NeuronJul 20, 2024

Ketamine reduces social avoidance after trauma by removing traumatic memories in emotion-related brain cells connected to the reward system

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 22, 2026

Abstract

A single intraperitoneal administration of subanesthetic-dose ketamine significantly alleviates social avoidance in a mouse model of trauma.

Acute social defeat stress (SDS) in mice leads to long-term social avoidance triggered by traumatic memories stored in specific brain cells.
Ketamine administration during the memory re-exposure time window reduces the number and activity of reactivated brain cells associated with trauma.
Manipulating dopamine pathways in the brain can either replicate or negate the effects of ketamine on social avoidance.
Single-cell RNA sequencing indicates that ketamine alters key memory-related biological pathways in the brain.

Simplified

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.

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Declaration of interests The authors declare no competing interests.

PubMed

Ketamine reduces social avoidance after trauma by removing traumatic memories in emotion-related brain cells connected to the reward system

Abstract

Full Text

Funding

Competing interests

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Abstract

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