Combined Nicotinic and Muscarinic Cholinergic and Serotonergic Blockade Selectively Impair Acquisition of Spatial Navigation

  • M. Riekkinen
  • P. RiekkinenJr.
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)

Abstract

Recent evidence suggests that the cholinergic and serotonergic systems interact in the brain to regulate different behavioral and physiological functions.34,40 Anatomical studies have shown that cholinergic and serotonergic interaction may occur in several brain regions.35,38 First, the interaction may occur in the basal forebrain as the basal forebrain cholinergic neurons may be directly modulated by ascending serotonergic fibers. Second, hippocampus and cortex may receive a diffuse input of fine axons (type I) from the serotonergic raphe dorsalis and another input of beaded axons (type II) from the serotonergic raphe medianus that has anatomically a restricted pattern of termination.12,37 Cholinergic fibers from the nucleus basalis and medial septum, respectively, also innervate cortex and hippocampus.35 Electrophysiological studies have revealed that hippocampal, thalamic and cortical electrical activity is regulated by cholinergic and serotonergic systems. For example, the serotonergic raphe dorsalis lesion aggravated the increase of waking immobility-related high-voltage spindles in rat neocortex induced by cholinergic nucleus basalis lesion.25 Vanderwolf 40 showed that the pharmacological blockade of both cholinergic and serotonergic function by systemic injections of scopolamine (a cholinergic antagonist) and p-chlorophenylanine (PCPA, an inhibitor of the synthesis of serotonin) abolished completely electrocortical desynchronized low voltage fast activity.

