Mechanisms Underlying Pharmacologic Modifications of the Hippocampal Lesion Syndrome
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.
KeywordsNucleus Accumbens Hippocampal Lesion Cholinergic Activity Hippocampal Damage Cholinergic Cell
Unable to display preview. Download preview PDF.
- Clark CVH (1968) Ph. D. Dissertation, University of RochesterGoogle Scholar
- Dunn AJ, Kramarcy NR (1985) Neurochemical responses in stress: relationships between the hy-pothalamic-pituitary-adrenal and catecholamine systems. In: Iversen LL, Iversen SD, Synder SH (eds) Handbook of psychopharmacology, vol 18. Plenum, New YorkGoogle Scholar
- Helmy L, Bohus B, Frey ZS, Endröczi E (1970) Direct metyrapone effect on the central nervous system. Endokrinologie 57: 139–141Google Scholar
- Isaacson RL, Hannigan JH Jr (1983) The hippocampus and age-related disorders. In: Gispen WH, Traber J (eds) Aging of the brain. Elsevier, Amsterdam, p 139Google Scholar
- McGeer EG, McGeer PL (1976) Neurotransmitter metabolism in the aging brain. Neurotransmitter metabolism in the aging brain. In: Terry RD, Gerson S (eds) Neurobiology of aging, vol 3. Raven, New York, p 389Google Scholar
- Rothballer AB (1959) The effects of catecholamines on the central nervous system. Pharmacol Rev II:494–547Google Scholar
- Ryan JP, Isaacson RL (to be published) The effects of catecholaminergic enhancement on the behavior of animals with hippocampal lesionsGoogle Scholar
- Springer JE, Ryan JP, Isaacson RL (1985) Acute choline administration produces transient reductions in the effects of hippocampal destruction. (to be published )Google Scholar
- Springer JE (1984) Ph. D. Dissertation, State University of New York at BinghamtonGoogle Scholar