Behavioral Pharmacology and Biochemistry of Central Cholinergic Neurotransmission

  • Hans C. Fibiger
  • Geert Damsma
  • Jamie C. Day
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 295)


Although there is no question that muscarinic receptor antagonists such as atropine and scopolamine can have deleterious effects on the acquisition and post-acquisition performance of a broad spectrum of learned behaviors, at present there is no consensus concerning the psychological mechanisms underlying these antimuscarinic-induced deficits and it has not been possible to characterize them in a unitary theoretical framework. For reasons that are discussed below, this should not be regarded as surprising.


Cholinergic Neuron Basal Forebrain Reference Memory Cholinergic Transmission Ibotenic Acid 
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  1. Abercrombie, E.D., Keefe, K.A., DiFrischia, D.S. and Zigmond, M.J., 1989, Differential effect of stress on in vivo dopamine release in striatum, nucleus accumbens, and medial frontal cortex, J. Neurochem., 52:1655.PubMedCrossRefGoogle Scholar
  2. Abercrombie, E.D., Keller, Jr., R.W., and Zigmond, M.J., 1988, Characterization of hippocampal norephinephrine release as measured by microdialysis perfusion: pharmacological and behavioral studies, Neuroscience. 27:987.CrossRefGoogle Scholar
  3. Arbogast, R.E., and Kozlowski, M.R., 1988, Quantitative morphometric analysis of the neurotoxic effects of the excitotoxin, ibotenic acid, on the basal forebrain, Neurotoxicoloqy. 9:39.Google Scholar
  4. Bartus, R.T., Flicker, C., Dean, R.L., Pontecorvo, M., Figueriredo, J.C., and Fisher, S.K., 1985, Selective memory loss following nucleus basalis lesions: long term behavioral recovery despite persistent cholinergic deficiencies, Pharmacol. Biochem. Behav., 23:125.CrossRefGoogle Scholar
  5. Brito, G.N.O., Davis, B.J., Stopp, L.C., and Stanton, M.E., 1983, Memory and the septo-hippocampal cholinergic system in the rat,P sychopharmacoloqv, 81:315.CrossRefGoogle Scholar
  6. Brown, K., and Warburton, D.M., 1971, Attenuation of stimulus sensitivity by scopolamine, Psychonomic Sei, 22:297.Google Scholar
  7. Buresova, O., Bolhuis, J.J., and Bures, J., 1986, Differential effects of cholinergic blockade on performance of rats in the water tank navigation task and in a radial water maze, Behav. Neurosci, 100:476.Google Scholar
  8. Carlton, P.L., 1963, Cholinergic mechanisms in the control of behavior by the brain, Psychol. Rev., 70:19.PubMedCrossRefGoogle Scholar
  9. Cheal, M, 1981, Scopolamine disrupts maintanance of attention rather than memory processes, Behav. Neural Biol., 33:163.CrossRefGoogle Scholar
  10. Damsma, G., Pfaus, J.G., Nomikos, G.G., Wenkstern, D.G., Blaha, C., Phillips, A.G., and Fibiger, H.C., 1990, Sexual behavior enhances central dopamine transmission in the male rat. Brain Res. Rev, (in press).Google Scholar
  11. Damsma, G., Westerink, B.H.C., de Vries, J.B., Van Den Berg, C.J., and Horn, A.S., 1987, Measurement of acetylcholine release in freely moving rats by means of automated intracerebral dialysis, J. Neurochem, 48:1523.PubMedCrossRefGoogle Scholar
  12. Damsma, G., Westerink, B.H.C., de Boer, P., de Vries, J.B., and Horn, A.S., 1988, Basal acetylcholine release in freely moving rats detected by on-line trans-striatal dialysis: pharmacological aspects. Life Sei, 43:1161.CrossRefGoogle Scholar
  13. Day, J.C., Damsma, G., and Fibiger, H.C., 1990, Acetylcholine release in the hippocampus, cortex and striatum of rats correlates with locomotor activity: an in vivo microdialysis study. Submitted.Google Scholar
  14. Dubois, B., Mayo, W., Agid, Y., LeMoal, M., and Simon, H., 1985, Profound disturbances of spontaneous and learned behaviors following lesions of the nucleus basalis magnocellularis in the rat. Brain Res., 338:249.PubMedCrossRefGoogle Scholar
