ArticleAggressive behavior2022
Opposing effects of NMDA receptor antagonists on early life stress-induced aggression in mice.
Article in Aggressive behavior, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Hypothalamic representation of aggressiveness across mouse strains.Nature communications · 2026Article
- Traumatic stress recruits an excitatory orbitofrontal-amygdala pathway to drive maladaptive aggression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- NMDA receptor-dependent structural plasticity links early life stress to persistent aggression.Neurobiology of stress · 2026Review
- The Anterior BNST Is Required for Novelty-Driven Social Interaction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Hydrogen sulfide/polysulfides signaling and neuronal diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Familiarity Gates Socially Transmitted Aggression via the Medial Amygdala.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Memantine leading to physical aggression in the treatment of chronic catatonia secondary to schizophrenia: A case report.The mental health clinician · 2025Article
- Ketamine's mechanism of action with an emphasis on neuroimmune regulation: can the complement system complement ketamine's antidepressant effects?Molecular psychiatry · 2024Review
- Acute social defeat during adolescence promotes long-lasting aggression through activation of the medial amygdala.Frontiers in neuroscience · 2024Article
- 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.Behavioral neuroscience · 2023Article
- Visualizing traumatic stress-induced structural plasticity in a medial amygdala pathway using mGRASP.Frontiers in molecular neuroscience · 2023Article
- Promises and Pitfalls of NMDA Receptor Antagonists in Treating Violent Aggression.Frontiers in behavioral neuroscience · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Rates of childhood trauma are high amongst violent offenders who frequently recidivate. Few clinical options are available to treat excessive and recurring violent aggression associated with childhood trauma. Those that do exist are largely ineffective and often replete with side effects. One promising pharmacological target is the glutamate binding N-methyl- d-aspartate receptor (NMDAR). Clinically available NMDAR antagonists have proven successful in mitigating violent and aggressive behavior associated with a host of psychiatric diseases and have both immediate and long-term effects on nervous system function and behavior. This study examined the impact of three NMDAR antagonists on long-lasting aggression brought on by early-life stress: MK-801, memantine, and ketamine. We find that social isolation early in adolescence followed by acute traumatic stress in the form of noncontingent foot shock (FS) late in adolescence works in tandem to promote long-lasting excessive aggression in mice when measured 1 week later. Systemic injections of MK-801 and memantine 30 min before FS suppressed the long-lasting attack behavior induced by our early life stress induction protocol. Systemic injections of ketamine, on the other hand, significantly enhanced the long-lasting attack behavior when injected before FS. These findings indicate that MK-801, memantine, and ketamine have distinct and opposing effects on early life stress-induced aggression, suggesting these drugs may be mechanistically distinct. This study identifies memantine as a promising pharmacological treatment for aggressive behavior associated with early life stress and demonstrates the need for greater care when using glutamate receptor antagonists to treat aggression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.