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)
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 |