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Nicotinic System Involvement in Alzheimer’s and Parkinson’s Diseases

Implications for Therapeutics

  • Review Article
  • Clinical Pharmacology
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Summary

Advances in our understanding of the structure, function and distribution of nicotinic acetylcholine receptors in the CNS have provided the impetus for new studies examining the role(s) that these receptors and associated processes may play in CNS functions. Further motivation has come from the realisation that such receptors must be involved in the maintenance of cigarette smoking, and from clues provided by studies of degenerative neurological diseases such as Alzheimer’s disease and Parkinson’s disease, in which the loss of nicotinic receptors has been described.

Ongoing investigations of the molecular substructure of central nicotinic receptors and their pharmacology have begun to open up new possibilities for novel CNS therapeutics with nicotinic agents. Exploiting these possibilities will require understanding of the role(s) that these receptor systems play in human cognitive, behavioural, motor and sensory functioning. Clues from careful studies of human cognition are beginning to emerge and will provide direction for studies of potentially therapeutic novel nicotinic agents.

Despite the promising results of acute studies, few long term studies with nicotine or nicotinic drugs have been performed in dementing disorders. Thus, there is uncertainty as to whether long term nicotinic treatment will provide sustained cognitive benefit. It is even more uncertain whether such cognitive benefit will have a significant clinical impact on patients and their families. To maximise the potential benefit of long term treatment with nicotinic agonists (or other cholinergic drugs), we suggest that drug treatment should be combined with cognitive rehabilitation strategies. This will enable patients and/or their families to focus on the particular cognitive domains that may be improved.

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References

  1. Arneri SP, Anderson D, Bannon A, et al. Preclinical pharmacology of ABT-418: a prototypical cholinergic channel activator for the potential treatment of Alzheimer’s disease. CNS Drugs Rev 1995; 1: 1–26

    Google Scholar 

  2. Changeux JP, Galzi JL, Devilliers-Thiery A, et al. The functional architecture of the acetylcholine nicotinic receptor explored by affinity labeling and site-directed mutagenesis. Q Rev Biophys 1992; 25: 395–432

    PubMed  CAS  Google Scholar 

  3. Elgoyen AB, Johnson D, Boulter J, et al. Cloning and functional expression of α9: a novel acetylcholine-gated ion channel [abstract]. In: Clarke PBS, Quik M, Thurau K, et al., editors. International symposium on nicotine: the effects of nicotine on biological systems: II. Basel: Birkhaüser Verlag, 1994: 7

    Google Scholar 

  4. Seguela P, Wadiche J, Dineley-Miller K, et al. Molecular cloning, functional properties, and distribution of rat brain α7: a nicotinic cation channel highly permeable to calcium. J Neurosci 1994; 13: 596–604

    Google Scholar 

  5. Luetje CW, Patrick J. Both α and β-subunits contribute to the agonist sensitivity of neuronal nicotinic receptors. J Neurosci 1991; 11: 837–45

    PubMed  CAS  Google Scholar 

  6. Anand R, Lindstrom J. Nucleotide sequence of the human nicotinic acetylcholine receptor β 2 subunit. Nucleic Acids Res 1990; 18: 4272–8

    PubMed  CAS  Google Scholar 

  7. Chini B, Clementi F, Hukovic N, et al. Neuronal type α-bungarotoxin receptors and the α5-nicotinic receptor subunit gene are expressed in neuronal and nonneuronal human cell lines. Proc Natl Acad Sci U S A 1992; 89: 1572–6

    PubMed  CAS  Google Scholar 

  8. Doucette-Stamm L, Monteggia L, Donnelly-Roberts D, et al. Cloning and sequence of the human α7 nicotinic acetylcholine receptor. Drug Dev Res 1993; 30: 252–6

    CAS  Google Scholar 

  9. Elliott KJ, Ellis SB, Berckhan KJ, et al. Comparative structure of human neuronal 2–7 and 2–4 nicotinic acetylcholine receptor subunits and functional expression of the 2, 3, 4, 7, 2 and 4 subunits. J Mol Neurosci 1996; 7: 217–28

    PubMed  CAS  Google Scholar 

  10. Decker MW, Brioni JD, Bannon AW, et al. Diversity of neuronal nicotinic acetylcholine receptors: lessons from behavior and implications for CNS therapeutics. Life Sci 1995; 56: 545–70

    PubMed  CAS  Google Scholar 

  11. Alkondon M, Albuquerque EX. Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons: I. Pharmacological and functional evidence for distinct structural subtypes. J Pharmacol Exp Ther 1993; 265: 1455–73

    PubMed  CAS  Google Scholar 

  12. Clarke PBS, Schwartz RD, Paul SM, et al. Nicotinic binding in rat brain: autoradiographic comparison of [3H]-acetylcholine, [3H]-nicotine and [125I]-α-bungarotoxin. J Neurosci 1985; 5: 1307–15

    PubMed  CAS  Google Scholar 

  13. Martin BR, Martin TJ, Fan F, et al. Central actions of nicotine antagonists. Med Chem Res 1993; 2: 564–77

    CAS  Google Scholar 

  14. Lena C, Changeux JP. Allosteric modulations of the nicotinic acetylcholine receptor. Trends Neurosci 1993; 16: 181–6

    PubMed  CAS  Google Scholar 

  15. Pereira EFR, Reinhardt-Maelicke S, Schrattenholz A, et al. Identification and functional characterization of a new agonist site on nicotinic acetylcholine receptors of cultured hippocampal neurons. J Pharmacol Exp Ther 1993; 265: 1474–91

    PubMed  CAS  Google Scholar 

  16. Arneri SP, Sullivan JP, Williams M. Neuronal nicotinic receptors: novel targets for central nervous system therapeutics. In: Bloom F, Kupfer D, editors. Psychopharmacology: the fourth generation of progress. New York: Raven Press, 1995: 95–110

    Google Scholar 

  17. Badio B, Daly JW. Epibatidine, a potent analgesic and nicotinic agonist. Mol Pharmacol 1994; 45: 563–9

    PubMed  CAS  Google Scholar 

  18. Meyer EM, de Fiebre CM, Hunter BE, et al. Effects of anabaseine-related analogs on rat brain nicotinic receptor binding and on avoidance behaviors. Drug Dev Res 1994; 31: 127–34

    CAS  Google Scholar 

  19. Arneri SP, Sullivan JP, Decker MW, et al. ABT-418: a novel cholinergic channel activator (ChCA) for the potential treatment of Alzheimer’s disease. Neuropsychopharmacology 1994; 10 (3 Suppl.): 395S

