1. Repeated administration of AC-5216, a ligand for the 18 kDa translocator protein, improves behavioral deficits in a mouse model of post-traumatic stress disorder.
- Author
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Qiu ZK, Zhang LM, Zhao N, Chen HX, Zhang YZ, Liu YQ, Mi TY, Zhou WW, Li Y, Yang RF, Xu JP, and Li YF
- Subjects
- Animals, Anti-Anxiety Agents pharmacology, Behavioral Symptoms psychology, Body Weight drug effects, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Immobility Response, Tonic drug effects, Ligands, Male, Maze Learning drug effects, Mice, Motor Activity drug effects, Purines pharmacology, Stress Disorders, Post-Traumatic psychology, Anti-Anxiety Agents therapeutic use, Behavioral Symptoms drug therapy, Purines therapeutic use, Receptors, GABA drug effects, Stress Disorders, Post-Traumatic drug therapy
- 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 18 kDa 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 © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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