Involvement of allopregnanolone in the anti-PTSD-like effects of AC-5216

Journal of Psychopharmacology
Li-Ming ZhangYun-Feng Li

Abstract

Cholesterol import into mitochondria through the translocator protein (18 KDa) (TSPO) is the starting point and an important rate-limiting step in neurosteroidogenesis. For this reason TSPO has received increased attention in the pathophysiology of post-traumatic stress disorder (PTSD). In an effort to explore the role of TSPO in mediating the anti-PTSD effect, we first assessed the effects of the TSPO ligand AC-5216 in alleviating the enhanced anxiety and fear response in a time-dependent sensitization (TDS) procedure, a rat PTSD animal model. In the present study, we showed that chronic treatment with AC-5216 caused significant suppression of the enhanced anxiety and contextual fear induced in post-TDS rats; these effects were blocked by PK11195. Furthermore, AC-5216 treatment increased the levels of allopregnanolone in the serum, prefrontal cortex, and hippocampus of post-TDS rats, and these effects were antagonized by PK11195. These results demonstrate that AC-5216 has a clear anti-PTSD-like effect, which might be partially mediated by binding to TSPO and the subsequent synthesis of allopregnanolone.

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Citations

Jun 22, 2018·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·G P IvanovaL M Vasilenko
Oct 18, 2020·Cancers·Laura-Marie AmmerPeter Hau
Aug 4, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhi-Kun QiuJi-Sheng Chen
Jun 20, 2020·Psychoneuroendocrinology·Sheila A M RauchUNKNOWN Consortium to Alleviate PTSD and the STRONG STAR Consortium
May 22, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shiyi ChenYiping Ye
May 19, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ai-Shan SuJing Zou

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Methods Mentioned

BETA
ELISA

Software Mentioned

GraphPad
GraphPad Prism

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