(2r,6r)-hydroxynorketamine Targeting the Basolateral Amygdala Regulates Fear Memory
Year: 2025
Type: conference-abstract
Abstract: Background (2R,6R)-Hydroxynorketamine (HNK), a ketamine metabolite, is a promising next-generation antidepressant known for its rapid and long-lasting effects. Recent studies have explored its impact on memory, yet its influence on fear memory extinction remains uncharted. Objective We investigated (2R,6R)-HNK's effects on synaptic transmission and plasticity in the basolateral amygdala (BLA) and its role in auditory fear memory extinction. Method Adult male C57BL/6J mice were utilized for extracellular electrophysiological recordings and fear conditioning tests. Result (2R,6R)-HNK at 30 mg/kg increased cfos-positive cell count in the BLA and dose-dependently enhanced long-term potentiation (LTP) induction and maintenance. Moreover, (2R,6R)-HNK improved BLA synaptic transmission. Both local and systemic administration of (2R,6R)-HNK reduced recent and remote fear memory retrieval and inhibited spontaneous remote fear memory recovery. Conclusion (2R,6R)-HNK could be a potential treatment for posttraumatic stress disorder (PTSD) patients by regulating BLA synaptic function and fear memory modulation.
Authors: *Yuanyuan Xu, Zhenlong Li, Chau-Shoun Lee, Hsien-Yu Peng, Tzer-Bin Lin, Ming-Chun Hsieh, Cheng-Yuan Lai, Dylan Chou
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,693
OpenAlex ID: W4407387114