Noradrenergic hyperactivity in hippocampus after partial denervation: pharmacological, behavioral, and electrophysiological studies.

Abstract

Previous studies have shown that, in addition to partial damage to the cholinergic system, partial fornix section causes changes in the noradrenergic (NA) system and an increase in NA activity in the dorsal hippocampus. Behaviorally, this NA hyperactivity contributes to the deficits observed in the radial arm maze, since a reduction of NA activity restores the performance of rats with a partial fornix lesion. The reorganization of the NA system after partial fornix section should modify its responsiveness, and the present series of experiments examines these changes. In the first experiment, sensitivity to the sedative effects of the alpha 2 agonist clonidine was evaluated by determining a dose-response curve to clonidine in a hole board. Rats with partial fornix lesion were resistant to the sedative effects of clonidine, suggesting differences in alpha 2-receptor sensitivity. In the second experiments, rats were submitted to a test for novelty-seeking behavior in the hole board with objects placed in some holes. Rats with fornix sections spent more time in contact with novel objects than the control rats, a behavior which has previously been observed in hyper-noradrenergic animals. Finally, single-unit recording of locus coeruleus (LC) cells in anesthetized rats showed there were no effects of the partial fornix lesion either on spontaneous firing rate of LC cells or on their responsiveness to clonidine. These last results suggest that the behavioral differences and differences in NA activity observed after partial denervation are a result of local regulation of release at the NA terminals and are not due to changes in the cell bodies within the LC.