School of Psychology, Shandong Second Medical University, 7166# Baotong West Street, Weifang, Shandong 261053, PR China; CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, PR China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, PR China. Electronic address: huxy@psych.ac.cn.
2 papers in the library · 12 citations · publishing 2024
Post-traumatic stress disorder affects 3-4% of people globally each year. In a rat model of PTSD induced by single prolonged stress, a single low dose of ketamine (10 mg/kg) prevented anxiety-like behaviors. Ketamine also reversed stress-induced changes in the hippocampus: it increased expression of glucocorticoid receptor, brain-derived neurotrophic factor, phosphorylated GSK-3β, FKBP5, and CRH, while decreasing GSK-3β protein expression, and it improved synaptic structure. A GSK-3β inhibitor produced similar behavioral effects, suggesting ketamine works by regulating GSK-3β/GR signaling to improve synaptic plasticity.
In rats exposed to a combined stress model (single prolonged stress plus plantar shock), those treated with (2R,6R)-hydroxyketamine (HNK) showed reduced depression- and anxiety-like behaviors, including increased exploratory activity. The compound reversed stress-induced disruptions in the PI3K/AKT signaling pathway in the hippocampus and prefrontal cortex, but not in the amygdala. Traumatic stress itself altered PI3K/AKT signaling in all three brain regions. These results suggest that (2R,6R)-HNK may alleviate negative emotional symptoms after trauma by modulating PI3K/AKT signaling, particularly in the hippocampus.