Intraventricular (ICV) infusion of norepinephrine (NE) produces locomotor activation in rats that is greatly potentiated by prior depletion of whole brain catecholamines by ICV injection of 6-hydroxydopamine (6OHDA). In a series of experiments, the neural substrates of this potentiated locomotor response were examined. One group of animals received ICV infusion of 6OHDA to deplete whole brain catecholamines. Other rats were pretreated with desmethylimipramine (DMI) and then received 6OHDA infusions into the nucleus accumbens (NAC) to selectively deplete dopamine (DA) from this region. One week later, all animals were tested for their locomotor response to ICV infusion of NE. Both groups of rats exhibited a greatly potentiated locomotor response to ICV NE compared to corresponding sham-lesioned animals. Both ICV and NAC 6OHDA-injected animals also exhibited a supersensitive locomotor response to the DA receptor agonist apomorphine. These results suggest that NE-induced locomotor activation in ICV 6OHDA-treated rats results from the actions of NE on supersensitive NAC DA receptors.