(2R, 6R)-hydroxynorketamine ameliorates PTSD-like behaviors during the reconsolidation phase of fear memory in rats by modulating the VGF/BDNF/GluA1 signaling pathway in the hippocampus.
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.