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.

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.

• Authors: Zhi-Kun Qiu, Li-Ming Zhang, Nan Zhao, Hong-Xia Chen, You-Zhi Zhang, Yan-Qin Liu, Tian-Yue Mi, Wen-Wen Zhou, Yang Li, Ri-Fang Yang, Jiang-Ping Xu, Yun-Feng Li
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 45 Pg. 40-6 (Aug 01 2013) ISSN: 1878-4216 [Electronic] England
• PMID: 23624119 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Anxiety Agents
• Bzrp protein, mouse
• Ligands
• N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide
• Purines
• Receptors, GABA

Topics

• Animals
• Anti-Anxiety Agents (pharmacology, therapeutic use)
• Behavioral Symptoms (drug therapy, 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, therapeutic use)
• Receptors, GABA (drug effects)
• Stress Disorders, Post-Traumatic (drug therapy, psychology)