Spatial learning deficits in the aged rat: neuroanatomical and neurochemical correlates

To assess neurochemical and neuroanatomical correlates of age and spatial learning, aged Sprague-Dawley male rats (20-22 mo) were divided into two groups based on their ability to locate a hidden platform in a Morris water maze. An "old good" group of rats acquired the task as rapidly as young (3-6 mo) animals, whereas an "old poor" group of rats failed to show improvement on subsequent testing days. Age-related changes included (a) a significant decrease in the number of choline acetyltransferase (CHAT) immunoreactive cells in the ventral cell group of the septal complex (28%); (b) a decrease in caudate dopamine levels (-11%); and (c) an increase in 5-HIAA levels in the n. accumbens (+25%) and hippocampus (+18%). Spatial learning related changes in aged rats included: (a) an increase in medial frontal cortex 5-HIAA levels (52%) in the old good learners but not old poor learners with (b) a decrease in medial frontal cortex dopamine levels (-24%) only in the old poor learners group and (c) a decrease in n. accumbens DOPAC (-22%) and HVA (-23%) in the old good learners group only. The present study demonstrates age-related but not spatial learning related decrease in CHAT immunoreactive cells in the ventral cell group of the septal complex. Therefore, either the cholinergic cell loss in the septum is unrelated to the acquisition of spatial learning measured by the Morris water maze, or it is a permissive effect along with specific alterations in forebrain dopaminergic and serotonergic systems, particularly in the medial frontal cortex and n. accumbens. The above findings are consistent with findings seen in Alzheimer's disease where both basal forebrain cholinergic nuclei and cortical projecting brainstem monoamine systems are affected.