  15. Dunnett, S. B., Low, W.C., Iversen, S.D., Stenevi, U., and Bjorklund, A., 1982, Septal transplants restore maze learning in rats with fornix-fimbria lesions. Brain Res, 251:335.PubMedCrossRefGoogle Scholar
  16. Dunnett, S.B., 1985, Comparative effects of cholinergic drugs and lesions of nucleus basalis or fimbria-fornix on delayed matching in rats, Psvchopharmacoloay, 87:357.CrossRefGoogle Scholar
  17. Dunnett, S.B., Toniolo, G., Fine, A., Ryan, C.N., Bjorklund, A., and Iversen, S.D., 1985, Transplantation of embryonic ventral forebrain neurons to the neocortex of rats with lesions of nucleus basalis magnocellularis. II. Sensorimotor and learning impairments, Neuroscience, 16:787.PubMedCrossRefGoogle Scholar
  18. Dunnett, S.B., Whishaw, I.Q., Jones, G.H., and Bunch, S.T., 1987, Behavioural, biochemical and histochemical effects of different neurotoxic amino acids injected into nucleus basalis magnocellularis of rats, Neuroscience, 20:653.PubMedCrossRefGoogle Scholar
  19. Dunnett, S.B., Rogers, D.C., and Jones, G.H., 1989, Effects of nucleus basalis magnocellularis lesions in rats on delayed matching and non-matching to position tasks, Eur. J. Neurosci.1:395.PubMedCrossRefGoogle Scholar
  20. Eckerman, D.A., Gordon, W.A., Edwards, J.D., MacPhail, R.C., Gage, M.I., 1988, Effects of scopolamine, pentobarbital, and amphetamine on radial arm maze performance in the rat, Pharmacol. Biochem. Behav., 12:595.CrossRefGoogle Scholar
  21. Ellen, P., Taylor, H.S., and Wages, C., 1986, Cholinergic blockade effects on spatial integration versus cue discrimination performance, Behav. Neurosci, 100:720.Google Scholar
  22. Etherington, R., Mittleman, G., and Robbins, T.W., 1987, Comparative effects of nucleus basalis and fimbria-fornix lesions on delayed matching and alternative tests of memory, Neurosci. Res. Commun., 1:135.Google Scholar
  23. Everitt, B.J., Robbins, T.W., Evenden, J.L., Marston, H.M., Jones, G.H., and Sirkia, T.E., 1987, The effects of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on the acquisition and retention of a conditional visual discrimination: implications for cholinergic hypotheses of learning and memory, Neuroscience, 22:441.PubMedCrossRefGoogle Scholar
  24. Fine, A., Dunnett, S.B., Bjorklund, A., and Iversen, S.D., 1985, Cholinergic ventral forebrain grafts into the neocortex improve passive avoidance memory in a rat model of Alzheimer disease, Proc. Natl. Acad. Sei. USA, 82:5227.CrossRefGoogle Scholar
  25. Flicker, C., Ferris, S.F., Bartus, R.T., and Crook, T., 1984, Effects of aging and dementia upon recent visuospatial memory, J. Neurobiol. Aging, 5:75.Google Scholar
  26. Hagan, J.J., Tweedie, F., and Morris, R.G.M., 1986, Lack of task specificity and absence of posttraining effects of atropine on learning, Behav. Neurosci, 100:483.Google Scholar
  27. Harvey, J.A., Gormezano, I., and Cool-Hauser, V.A., 1983, Effects of scopolamine and methylscopolamine on classical conditioning of the rabbit nictitating membrane response, J. Pharmacol. Exp. Ther, 225:42.PubMedGoogle Scholar
  28. Heise, G.A., Conner, R., and Martin, R.A, 1976, Effects of scopolamine on variable intertrial interval spatial alternation and memory in the rat, Psychopharmacology, 49:131.PubMedCrossRefGoogle Scholar
  29. Hepler, D.J., Olton, D.S., Wenk, G.L., and Coyle, J.T., 1985a, Lesions in nucleus basalis magnocellularis and medial septal area of rats produce qualitatively similar memory impairments, J. Neurosci, 5:866.PubMedGoogle Scholar
  30. Hepler, D.J., Wenk, G.L., Cribbs, B.L., Olton, D.S., and Coyle, J.T., 1985b, Memory impairments following basal forebrain lesions. Brain Res, 346:8.PubMedCrossRefGoogle Scholar
  31. Imperato, A., and Di Chiara, G., 1984, Trans-striatal dialysis coupled to reverse phase high performance liquid chromatography with electrochemical detection: a new method for the study of the in vivorelease of endogenous dopamine and metabolites, J. Neurosci, 4:966.PubMedGoogle Scholar
  32. Johnson, R.D., and Justice, J.B., 1983, Model studies for brain dialysis. Brain Res. Bull., 10:567.PubMedCrossRefGoogle Scholar
