The effect of ATP on release of dopamine (DA) and its metabolism in the rat striatum was investigated by use of in vivo microdialysis. DA release was increased and the level of 3,4-dihydroxyphenylacetic acid (DOPAC) was decreased by treatment with 1 mM ATP or ADP for 20 min, while such treatment failed to change the extracellular level of homovanillic acid (HVA). The ATP-induced increase in DA and decrease in DOPAC were inhibited by suramin, a nonselective P-2 purinoceptor antagonist, and by reactive blue 2, a P-2Y purinoceptor antagonist, but not by xanthine amine congener, an adenosine receptor antagonist, indicating that P-2Y purinoceptors were involved in the present observation. The effects of ATP were extracellular Ca2+-dependent and sensitive to omega-conotoxin and tetrodotoxin, which indicates that the opening of voltage-sensitive calcium channels and sodium channels to depolarize the DA neuron is required for both ATP-induced DA release and DOPAC decrease in the rat striatum. Pretreatment with alpha-methyl-p-tyrosine, but not with reserpine, suppressed the ATP-induced release of DA. These findings suggest that the newly synthesized pool, but not the vesicular pool, of DA is involved in the ATP-induced release of DA in the rat striatum. (C) 1996 Elsevier Science Ltd.