A systematic review of ketamine's anxiolytic potential in rodent behavioral models of anxiety and PTSD.

Abstract

BACKGROUND: Ketamine, a nonselective NMDA-receptor antagonist, is an emerging therapeutic for treatment-resistant depression and could also be a promising treatment for anxiety and post-traumatic stress disorders. However, preclinical studies in these areas lack methodological standardization, limiting clinical translatability. This review evaluates ketamine's anxiolytic potential in rodents by examining outcomes among different animal models, dosages, and treatment timing. METHODS & RESULTS: A PubMed search of studies published up to July 21, 2025, identified 562 articles assessing ketamine's effects on anxiety and PTSD in rodent models. After applying inclusion and exclusion criteria, 35 studies were analyzed. Key methodological variables, model type, dosage, and timing were summarized to assess consistency and effectiveness across studies. CONCLUSION: Current research on ketamine's anxiolytic potential in rodents is limited by inconsistent methods and inadequate sex inclusion. Evidence suggests that administering 10 to 30 mg/kg intraperitoneally and waiting ≥24 h before behavioral testing procedures produces anxiolytic effects, in deficit models. Future studies should include female subjects and standardized designs to enhance clinical translatability and relevance.