Effect of Cholinergic Enhancers on Basal Forebrain Function Governing Cortical Cerebral Blood Flow

  • Joanna L. Raszkiewicz
  • James P. Sullivan
  • Stephen P. Arneric
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)


Among the losses of brain functions in Alzheimers disease (AD) are reductions in cerebral blood flow (CBF), decrements in cerebral glucose utilization and abnormal electrocorticograms (Dastur, 1985; Petit et al., 1983). Topographically, these impaired brain functions correspond to the loss of the cholinergic innervation to the cortex and hippocampus arising out of the basal forebrain (BF) (Bartus et al., 1982).


Mean Arterial Pressure Basal Forebrain Neuronal Nicotinic Acetylcholine Receptor Cortical Perfusion Cerebral Blood Flow Response 
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  1. Apud, J.A., 1993, The 5-HT, receptor in mammalian brain, A new target for the development of psychotropic drugs? Neuropsychopharmacology 8: 117.PubMedCrossRefGoogle Scholar
  2. Americ, S.P., 1989, Cortical cerebral blood flow is modulated by cholinergic basal forebrain neurons: effects of ibotinic acid lesions and electrical stimulation, in: “Neurotransmission and Cerebrovascular Function”, J. Seylaz and E.T. Mackenzie, eds., Vol. 1, Excerpts Medica International Congress Series, 381–384.Google Scholar
  3. Arneric, S.P., and Williams, M., 1993, Nicotinic agonist in Alzheimer’s Disease: Does the molecular diversity of nicotine receptors offer the opportunity for developing CNS selective cholinergie channel activators? in: “Recent Advances in the Treatment of Neurodegenerative Disorders and Cognitive Function’, G. Racagni, N. Brunello, S.Z. Langer, eds., Capri, Italy.Google Scholar
  4. Aubert, I., Araujo, D.M., Cecyre, D., Robitaille, Y., Gauthier, S., and Quirion, R., 1992, Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer’s and Parkinson’s diseases, J. Neurochem. 58: 529–541.PubMedCrossRefGoogle Scholar
  5. Barnes, J.M., Barnes, N.M., Costall, B., Naylor, R.J., and Tyers, M.B., 1989, 5-HT, receptors mediates inhibition of acetylcholine release in cortical tissue, Nature 338: 762–763.Google Scholar
  6. Barnes, J.M., Costall, B., Coughlan, J., Doweney, A.M., Gerrard, P.A., Kelly, M.E., Naylor, R.J., Onaivi, E.S., Tomkins, D.M., and Tyers, M.B, 1990, The effects of ondansetron, a 5-HT, receptor antagonist, on cognition in rodents and primates, Pharmacol. Biochem. Behay. 35: 955–962.CrossRefGoogle Scholar
  7. Bartus, R.T., Dean, R.L., III, Beer, B., Lipps, A.S., 1982, The cholinergic hypothesis of geriatric memory dysfunction, Science 217: 408.PubMedCrossRefGoogle Scholar
  8. Benowitz, N.L., 1992, Nicotine and coronary heart disease, Trends Cardiovasc. Med. 1: 315–321.CrossRefGoogle Scholar
  9. Briggs, C.A., Sullivan, J.P., Decker, M.W., Brioni, J.D., Raszkiewicz, J.L., Hughes, M., Buckley, M.J., and Arneric, S.P., 1994, (+)2-Methylpiperidine: An Allosteric Modulator of Neuronal NicotinicGoogle Scholar
  10. Acetylcholine Receptor Function, J. Pharmacol. Exp. Therap. (In Preparation). Cook, L., Nickolson, V.J., Steinfels, G.F., Rohrbach, K.W., and DeNoble, V.J., 1990, Cognition enhancement by the acetylcholine releaser DuP 99, Drug Devel. Res. 19:301–314.Google Scholar
  11. Dastur, D.K., 1985, Cerebral blood flow and metabolism in normal human aging, pathological aging and senile dementia, J. Cerebral Blood Flow & Metabol. 5: 1.CrossRefGoogle Scholar
  12. Dauphin, F., Lacombe, P., Sercombe, R., Hamel, E. and Seylaz, J., 1991, Hypercapnia and stimulation of the substantia innominata increase rat frontal cortical blood flow by different cholinergic mechanisms, Brain Res. 553: 75.PubMedCrossRefGoogle Scholar
  13. Decker, M.W., and McGaugh, J.L., 1991, The role of interactions between the cholinergic system and other neuromodulatory systems in learning and memory, Synapse 7: 151–168.PubMedCrossRefGoogle Scholar
  14. Decker, M.W., Majchrzak, M.J., and Arneric, S.P., 1993, Effects of lobeline, a nicotinic receptor agonist, on learning and memory, Pharm. Biochem and Behay ., 45: 571CrossRefGoogle Scholar
  15. Dent, G.W., Rule, B.L., Tam, W.S., and DeSouza, E.B., 1993, Effects of the memory enhancer linopiridine (DuP 996) on cerebral glucose metabolism in naive and hypoxia-exposed rats, Brain Res. 620: 7.PubMedCrossRefGoogle Scholar
