AbstractThe effect of cocaine (neuronal uptake inhibitor) in combination with either hydrocortisone or corticosterone (extraneuronal uptake inhibitors) on the metabolism of3H‐noradrenaline (3H‐NA) released spontaneously or by electrical‐field stimulation was studied on the isolated rabbit aorta preloaded with3H‐NA. In the spontaneous outflow3H‐O‐methylated and deaminated metabolites (3H‐OMDA) accounted for 41% of the total radioactivity whereas3H‐NA represented only 22%. Cocaine (3 × 10‐5M) + hydrocortisone (10‐4M) neither changed the spontaneous outflow of total tritium nor the distribution of the3H‐outflow on3H‐NA and its3H‐metabolites. However, cocaine (3 × 100‐5M) + corticosterone (4 × 10‐5M) enhanced the passive3H‐outflow, increased the percentage recovered as3H‐3,4‐dihydroxyphenylglycol (3H‐DOPEG), and reduced the percentage of3H‐OMDA +3H‐NMN. The effect of field‐stimulation was investigatedduringandofterstimulation at two frequencies: 3 and 10 Hz. The stimulation‐induced3H‐overflow consisted mainly of unmetabolized3H‐NA and3H‐OMDA in the sample collectedduringstimulation. The ratio between3H‐NA and3H‐OMDA was strongly dependent on the frequency of stimulation, Thus it was 1:2 at 3 Hz, but 3:1 at 10 Hz. These ratios were about the same during the poststimulation period. On the other hand, whereas the formation of3H‐DOPEG from3H‐NA releasedduringstimulation at both frequencies was small, it increased rapidly in the poststimulation sample. At 3 Hz, inhibition of neuronal and extraneuronal uptake by cocaine + steroids did not change the stimulation‐induced3H‐overflow, but the distribution on3H‐NA and3H‐metabolites was markedly altered. Thus the percentage of3H‐N A was doubled,3H‐OMDA was halved, and3H‐DOPEG was almost abolished. At 10 Hz, however, cocaine + corticosterone decreased the stimulation‐induced3H‐overflow, but did not change the proportions of3H‐NA and3H‐OMDA. Only the formation of3H‐DOPEG was markedly reduced. It is concluded that the distribution of stimulation‐induced3H‐overflow on3H‐NA and its3H‐metabolites and the effect of neuronal and extraneuronal uptake inhibition on this is strongly influenced by the frequency of stimulation. Furthermore, inhibition of both neuronal and extraneur