ANTICHOLINERGIC SENSITIVITY IN THE AGING RAT SEPTOHIPPOCAMPAL SYSTEM AS ASSESSED IN A SPATIAL MEMORY TASK

The effects of central cholinergic blockade on spatial memory were tes ted in aged and basal forebrain-lesioned rats using the Morris Water M aze. In Experiment 1, aged rats (18-21 months old) were characterized as behaviorally impaired or nonimpaired based on water maze performanc e prior to an atropine sulfate challenge. In the atropine test (50 mg/ kg, IP), both the impaired and the nonimpaired rats showed a severe di sruption of their search behavior compared to young subjects. This eff ect was due to blockade of central receptors since peripheral choliner gic blockade using atropine methylbromide did not produce any impairme nts. Experiment 2 investigated effects of atropine on rats with septal lesions (SL), nucleus basalis lesions (NBL), and rats with both lesio ns combined (SL + NBL). Before drug treatment, the groups with septal lesions (SL and SL + NBL groups) displayed a moderate impairment in lo cating the platform site. However, similar to the aged rats, the septa l-lesioned rats exhibited severe impairments in the water maze during atropine treatment. This effect was not seen in the normal controls or in the NBL rats. Aged rats, either impaired or nonimpaired in a spati al memory task, showed a pronounced sensitivity to pharmacological blo ckade of central cholinergic neurotransmission which resulted in sever e deficits in spatial navigation in the water maze. Since the same beh avioral deficit was produced by cholinergic blockade in young rats wit h septal lesions, we concluded that the impaired water maze performanc e seen in the aged rats during cholinergic blockade resulted from impa ired function in the septohippocampal system.