(2R,6R)-hydroxynorketamine alleviates PTSD-like endophenotypes by regulating the PI3K/AKT signaling pathway in rats.
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.