Rapid anti-PTSD-like activity of the TSPO agonist YL-IPA08: emphasis on brain GABA, neurosteroids and HPA axis function.

Rapid anti-PTSD-like activity of the TSPO agonist YL-IPA08: emphasis on brain GABA, neurosteroids and HPA axis function. Behav Brain Res. 2019 Oct 24;:112320 Authors: Shang C, Guo Y, Yao JQ, Fang XX, Sun LJ, Jiang XY, Ding ZC, Ran YH, Wang HL, Zhang LM, Li YF Abstract There is a serious need for fast-acting drugs to treat post-traumatic stress disorder (PTSD). Our previous studies revealed that YL-IPA08, a novel small-molecule TSPO agonist, exerted significant anti-PTSD effects in various animal models. However, the onset time of YL-IPA08 and its underlying mechanisms remain unclear. In the present study, we first investigated the time course of YL-IPA08 compared to selective serotonin reuptake inhibitors (SSRIs) in the well-known time-dependent sensitization model of PTSD. YL-IPA08 required only 2-4 days of treatment to take effect in behavioural models of PTSD, whereas sertraline required 7-8 days. Furthermore, the mechanism study revealed that YL-IPA08 elicited anti-PTSD-like effects associated with increased GABA levels and allopregnanolone efflux in the hippocampus and prefrontal cortex and increased corticosterone levels in the serum after only 5 days of treatment, whereas sertraline required 9 days. Our results demonstrate that YL-IPA08 can exert fast-onset anti-PTSD-like effects, and its mechanisms may be related to the increased GABA levels, allopregnanolone efflux and the hypothalamic-pituitary-adrenal (HPA) axis function. ...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research