    Google Scholar 

  20. Lipiello PM, Bencherif M, Gray JA, et al. RJR-2403: a nicotinic agonist with CNS selectivity: II. In vivo characterization. J Pharmacol Exp Ther 1996; 279: 1422–9

    Google Scholar 

  21. Menzaghi F, Whelan KT, Risbrough VB, et al. Interactions between a novel cholinergic ion channel agonist SIB-1765F and L-DOPA in the reserpine model of Parkinson’s disease in rats. J Pharmacol Exp Ther 1997; 280: 393–401

    PubMed  CAS  Google Scholar 

  22. Menzaghi F, Whelan KT, Risbrough VB, et al. Effects of a novel cholinergic ion channel agonist SIB-1765F on locomotor activity in rats. J Pharmacol Exp Ther 1997; 280: 384–92

    PubMed  CAS  Google Scholar 

  23. Cosford ND, Bleicher L, Herbaut A, et al. (S)-(−)-5-ethynyl-3-(l-methyl-2-pyrrolidinyl) pyridine maleate (SIB-1508Y): a novel antiparkinsonian agent with selectivity for neuronal nicotinic acetylcholine receptors. J Med Chem 1996; 39: 3235–7

    PubMed  CAS  Google Scholar 

  24. Wonnacott S, Irons J, Rapier C, et al. Presynaptic modulation of transmitter release by nicotinic receptors. In: Nordberg A, Fuxe K, Holmstedt B, et al., editors. Progress in brain research. Amsterdam: Elsevier, 1990: 157–63

    Google Scholar 

  25. Araujo DM, Lapchak PA, Collier B, et al. Characterization of N-[3H]methylcarbamylcholine binding sites and the effect of N-methylcarbamylcholine on acetylcholine release in rat brain. J Neurochem 1988; 51: 292–9

    PubMed  CAS  Google Scholar 

  26. De Sarno P, Giacobini E. Modulation of acetylcholine release by nicotinic receptors in the rat brain. J Neurosci Res 1989; 22: 194–200

    PubMed  Google Scholar 

  27. Rowell PP, Winkler DL. Nicotinic stimulation of [3H]acetyl-choline release from mouse cerebral cortical synaptosomes. J Neurochem 1984; 43: 1593–8

    PubMed  CAS  Google Scholar 

  28. Quirion R, Richard J, Wilson A. Muscarinic and nicotinic modulation of cortical acetylcholine release monitored by in vivo microdialysis in freely moving rats. Synapse 1994; 17: 92–100

    PubMed  CAS  Google Scholar 

  29. Marchi M, Raiteri M. Nicotinic autoreceptors mediating enhancement of acetylcholine release become operative in conditions of ‘impaired’ cholinergic presynaptic function. J Neurochem 1996; 67: 1974–81

    PubMed  CAS  Google Scholar 

  30. Itoh A, Nitta A, Nadai M, et al. Dysfunction of cholinergic and dopaminergic neuronal systems in β-amyloid protein-infused rats. J Neurochem 1996; 66: 1113–7

    PubMed  CAS  Google Scholar 

  31. McGehee DS, Heath MJ, Gelber S, et al. Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. Science 1995; 269: 1692–6

    PubMed  CAS  Google Scholar 

  32. Levin ED, Torry D, Christopher NC, et al. Is binding to nicotinic acetylcholine and dopamine receptors related to working memory in rats? Brain Res Bull. In press

  33. Linville DG, Arneri SP. Cortical cerebral blood flow governed by the basal forebrain: age related impairments. Neurobiol Aging 1991; 12: 503–10

    PubMed  CAS  Google Scholar 

  34. Linville DG, Williams S, Arneri SP. Basal forebrain control of cortical cerebral blood flow is independent of local cortical neurons. Brain Res 1993; 622: 26–34

    PubMed  CAS  Google Scholar 

  35. London E, Fanelli RJ, Kimes A, et al. Effects of chronic nicotine on cerebral glucose utilization in the rat. Brain Res 1990; 520: 208–14

    PubMed  CAS  Google Scholar 

  36. Wesnes K, Warburton DM. Smoking, nicotine and human performance. Pharmacol Ther 1982; 21: 189–208

    Google Scholar 

  37. McCormick DA. Cellular mechanism of cholinergic control of neocortical and thalamic neuronal excitability. In: Steriade M, Biesold D, editors. Brain cholinergic systems. New York: Oxford University Press, 1990: 236–64

    Google Scholar 

  38. Levin E. Nicotinic systems and cognitive function. Psychopharmacol 1992; 108: 417–31

    CAS  Google Scholar 

  39. Jackson WJ, Elrod K, Buccafusco JJ. Delayed matching-tosample in monkeys as a model for learning and memory deficits: role of brain nicotinic receptors. In: Meyer EM, Simpkins JW, Yamamoto J, editors. Novel approaches to the treatment of Alzheimer’s disease. New York: Plenum Publishing Corporation, 1989: 39–52

    Google Scholar 

  40. Decker MW, Majchrzak MJ, Arneric SP Effects of lobeline, a nicotinic receptor agonist, on learning and memory. Pharmacol Biochem Behav 1993; 45: 571–6

    PubMed  CAS  Google Scholar 

  41. Levin ED, Rose JE, Abood L. Effects of nicotinic dimethyl-aminoethyl esters on working memory performance of rats in the radial-arm maze. Pharmacol Biochem Behav 1995; 51: 369–73

    PubMed  CAS  Google Scholar 

  42. Decker MW, Brioni JD, Sullivan JP, et al. ABT 418: a novel cholinergic ligand with cognition enhancing and anxiolytic activities: II. In vivo characterization. J Pharmacol Exp Ther 1994; 270: 319–28

    PubMed  CAS  Google Scholar 

  43. Woodruff-Pak DS, Li YT, Kern WR. A nicotinic agonist (GTS-21), eyeblink classical conditioning, and nicotinic receptor binding in rabbit brain. Brain Res 1994; 645: 309–17

    PubMed  CAS  Google Scholar 

  44. Dunnett SB, Martel FL. Proactive interference effects on short-term memory in rats: 1. Basic parameters and drug effects. Behav Neurosci 1990; 104: 655–65

    PubMed  CAS  Google Scholar 

  45. Levin ED, Rose JE. Nicotinic and muscarinic interactions and choice accuracy in the radial-arm maze. Brain Res Bull 1991; 27: 125–8

    PubMed  CAS  Google Scholar 

  46. Terry AV, Buccafusco JJ, Jackson WJ. Scopolamine reversal of nicotine enhanced delayed matching-to-sample performance in monkeys. Pharmacol Biochem Behav 1993; 45: 925–9

