The anxiolytic-like effects of estazolam on a PTSD animal model
Section snippets
Background
Post-traumatic stress disorder (PTSD) is a serious psychiatry that may occur following experience or witnessing of life-threatening events (Sareen et al., 2014). The avoidance on stimuli could serve as reminders of events and induce fear (Pugh et al., 2015). Consensus regarding the nature of factors remains unclear, although the pathophysiology of PTSD has been widely researched.
Changed levels of serotonin (5-HT) are associated with PTSD pathophysiology (Liu et al., 2013). For instance, levels
Drugs
Fetal bovine serum (FBS) and Dulbecco's modified Eagle's medium (DMEM) were purchased from GIBCO (USA) and Invitrogen (USA), respectively. Estazolam, sertraline, trilostane and finasteride were dissolved in dimethyl sulfoxide (DMSO) (less than 0.1%).
Animals
Male Sprague-Dawley rats (Vital River Laboratory Animal Technology Company, China) weighing 200 ± 20 g were maintained in temperature- (23 ± 1 °C), and humidity- controlled (45–50%) condition. The total number of animals was 60 and 10 in each group.
Effects of estazolam on PTSD-associated contextual freezing behavior in contextual fear paradigm
The effects of estazolam on PTSD-associated freezing behavior were shown in Fig. 2. One-way ANOVA showed that freezing time (F5,54 = 11.20, p < 0.05) was significantly increased after exposure to single prolonged stress. However, consistent with the effects of sertraline (15 mg/kg, i.p.), elevated freezing time was markedly reversed by estazolam (1 and 2 mg/kg, i.p.). Accordingly, PTSD-associated contextual freezing behavior could be attenuated by estazolam in contextual fear paradigm.
Effects of estazolam on PTSD-associated anxiety-like behavior in elevated plus maze test
The
Discussion
The present study indicated that the anxiolytic-like behavioral deficits were ameliorated by estazolam without affecting locomotor activity following exposure to single prolonged stress. In addition, lowered levels on allopregnanolone were blocked by estazolam, suggesting anti-PTSD-like effects of estazolam were associated with biosynthesis of allopregnanolone.
PTSD-like behavioral deficits were induced by single prolonged stress, which was evidenced by the increased freezing time (Fig. 2) and
Conclusion
Summary, the anti-PTSD-like effects of estazolam are associated with biosynthesis of allopregnanolone. These findings promote the advancement in our knowledge regarding the importance of neurosteroid biosynthesis for anti-PTSD-like effects of estazolam.
Competing interests
The authors declare that they have no competing interests.
Acknowledgement
We thank Zhi-Kun Qiu and Ji-Sheng Chen for the literature investigation.
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