The effect of striatal perfusion with the intestinal peptide PEC-60 on endogenous dopamine (DA) and gamma-aminobutyric acid (GABA) release in the dorsolateral striatum and GABA release in the globus pallidus was monitored using in vivo microdialysis in the halothane anaesthetized rat. The results show that PEC-60 (100 nM) increases DA release in the dorsolateral striatum without influencing GABA release in the dorsolateral striatum or in the globus pallidus. In addition, PEC-60 failed to influence the extracellular striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. The PEC-60 induced increase in striatal DA was abolished by the addition of tetrodotoxin (1 microM) to the perfusion medium. These data suggest that PEC-60 plays a role in modulating striatal DA release but not DA metabolism and that this effect is primarily targeted on the presynaptic DA terminals of the nigrostriatal DA pathway rather than on the postsynaptic striatopallidal GABA projection neurons in the dorsolateral striatum.