A commonly held view is that dopamine exerts its effects via binding to D1- and D2-dopaminergic receptors. However, recent data have emerged supporting the existence of a direct interaction of dopamine with adrenergic but this interaction has been poorly investigated. In this study, the pharmacological basis of possible in vivo interactions between dopamine and alpha(2)-adrenergic receptors was investigated in zebra finches. A binding competition study showed that dopamine displaces the binding of the alpha(2)-adrenergic ligand, [(3)H]RX821002, in the brain. The affinity of dopamine for the adrenergic sites does not differ between the sexes and is 10- to 28-fold lower than that for norepinephrine. To assess the anatomical distribution of this interaction, binding competitions were performed on brain slices incubated in 5nM [(3)H]RX821002 in the absence of any competitor or in the presence of norepinephrine [0.1microM] or dopamine [1microM]. Both norepinephrine and dopamine displaced the binding of the radioligand though to a different extent in most of the regions studied (e.g., area X, the lateral part of the magnocellular nucleus of anterior nidopallium, HVC, arcopallium dorsale, ventral tegmental area and substantia grisea centralis) but not in the robust nucleus of the arcopallium. Together these data provide evidence for a direct interaction between dopamine and adrenergic receptors in songbird brains albeit with regional variation.