  33. Kirk, R.C., White, K.G., and McNaughton, N., 1988, Low dose scopolamine affects discriminability but not rate of forgetting in delayed conditional discrimination, Psychopharmacology, 96:541.PubMedCrossRefGoogle Scholar
  34. Knowlton, B.J., Wenk, G.L., Olton, D.S., and Coyle, J.T., 1985, Basal forebrain lesions produce a dissociation of trial-dependent and trial-independent memory performance. Brain Res345:315.PubMedCrossRefGoogle Scholar
  35. Levy, A., Kant, G.J., Meyerhoff, J.L., and Jarrard, L.E., 1984, Non-cholinergic neurotoxic effects of AF64A in the substantia nigra. Brain Res, 305:169.PubMedCrossRefGoogle Scholar
  36. Low, W.C., Lewis, P.R., Bunch, S.T., Dunnett, S.B., Thomas, S.R., Iversen, S.D., Bjorklund, A., and Stenevi, U., 1982, Function recovery following neural transplantation of embryonic septal nuclei in adult rats with septo- hippocampal lesions, Nature, 300:260.PubMedCrossRefGoogle Scholar
  37. Mash, D.C., and Potter, L.T., 1986, Autoradiographic localization of Ml and M2 muscarine receptors in the rat brain, Neuroscience, 19:551.PubMedCrossRefGoogle Scholar
  38. McGurk, S.R., Hartgraves, S.L., Kelly, P.H., Gordon, M.N., and Butcher, L.L., 1987, Is ethylcholine mustard aziridinium ion a specific cholinergic neurotoxin?, Neuroscience, 22:215.PubMedCrossRefGoogle Scholar
  39. Miyamoto, M. Kato, J., Narumi, S., and Nagaoka, A., 1987, Characteristics of memory impairment following lesioning of the basal forebrain and medical septal nucleus in rats. Brain Res., 419:19.PubMedCrossRefGoogle Scholar
  40. Murray, C.L., and Fibiger, H.C., 1985, Learning and memory deficits after lesions of the nucleus basalis magno- cellularis: reversal by physostigmine, Neuroscience, 14:1025.PubMedCrossRefGoogle Scholar
  41. Murray, C.L., and Fibiger, H.C., 1986, Piolcarpine and physostigmine attenuate spatial memory impairments produced by lesions of the nucleus basalis magnocellularis, Behav. Neurosci., 100:23.PubMedCrossRefGoogle Scholar
  42. Myers, R.D., 1971, Methods for chemical stimulation of the brain in “Methods in Psychobiology, Vol. 1,”: R.D. Myers, ed.. Academic Press, New York, p. 247.Google Scholar
  43. Nilsson, O.G., Kalen, P., Rosengren, E., and Bjorklund, A., 1990, Acetylcholine release in the rat hippocampus as studied by microdialysis is dependent on axonal impulse flow and increases during behavioural activation, Neuroscience, (in press).Google Scholar
  44. Okaichi, H., and Jarrard, L.E., 1982, Scopolamine impairs performance of a place and cue task in rats, Behav. Neural Biol, 35:319.CrossRefGoogle Scholar
  45. Peternel, A., Haughey, D., Wenk, G., and Olton, D., 1988, Basal forebrain and memory: neurotoxic lesions impair serial reversals of a spatial discrimination, Psychobiology, 16:54.Google Scholar
  46. Radhakishun, F.S., Van Ree, M., and Westernik, B.H.C., 1988, Scheduled eating increases dopamine release in the nucleus accumbens of food-deprived rats as assessed with on-line brain dialysis, Neurosci. Lett., 85:351.PubMedCrossRefGoogle Scholar
  47. Robbins, T.W., Everitt, B.J., Ryan, C.N., Marston, Marston, H. M. Jones, G.H., and Page, K.J., 1989, Comparative effects of quisqualic and ibotenic acid-induced lesions of the substantia innominata and globus pallidus on the acquisition of a conditional visual discrimination: differential effects on cholinergic mechanisms, Neuroscience, 28:337.PubMedCrossRefGoogle Scholar
  48. Rotter, A., Birdsall, N.J.M., Burgen, A.S.V., Field, P.M., Hulme, E.C., and Raisman, G., 1979a, Muscarinic receptors in the central nervous system of the rat. I. Technique for autoradiographic localization of the binding of [3H]propylbenzilylcholine mustard and its distribution in the forebrain, Brain Res. Rev., 1:141.CrossRefGoogle Scholar
