According to the National Institute of Mental Health (NIMH, 2021), the estimated prevalence of major depressive disorder among adolescent females, is 25.2%. Currently, pharmacological treatments for adolescents are limited. Ketamine has been shown to produce rapid and robust effects in adults with major depression. The aim of this study was to investigate the potential antidepressant effects of subanesthetic doses of ketamine in the naturally depressed Wistar-Kyoto (WK) rat, while using the Wistar (WIS) strain as a control. Adolescent female rats received a single dose of ketamine at different concentrations (0.0, 5.0, or 10.0 mg/kg) and were tested at specific time intervals: 24 hours, 7 days, 14 days, and 21 days post-injection. Results showed that in the WK rats, ketamine administration led to a significant reduction in immobility time during the forced swim test, indicating improved depression-like symptoms. However, ketamine did not show notable results in other behavioral measures, including the two-bottle saccharin test, novel object recognition test, and tests measuring anxiety-like behavior (open field and light-dark tests). The WIS rats did not display any adverse effects in the two-bottle saccharin test, novel object recognition test, open field test, or light-dark test following ketamine administration. However, ketamine did induce depressive-like behavior in the forced swim test. The study's findings provide novel evidence in adolescent WK rats that a single low dose of ketamine can effectively alleviate depression and anxiety-like symptoms.