    PubMed  CAS  Google Scholar 

  47. Levin ED, Briggs SJ, Christopher NC. Chronic nicotinic stimulation and blockade effects on working memory. Behav Pharmacol 1993; 4: 179–82

    PubMed  CAS  Google Scholar 

  48. Levin ED, Lee C, Rose JE, et al. Chronic nicotine and withdrawal effects on radial-arm maze performance in rats. Behav Neural Biol 1990; 53: 269–76

    PubMed  CAS  Google Scholar 

  49. Levin E, Rose JE. Anticholinergic sensitivity following chronic nicotine administration as measured by radial-arm maze performance in rats. Behav Pharmacol 1990; 1: 511–20

    PubMed  Google Scholar 

  50. Levin ED, Rose JE. Acute and chronic nicotinic interactions with dopamine systems and working memory performance. In: Lajtha A, Abood L, editors. Functional diversity of interacting receptors. New York: New York Academy of Sciences, 1995: 218–21

    Google Scholar 

  51. Levin ED, Torry D. Nicotine effects on memory performance. In: Clarke PBS, Quik M, Thurau K, et al., editors. International symposium on nicotine: the effects of nicotine on biological systems: II. Basel: Birkhauser Verlag, 1995: 329–36

    Google Scholar 

  52. Levin ED, Torry D. Acute and chronic nicotine effects on working memory in aged rats. Psychopharmacology 1996; 123: 88–97

    PubMed  CAS  Google Scholar 

  53. Levin ED, Briggs SJ, Christopher NC, et al. Persistence of chronic nicotine-induced cognitive facilitation. Behav Neural Biol 1992; 58: 152–8

    PubMed  CAS  Google Scholar 

  54. Andrews JS, Jansen JHM, Linders S, et al. Effects of disrupting the cholinergic system on short-term spatial memory in rats. Psychopharmacology 1994; 115: 485–94

    PubMed  CAS  Google Scholar 

  55. Levin E, Castonguay M, Ellison GD. Effects of the nicotinic receptor blocker, mecamylamine, on radial arm maze performance in rats. Behav Neural Biol 1987; 48: 206–12

    PubMed  CAS  Google Scholar 

  56. Moran PM. Differential effects of scopolamine and mecamylamine on working and reference memory in the rat. Pharmacol Biochem Behav 1993; 45: 533–8

    PubMed  CAS  Google Scholar 

  57. Oliverio A. Effects of mecamylamine on avoidance conditioning and maze learning of mice. J Pharmacol Exp Ther 1996; 154: 350–6

    Google Scholar 

  58. Riekkinen PJ, Sirviö J, Aaltonen M, et al. Effects of concurrent manipulations of nicotinic and muscarinic receptors on spatial and passive avoidance learning. Pharmacol Biochem Behav 1990; 37: 405–10

    PubMed  CAS  Google Scholar 

  59. Brucato FH, Levin ED, Rose JE, et al. Intercerebroventricular nicotine and mecamylamine alters radial-arm maze performance in rats. Drug Dev Res 1994; 31: 18–23

    CAS  Google Scholar 

  60. Decker MW, Majchrzak MJ. Effects of systemic and intracerebroventricular administration of mecamylamine, a nicotine cholinergic antagonist, on spatial memory in rats. Psychopharmacology 1992; 107: 530–4

    PubMed  CAS  Google Scholar 

  61. Curzon P, Brioni JD, Decker MW. Effect of intraventricular injections of dihydro-beta-erythroidine (DHBE) on spatial memory in the rat. Brain Res 1996; 714: 185–91

    PubMed  CAS  Google Scholar 

  62. Levin ED, Christopher NC, Briggs SJ, et al. Chronic nicotine reverses working memory deficits caused by lesions of the fimbria or medial basalocortical projection. Cognit Brain Res 1993; 1: 137–43

    CAS  Google Scholar 

  63. Decker MW, Majchrzak MJ, Anderson DJ. Effects of nicotine on spatial memory deficits in rats with septal lesions. Brain Res 1992; 572: 281–5

    PubMed  CAS  Google Scholar 

  64. Decker MW, Curzon P, Brioni JD, et al. Effects of ABT-418, a novel cholinergic channel ligand, on place learning in septallesioned rats. Eur J Pharmacol 1994; 261: 217–22

    PubMed  CAS  Google Scholar 

  65. Grigoryan G, Hodges H, Mitchell S, et al. 6-OHDA lesions of the nucleus accumbens accentuate memory deficits in animals with lesions to the forebrain cholinergic projection system: effects of nicotine administration on learning and memory in the water maze. Neurobiol Learn Memory 1996; 65: 135–53

    CAS  Google Scholar 

  66. Grigoryan GA, Mitchell SN, Hodges H, et al. Are the cognitive-enhancing effects of nicotine in the rat with lesions to the forebrain cholinergic projection system mediated by an interaction with the noradrenergic system? Pharmacol Biochem Behav 1994; 49: 511–21

    PubMed  CAS  Google Scholar 

  67. Muir JL, Everitt BJ, Robbins TW. Reversal of visual attentional dysfunction following lesions of the cholinergic basal forebrain by physostigmine and nicotine but not by the 5-HT3 receptor antagonist, ondansetron. Psychopharmacology 1995; 118: 82–92

    PubMed  CAS  Google Scholar 

  68. Ridley RM, Murray TK, Johnson JA, et al. Learning impairment following lesion of basal nucleus of Meynert in the marmoset: modification by cholinergic drugs. Brain Res 1986; 376: 108–16

    PubMed  CAS  Google Scholar 

  69. Nitta A, Katono Y, Itoh A, et al. Nicotine reverses scopolamine-induced impairment of performance in passive avoidance task in rats through its action on the dopaminergic neuronal system. Pharmacol Biochem Behav 1994; 49: 807–12

    PubMed  CAS  Google Scholar 

  70. Hiramatsu M, Satoh H, Kameyama T, et al. Nootropic effect of nicotine on carbon monoxide (CO)-induced delayed amnesia in mice. Psychopharmacology 1994; 116: 33–9

    PubMed  CAS  Google Scholar 

  71. Arendash GW, Sanberg PR, Sengstock GJ. Nicotine enhances the learning and memory of aged rats. Pharmacol Biochem Behav 1995; 52: 517–23

    PubMed  CAS  Google Scholar 

  72. Socci DJ, Sanberg PR, Arendash GW. Nicotine enhances Morris water maze performance of young and aged rats. Neurobiol Aging 1995; 16: 857–60

