Animal model of PTSD based on clinically relevant features of trauma susceptibility and expression
Rationale/statement of the problem : There is an insufficient understanding of the neurobiology of post-traumatic stress disorder (PTSD). Therefore, the development of an animal model of PTSD that takes into account clinical features of the disorder is of value toward enhancing our understanding of...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2012-09-01
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| Series: | European Journal of Psychotraumatology |
| Subjects: |
| _version_ | 1818806743506878464 |
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| author | David Diamond Tania L. Roth Monika Fleshner Phillip R. Zoladz |
| author_facet | David Diamond Tania L. Roth Monika Fleshner Phillip R. Zoladz |
| author_sort | David Diamond |
| collection | DOAJ |
| description | Rationale/statement of the problem : There is an insufficient understanding of the neurobiology of post-traumatic stress disorder (PTSD). Therefore, the development of an animal model of PTSD that takes into account clinical features of the disorder is of value toward enhancing our understanding of the mechanisms, and in the development of novel treatments, of emotional trauma. Methods : Adult male rats were administered chronic psychosocial stress composed of two 1-hour periods of inescapable exposure to a cat, in conjunction with daily unstable pair housing, over a 31 day period. The rats were then given a battery of tests, including measures of behavior (anxiety testing, startle response), cognition (predator-based fear memory and new memory testing), hormone levels (basal and evoked glucocorticoids), responses to pharmacological agents (dexamethasone and yohimbine) and cardiovascular activity (blood pressure/heart rate). In addition, we measured epigenetic alterations (methylation) of the brain-derived neurotrophic factor (BDNF) gene. Results : Psychosocially stressed rats exhibited a PTSD-like phenotype. The stressed rats exhibited a strong fear-conditioned memory of the two cat exposures, an increase in behavioral signs of anxiety, an exaggerated startle response, increased blood pressure, greater sensitivity to yohimbine and a hippocampus-dependent memory impairment, relative to controls. In addition, stressed rats exhibited reduced basal glucocorticoid levels, greater sensitivity to dexamethasone and hypermethylation of the BDNF gene in the hippocampus. Conclusion : These findings demonstrate that intense psychosocial stress produced dramatic changes in physiology and behavior in rats which are comparable to those observed in people diagnosed with PTSD. This rat model, therefore, may enhance our understanding of the mechanisms underlying human trauma and in the development of more effective pharmacotherapy for people with PTSD. |
| first_indexed | 2024-12-18T19:14:37Z |
| format | Article |
| id | doaj.art-9893e05ede7c4e188f4cdfa755eecc32 |
| institution | Directory Open Access Journal |
| issn | 2000-8066 |
| language | English |
| last_indexed | 2024-12-18T19:14:37Z |
| publishDate | 2012-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | European Journal of Psychotraumatology |
| spelling | doaj.art-9893e05ede7c4e188f4cdfa755eecc322022-12-21T20:56:09ZengTaylor & Francis GroupEuropean Journal of Psychotraumatology2000-80662012-09-01301110.3402/ejpt.v3i0.19601Animal model of PTSD based on clinically relevant features of trauma susceptibility and expressionDavid DiamondTania L. RothMonika FleshnerPhillip R. ZoladzRationale/statement of the problem : There is an insufficient understanding of the neurobiology of post-traumatic stress disorder (PTSD). Therefore, the development of an animal model of PTSD that takes into account clinical features of the disorder is of value toward enhancing our understanding of the mechanisms, and in the development of novel treatments, of emotional trauma. Methods : Adult male rats were administered chronic psychosocial stress composed of two 1-hour periods of inescapable exposure to a cat, in conjunction with daily unstable pair housing, over a 31 day period. The rats were then given a battery of tests, including measures of behavior (anxiety testing, startle response), cognition (predator-based fear memory and new memory testing), hormone levels (basal and evoked glucocorticoids), responses to pharmacological agents (dexamethasone and yohimbine) and cardiovascular activity (blood pressure/heart rate). In addition, we measured epigenetic alterations (methylation) of the brain-derived neurotrophic factor (BDNF) gene. Results : Psychosocially stressed rats exhibited a PTSD-like phenotype. The stressed rats exhibited a strong fear-conditioned memory of the two cat exposures, an increase in behavioral signs of anxiety, an exaggerated startle response, increased blood pressure, greater sensitivity to yohimbine and a hippocampus-dependent memory impairment, relative to controls. In addition, stressed rats exhibited reduced basal glucocorticoid levels, greater sensitivity to dexamethasone and hypermethylation of the BDNF gene in the hippocampus. Conclusion : These findings demonstrate that intense psychosocial stress produced dramatic changes in physiology and behavior in rats which are comparable to those observed in people diagnosed with PTSD. This rat model, therefore, may enhance our understanding of the mechanisms underlying human trauma and in the development of more effective pharmacotherapy for people with PTSD.PTSDanimal modeltrauma susceptibilitygene expressioncognitionhormone levels |
| spellingShingle | David Diamond Tania L. Roth Monika Fleshner Phillip R. Zoladz Animal model of PTSD based on clinically relevant features of trauma susceptibility and expression European Journal of Psychotraumatology PTSD animal model trauma susceptibility gene expression cognition hormone levels |
| title | Animal model of PTSD based on clinically relevant features of trauma susceptibility and expression |
| title_full | Animal model of PTSD based on clinically relevant features of trauma susceptibility and expression |
| title_fullStr | Animal model of PTSD based on clinically relevant features of trauma susceptibility and expression |
| title_full_unstemmed | Animal model of PTSD based on clinically relevant features of trauma susceptibility and expression |
| title_short | Animal model of PTSD based on clinically relevant features of trauma susceptibility and expression |
| title_sort | animal model of ptsd based on clinically relevant features of trauma susceptibility and expression |
| topic | PTSD animal model trauma susceptibility gene expression cognition hormone levels |
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