Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells.
Ming Li, Xue-Ke Yang, Jian Yang, Tong-Xia Li, Chi Cui, Xiang Peng, Jie Lei, Kun Ren, Jie Ming, Pei Zhang, Bo Tian
Neuron September 25, 2024 DOI: 10.1016/j.neuron.2024.06.026 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Ketamine |
| Dose | subanesthetic-dose |
| Topics | Ketamine PTSD Esketamine |
| Keywords | Basolateral amygdala Dopamine d2 receptor Memory engram cells Trauma Therapy PTSD Psychopharmacology ketamine Drugs Medication Recall Fear memory Brain anatomy basolateral |
| Citations | 30 |
| Key findings | A single subanesthetic dose of ketamine given within the re-exposure time window reduces social avoidance in mice by decreasing the activity and quantity of reactivated basolateral amygdala engram cells, an effect dependent on dopamine D2 receptor signaling from the ventral tegmental area. |
Abstract
Erasing traumatic memory during memory reconsolidation is a promising retrieval-extinction strategy for post-traumatic stress disorder (PTSD). Here, we developed an acute social defeat stress (SDS) mouse model with short-term and re-exposure-evoked long-term social avoidance. SDS-associated traumatic memories were identified to be stored in basolateral amygdala (BLA) engram cells. A single intraperitoneal administration of subanesthetic-dose ketamine within, but not beyond, the re-exposure time window significantly alleviates SDS-induced social avoidance, which reduces the activity and quantity of reactivated BLA engram cells. Furthermore, activation or inhibition of dopaminergic projections from the ventral tegmental area to the BLA effectively mimics or blocks the therapeutic effect of re-exposure with ketamine and is dopamine D2 receptor dependent. Single-cell RNA sequencing reveals that re-exposure with ketamine triggered significant changes in memory-related pathways in the BLA. Together, our research advances the understanding of how ketamine mitigates PTSD symptoms and offers promising avenues for developing more effective treatments for trauma-related disorders.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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A single subanesthetic dose of ketamine given within the re-exposure time window reduced social avoidance in mice by decreasing activity and quantity of reactivated basolateral amygdala engram cells.
Synthesized
Comparable studies
Other preclinical and animal studies on ketamine for PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 | |
| Esketamine attenuates post-traumatic stress disorder via suppressing neuroinflammation and abnormal myelination. Mice | 2025 | Animal experimental study |