    PubMed  CAS  Google Scholar 

  73. Widzowski DV, Cregan E, Bialobok P. Effects of nicotinic agonists and antagonists on spatial working memory in normal adult and aged rats. Drug Dev Res 1994; 31: 24–31

    CAS  Google Scholar 

  74. Meguro K, Yamaguchi S, Arai H, et al. Nicotine improves cognitive disturbance in senescence-accelerated mice. Pharmacol Biochem Behav 1994; 49: 769–72

    PubMed  CAS  Google Scholar 

  75. Buccafusco JJ, Jackson WJ. Beneficial effects of nicotine administered prior to a delayed matching-to-sample task in young and aged monkeys. Neurobiol Aging 1991; 12: 233–8

    PubMed  CAS  Google Scholar 

  76. Arendash GW, Sengstock GJ, Sanberg PR, et al. Improved learning and memory in aged rats with chronic administration of the nicotinic receptor agonist GTS-21. Brain Res 1995; 674: 252–9

    PubMed  CAS  Google Scholar 

  77. Buccafusco JJ, Jackson WJ, Terry AV, et al. Improvement in performance of a delayed matching-to-sample task by monkeys following ABT-418: a novel cholinergic channel activator for memory enhancement. Psychopharmacology 1995; 120: 256–66

    PubMed  CAS  Google Scholar 

  78. Newhouse PA, Potter A, Corwin J, et al. Age-related effects of the nicotinic antagonist mecamylamine on cognition and behavior. Neuropsychopharmacology 1994; 10: 93–107

    PubMed  CAS  Google Scholar 

  79. Levin E, McGurk SR, Rose JE, et al. Cholinergic-dopaminergic interactions in cognitive performance. Behav Neural Biol 1990; 54: 271–99

    PubMed  CAS  Google Scholar 

  80. Levin E, McGurk SR, Rose JE, et al. Reversal of a mecamyl-amine-induced cognitive deficit with the D2 agonist, LY 171555. Pharmacol Biochem Behav 1992; 33: 919–22

    Google Scholar 

  81. Grady S, Marks MJ, Wonnacott S, et al. Characterization of nicotinic receptor mediated [3H]dopamine release from synaptosomes prepared from mouse striatum. J Neurochem 1992; 59: 848–56

    PubMed  CAS  Google Scholar 

  82. Levin ED. Chronic haloperidol administration does not block acute nicotine-induced improvements in radial-arm maze performance in the rat. Pharmacol Biochem Behav. In press

  83. Levin ED, Christopher NC, Briggs SJ. Chronic nicotinic agonist and antagonist effects on T-maze alternation. Physiol Behav. In press

  84. Levin ED, Wilson W, Rose JE, et al. Nicotine-haloperidol interactions and cognitive performance in schizophrenics. Neuropsychopharmacology 1996; 15: 429–36

    PubMed  CAS  Google Scholar 

  85. Spillich GJ, June L, Renner J. Cigarette smoking and cognitive performance. Br J Addict 1992; 87: 1313–26

    Google Scholar 

  86. Heishman SJ, Taylor RC, Henningfield JE. Nicotine and smoking: a review of effects on human performance. Exp Clin Psychopharmacol 1994; 2: 345–95

    CAS  Google Scholar 

  87. Snyder FR, Henningfield JE. Effects of nicotine administration following 12 hours of tobacco deprivation: assessment on computerized performance tasks. Psychopharmacology 1989; 97: 17–22

    PubMed  CAS  Google Scholar 

  88. Provost SC, Woodward R. Effects of nicotine gum on repeated administration of the Stroop test. Psychopharmacology 1991; 104: 536–40

    PubMed  CAS  Google Scholar 

  89. Le Houezec J, Halliday R, Benowitz NL, et al. A low dose of nicotine improves information processing in non-smokers. Psychopharmacology 1994; 114: 628–34

    PubMed  Google Scholar 

  90. Rusted J, Graupner L, O’Connell N, et al. Does nicotine improve cognitive function? Psychopharmacology 1994; 115: 547–9

    PubMed  CAS  Google Scholar 

  91. Wesnes K, Revell A. The separate and combined effects of scopolamine and nicotine on human information processing. Psychopharmacology 1984; 84: 5–11

    PubMed  CAS  Google Scholar 

  92. Newhouse PA, Penetar D, Fertig J. Stimulant drug effects after prolonged total sleep deprivation: a comparison of amphetamine, nicotine, and deprenyl. Mil Psychol 1992; 4: 207–34

    Google Scholar 

  93. Selkoe DJ. Alzheimer’s disease: genotypes, phenotypes, and treatments. Science 1997; 275: 630–1

    PubMed  CAS  Google Scholar 

  94. Drachman D, Leavitt J. Human memory and the cholinergic system. Arch Neurol 1974; 30: 113–21

    PubMed  CAS  Google Scholar 

  95. Bartus R, Dean R, Beer B, et al. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982; 217: 408–17

    PubMed  CAS  Google Scholar 

  96. Corkin S. Acetylcholine, aging, and Alzheimer’s disease: implications of treatment. Trends Neurosci 1981; 4: 287–90

    CAS  Google Scholar 

  97. Whitehouse PJ, Price DL, Struble RG, et al. Alzheimer’s disease and senile dementia — loss of neurons in the basal fore-brain. Science 1982; 215: 1237–9

    PubMed  CAS  Google Scholar 

  98. Peterson R. Scopolamine-induced learning failures in man. Psychopharmacology 1977; 52: 283–9

    Google Scholar 

  99. Sitaram N, Weingartner H, Gillin J. Human serial learning: enhancement with arecholine and choline and impairment with scopolamine. Science 1978; 201: 274–6

    PubMed  CAS  Google Scholar 

  100. Caine E, Weingartner H, Ludlow DL, et al. Qualitative analysis of scopolamine-induced amnesia. Psychopharmacology 1981; 74: 74–80

    PubMed  CAS  Google Scholar 

  101. Ghoneim M, Mewaldt S. Studies on human memory: the interactions of diazepam, scopolamine and physostigmine. Psychopharmacology 1977; 52: 1–6

    PubMed  CAS  Google Scholar 

  102. Sunderland T, Tariot P, Weingartner H, et al. Pharmacologic modelling of Alzheimer’s disease. Prog Neuropsycho-pharmacol Biol Psychiatry 1986; 10: 599–610

    CAS  Google Scholar 

  103. Newhouse PA, Sunderland T, Tariot PN. The effects of acute scopolamine in geriatric depression. Arch Gen Psychiatry 1988; 45: 906–12

    PubMed  CAS  Google Scholar 

  104. Beatty WW, Butters N, Janowsky D. Patterns of memory failure after scopolamine treatment: implications for the cholinergic hypothesis of dementia. Behav Neural Biol 1986; 45: 196–211

