promising, but mixed results were obtained with the acute drug interventions. Propranolol had no effect, and mifepristone had only a modest effect on extinction. Nonetheless, this project has been very productive, as we will continue to use this model in other ongoing studies. If PTSD is indeed best modeled by a combined chronic + acute stress, acute drug intervention may not be a feasible strategy. SUBJECT TERMSchronic and acute stress, PTSD, open field t...

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PTSD and stress sensitisation: A tale of brain and body Part 2: Animal models

Cited by 103 publications

References 187 publications

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

Post-Stress Combined Administration of Beta-Receptor and Glucocorticoid Antagonists as a Novel Preventive Treatment in an Animal Model of PTSD

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