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.
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.
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DOI：
10.3389/fnbeh.2022.848232
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发表时间：
2022
影响因子：
3
通讯作者：
中科院分区：
文献类型：
--
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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.
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影响因子：
25.8
作者：
Liu H;Petukhova MV;Sampson NA;Aguilar-Gaxiola S;Alonso J;Andrade LH;Bromet EJ;de Girolamo G;Haro JM;Hinkov H;Kawakami N;Koenen KC;Kovess-Masfety V;Lee S;Medina-Mora ME;Navarro-Mateu F;O'Neill S;Piazza M;Posada-Villa J;Scott KM;Shahly V;Stein DJ;Ten Have M;Torres Y;Gureje O;Zaslavsky AM;Kessler RC;World Health Organization World Mental Health Survey Collaborators
通讯作者：
World Health Organization World Mental Health Survey Collaborators
影响因子：
5.3
作者：
Leith, J. Lianne;Koutsikou, Stella;Apps, Richard
通讯作者：
Apps, Richard
影响因子：
5.3
作者：
Felger JC
通讯作者：
Felger JC
影响因子：
3.6
作者：
Berrino, L;Oliva, P;Rossi, F
通讯作者：
Rossi, F
影响因子：
8.2
作者：
Dominguini, Diogo;V. Steckert, Amanda;Dal-Pizzol, Felipe
通讯作者：
Dal-Pizzol, Felipe