    PubMed  CAS  Google Scholar 

  105. Grober E, Leipzig R, Lipton R, et al. Scopolamine does not produce genuine memory deficits [abstract]. Alzheimer Dis Assoc Disord 1988; 2: 169

    Google Scholar 

  106. Dunne MP, Hartley LR. The effects of scopolamine upon verbal memory: evidence for an attentional hypothesis. Acta Psychol (Amst) 1985; 58: 205–17

    CAS  Google Scholar 

  107. Callaway E, Halliday R, Naylor H, et al. Effects of oral scopolamine on human stimulus evaluation. Psychopharmacology 1985; 85: 133–8

    PubMed  CAS  Google Scholar 

  108. Rogers SL, Friedhoff LT, Donepezil Study Group. The efficacy and safety of donepezil in Alzheimer’s disease: results of a multicentre, randomized, double-blind, placebo-controlled trial. Dementia 1996; 7: 293–303

    PubMed  CAS  Google Scholar 

  109. Tariot P, Cohen R, Welkowitz J, et al. Multiple dose arecoline infusions in Alzheimer’s disease. Arch Gen Psychiatry 1988; 45: 901–5

    PubMed  CAS  Google Scholar 

  110. Bruno G, Mohr E, Gillespie M, et al. Muscarinic agonist therapy of Alzheimer’s disease. Arch Neurol 1986; 43: 659–61

    PubMed  CAS  Google Scholar 

  111. James JR, Nordberg A. Genetic and environmental aspects of the role of nicotinic receptors in neurodegenerative disorders: emphasis on Alzheimer’s disease and Parkinson’s disease. Behav Genet 1995; 25: 149–59

    PubMed  CAS  Google Scholar 

  112. Nordberg A. Human nicotinic receptors — their role in aging and dementia. Neurochem Int 1994; 25: 93–7

    PubMed  CAS  Google Scholar 

  113. Whitehouse P, Martino A, Antuono P, et al. Nicotinic acetylcholine binding sites in Alzheimer’s disease. Brain Res 1986; 371: 146–51

    PubMed  CAS  Google Scholar 

  114. Flynn D, Mash D. Characterization of 1-[3H]nicotine binding in human cerebral cortex: comparison between Alzheimer’s disease and the normal. J Neurochem 1986; 47: 1948–54

    PubMed  CAS  Google Scholar 

  115. Aubert I, Araujo DM, Cécyre D, et al. Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer’s and Parkinson’s diseases. J Neurochem 1992; 58: 529–41

    PubMed  CAS  Google Scholar 

  116. Warpman U, Nordberg A. Epibatidine and ABT 418 reveal selective losses of oc4β2 nicotinic receptors in Alzheimer’s brains. Neuroreport 1995; 6: 2419–23

    PubMed  CAS  Google Scholar 

  117. Perry EK, Court JA, Lloyd S, et al. β-Amyloidosis in normal aging and transmitter signaling in the human temporal lobe. Ann N Y Acad Sci 1996; 777: 388–92

    PubMed  CAS  Google Scholar 

  118. Perry EK, Morris CM, Court JA, et al. Alteration in nicotinic binding sites in Parkinson’s disease, Lewy body dementia, and Alzheimer’s disease: possible index of early neuropathology. Neuroscience 1995; 64: 385–95

    PubMed  CAS  Google Scholar 

  119. Wesnes K, Warburton D. Smoking, nicotine, and human performance. Pharmacol Ther 1983; 21: 189–208

    PubMed  CAS  Google Scholar 

  120. Wesnes K, Warburton D. Effects of scopolamine and nicotine on human performance. Psychopharmacology 1985; 82: 147–50

    Google Scholar 

  121. Myrsten A, Post B, Frankenhaeuser M, et al. Changes in behavioral and physiological activation induced by cigarette smoking in habitual smokers. Psychopharmacology (Berl) 1972; 76: 232–5

    Google Scholar 

  122. Newhouse PA, Sunderland T, Tariot PN, et al. Intravenous nicotine in Alzheimer’s disease: a pilot study. Psychopharmacology 1988; 95: 171–5

    PubMed  CAS  Google Scholar 

  123. Fuld P, Katzman R, Davies P, et al. Intrusions as a sign of Alzheimerdementia: chemical and pathological verification. Ann Neurol 1982; 11: 155–9

    PubMed  CAS  Google Scholar 

  124. Ksir C, Benson D. Enhanced behavioral response to nicotine in an animal model of Alzheimer’s disease. Psychopharmacology 1983; 81: 272–3

    PubMed  CAS  Google Scholar 

  125. Gray R, Rajan AS, Radcliffe KA, et al. Hippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature 1996; 383: 713–6

    PubMed  CAS  Google Scholar 

  126. Prohovnik I, Mayeux R, Sackheim HA, et al. Cerebral profusion as a diagnostic marker of early Alzheimer’s disease. Neurology 1988; 38: 931–7

    PubMed  CAS  Google Scholar 

  127. Gitelman DR, Prohovnik I. Muscarinic and nicotinic contributions to cognitive function and cortical blood flow. Neurobiol Aging 1992; 13: 313–8

    PubMed  CAS  Google Scholar 

  128. Arneri SP. Basal forebrain neurons modulate cortical cerebral blood flow: increases by nicotinic cholinergic mechanisms [abstract]. J Cereb Blood Flow Metab 1989; 9 Suppl. 1: S502

    Google Scholar 

  129. Nordberg A. In vivo detection of neurotransmitter changes in Alzheimer’s disease. Ann N Y Acad Sci 1993; 695: 27–33

    PubMed  CAS  Google Scholar 

  130. Nordberg A, Lundqvist H, Hartvig P, et al. Kinetic analysis of regional (S) (−) 11C-nicotine binding in normal and Alzheimer brains — in vivo assessment using positron emission tomography. Alzheimer Dis Assoc Disord 1995; 9: 21–7

    PubMed  CAS  Google Scholar 

  131. Nordberg A. Effect of long-term treatment with tacrine (THA) in Alzheimer’s disease as visualized with PET. Acta Neurol Scand 1993; 149 Suppl.: 62–5

    CAS  Google Scholar 

  132. Lee PN. Smoking and Alzheimer’s disease: a review of the epidemiologic evidence. Neuroepidemiology 1994; 13: 131–44

    PubMed  Google Scholar 

  133. Van Duijn CM, Havekes LM, Van Broeckhoven C, et al. Apolipoprotein E genotype and association between smoking and early onset Alzheimer’s disease. BMJ 1995; 310: 627–31

