BACKGROUND Isoflurane anesthesia has been shown to have a possibility of inducing a biphasic effect on dopamine release in rat striatum. The current study investigated the effect of isoflurane on the extracellular concentration of dopamine in the rat striatum pretreated by a classical antidepressant, imipramine, using in vivo microdialysis techniques. METHODS After intraperitoneal administration of 5 and 10 mg x kg(-10 of imipramine, the rats were anesthetized with 1 and 2.5% isoflurane inhalation. The control group was injected saline. Isoflurane anesthesia increased the extracellular concentration of dopamine metabolites without any change in dopamine concentration. RESULTS Under pretreatment of 5 mg x kg(-1) of imipramine, the effect of isoflurane on the change in dopamine and its metabolites was preserved. Whereas, 10 mg x kg(-1) of imipramine pretreatment induced a marked increase in the extracellular concentration of dopamine when only 1% isoflurane was applied but not with 2.5% isoflurane. In the rat administered 10 mg x kg(-1) of imipramine, anesthesia-induced increase of 3-methoxytyramine was not found. CONCLUSIONS Our previous investigation suggested that the isoflurane anesthesia has a biphasic effect on dopamine release in rat striatum under pargyline pretreatment. The same effect was shown in the rat administered imipramine. Isoflurane anesthesia might modify dopaminergic neural activity and release of neurotransmitters through different and complex ways.