Applying ketamine to alleviate the PTSD-like effects by regulating the HCN1-related BDNF.
Lanwei Hou, Yirui Qi, Hongwei Sun, Gang Wang, Qi Li, Yanyu Wang, Zuoji Zhang, Zhongde Du, Lin Sun
Progress in Neuro-Psychopharmacology and Biological Psychiatry August 30, 2018 DOI: 10.1016/j.pnpbp.2018.03.019 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats subjected to the SPS&S procedure to induce PTSD-like effects |
| Intervention | Ketamine |
| Dose | 5, 10, 15 and 20 mg/kg IP |
| Measures | open field test, elevated plus maze test, forced swim test |
| Topics | Ketamine PTSD Esketamine |
| Keywords | Brain-derived neurotrophic factor Prefrontal cortex |
| Key findings | The SPS&S procedure produced PTSD-like behaviors with lower BDNF and higher HCN1 protein in the prefrontal cortex, and a single ketamine injection reversed these changes. The 15 mg/kg dose increased open-field locomotion, elevated plus maze exploration, and reduced forced swim immobility, while increasing BDNF and down-regulating HCN1; BDNF and HCN1 levels were negatively correlated. The authors propose ketamine alleviates PTSD-like effects via HCN1-related BDNF signaling. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on ketamine for PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells. Mice | 2024 | Experimental animal study | |
| Molecular signatures of astrocytes and microglia maladaptive responses to acute stress are rescued by a single administration of ketamine in a rodent model of PTSD. Rats | 2024 | Animal study | |
| Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Rodents | 2024 | Review | |
| Ketamine alleviates PTSD-like effect and improves hippocampal synaptic plasticity via regulation of GSK-3β/GR signaling of rats. Single prolonged stress-induced PTSD rat model | 2024 | Animal study | |
| (2R, 6R)-hydroxynorketamine ameliorates PTSD-like behaviors during the reconsolidation phase of fear memory in rats by modulating the VGF/BDNF/GluA1 signaling pathway in the hippocampus. Rats (single prolonged stress and contextual fear conditioning models) | 2025 | Animal study |
Citations in the library
Cited by 7
- A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. American Journal of Psychiatry January 5, 2021
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
- Therapeutic potential of ketamine for alcohol use disorder. Neuroscience & Biobehavioral Reviews July 1, 2021
- Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD. Psychopharmacology June 1, 2025
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers. Journal of Anesthesia and Translational Medicine September 1, 2025
and 2 more in the library
Cites 5
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats Anesthesiology October 1, 2011
- NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses Nature June 15, 2011
- Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biological Psychiatry January 15, 2010
- Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 1, 2008