  49. Rotter, A., Birdsall, N.J.M., Burgen, A.S.V., Field, P.M., Hulme, E.G., Raisman, G., 1979b. Muscarinic receptors in the central nervous system of the rat. II. Distribution of binding of [3H]propylbenzilylcholine mustard in the midbrain and hindbrain. Brain Res. Rev.. 1:167.CrossRefGoogle Scholar
  50. Satoh, K., Armstrong, D.M., and Fibiger, H.C., 1983, A comparison of the distribution of central cholinergic neurons as demonstrated by acetylcholinesterase pharmaco- histochemistry and choline acetyltransferase immunohistochemistry. Brain Res. Bull., 11:693.PubMedCrossRefGoogle Scholar
  51. Schwaber, J.S., Rogers, W.T., Satoh, K., and Fibiger, H.C., 1987, Distribution and organization of cholinergic neurons in the rat forebrain demonstrated by computer-aided data acquisition and three-dimensional reconstruction, J. Comp. Neurol, 263:309.PubMedCrossRefGoogle Scholar
  52. Semba, K., and Fibiger, H.C., 1989, Organization of central cholinergic systems, Proa. Brain Res., 79:37.CrossRefGoogle Scholar
  53. Spencer, Jr., D.G., and Lai, H., 1987, Effects ofGoogle Scholar
  54. anticholinergic drugs on learning and memory. Drug Development Res., 3:489–502, (1987).Google Scholar
  55. Spencer, Jr., D.G. Pontecorvo, M.J., and Heise, G.A., 1985, Central cholinergic involvement in working memory: effects of scopolamine on continuous nonmatching and discrimination performance in the rat, Behav. Neurosci., 99:1049.PubMedCrossRefGoogle Scholar
  56. Sutherland, R.J., Whishaw, I.Q., and Regehr, J.C., 1982, Cholinergic receptor blockade impairs spatial localization by use of distal cues in the rat, J. Comp. Physiol. Psvchol, 96:563.CrossRefGoogle Scholar
  57. Toide, K., 1989, Effects of scopolamine on extracellular acetylcholine and choline levels and on spontaneous motor activity in freely moving rats measured by brain dialysis, Pharmacol. Biochem. Behav., 33:109.CrossRefGoogle Scholar
  58. Ungerstedt, U, 1984, Measurement of neurotransitter release by intracranial dialysis, “Measurement of Neurotransmitter Release In Vivo,”C.A. Marsden, ed., John Wiley & Sons Ltd., New York, pp. 81.Google Scholar
  59. Wagman, W.D., and Maxey, G.C., 1969, The effects of scopolamine hydrobromide and methyl scopolamine hydrobromide upon the discrimination of interoceptive and exteroceptive stimuli, Psychopharmacologia, 15:280.PubMedCrossRefGoogle Scholar
  60. Warburton, D. M., and Brown, K., 1971, Attenuation of stimulus sensitivity induced by scopolamine. Nature, 230:126.PubMedCrossRefGoogle Scholar
  61. Watanabe, H., and Shimizu, H., 1989, Effect of anticholinergic drugs on striatal acetylcholine release and motor activity in freely moving rats studied by brain microdialysis, Jpn. J. Pharmacol., 51:75.Google Scholar
  62. Watts, J., Stevens, R., and Robinson, C., 1981, Effects of scopolamine on radial maze performance in rats, Phvsiol. Behav., 26:845.CrossRefGoogle Scholar
  63. Wenk, G.L., Markowski, A.L., and Olton, D.S., 1989, Basal forebrain lesions and memory: alterations in neurotensin, not acetylcholine, may cause amnesia, Behav. Neurosci., 103:1624.Google Scholar
  64. Westerink, B.H.C., Damsma, G., Rollema, H., De Vries, J.B., and Horn, A.S., 1987, Scope and limitations of in vivo brain dialysis: a comparison of its application to various neurotransmitter systems, Life Sei, 41:1763.CrossRefGoogle Scholar
  65. Whishaw, I.Q., and Petrie, B.F., 1988, Cholinergic blockade in the rat impairs strategy selection but not learning and retention of nonspatial visual discrimination problems in a swimming pool, Behav. Neurosci, 102:662.Google Scholar
  66. Wirsching, B.A., Beninger, R.J., Jhamandas, K., Boegman, R.J., and El-Defrawy, S.R., 1984, Differential effects of scopolamine on working and reference memory of rats in the radial maze, Pharmacol. Biochem. Behav. 20:659.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Hans C. Fibiger
    • 1
  • Geert Damsma
    • 1
  • Jamie C. Day
    • 1
  1. 1.Division of Neurological Sciences, Department of PsychiatryUniversity of British ColumbiaVancouverCanada

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