    PubMed  Google Scholar 

  134. Whitehouse PJ, Hedreen JC, White CL, et al. Basal forebrain neurons in dementia of Parkinson’s disease. Ann Neurol 1983; 13: 243–8

    PubMed  CAS  Google Scholar 

  135. Perry EK, Curtis M, Dick DJ, et al. Cholinergic correlates of cognitive impairment in Parkinson’s disease: comparisons with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1985; 48: 413–21

    PubMed  CAS  Google Scholar 

  136. Whitehouse PJ, Martino AM, Marcus KA, et al. Reductions in acetylcholine and nicotine binding in several degenerative diseases. Arch Neurol 1988; 45: 722–4

    PubMed  CAS  Google Scholar 

  137. Ruberg M, Ploska F, Javoy-Agid F, et al. Muscarinic binding and choline acetyltransferase activity in parkinsonian subjects with reference to dementia. Brain Res 1982; 232: 129–39

    PubMed  CAS  Google Scholar 

  138. Dubois B, Danze F, Pillon B, et al. Cholinergic-dependent cognitive deficits in Parkinson’s disease. Ann Neurol 1987; 22: 26–30

    PubMed  CAS  Google Scholar 

  139. Schwartz RD, Lehmann J, Kellar KJ, et al. Presynaptic nicotinic cholinergic receptors labeled by [3H]acetylcholine on catecholamine and serotonin receptors in brain. J Neurochem 1984; 42: 1495–8

    PubMed  CAS  Google Scholar 

  140. Baumann RJ, Jameson HD, McKean HD, et al. Cigarette smoking and Parkinson’s disease: 1. Comparison of cases with matched neighbors. Neurology 1980; 30: 839–43

    PubMed  CAS  Google Scholar 

  141. Baron JA. Cigarette smoking and Parkinson’s disease. Neurology 1986; 36: 1490–6

    PubMed  CAS  Google Scholar 

  142. Baron JA. Epidemiology of smoking and Parkinson’s disease [abstract]. In: Clarke PBS, Quik M, Thurau K, et al., editors. Effects of nicotine on biological systems: II. Boston: Birkhauser, 1994: S42

    Google Scholar 

  143. Morens DM, Grandinetti A, Reed D, et al. Cigarette smoking and protection from Parkinson’s disease: false association or etiologic clue? Neurology 1995; 45: 1041–51

    PubMed  CAS  Google Scholar 

  144. Moll H. The treatment of postencephalitic parkinsonism by nicotine. BMJ 1926; I: 1079–81

    Google Scholar 

  145. Sershen H, Hashim A, Lajtha A, et al. Behavioral and biochemical effects of nicotine in an MPTP-induced mouse model of Parkinson’s disease. Pharmacol Biochem Behav 1987; 28: 299–303

    PubMed  CAS  Google Scholar 

  146. Dubois B, Pillon R, Lhermitte F, et al. Cholinergic deficiency and frontal dysfunction in Parkinson’s disease. Ann Neurol 1990; 28: 117–21

    PubMed  CAS  Google Scholar 

  147. Reid WGJ, Broe GA, Morris JGL, et al. The role of cholinergic deficiency in neuropsychological deficits in idiopathic Parkinson’s disease. Dementia 1990; 3: 114–20

    Google Scholar 

  148. Demonet JF, Celsis P, Agniel A, et al. Activation of regional cerebral blood flow by a memorization task in early Parkinson’s disease patients and normal subjects. J Cereb Blood Flow Metab 1994; 14: 431–8

    PubMed  CAS  Google Scholar 

  149. Newhouse PA, Potter A, Corwin J, et al. Acute nicotinic blockade produces cognitive impairment in normal humans. Psychopharmacology 1992; 108: 480–4

    PubMed  CAS  Google Scholar 

  150. Newhouse PA, Potter A, Lenox RH, et al. Effects of nicotinic agents on human cognition: possible therapeutic applications in Alzheimer’s and Parkinson’s diseases. Med Chem Res 1993; 2: 628–42

    CAS  Google Scholar 

  151. Snodgrass JG, Corwin J. Pragmatics of measuring recognition memory: applications to dementia and amnesia. J Exp Psychol Gen 1988; 117: 34–50

    PubMed  CAS  Google Scholar 

  152. Newhouse PA, Potter A, Piasecki M, et al. Nicotinic modulation of cognitive functioning in humans. In: Clarke PBS, Quik M, Adlkofer F, et al., editors. Effects of nicotine on biological systems: II. Basel: Birkhauser Verlag, 1995: 345–51

    Google Scholar 

  153. Newhouse PA, Sunderland T, Narang PK, et al. Neuroendocrine, physiologic, and behavioral responses following intravenous nicotine in nonsmoking healthy volunteers and in patients with Alzheimer’s disease. Psychoneuroendocrinology 1990; 15: 471–84

    PubMed  CAS  Google Scholar 

  154. Newhouse PA, Potter A, Corwin J, et al. Effects of nicotinic cholinergic agents on cognitive functioning in Alzheimer’s and Parkinson’s disease. Drug Dev Res 1996; 38: 278–89

    CAS  Google Scholar 

  155. Jones GMM, Sahakian BJ, Levy R, et al. Effects of acute subcutaneous nicotine on attention, information processing and short term memory in Alzheimer’s disease. Psychopharmacology 1992; 108: 485–94

    PubMed  CAS  Google Scholar 

  156. Sahakian BJ, Coull JT. Nicotine and THA: evidence for improved attention in patients with dementia of the Alzheimer type. Drug Dev Res 1994; 31: 80–8

    Google Scholar 

  157. Katayama S, Hirata K, Tanaka H, et al. Efficacy of transdermal nicotine in dementia: a study using event-related potentials and a middle latency response. In: Domino EF, editor. Brain imaging of nicotine and tobacco smoking. Ann Arbor (MI): NPP Books, 1995: 289–302

    Google Scholar 

  158. Parks RW, Young CS, Rippey RF, et al. Nicotinic stimulation of anterior regional glucose metabolism in Alzheimer’s disease: preliminary study with transdermal patches. In: Giacobini E, Becker R, editors. Alzheimer’s disease: therapeutic strategies. Boston: Birkhauser, 1994: 424–7

    Google Scholar 

  159. Wilson AL, Langley LK, Monley J, et al. Nicotine patches in Alzheimer’s disease: pilot study on learning, memory, and safety. Pharmacol Biochem Behav 1995; 51: 509–14

