Mechanisms Underlying Pharmacologic Modifications of the Hippocampal Lesion Syndrome

Abstract

In the volume arising from the first Tropon Conference 2 years ago, Hannigan and I noted that many people interpret the unfortunate mental and behavioral effects of aging as reflecting alterations in the functions of the hippocampal system (Isaacson and Hannigan 1983). In fact, there are many similarities between animals with hippocampal damage and symptoms of senility. The view that the animal with hippocampal damage is a reasonable model for Alzheimer’s disease would find even greater endorsement if the interface between the hippocampal systems and the ascending dopaminergic systems at the basal ganglia level that, in turn, modulate the forebrain cholinergic systems were included. Indeed, reductions of dopamine and the enzymes necessary for its synthesis are correlated with advancing age (Adolfsson et al. 1979; McGeer and McGeer 1976). It has been proposed that aging is correlated with a reduction in a particular type of dopamine receptor (D1) at least in animals (Memo et al. 1980). Moreover, recent evidence indicates that Alzheimer’s disease may not be entirely due to cell loss in the nucleus basalis, at least for patients with Parkinson’s disease (Nakano and Hirano 1984). It is possible that losses of these cholinergic cells must be coupled with other structural and functional alterations before senile dementia of the Alzheimer type (SDAT) occurs.