The aim of this study is to evaluate the dose‑dependent effect of bee venom (BV) on behavioral functions in rats and the physiological role of leptin in the prefrontal cortex, hippocampus, and amygdala tissues. Adult Sprague‑Dawley male rats were used in the experiments. The rats were divided into three groups of control, 0.1 mg/kg BV, and 0.5 mg/kg BV. The rats were injected with BV subcutaneously for 15 consecutive days. The open field test (OFT), the elevated plus maze test (EPM), and the forced swimming test (FST) were performed as behavioral assessments. Animals were sacrificed, and brain regions were removed. Leptin levels were measured in various brain regions by ELISA. In the OFT, the total distance and speed for the 0.1 mg/kg BV group increased compared to controls and the 0.5 mg/kg BV group. In the EPM, the 0.1 mg/kg BV group remained in the open arm for a significantly longer period of time compared to the other groups. In the FST, the 0.5 mg/kg BV group was more mobile than the other groups. Leptin levels in the prefrontal cortex were significantly higher in the 0.1 mg/kg BV group compared to the control and 0.5 mg/kg groups. There were no significant differences between groups in hippocampus and amygdala leptin levels. The results of the study show that BV has a positive effect on behavioral parameters. BV may have a positive effect on anxiety‑ and depression‑like behaviors by increasing leptin levels in the prefrontal cortex.
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