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.
Psychopathology
March 27, 2026
Xiaoran Ding, Yaping Wu, Juan Yang et al.
1 citation
Ketamine is a rapid-acting antidepressant, especially for treatment-resistant depression, working through multiple targets in the glutamatergic system. It blocks NMDA receptors, which disinhibits dopamine reward pathways and increases BDNF expression via eEF2K suppression, activating the mTOR pathway and enhancing synaptic plasticity. Neuroimaging shows ketamine rapidly reshapes prefrontal-limbic connectivity and normalizes brain activity. It has a fast onset and broad therapeutic window, but enantiomers and metabolites differ in effects. Long-term safety, dependence risk, and cognitive effects require monitoring. Future work should explore synergistic treatments and safer ketamine derivatives for precision psychiatry.
Zhonghua xingwei yixue yu naokexue zazhi
December 20, 2017
Haonan Li, Hongwei Sun, Yanyu Wang et al.
In a rat model of depression induced by chronic unpredictable mild stress, melatonin produced antidepressant-like effects comparable to those of ketamine. Rats exposed to 42 days of stress showed depressive-like behavior, indicated by reduced sucrose preference and increased immobility time in the forced swim test. After 14 days of treatment, both melatonin and ketamine significantly decreased immobility time and increased the number of BDNF-positive cells in the prefrontal cortex compared to stressed controls. Melatonin also increased BDNF cell counts more than ketamine did. However, only ketamine, not melatonin, significantly raised GluR1 cell counts. These findings suggest melatonin's antidepressant action may involve upregulation of BDNF.