The pharmacology of the neurotensin response of dopamine-sensitive neurons in the substantia nigra compacta was examined by testing the effect of a novel neurotensin receptor antagonist, SR48692, on the response to neurotensin(8-13). Extracellular recordings of action potentials from neurons were made from coronal rat brain slices maintained in vitro. SR48692 was unable to antagonise the actions of neurotensin(8-13) until microM concentrations were applied. The equilibrium constant for SR48692 was 4.9 microM compared with low nM Ki values reported in binding experiments. The data suggests that the pharmacology of the neurotensin response in the rat substantia nigra may be different to that predicted from radioligand-binding studies in cell lines and brain homogenates.