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The aim of this study was to determine whether propofol reduces extracellular concentrations of dopamine in the rat nucleus accumbens and, if so, whether this effect is potentiated by midazolam. Propofol and midazolam were administered intravenously, via the external jugular vein, to freely‐moving rats. The extracellular concentrations of dopamine in the nucleus accumbens were measured consecutively every 25 min by using in vivo brain microdialysis with electrochemical detection. Propofol (2.5, 5.0 and 10.0 mg/kg) decreased the accumbal dopamine concentrations in a dose‐dependent manner. The largest dose (10.0 mg/kg) decreased dopamine concentration by a maximum of 34% (P < 0.01) at its peak effect. The smallest dose of propofol (2.5 mg/kg) did not affect dopamine concentrations when given alone, but decreased concentrations by 23% (P < 0.05) when combined with a dose of midazolam (0.075 mg/kg) having only a minimal effect on dopamine concentrations. The present study demonstrates that propofol dose‐dependently reduces dopamine release in rat nucleus accumbens, and that the effect is facilitated by midazolam; a similar interaction is also seen clinically, on preoperative anxiety and on anaesthesia.