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- Title
Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) in animal models of post-traumatic stress disorder.
- Authors
Li-Ming Zhang; Zhi-Kun Qiu; Nan Zhao; Hong-Xia Chen; Yan-Qin Liu; Jiang-Ping Xu; You-Zhi Zhang; Ri-Fang Yang; Yun-Feng
- Abstract
Recently, the translocator protein (18 kDa) (TSPO), previously called peripheral benzodiazepine receptor (PBR) and both the starting point and an important rate-limiting step in neurosteroidogenesis, has received increased attention in the pathophysiology of post-traumatic stress disorder (PTSD) because it affects the production of neurosteroids, reinforcing the hypothesis that selective TSPO ligands could potentially be used as anti-PTSD drugs. As expected, we showed that chronic treatment with YL-IPA08 [N-ethyl-N-(2-pyridinylmethyl)-2-(3,4- ichlorophenyl)-7-methylimidazo [1,2-a] pyridine-3-acetamide hydrochloride], a potent and selective TSPO ligand synthesized by our institute, caused significant suppression of enhanced anxiety and contextual fear induced in the inescapable electric foot-shock-induced mouse model of PTSD and the time-dependent sensitization (TDS) procedure. These effects were completely blocked by the TSPO antagonist PKl1195. Furthermore, YL-IPA08 could increase the level of allopregnanolone in the prefrontal cortex and serum of post-TDS rats, and these effects were antagonized by PKl1195. In summary, the findings from the current study showed that YL-IPA08, a potent and selective TSPO ligand, had a clear anti-PTSD-like effect, which might be partially mediated by binding to TSPO and the subsequent synthesis of allopregnanolone.
- Subjects
TRANQUILIZING drugs; LIGANDS (Biochemistry); BENZODIAZEPINE receptors; PATHOLOGICAL physiology; TREATMENT of post-traumatic stress disorder; ANXIETY; BLOOD serum analysis
- Publication
International Journal of Neuropsychopharmacology, 2014, Vol 17, Issue 10, p1659
- ISSN
1461-1457
- Publication type
Article
- DOI
10.1017/S1461145714000479