Midazolam ameliorates the behavior deficits of a rat posttraumatic stress disorder model through dual 18 kDa translocator protein and central benzodiazepine receptor and neurosteroidogenesis.
Post-traumatic stress disorder (PTSD) is a debilitating anxiety disorder that may develop after an individual has experienced or witnessed a severe traumatic event. It has been shown that the 18 kDa translocator protein (TSPO) may be correlated with PTSD and that the TSPO ligand improved the behavio...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4079590?pdf=render |
| _version_ | 1818363098018349056 |
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| author | Yu-Liang Miao Wen-Zhi Guo Wen-Zhu Shi Wei-Wu Fang Yan Liu Ji Liu Bao-Wei Li Wei Wu Yun-Feng Li |
| author_facet | Yu-Liang Miao Wen-Zhi Guo Wen-Zhu Shi Wei-Wu Fang Yan Liu Ji Liu Bao-Wei Li Wei Wu Yun-Feng Li |
| author_sort | Yu-Liang Miao |
| collection | DOAJ |
| description | Post-traumatic stress disorder (PTSD) is a debilitating anxiety disorder that may develop after an individual has experienced or witnessed a severe traumatic event. It has been shown that the 18 kDa translocator protein (TSPO) may be correlated with PTSD and that the TSPO ligand improved the behavioral deficits in a mouse model of PTSD. Midazolam, a ligand for TSPO and central benzodiazepine receptor (CBR), induces anxiolytic- and anti-depressant-like effects in animal models. The present study aimed to determine whether midazolam ameliorates PTSD behavior in rats as assessed by the single prolonged stress (SPS) model. The SPS rats received daily Sertraline (Ser) (15 mg/kg, i.p.) [corrected] and midazolam (0.125, 0.25, 0.5, and 1 mg/kg, i.p.) [corrected] during the exposure to SPS and behavioral assessments, which included the open field (OF) test, the contextual fear paradigm (CFP), and the elevated plus-maze (EPM). The results showed that, like Ser (15 mg/kg, i.p.) [corrected], midazolam (0.25 and 0.5 mg/kg, i.p.) [corrected] significantly reversed the behavioral deficiencies of the SPS rats, including PTSD-associated freezing and anxiety-like behavior but not the effects on spontaneous locomotor activity. In addition, the anti-PTSD effects of midazolam (0.5 mg/kg, i.p.) [corrected] were antagonized by the TSPO antagonist PK11195 (3 mg/kg, i.p.), the CBR antagonist flumazenil (15 mg/kg, i.p.) [corrected] and the inhibitor of steroidogenic enzymes finasteride (30 mg/kg, i.p.) [corrected], which by themselves had no effect on PTSD-associated freezing and anxiety-like behavior. In summary, this study demonstrated that midazolam improves the behavioral deficits in the SPS model through dual TSPO and CBR and neurosteroidogenesis. |
| first_indexed | 2024-12-13T21:43:04Z |
| format | Article |
| id | doaj.art-5f380be667424436a79fc9a1c2edceb4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T21:43:04Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-5f380be667424436a79fc9a1c2edceb42022-12-21T23:30:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10145010.1371/journal.pone.0101450Midazolam ameliorates the behavior deficits of a rat posttraumatic stress disorder model through dual 18 kDa translocator protein and central benzodiazepine receptor and neurosteroidogenesis.Yu-Liang MiaoWen-Zhi GuoWen-Zhu ShiWei-Wu FangYan LiuJi LiuBao-Wei LiWei WuYun-Feng LiPost-traumatic stress disorder (PTSD) is a debilitating anxiety disorder that may develop after an individual has experienced or witnessed a severe traumatic event. It has been shown that the 18 kDa translocator protein (TSPO) may be correlated with PTSD and that the TSPO ligand improved the behavioral deficits in a mouse model of PTSD. Midazolam, a ligand for TSPO and central benzodiazepine receptor (CBR), induces anxiolytic- and anti-depressant-like effects in animal models. The present study aimed to determine whether midazolam ameliorates PTSD behavior in rats as assessed by the single prolonged stress (SPS) model. The SPS rats received daily Sertraline (Ser) (15 mg/kg, i.p.) [corrected] and midazolam (0.125, 0.25, 0.5, and 1 mg/kg, i.p.) [corrected] during the exposure to SPS and behavioral assessments, which included the open field (OF) test, the contextual fear paradigm (CFP), and the elevated plus-maze (EPM). The results showed that, like Ser (15 mg/kg, i.p.) [corrected], midazolam (0.25 and 0.5 mg/kg, i.p.) [corrected] significantly reversed the behavioral deficiencies of the SPS rats, including PTSD-associated freezing and anxiety-like behavior but not the effects on spontaneous locomotor activity. In addition, the anti-PTSD effects of midazolam (0.5 mg/kg, i.p.) [corrected] were antagonized by the TSPO antagonist PK11195 (3 mg/kg, i.p.), the CBR antagonist flumazenil (15 mg/kg, i.p.) [corrected] and the inhibitor of steroidogenic enzymes finasteride (30 mg/kg, i.p.) [corrected], which by themselves had no effect on PTSD-associated freezing and anxiety-like behavior. In summary, this study demonstrated that midazolam improves the behavioral deficits in the SPS model through dual TSPO and CBR and neurosteroidogenesis.http://europepmc.org/articles/PMC4079590?pdf=render |
| spellingShingle | Yu-Liang Miao Wen-Zhi Guo Wen-Zhu Shi Wei-Wu Fang Yan Liu Ji Liu Bao-Wei Li Wei Wu Yun-Feng Li Midazolam ameliorates the behavior deficits of a rat posttraumatic stress disorder model through dual 18 kDa translocator protein and central benzodiazepine receptor and neurosteroidogenesis. PLoS ONE |
| title | Midazolam ameliorates the behavior deficits of a rat posttraumatic stress disorder model through dual 18 kDa translocator protein and central benzodiazepine receptor and neurosteroidogenesis. |
| title_full | Midazolam ameliorates the behavior deficits of a rat posttraumatic stress disorder model through dual 18 kDa translocator protein and central benzodiazepine receptor and neurosteroidogenesis. |
| title_fullStr | Midazolam ameliorates the behavior deficits of a rat posttraumatic stress disorder model through dual 18 kDa translocator protein and central benzodiazepine receptor and neurosteroidogenesis. |
| title_full_unstemmed | Midazolam ameliorates the behavior deficits of a rat posttraumatic stress disorder model through dual 18 kDa translocator protein and central benzodiazepine receptor and neurosteroidogenesis. |
| title_short | Midazolam ameliorates the behavior deficits of a rat posttraumatic stress disorder model through dual 18 kDa translocator protein and central benzodiazepine receptor and neurosteroidogenesis. |
| title_sort | midazolam ameliorates the behavior deficits of a rat posttraumatic stress disorder model through dual 18 kda translocator protein and central benzodiazepine receptor and neurosteroidogenesis |
| url | http://europepmc.org/articles/PMC4079590?pdf=render |
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