To clarify the involvement of dopaminergic neuronal systems in anxiety or fear, the present study was undertaken to elucidate the effect of an anxiogenic agent, idazoxan, a selective alpha2-adrenoceptor antagonist, on dopamine release from the rat prefrontal cortex by use of in vivo microdialysis. Systemic administration of idazoxan (0.25 mg/kg, i.p.) produced significant increases in extracellular levels of dopamine. The maximum response of the facilitatory effect of dopamine release was 241.5%, which was detected 80 min after the injection of idazoxan. Idazoxan-induced (0.25 mg/kg, i.p.) increases in dopamine release were prevented by an established anxiolytic agent, diazepam (0.5 mg/kg, i.p.) and a putative anxiolytic agent tropisetron (100 microg/kg, i.p.). These results suggest that the excessive dopaminergic neuronal activity in the rat prefrontal cortex is related to idazoxan-induced anxiogenic effects. The idazoxan-induced (0.25 mg/kg, i.p.) enhancement of dopamine release was further prevented by pretreatment with serotonin (5-hydroxytryptamine; 5-HT) neurotoxin, 5,7-dihydroxytryptamine (200 microg/kg, i.c.v.). The basal output of dopamine release was not altered in 5-HT lesioned rats. These findings indicate that intact serotonergic neurons are required for the facilitatory effects of idazoxan on dopamine release. In other words, the functional interaction between dopaminergic and serotonergic neuronal systems in the rat prefrontal cortex might be involved in anxiety or fear.