RESUMEN
BACKGROUND: Post-traumatic stress disorder (PTSD) is a mental illness caused by either experiencing or observing a traumatic event that is perceived to pose a serious risk to one's life. (2R,6R)-HNK has an alleviating effect on negative emotions, nevertheless, the mechanism of (2R,6R)-HNK action is unclear. METHODS: In this study, the single prolonged stress and electric foot shock (SPS&S) method was used to establish a rat model of PTSD. After determining the validity of the model, (2R,6R)-HNK was administered to the NAc by microinjection using a concentration gradient of 10, 50, and 100 µM, and the effects of the drug in the SPS&S rat model were evaluated. Moreover, our study measured changes in related proteins in the NAc (BDNF, p-mTOR/mTOR, and PSD95) and synaptic ultrastructure. RESULTS: In the SPS&S group, the protein expression of brain-derived neurotrophic factor (BDNF), mammalian target of rapamycin (mTOR), and PSD95 was reduced and synaptic morphology was damaged in the NAc. In contrast, after the administration of 50 µM (2R,6R)-HNK, SPS&S-treated rats improved their exploration and depression-linked behavior, while protein levels and synaptic ultrastructure were also restored in the NAc. With the administration of 100 µM (2R,6R)-HNK, locomotor behavior, and social interaction improved in the PTSD model. LIMITATIONS: The mechanism of BDNF-mTOR signaling after (2R,6R)-HNK administration was not explored. CONCLUSION: (2R,6R)-HNK may ameliorate negative mood and social avoidance symptoms in PTSD rats by regulating BDNF/mTOR-mediated synaptic structural plasticity in the NAc, providing new targets for the development of anti-PTSD drugs.