    PubMed  CAS  Google Scholar 

  160. Snaedal J, Johannesson T, Jonsson JE, et al. The effects of nicotine in dermal plaster on cognitive functions in patients with Alzheimer’s disease. Dementia 1996; 7: 47–52

    PubMed  CAS  Google Scholar 

  161. Newhouse PA, Potter A, Corwin J, et al. Acute administration of the nicotinic agonist ABT-418 improves learning in Alzheimer’s disease. Presented at 149th Annual Meeting of the American Psychiatric Association; 1996: New York. New York: New Research Proceedings, 1996: NR 488; 203

    Google Scholar 

  162. Newhouse PA, Potter A, Corwin J. The potential for nicotinic modulation of cognitive and motor functioning in Parkinson’s disease. Presented at the 4th Conference on Neurodegenerative Disorders: common molecular mechanisms; 1997 Feb 23–8: Ocho Rios, Jamaica

  163. Warburton DM, Rusted JM. Cholinergic control of cognitive resources. Neuropsychobiology 1993; 28: 43–6

    PubMed  CAS  Google Scholar 

  164. Brioni JD, Decker MW, Sullivan JP, et al. The pharmacology of (−)-nicotine and novel cholinergic modulators. Adv Pharmacol 1996; 37: 153–214

    Google Scholar 

  165. Fowler JS, Volkow ND, Wang GJ, et al. Inhibition of monoamine oxidase B in the brains of smokers. Nature 1996; 379(6567): 733–6

    PubMed  CAS  Google Scholar 

  166. Shimohama S, Akaike A, Kimura J, et al. Nicotine-induced protection against glutamate cytotoxicity: nicotinic cholinergic receptor-mediated inhibition of nitric oxide formation. Ann N Y Acad Sci 1996; 777: 356–61

    PubMed  CAS  Google Scholar 

  167. Akaike A, Tamura Y, Yokaota T, et al. Nicotine-induced protection of cultured cortical neurons against N-methyl-d-aspartate receptor-mediated glutamate cytotoxicity. Brain Res 1994; 644: 181–7

    PubMed  CAS  Google Scholar 

  168. Owman C, Fuxe K, Jason A, et al. Studies of the protective actions of nicotine on neuronal and vascular functions in rats: comparison between sympathetic noradrenergic and mesostriatal dopaminergic fiber system and the effect of a dopamine agonist. Prog Brain Res 1989; 79: 267–76

    PubMed  CAS  Google Scholar 

  169. Marin P, Maus M, Deagher S, et al. Nicotine protects cultured striatal neurons against N-methyl-d-aspartate receptor-mediated neurotoxicity. Neuroreport 1994; 5: 1977–80

    PubMed  CAS  Google Scholar 

  170. Freedman R, Wetmore C, Stromberg I, et al. α-Bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth-factor expression. J Neurosci 1993; 13: 1965–75

    PubMed  CAS  Google Scholar 

  171. Yamashita H, Nakamura S. Nicotine rescues PC 12 cells from death induced by nerve growth factor deprivation. Neurosci Lett 1996; 213: 145–7

    PubMed  CAS  Google Scholar 

  172. Salomon AR, Marcinowski KJ, Zagorski M. Nicotine inhibits amyloid formation by the β-peptide. Biochemistry 1996; 35: 13568–78

    PubMed  CAS  Google Scholar 

  173. Monteggia LM, Arneri SP, Giordano T. Nicotine effects on the regulation of amyloid precursor protein splicing, neurotrophin and glucose transporter RNA levels in aged rats. Int J Dev Neurosci 1994; 12: 133–41

    PubMed  CAS  Google Scholar 

  174. Robbins TW, Everitt BJ, Marston HM, et al. Comparative effects of ibotenic acid- and quisqualic acid-induced lesions of the substantia innominata on attentional function in the rat: further implications for the role of the cholinergic neurons of the nucleus basalis in cognitive processes. Behav Brain Res 1989; 35: 221–4

    PubMed  CAS  Google Scholar 

  175. Muir JL, Dunnett SB, Robbins TW, et al. Attentional functions of the forebrain cholinergic systems: effects of intraventricular hemicholinium, physostigmine, basal forebrain lesions and intracortical grafts on a multiple-choice serial reaction time task. Exp Brain Res 1992; 89: 611–22

    PubMed  CAS  Google Scholar 

  176. Vidal C. Nicotinic potentiation of glutamatergic synapses in the prefrontal cortex: new insight into the analysis of the role of nicotinic receptors in cognitive functions. Drug Dev Res 1994; 31: 120–6

    CAS  Google Scholar 

  177. Vidal C. The functional role of nicotinic receptors in the rat prefrontal cortex: electrophysiological, biochemical, and behavioral characterizations [abstract]. In: Clarke PBS, Quik M, Thurau K, et al., editors. Effects of nicotine on biological systems: II. Boston: Birkhauser, 1994: P70

    Google Scholar 

  178. Callaway E, Halliday R, Naylor H. Cholinergic activity and constraints on information processing. Biol Psychology 1992; 33: 1–21

    CAS  Google Scholar 

  179. Halliday R, Gregory K, Naylor H, et al. Beyond drug effects and dependent variables: the use of the Poisson-Erlang model to assess the effects of d-amphetamine on information processing. Acta Psychol (Amst) 1990; 73: 35–54

    CAS  Google Scholar 

  180. Dunne MP, Hartley LR. Scopolamine and the control of attention in humans. Psychopharmacology 1986; 89: 94–7

    PubMed  CAS  Google Scholar 

  181. Sunderland T, Tariot P, Newhouse PA. Differential responsivity of mood, behavior, and cognition to cholinergic agents in elderly neuropsychiatric populations. Brain Res Rev 1988; 13: 371–89

    Google Scholar 

  182. Parrott AC, Craig D. Cigarette smoking and nicotine gum (0, 2 and 4mg): effects upon four visual attention tasks. Neuropsychobiology 1992; 25: 34–43

    PubMed  CAS  Google Scholar 

  183. Parasuraman R, Haxby JV. Attention and brain function in Alzheimer’s disease. Neuropsychology 1993; 7: 242–72

    Google Scholar 

  184. Brazzelli M, Cocchini G, Della Sala S, et al. Alzheimer patients show a sensitivity decrement over time on a tonic alertness task. J Clin Exp Neuropsych 1994; 16: 851–60

    CAS  Google Scholar 

  185. Parasuraman R, Greenwood PM, Haxby JV, et al. Visuospatial attention in dementia of the Alzheimer type. Brain 1992; 115: 711–33

    PubMed  Google Scholar 

  186. Oken BS, Kishiyama SS, Kaye JA, et al. Attention deficit in Alzheimer’s disease is not stimulated by an anticholinergic/antihistaminergic drug and is distinct from deficits in healthy aging. Neurology 1994; 44: 657–62

