Mechanisms Underlying Pharmacologic Modifications of the Hippocampal Lesion Syndrome

  • R. L. Isaacson
  • J. P. Ryan
Conference paper
Part of the Advances in Applied Neurological Sciences book series (NEUROLOGICAL, volume 2)


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.


Nucleus Accumbens Hippocampal Lesion Cholinergic Activity Hippocampal Damage Cholinergic Cell 
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  1. Adolfsson R, Gottfries CG, Ross BE (1979) Postmortem distribution of dopamine and hornovanillic acid in human brain, variations related to age and a review of the literature. J Neural Trans 45: 81–106CrossRefGoogle Scholar
  2. Bär PR, Gispen WH, Isaacson RL (1981) Behavioral and regional neurochemical sequelae of hippocampal destruction in the rat. Pharm Biochem Behav 14: 305–312CrossRefGoogle Scholar
  3. Chart JJ, Sheppard H (1959) Amphenone analogues as adrenal cortical inhibitors. J Med Pharm Chem 1: 407–441PubMedCrossRefGoogle Scholar
  4. Clark CVH (1968) Ph. D. Dissertation, University of RochesterGoogle Scholar
  5. Clark CVH (1970) Effect of hippocampal and neocortical ablation on scopolamine-induced activity in the rat. Psychopharm 17: 289–301CrossRefGoogle Scholar
  6. 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
  7. Helmy L, Bohus B, Frey ZS, Endröczi E (1970) Direct metyrapone effect on the central nervous system. Endokrinologie 57: 139–141Google Scholar
  8. Isaacson RL (1984) Hippocampal damage: effect on dopaminergic systems of the basal ganglia. Int Rev Neurobiol 25: 339–359PubMedCrossRefGoogle Scholar
  9. 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
  10. Iuvone PM, Van Hartesveldt C (1976) Locomotor activity and plasma corticosterone in rats with hippocampal lesions. Behav Biol 16: 515–520PubMedCrossRefGoogle Scholar
  11. Iuvone PM, Van Hartesveldt C (1977) Diurnal locomotor activity in rats: effects of hippocampal ablation and adrenalectomy. Behav Biol 19: 228–237PubMedCrossRefGoogle Scholar
  12. Jenkins JJ, Meakin JW, Nelson DH, Thorn GW (1958) Inhibition of adrenal steroid 11-oxygenation in the dog. Science 128: 478–479PubMedCrossRefGoogle Scholar
  13. 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
  14. Memo M, Lucchi L, Spano PF, Trabucchi M (1980) Aging process affects a single class of dopamine receptors. Brain Res 202: 488–492PubMedCrossRefGoogle Scholar
  15. Nakano I, Harano Y (1984) Parkinson’s disease: neuron loss in nucleus basalis without concomitant Alzheimer’s disease. Ann Neurol 15: 415–418PubMedCrossRefGoogle Scholar
  16. Nyakas CS, De Kloet ER, Veldhuis HD, Bohus B (1983) Hippocampal corticosterone receptors and novelty-induced behavioral activity: effect of kainic acid lesion in the hippocampus. Brain Res 288: 219–228PubMedCrossRefGoogle Scholar
  17. Reinstein DK, Hannigan JH Jr, Isaacson RL (1982) The time course of certain behavioral changes after hippocampal damage and their alteration by dopaminergic intervention into nucleus accumbens. Pharm Biochem Behav 17: 193–202CrossRefGoogle Scholar
  18. Rothballer AB (1959) The effects of catecholamines on the central nervous system. Pharmacol Rev II:494–547Google Scholar
  19. Ryan JP, Isaacson RL (to be published) The effects of catecholaminergic enhancement on the behavior of animals with hippocampal lesionsGoogle Scholar
  20. Ryan JP, Springer JE, Hannigan JH Jr, Isaacson RL (1985) Suppression of corticosterone syn-thesis alters the behavior of hippocampally lesioned rats. Behav Neural Biol 44: 47–59PubMedCrossRefGoogle Scholar
  21. Schmidt EI, Wecker L (1981) CNS effects of choline administration: evidence for temporal de-pendence. Neuropharmacology 20: 535–539PubMedCrossRefGoogle Scholar
  22. Speth RC, Yamamura H (1979) On the ability of choline and its analogues to interact with muscarinic receptors in the rat brain. Eur J Phharmacol 58: 197–201CrossRefGoogle Scholar
  23. Springer JE, Ryan JP, Isaacson RL (1985) Acute choline administration produces transient reductions in the effects of hippocampal destruction. (to be published )Google Scholar
  24. Springer JE (1984) Ph. D. Dissertation, State University of New York at BinghamtonGoogle Scholar
  25. Wecker L, Dettbarn W-D (1979) Relationship between choline availability and acetylcholine synthesis in discrete regions of rat brain. J Neurochem 32: 961–967PubMedCrossRefGoogle Scholar
  26. Wecker L, Schmidt DE (1979) Central cholinergie function: Relationship to choline administration. Life Sci 25, 375–3844CrossRefGoogle Scholar
  27. Wecker L, Dettbarn W-D, Schmidt DT (1978) Choline administration: modification of the central actions of atropine. Science 199: 86–87PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • R. L. Isaacson
  • J. P. Ryan
    • 1
  1. 1.University Center at BinghamtonBinghamtonUSA

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