Antidepressant and Anxiolytic Effects of Geraniol in Mice: The Possible Role of Oxidative Stress and Apoptosis

Background: Depression is a severe mental disorder. Current antidepressants are effective in only one-half to one-third of the patients. Besides, these medications might bring about adverse effects. Therefore, the need for newer anti-depressant medications or complementary compounds is utterly felt. Objectives: We tested the hypothesis that geraniol (GE) attenuates anxiety and depression via the amelioration of oxidative stress and apoptosis in mice. Methods: In an experimental study, thirty-six BALB/c mice were randomly divided into three control, chronic restraint stress (CRS), and GE groups. CRS and GE groups underwent CRS for two weeks. Accordingly, the CRS group received normal saline (2 mL/kg, i.p.) whereas the GE group received GE (50 mg/kg, i.p.). The behavioral outcomes were assessed using the open-field test (OFT), elevated plus maze (EPM), and tail suspension test (TST). Moreover, superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-px) activity, total antioxidant capacity (TAC), and reactive oxidative species (ROS) levels in the brain were assessed using the spectrophotometric method. The brain's BAX, Bcl-2, and caspase-3 levels were measured using Western blotting. Results: CRS increased anxiety in stressed mice compared to the control group as indicated by OFT and EPM (P < 0.01 for both comparisons). Furthermore, CRS increased the immobility time in TST compared to control animals (P < 0.001). Biochemically, CRS decreased SOD activity (P < 0.01), GSH-px activity (P < 0.01), TAC level (P < 0.001), and ROS level (P < 0.001). It also increased the BAX/Bcl-2 ratio (P < 0.001) and caspase-3 level (P < 0.001) compared to the control group. GE reversed all the behavioral and biochemical changes in stressed mice compared to the CRS group. Conclusions: GE renders potent anxiolytic and antidepressant effects possibly through the modulation of oxidative stress and apoptosis in the mouse brain.