We have previously reported that halothane anesthesia increases extracellular concentrations of dopamine (DA) metabolites in rat striatum using in vivo microdialysis techniques. Aging induces many changes in the brain, including neurotransmission. However, the relationship between aging and changes in neurotransmitter release during inhalational anesthesia has not been fully investigated. The aim of the present investigation was to evaluate the effect of sevoflurane on methamphetamine (MAPT)-induced DA release and metabolism in young and middle-aged rats. Male Sprague-Dawley rats were implanted with a microdialysis probe into the right striatum. The probe was perfused with a modified Ringer's solution and 40μl of dialysate was directly injected to an HPLC every 20min. Rats were administered saline, the same volume of 2mgkg(-1) MAPT intraperitoneally, or 5μM MAPT locally perfused. After treatments, the rats were anesthetized with 1% or 3% sevoflurane for 1h. Sevoflurane anesthesia significantly increased the extracellular concentration of DA only in middle-aged rats (52-weeks-old). In young rats (8-weeks-old), sevoflurane significantly enhanced MAPT-induced DA when administered both intraperitoneally and perfused locally, whereas no significant additive interaction was found in middle-aged rats. These results suggest that aging changes DA release and metabolism in rat brains primarily by decreasing the DA transporter.