  16. Gitelman D.R., and Prohovnik, I., 1992, Muscarinic and nicotinic contributions to cognitive function and cortical blood flow, Neurobiol. Aging 13: 313–318.PubMedCrossRefGoogle Scholar
  17. Kilpatrick, G.J., Jones, B.J., and Tyers, M.B., 1988, The distribution of specific binding of the 5-HT3 receptor ligand [3H] GR65630 in rat brain using quantitative autoradiography, Neurosci. Lett. 94: 156–160.PubMedCrossRefGoogle Scholar
  18. Kimura, A., Sato, A., Takano, Y., 1990, Stimulation of the nucleus basalis of Meynert does not influence glucose utilization of the cerebral cortex in anesthetized rats, Neurosci. Lett. 119: 109.Google Scholar
  19. Levin, E.D., 1992, Nicotinic systems in cognitive function, Psychopharmacology 108: 417–431.PubMedCrossRefGoogle Scholar
  20. Linville, D.G., Williams, S., Raszkiewicz, J.L., and Arneric, S.P., 1993, Nicotinic agonists modulate basalGoogle Scholar
  21. forebrain control of cortical cerebral blood flow in anesthetized rats, J. Pharm. Exp. Ther. 267:4.40–448. Linville, D.G., and Arneric, S.P., 1991, Cortical cerebral blood flow governed by the basal forebrain: agerelated impairments, Neurobiol. Aging 12:503–510.Google Scholar
  22. Marchi, M., Raiteri, M., 1984, On the presence in the cerebral cortex of muscarinic receptor subtypes that differ in neuronal localization, function and pharmcological properties, J. Pharm. Exp. Ther. 235: 230.Google Scholar
  23. Nickolson, V.G., Tam, S.W., Myers, M.J., Cook, L., 1990, DuP 996 [3,3-bis[4-pyrindinylmethyl]-1phenylindoline-2–1-one] enhances the stimulus-induced release of acetylcholine from rat brain in vitro and in vivo, Drug Dev. Res. 19: 285.CrossRefGoogle Scholar
  24. Petit, D., Lorrain, D., Gauthier, S., Montplaisir, J., 1993, Regional spectral analysis of the REM sleep EEG in mild to moderate Alzheimer’s disease, Neurobiol. Aging 14: 141.PubMedCrossRefGoogle Scholar
  25. Pomponi, M., Giacobini, E., Brufani, M., 1990, Present state and future development of the therapy of Alzheimer’s disease, Neurobiol. Aging 2: 125.Google Scholar
  26. Raszkiewicz, J.L., Linville, D.G., Kerwin, J.F., Jr., Wagenaar, F., and Arneric, S.P., 1992, Nitric oxide synthase is critical in mediating basal forebrain regulation of cortical cerebral circulation, J. Neurosci. Res. 33: 129–135.PubMedCrossRefGoogle Scholar
  27. Risberg, J., Gustafson, L., and Brun, A., 1990, High resolution regional cerebral blood flow measurements in Alzheimer’s disease and other dementia disorders in Alzheimer’s Disease, in: “Epidemiology, Neuropathology, Neurochemistry, and Clinics”, L. Maurer, P. Riederer, H. Beckmann, eds., Springer-Verlag, Berlin 509–516.CrossRefGoogle Scholar
  28. Sargent, P.B., 1993, The diversity of neuronal nicotinic acetylcholine receptors, Ann. Rev. Neurosci. 16: 403–443.PubMedCrossRefGoogle Scholar
  29. Sloan, J.W., Martin, W.R., Hook, R., Bostwick, M., Howell, A., Smith, W.T., 1985, Stereospecificity of 2-methylpiperidine binding to a nicotinic up-regulatory site in the rat brain P2 preparation, Life Sci. 37: 1367.PubMedCrossRefGoogle Scholar
  30. Soldatos, C.R., Kales, J.D., Scharf, M.B., Bixler, E.O., and Kales, A., 1980, Cigarette smoking associated with sleep difficulty, Science 207: 551–553.PubMedCrossRefGoogle Scholar
  31. Sunderland, T., Tariot, P.N., and Newhouse, P.A., 1988, Differential responsivity of mood, behavior andGoogle Scholar
  32. cognition to cholinergic agonists in elderly neuropsychiatric populations, Brain Res. Rev. 13:371–389.Google Scholar
  33. White, A., Corn, T.H., Feetman, C., and Faulconbridge, C., 1991, Ondansetron in treatment of schizophrenia, Lancet 337: 1173.Google Scholar
  34. Wonnacott, S., Irons, J. Rapier, C., Thorne, B., and Lnt, G.G., 1990, Presynaptic modulation of transmitter release by nicotinic receptors, in: “Progress in Brain Research’, Amsterdam: Elsevier, pp. 157–163.Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Joanna L. Raszkiewicz
    • 1
  • James P. Sullivan
    • 1
  • Stephen P. Arneric
    • 1
  1. 1.Neuroscience ResearchAbbott LaboratoriesUSA

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