The effects of norepinephrine (NE) on in vitro [3H]glycogenolysis were assessed in slices of cerebral cortex from mice whose cortical noradrenergic innervation had been severely reduced by intracisternal 6-hydroxydopamine (6-OHDA) injections. A supersensitive response to NE was observed, as demonstrated by a decrease in the EC50 of the catecholamine in the lesioned mice from 533 +/- 88 nM to 39.3 +/- 7.9 nM. This supersensitive response, observed two weeks after the lesion, was post-synaptic since isoproterenol, a beta-adrenergic agonist not accumulated by pre-synaptic uptake mechanisms, also gave an equally supersensitive response.