Journal of psychiatric research
October 1, 2024
Zixun Wang, Xinyu Hu, Zhongyi Wang et al.
9 citations
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.
Behavioural brain research
January 5, 2025
Han Wang, Yuxuan He, Jiahao Tang et al.
5 citations
Injecting (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) into the brain's lateral ventricle of rats with PTSD-like behaviors most effectively reduces anxiety and fear when given during the reconsolidation phase of fear memory—the period after a memory is recalled and before it is stored again. The drug restored levels of three proteins in the hippocampus (GluA1, VGF, and BDNF) that were lowered by stress and fear conditioning. No significant improvements occurred when the drug was given during the acquisition or extinction phases. The findings suggest that (2R,6R)-HNK works through the VGF/BDNF/GluA1 signaling pathway in the hippocampus to alleviate PTSD-like symptoms specifically during memory reconsolidation.
Pharmacology, biochemistry, and behavior
December 1, 2024
Lifen Liu, Rui Li, Lanxia Wu et al.
3 citations
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.