Antidepressant- and Anxiolytic-Like Effects of Nutmeg Essential Oil (Myristica Fragrans Houtt.) In A Chronic Unpredictable Mild Stress-Induced Mouse Model

Abstract

Depression and anxiety are among the most prevalent psychiatric disorders worldwide, yet pharmacotherapies are associated with significant adverse effects and delay onset of action. Nutmeg oil has demonstrated central nervous system activity in preclinical models, but its efficacy in chronic stress-induced depression and anxiety remains unexplored. This study was done to evaluate the antidepressant- and anxiolytic-like effects of nutmeg essential oil (NEO) in chronic unpredictable mild stress (CUMS) mouse model. Mice were exposed to CUMS and treated with NEO at 5, 10, or 20 mg/kg , fluoxetine, or vehicle. Body weight was monitored over 14 days. Behavioral outcomes were assessed using the Elevated plus maze (EPM) open field test (OFT), splash test, light and dark box test, forced swimming test (FST) , and tail suspension test (TST).   Results demonstrated a significant dose-dependent response, with 5mg/kg identified as the most effective dose across all behavioral metrics. In the FST and TST, the 5mg/kg dose significantly reduced immobility time compared to the 10 and 20 mg/kg cohorts, showing effects comparable to the fluoxetine control. Similarly, in anxiety models (EPM, OFT, and light/dark box test) , the 5mg/kg dose effectively restored behavioral patterns closer to those of non-stressed control group, Notably, higher doses (10 and 20 mg/kg ) exhibited diminished efficacy across most parameters, including a non-monotonic, inverted U-shaped dose-response relationship. NEO reveals potent anxiolytic and antidepressant-like activities. The findings indicate that 5mg/kg is the optimal therapeutic dose in this CUMS model, while higher doses may lose efficacy, suggesting a narrow therapeutic window. These findings highlight the critical importance of dose optimization when evaluating the psychopharmacological potential of essential oils