Keywords

Serotonergic System Spatial Navigation Spatial Bias Cholinergic Antagonist Impaired Acquisition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. R.T. Bartus, R.L.Dean, B. Beer, and A.S. Lippa, The cholinergic hypothesis of geriatric memory dysfunction, Science 217: 256–265 (1982).CrossRefGoogle Scholar
  2. D.M. Bowen, S.J. Allen, J.S. Benton, M.J. Goodhardt, E.A. Haan, A.M. Palmer, N.R. Sims, C.C.T. Smith, J.A. Spillane, G.K. Esira, D. Neary, J.S. Snowden, G.K. Wilcock, and A.N. Davison, Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer’s disease, J. Neurochem. 41: 266–272 (1983).PubMedCrossRefGoogle Scholar
  3. K. Wittig, The effects of pre-and posttraining application of nicotine on the 12 problems of Hebb-Williams test in the rat, Psychopharmacologia 18: 68–76 (1970).CrossRefGoogle Scholar
  4. S.B. Dunnett, J.E. Barry, and T. Robbins, The basal forebrain-cortical cholinergic system: interpreting the functional consequences of excitotoxic lesions, Trends Neurosci. 14: 494–501 (1991).PubMedCrossRefGoogle Scholar
  5. J.J. Hagan, and R.G.M. Morris, The cholinergic hypothesis of memory: a review of animal experiments, in: “Psychopharmacology of the aging nervous system. Handbook of Psychopharmacology”, L.L. Iversen, S.D Iversen, S.H. Snyder, eds., Vol. 20, pp. 237–323 (1988).Google Scholar
  6. E. Hollander, R. Mohs and K. Davies, Cholinergic approaches to the treatment of Alzheimer’s disease, Br. Med. Bull. 42: 97–100 (1986).PubMedGoogle Scholar
  7. P. Jäkälä, J. Sirviö, J. Jolkkonen, P. Riekkinen Jr., and P. Riekkinen, The effects of p-chlorophenylalanine induced serotonin synthesis inhibition and muscarinic blockade on the performance of rats in a 5-choice serial reaction time task, Behay. Brain Res. 51: 29–40 (1992).CrossRefGoogle Scholar
  8. P. Jäkalä, J. Sirviö, P. Riekkinen Jr., and P. Riekkinen, Effects of p-chloroamphetamine and methysergide on the performance of a working memory task, Pharmacol. Biochem. Behay. 44: 411–418 (1993).CrossRefGoogle Scholar
  9. E.D. Levin, S. McGurk, D. South, and L. Butcher, Effects of combined muscarinic and nicotinic blockade on choice accuracy in the radial arm maze, Behay. Neural. Biol. 51: 270–277 (1989).CrossRefGoogle Scholar
  10. E.D. Levin, J.D. Rose, S.R. McGurk, and L. Butcher, Characterization of cognitive effects of combined muscarinic and nicotinic blockade, Behay. Neural. Biol. 53: 103–113 (1990).CrossRefGoogle Scholar
  11. E.D. Levin, S.D. McGurk, and J.E. Rose, Cholinergic-dopaminergic interactions in cognitive performance, Behay. Neural. Biol. 54: 271–299 (1990).CrossRefGoogle Scholar
  12. L.A. Mamounas, C.A. Mullen, E. O’Hearn, and M.E. Mollivier, M.E. Dual serotonergic projections to the forebrain in the rat: morphologically distinct 5HT axons terminals exhibit differential vulnerability to neurotoxic amphetamine derivates, J. Comp. Neurol. 314: 558–586 (1991).PubMedCrossRefGoogle Scholar
  13. R.J. Mandel, and L.J. Thal, Physostigmine improves water maze performance following nucleus basalis magnocellularis lesions in rats, Psychopharmacology 96: 421–425 (1988).PubMedCrossRefGoogle Scholar
  14. R.C. Mohs, B.M. Davis, C.A. Johns, A.A. Mathe, B.S. Greenwald, T.B. Horvath, and K.L. Davis, Oral physostigmine treatment of patients with Alzheimer’s disPqqe, Am. J. Psychiatry 142: 28–33 (1985).PubMedGoogle Scholar
  15. W.R. Mundy, and E.T. Iwamoto, Nicotine impairs acquisition of radial arm maze performance in rats, Pharmacol. Biochem. Behay. 30: 119–122 (1988).CrossRefGoogle Scholar
  16. O.G. Nilsson, P. Brundin, and A. Björklund, Amelioration of spatial memory impairment by intrahippocampal grafts of mixed septal and raphe tissue in rats with combined cholinergic and serotonergic denervation of the forebrain, Brain Res. 515: 193–206 (1990).PubMedCrossRefGoogle Scholar
  17. K. Reinikainen, P. Riekkinen, L. Paljärvi, H. Soininen, E-L. Helkala, J. Jolkkonen, and M. Laakso, Cholinergic deficit in Alzheimer’s disease: a study based on CSF and autopsy data, Neurochem Res. 13: 135–146 (1988).PubMedCrossRefGoogle Scholar
  18. G. Richter-Levin, 2 and M. Segal, Spatial performance is severely impaired in rats with combined reduction of serotonergic and cholinergic transmission, Brain Res. 477: 404–407 (1989).PubMedCrossRefGoogle Scholar
  19. M. Riekkinen, P. Riekkinen, and P. Riekkinen Jr., Effects of combined methysergide and mecamylamine/scopolamine treatment on spatial navigation, Brain Res. 585: 322–326 (1992).PubMedCrossRefGoogle Scholar
  20. M. Riekkinen, J. Sirviö, P. Riekkinen Jr., Pharmacological consequences of combined nicotinic and serotonergic manipulations, Brain Res. 662: 139–146 (1993).CrossRefGoogle Scholar
  21. M. Riekkinen, and P. Riekkinen Jr., Effects of THA and physostigmine on spatial navigation and passive avoidance in mecamylamine+PCPA-treated rats, Exp. Neurol.,in press (1993).Google Scholar
  22. P. Riekkinen Jr., P. Jäkälä, J. Sirviö, and P. Riekkinen, The effects of increased) serotonergic and decreased cholinergic activities on spatial navigation performance in rats, Pharmacol. Biochem. Behay. 39: 25–29 (1991).CrossRefGoogle Scholar
  23. P. Riekkinen Jr., M. Riekkinen, J. Sirviö, and P. Riekkinen, Effects of concurrent nicotinic antagonist and PCPA treatments on spatial and passive avoidance learning, Brain Res. 575: 347–350 (1992).CrossRefGoogle Scholar
