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

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 45; pp. 40 - 46
• Main Authors: QIU, Zhi-Kun, ZHANG, Li-Ming, XU, Jiang-Ping, LI, Yun-Feng, NAN ZHAO, CHEN, Hong-Xia, ZHANG, You-Zhi, LIU, Yan-Qin, MI, Tian-Yue, ZHOU, Wen-Wen, YANG LI, YANG, Ri-Fang
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01.08.2013
• Subjects: Adult and adolescent clinical studies; Animals; Anti-Anxiety Agents - pharmacology; Anti-Anxiety Agents - therapeutic use; Anxiety disorders. Neuroses; Behavioral Symptoms - drug therapy; Behavioral Symptoms - psychology; Biological and medical sciences; Body Weight - drug effects; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Immobility Response, Tonic - drug effects; Ligands; Male; Maze Learning - drug effects; Medical sciences; Mice; Motor Activity - drug effects; Neuropharmacology; Pharmacology. Drug treatments; Post-traumatic stress disorder; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Purines - pharmacology; Purines - therapeutic use; Receptors, GABA - drug effects; Stress Disorders, Post-Traumatic - drug therapy; Stress Disorders, Post-Traumatic - psychology; Animal model; Metabolite; Ligand; Post-traumatic stress disorder (PTSD); Rodentia; Anxiety disorder; Posttraumatic stress disorder; 18 kDa translocator protein (TSPO); Freezing behavior; Ovarian hormone; Protein; Stress; Progestagen; Allopregnanolone; Multiple dose; AC-5216; Vertebrata; Mammalia; Mouse; Animal; Progesterone; Behavior; Sex steroid hormone; Tonic immobility; Ser; central benzodiazepine receptor; post-traumatic stress disorder; EPM; staircase test; SSRIs; inner mitochondrial membrane; 18kDa translocator protein (TSPO); outer mitochondrial membrane; CNS; CBR; open field; SBSSs; analysis of variance; ANOVA; selective serotonin reuptake inhibitors; OF; SPS; situational reminders; N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl) acetamide; TSPO; sertraline; elevated plus-maze; single prolonged stress; ST; 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; gamma-amino-butyric acid type A receptor; PK11195; hypothalamic–pituitary–adrenal; IMM; selective brain steroidogenic stimulants; OMM; central nervous system; PTSD; GABA(A); SRs; HPA; 18kDa translocator protein
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2013.04.010

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.