1. Repeated administration of AC-5216, a ligand for the 18kDa translocator protein, improves behavioral deficits in a mouse model of post-traumatic stress disorder.
- Author
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Qiu, Zhi-Kun, Zhang, Li-Ming, Zhao, Nan, Chen, Hong-Xia, Zhang, You-Zhi, Liu, Yan-Qin, Mi, Tian-Yue, Zhou, Wen-Wen, Li, Yang, Yang, Ri-Fang, Xu, Jiang-Ping, and Li, Yun-Feng
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LIGANDS (Biochemistry) , *PROTEINS , *POST-traumatic stress disorder , *ANXIETY disorders , *GENE expression , *BENZODIAZEPINES - Abstract
Abstract: Post-traumatic stress disorder (PTSD) is a severely disabling anxiety disorder that may occur following exposure to a serious traumatic event. It is a psychiatric condition that can afflict anyone who has experienced a life-threatening or violent event. Previous studies have shown that changes in 18kDa translocator protein (TSPO) expression (or function), a promising target for treating neurological disorders without benzodiazepine-like side effects, may correlate with PTSD. However, few studies have investigated the anti-PTSD effects of TSPO ligands. AC-5216, a ligand for TSPO, induces anxiolytic- and anti-depressant-like effects in animal models. The present study aimed to determine whether AC-5216 ameliorates PTSD behavior in mice. Following the training session consisting of exposure to inescapable electric foot shocks, animals were administered AC-5216 daily during the behavioral assessments, i.e., situational reminders (SRs), the open field (OF) test, the elevated plus-maze (EPM) test, and the staircase test (ST). The results indicated that exposure to foot shocks induced long-term behavioral deficiencies in the mice, including freezing and anxiety-like behavior, which were significantly ameliorated by repeated treatment with AC-5216 but without any effect on spontaneous locomotor activity or body weight. In summary, this study demonstrated the anti-PTSD effects of AC-5216 treatment, suggesting that TSPO may represent a therapeutic target for anti-PTSD drug discovery and that TSPO ligands may be a promising new class of drugs for the future treatment of PTSD. [Copyright &y& Elsevier]
- Published
- 2013
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