  24. P. Riekkinen Jr., J. Sirviö, M. Aaltonen, and P. Riekkinen. 1990. Effects of concurrent manipulations of nicotinic and muscarinic receptors on spatial learning, Pharmacol. Biochem. Behay. 37: 405–410.CrossRefGoogle Scholar
  25. P. Riekkinen Jr., J. Sirviö, R. Miettinen, and P. Riekkinen, Interaction between raphe dorsalis and nucleus basalis magnocellularis in the regulation of high-voltage spindle activity in rat neocortex, Brain Res. 526:31–36 (1990).Google Scholar
  26. P. Riekkinen Jr., J. Sirviö, and P. Riekkinen, Similar memory impairments found in medial septal-vertical diagonal band of Broca and nucleus basalis lesioned rats: are memory defects induced by nucleus basalis lesions related to the degree of non-specific subeortical cell loss, Behay. Brain Res. 37: 81–88 (1990).CrossRefGoogle Scholar
  27. P. Riekkinen Jr., J. Sirviö, A. Valjakka, R. Miettinen, and P. Riekkinen, Pharmacological consequencies of cholinergic plus serotonergic manipulations, Brain Res. 552: 23–26 (1991).PubMedCrossRefGoogle Scholar
  28. P. Riekkinen Jr., J. Sirviö, T. Ekonsalo, and P. Riekkinen, Effects of noradrenergic DSP4 lesion on the effectiveness of pilocarpine in reversing scopolamine-induced amnesia, Brain Res. Bull. 28: 919–922 (1992).PubMedCrossRefGoogle Scholar
  29. A. Sahgal, A.B. Keith, and S. Lloyd, Effects of nicotine, oxotremorine and 9-amino 1,2,3,4-tetrahydroacridine (tacrine) on matching and non-matching to position task in rats: no evidence for mnemonic enhancement, J. Psychopharmacol. 4: 210–218 (1990).PubMedCrossRefGoogle Scholar
  30. A. Sahgal, A.B. Lloyd, J.M. Kerwin, E.K. Perry, and J.A. Edwardson, Memory following cholinergie (NBM) and noradrenergic (DNAB) lesions made single or in combination: potentiation by disruption by scopolamine. Pharmacol, Biochem. Behay. 37: 597–605 (1990).CrossRefGoogle Scholar
  31. A. Sakurai, and G.L. Wenk, The interaction of acetylcholinergic and serotonergic neural systems on performance in a continuous non-matching to sample task, Brain Res. 519: 118–121 (1990).PubMedCrossRefGoogle Scholar
  32. A.C. Santucci, E. Moody, and J. Demetriades, Effects of scopolamine on memory in rats pretreated with the serotonergic depleter PCA, Soc. Neurosci. Abstr. Vol 19, Part 3, p. 1812 (1993).Google Scholar
  33. K.A. Sherman, and E. Messamore, Blood cholinesterase inhibition as a guide to the efficacy of putative therapies for Alzheimer’s dementia: Comparison of tacrine and physostigmine, in: “Current Research in Alzheimer’s Therapy: Cholinesterase Inhibitors”. E. Giacobini and R. Becker, eds., Taylor & Francis, New York.Google Scholar
  34. J. Sirviö, M. Harju, P. Riekkinen Jr., A. Haapalinna, and P.J. Riekkinen, Comparative effects of alpha-2 receptor agents and THA on the performance of adult and aged rats in the delayed non-matching to position task, Psychopharmacology 109: 127–133 (1992).PubMedCrossRefGoogle Scholar
  35. H.W.M. Steinbusch, Serotonin-immunoreactive neurons and their projections in the CNS, in: “Handbook of Chemical Neuroanatomy”, A. Björklund, T. Hökfelt, M.J. Kuhar, eds., Vol.3, Elsevier, Amsterdam, pp. 68–125 (1984).Google Scholar
  36. W.K. Summers, L.V. Majovski, G.M. Marsh, K. Tachiki, and A. Kling, Oral tetrahydroaminoacridine in a long-term treatment of senile dementia, Alzheimer type, N. Engl. J. Med. 315: 1241–1245 (1986).PubMedCrossRefGoogle Scholar
  37. I. Törk, Anatomy of the serotonergic system, in: “The Neuropharmacology of Serotonin”, P.M. Whitaker-Azmitia and S.J. Peroutka, eds. The New York Academy of Sciences: New York pp. 9–35, (1990).Google Scholar
  38. B.H. Wainer, and M.M. Mesulam, Ascending cholinergic pathways in the rat brain, in: “Brain Cholinergie systems”, M. Steriade and D. Biesold, eds, Oxford University Press, pp. 65–119 (1990).Google Scholar
  39. C.H. Vanderwolf, Near total loss of ‘learning’ and ‘memory’ as a result of combined cholinergic and serotonergic blockade in the rat, Behay. Brain Res. 23: 43–57 (1987).CrossRefGoogle Scholar
  40. C.H. Vanderwolf, G.B. Baker and C. Dickson, Serotonergic control of cerebral activity and behavior: models of dementia, in: “The Neuropharmacology of Serotonin”, P.M. Whitaker-Azmitia and S.J. Peroutka, eds., The New York Academy of Sciences: New York pp:366–383. (1990).Google Scholar
  41. C.H. Vanderwolf, C.T. Dickson, and G. Baker, Effects of p-chlorophenylalanine and scopolamine on retention of habits in rats, Pharmacol. Biochem. Behay. 35: 847–853 (1990).CrossRefGoogle Scholar
  42. I.Q. Whishaw, W.T. O’Connor, and S.B. Dunnett, Disruption of central cholinergic systems in the rat by basal forebrain lesions and atropine: Effects on feeding, sensorimotor behavior, locomotor activity and spatial navigation, Behay. Brain. Res. 17: 103–115 (1985).CrossRefGoogle Scholar
  43. P. Whitehouse, D.L. Price, R.G Struble, A.W. Clark, J.T. Coyle, and R.M. DeLong, Alzheimer’s disease and senile dementia: Loss of neurons in the basal forebrain, Science 215: 1237–1239 (1982).PubMedCrossRefGoogle Scholar
  44. P. Whitehouse, A.M. Martino, P.G. Antuano, P.R. Lowenstein, J.T. Coyle, D.L. Price, and K.J. Kellar, Nicotinic acetylcholine binding sites in Alzheimer’s disease, Brain Res. 371: 146–151 (1985).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • M. Riekkinen
    • 1
  • P. RiekkinenJr.
    • 1
  1. 1.Department of Neurology Canthia BuildingUniversity of KuopioKuopioFinland

Personalised recommendations