Scopolamine-disruption of radial arm maze performance: modification by noradrenergic depletion

Administration of muscarinic cholinergic antagonists impairs performance on a variety of memory tasks. We examined the hypothesis that denervation of norepinephrine input to the forebrain would augment this effect of cholinergic antagonists. Administration of 6-hydroxydopamine into the dorsal noradrenergic bundle did not by itself alter the performance of rats on a radial maze working memory task. In Experiment 1, scopolamine, a muscarinic antagonist, impaired the performance of the NE-depleted animals more than that of animals in an operated control group. This result was again observed in Experiment 2; but here a lesion by order of dose administration interaction provided evidence for recovery from the effects of NE-depletion. In Experiment 3, it was found that NE denervation did not alter the functional status of basal forebrain cholinergic neurons as reflected in in vitro determination of sodium-dependent, high affinity choline uptake in hippocampus and cortex. These results suggest that an age-related decline in brain NE neurons, as well as further deterioration in this system in some cases of Alzheimer's disease, may contribute to the cognitive and memory deficits more typically ascribed to cholinergic dysfunction.