Applying ketamine to alleviate the PTSD-like effects by regulating the HCN1-related BDNF

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2018-08, Vol.86, p.313-321
• Main Authors: Hou, Lanwei, Qi, Yirui, Sun, Hongwei, Wang, Gang, Li, Qi, Wang, Yanyu, Zhang, Zuoji, Du, Zhongde, Sun, Lin
• Format: Article
• Language: English
• Subjects: Animals; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Disease Models, Animal; Dose-Response Relationship, Drug; Hyperpolarization-activated cyclic nucleotide-gated channel 1; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - metabolism; Ketamine; Ketamine - pharmacology; Male; Post-traumatic stress disorder; Potassium Channels - metabolism; Prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Prefrontal Cortex - pathology; Psychotropic Drugs - pharmacology; Random Allocation; Rats, Sprague-Dawley; Signal Transduction - drug effects; Stress Disorders, Post-Traumatic - drug therapy; Stress Disorders, Post-Traumatic - metabolism; Stress Disorders, Post-Traumatic - pathology
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2018.03.019

Post-traumatic stress disorder (PTSD) is commonly associated with concurrent anxiety and depression symptoms, and reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF) which promotes the proliferation and survival of neurons. The hyperpolarization-activated cyclic nucleotide-gated channel 1(HCN1) could be inhibited by the ketamine, a drug to alleviate depression and anxiety, and regulated the BDNF expression, however, the effects of ketamine in alleviating PTSD symptoms by regulating the HCN1-related BDNF have been poorly perceived. In the present study, the effects of ketamine were examined on the PTSD-like effects in a rat model of PTSD induced by SPS&S procedure. After the SPS&S procedure and model testing, PTSD rats were subjected to behavioral testing and biochemical assessments, followed by single treatment with certain doses of ketamine (5, 10, 15 and 20 mg/kg IP). The results showed that the SPS&S procedure induced severe PTSD-like behaviors, with lower levels of BDNF protein levels and higher level of the HCN1 protein in the prefrontal cortex (PFC). These were reversed by a single administration of ketamine. The ketamine with dose of 15 mg/kg significantly increased locomotor behavior in the open field test, aggrandized exploratory behavior in the elevated plus maze test, and decreased immobility time spent in the forced swim test. Meanwhile, ketamine with dose of 15 mg/kg could increase the BDNF protein level, while down-regulate the expression of the HCN1. Eventually, there was a negative correlation between the level of BDNF and HCN1 in the PFC. Ketamine affects the HCN1-related BDNF signaling pathways to alleviate PTSD-like effects in rat. •BDNF protein could be regulated by the HCN1 level in the PFC.•The HCN1-related BDNF pathways are involved in the PTSD-like effects.•Ketamine alleviates the PTSD-like effects by regulating the HCN1-related BDNF.•The ketamine with15 mg/kg dose could alleviate PTSD-like effects preferably.