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A single dose of ketamine enhances early life stress-induced aggression with no effect on fear memory, anxiety-like behavior, or depression-like behavior in mice

Caitlyn J Bartsch, Sophia Aaflaq, Jessica T. Jacobs, Molly Smith, Fletcher Summa, Savannah Skinner, Elana Qasem, Rylee Thompson, Zheng Li, Jacob C. Nordman

Behavioral Neuroscience June 15, 2023 DOI: 10.1037/bne0000560 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population 7–8-week-old socially isolated male mice
Intervention Ketamine
Dose 10 mg/kg
Duration Single injection 30 minutes before foot shock, assessed 7 days later
Topics Anxiety Depression Esketamine Ketamine
Key findings Ketamine selectively increases long-lasting aggression in mice exposed to foot shock but does not affect mood-related behaviors or locomotion.

Abstract

Ketamine is a dissociative anesthetic that has been shown to have antidepressant effects in humans and has been proposed as a potential treatment for mood disorders such as PTSD and aggression. However, previous studies from our lab and others have demonstrated that ketamine’s effects are highly context- and dose-dependent. In a recent study, we found that 10 mg/kg ketamine could exacerbate the effects of early life stress on excessive aggression in mice. To further investigate the effect of ketamine on moods, such as fear, anxiety, depression, and aggression, we used a mouse model of early life stress, involving chronic social isolation followed by acute traumatic stress in the form of non-contingent, unpredictable foot shock during adolescence. We find this is necessary to induce long-lasting excessive aggression in a novel environment. 7–8-week-old socially isolated mice were given IP injections of 10 mg/kg ketamine 30 minutes before being subjected to foot shock and then assessed 7 days later for changes in sociability, aggression, mobility, anxiety-like behavior, and depression-like behavior. The results show that ketamine selectively increases long-lasting aggression in mice exposed to foot shock, but does not affect mood-related behaviors or locomotion. These findings suggest that during early life stress, ketamine may exert its effects by specifically targeting aggression brain circuitry that is distinct from brain circuits responsible for non-aggressive social or emotional behaviors. Therefore, while ketamine may be a promising treatment for various mood disorders, caution should be exercised when using ketamine to treat disorders associated with early life stress.

Comparable studies

Other preclinical and animal studies on ketamine for anxiety, most cited first.

Study Year Design Participants
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats 2020 Preclinical study
Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats Wistar rats 2018 Experimental study n = 40
Repeated Dosing of Ketamine in the Forced Swim Test: Are Multiple Shots Better Than One? Rodents 2021 Review
Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Rodents 2024 Review
Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration Arc-CreERT2 × CAG-Sun1/sfGFP mice 2020 Experimental study

Citations in the library

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