S-Ketamine Pretreatment Alleviates Anxiety-Like Behaviors and Mechanical Allodynia and Blocks the Pro-inflammatory Response in Striatum and Periaqueductal Gray From a Post-traumatic Stress Disorder Model
Shuai Yang, Ke Xu, Xuan Xu, Jixiang Zhu, Yinan Jin, Qi Liu, Rui Xu, X. Gu, Yue Liu, Yulin Huang, Zhengliang Ma
Frontiers in Behavioral Neuroscience April 14, 2022 DOI: 10.3389/fnbeh.2022.848232 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Adult male rats exposed to single-prolonged stress (SPS) model of PTSD |
| Intervention | S-ketamine |
| Dose | 5 mg/kg |
| Duration | 28 days post-injection |
| Topics | Anxiety Esketamine Ketamine PTSD |
| Key points | S-ketamine alleviated mechanical allodynia, anxiety-like behaviors, and pro-inflammatory responses in discrete brain regions in a rat model of PTSD. |
Abstract
This study aims to explore the regulatory effect of S-ketamine on the mechanical allodynia, anxiety-like behaviors and microglia activation in adult male rats exposed to an animal model of post-traumatic stress disorder (PTSD). The rat PTSD model was established by the exposure to single-prolonged stress (SPS), and 1 day later, rats were intraperitoneally injected with 5 mg/kg S-ketamine or normal saline, respectively. Paw withdrawal mechanical threshold was measured 2 days before, and 1, 3, 5, 7, 10, 14, 21 and 28 days after injection to assess mechanical allodynia in the SPS-exposed rats. For anxiety-like behaviors, the open field test and elevated plus maze test were performed at 7 and 14 days after S-ketamine treatment in the SPS-exposed rats, respectively. SPS-induced rats presented pronounced mechanical allodynia and anxiety-like behaviors, which were alleviated by S-ketamine treatment. After behavioral tests, rats were sacrificed for collecting the anterior cingulate cortex (ACC), prefrontal cortex (PFC), dorsal striatum, and periaqueductal gray (PAG). Protein levels of TNF-α, IL-1β, p-NF-κB, and NF-κB in brain regions were examined by Western blot. In addition, microglia activation in each brain region was determined by immunofluorescence staining of the microglia-specific biomarker Iba-1. Interestingly, pro-inflammatory cytokines were significantly upregulated in the dorsal striatum and PAG, rather than ACC and PFC. Activated microglia was observed in the dorsal striatum and PAG as well, and upregulated p-NF-κB was detected in the dorsal striatum. Inflammatory response, phosphorylation of NF-κB and microglia activation in certain brain regions were significantly alleviated by S-ketamine treatment. Collectively, S-ketamine is a promising drug in alleviating mechanical allodynia, anxiety-like behaviors, and pro-inflammatory responses in discrete brain regions in a model of PTSD.
Comparable studies
Other preclinical and animal studies on esketamine for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| N,N-dimethyltryptamine elicits antidepressant and anxiolytic effects in helpless mice: a comparative study with S-ketamine. Male helpless mice (single-housed and group-housed) | 2026 | Animal study | |
| Esketamine alleviates trigeminal neuralgia and anxiety-like behaviors in mice by inhibiting RIPK1/RIPK3/MLKL-mediated necroptosis. Mice with partial infraorbital nerve transection (pIONT) | 2026 | Animal study | |
| S-ketamine mitigates paclitaxel-induced pain-related anxiety-like behavior through downregulation of mGluR5 and activation of the BDNF/TrkB signaling pathway Mice with paclitaxel-induced peripheral neuropathy | 2026 | Preclinical experimental study | |
| Esketamine ameliorates post-stroke anxiety by modulating microglial HDAC3/NF-κB/COX1 inflammatory signaling in ischemic cortex. Male C57BL/6 mice with photothrombotic stroke combined with chronic restraint stress... | 2023 | Animal experimental study |