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.
Keywords: 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; 18kDa translocator protein; 18kDa translocator protein (TSPO); AC-5216; ANOVA; Allopregnanolone; CBR; CNS; EPM; Freezing behavior; GABA(A); HPA; IMM; N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl) acetamide; OF; OMM; PK11195; PTSD; Post-traumatic stress disorder (PTSD); SBSSs; SPS; SRs; SSRIs; ST; Ser; TSPO; analysis of variance; central benzodiazepine receptor; central nervous system; elevated plus-maze; gamma-amino-butyric acid type A receptor; hypothalamic–pituitary–adrenal; inner mitochondrial membrane; open field; outer mitochondrial membrane; post-traumatic stress disorder; selective brain steroidogenic stimulants; selective serotonin reuptake inhibitors; sertraline; single prolonged stress; situational reminders; staircase test.
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