Combined Nicotinic and Muscarinic Cholinergic and Serotonergic Blockade Selectively Impair Acquisition of Spatial Navigation
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.
KeywordsSerotonergic System Spatial Navigation Spatial Bias Cholinergic Antagonist Impaired Acquisition
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- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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