期刊
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
卷 17, 期 10, 页码 1659-1669出版社
OXFORD UNIV PRESS
DOI: 10.1017/S1461145714000479
关键词
Allopregnanolone; neurosteroids; post-traumatic stress disorder; translocator protein 18 kDa; YL-IPA08
资金
- National Natural Science Foundation of China [81001653, 30973516, 81102423, 81072624, 81173036]
- National Key New Drug Creation Program [2012ZX09102101-004, 2012ZX09J12110-02C, 2012ZX09J12201-004]
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 PK11195. 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 PK11195. 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据