    PubMed  CAS  Google Scholar 

  187. Baddeley AD, Bressi S, Sala SD, et al. The decline of working memory in Alzheimer’s disease. Brain 1991; 114: 2521–42

    PubMed  Google Scholar 

  188. Baddeley A, Logie R, Bressi S, et al. Dementia and working memory. J Exp Psychol 1986; 38A: 603–18

    Google Scholar 

  189. Cossa FM, Della Sala S, Spinnler H. Selective visual attention in Alzheimer’s and Parkinson’s patients: memory- and data-driven control. Neuropsychologia 1989; 27: 887–92

    PubMed  CAS  Google Scholar 

  190. Nestor PG, Parasuraman R, Haxby JV, et al. Divided attention and metabolic brain dysfunction in mild dementia of the Alzheimer’s type. Neuropsychologia 1991; 29: 379–87

    PubMed  CAS  Google Scholar 

  191. Snodgrass J, Corwin J. Pragmatics of recognition memory: application to dementia and amnesia. J Exp Psychol (Gen) 1988; 117: 34–50

    CAS  Google Scholar 

  192. Brown RG, Marsden CD. Cognitive function in Parkinson’s disease: from description to theory. Trend Neurosci 1990; 13: 21–9

    PubMed  CAS  Google Scholar 

  193. Goldenberg G, Lang W, Podreka I, et al. Are cognitive deficits in Parkinson’s disease caused by frontal lobe dysfunction? J Psychophysiology 1990; 4: 137–44

    Google Scholar 

  194. Stam CJ, Visser SL, Op de Coul AAW, et al. Disturbed frontal regulation of attention in Parkinson’s disease. Brain 1993; 116: 1139–58

    PubMed  Google Scholar 

  195. Dalrymple-Alford JC, Kalders AS, Jones RD, et al. A central executive deficit in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 1994; 57: 360–7

    PubMed  CAS  Google Scholar 

  196. Taylor AE, Saint-Cyr JA, Lang AE. Frontal lobe dysfunction in Parkinson’s disease: the cortical focus of neostriatal outflow. Brain 1986; 109: 845–83

    PubMed  Google Scholar 

  197. Reading PJ. Frontal lobe dysfunction in schizophrenia and Parkinson’s disease — a meeting point for neurology, psychology and psychiatry: discussion paper. J Royal Soc Med 1991; 84: 349–53

    CAS  Google Scholar 

  198. Downes JJ, Sharp HM, Sagar HJ. The time course of negative priming in Parkinson’s disease. J Clin Exp Neuropsychol 1991; 13: 75

    Google Scholar 

  199. Downes JJ, Sharp HM, Costall BM, et al. Alternating fluency in Parkinson’s disease: an evaluation of the attentional control theory of cognitive impairment. Brain 1993; 116: 887–902

    PubMed  Google Scholar 

  200. Adler LE, Pachtman E, Franks RD, et al. Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biol Psychiatry 1982; 17: 639–54

    PubMed  CAS  Google Scholar 

  201. Braff DL, Geyer MA. Sensorimotor gating and schizophrenia: human and animal model studies. Arch Gen Psychiatry 1990; 47: 181–8

    PubMed  CAS  Google Scholar 

  202. Wilson CL, Babb TL, Halgren E, et al. Habituation of human limbic neuronal response to sensory stimulation. Exp Neurol 1984; 84: 74–97

    PubMed  CAS  Google Scholar 

  203. Adler LE, Hoffer LD, Wiser A, et al. Normalization of auditory physiology by cigarette smoking in schizophrenic patients. Am J Psychiatry 1993; 150: 1856–61

    PubMed  CAS  Google Scholar 

  204. Adler LE, Hoffer LD, Griffith J, et al. Normalization of the deficient auditory sensory gating in the relatives of schizophrenics by nicotine. Biol Psychiatry 1992; 32: 607–16

    PubMed  CAS  Google Scholar 

  205. Freedman R, Adler LE, Bickford P, et al. Nicotine, auditory gating and schizophrenia. In: Clarke PBS, Quik M, Thurau K, et al., editors. Effects of nicotine on biological systems: II. Boston: Birkhauser, 1994: S41

    Google Scholar 

  206. McCracken JT. A two-part model of stimulant action on attention-deficit hyperactivity disorder in children. J Neuropsychiatry 1991; 3: 201–8

    CAS  Google Scholar 

  207. Kirch DG, Alho AM, Wyatt RJ. Hypothesis: a nicotine-dopamine interaction linking smoking with Parkinson’s disease and tardive dyskinesia. Cell Mol Neurobiol 1988; 8: 285–91

    PubMed  CAS  Google Scholar 

  208. Rapier C, Lunt GG, Wonnacott S. Nicotinic modulation of [3H]dopamine release from striatal synaptosomes: pharmacological characterisation. J Neurochem 1990; 54: 937–45

    PubMed  CAS  Google Scholar 

  209. Clarke PBS, Pert A. Autoradiographic evidence for nicotine receptors on nigrostriatal and mesolimbic dopaminergic neurons. Brain Res 1985; 348: 355–8

    PubMed  CAS  Google Scholar 

  210. Levin E, Connors CK, Sparrow E, et al. Nicotine effects on adults with attention deficit/hyperactivity disorder. Psychopharmacology 1996; 123: 55–63

    PubMed  CAS  Google Scholar 

  211. Lawrence AD, Sahakian BJ. Alzheimer’s disease, attention, and the cholinergic system. Alzheimer Dis Assoc Disord 1995; 9 Suppl. 2: 43–9

    PubMed  Google Scholar 

  212. Cordell B. β-Amyloid formation as a potential therapeutic target for Alzheimer’s disease. Ann Rev Pharmacol Toxicol 1994; 34: 69–89

    CAS  Google Scholar 

  213. Maurice T, Lockhart BP, Privat A. Amnesia induced in mice by centrally administered β-amyloid peptides involves cholinergic dysfunction. Brain Res 1996; 706: 181–93

    PubMed  CAS  Google Scholar 

  214. Riekkinen P, Riekkinen M. Effects of tetrahydroaminoacridine and nicotine in nucleus basalis and serotonin-lesioned rats. Eur J Pharmacol 1995; 279: 65–73

    PubMed  CAS  Google Scholar 

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Newhouse, P.A., Potter, A. & Levin, E.D. Nicotinic System Involvement in Alzheimer’s and Parkinson’s Diseases. Drugs & Aging 11, 206–228 (1997). https://doi.org/10.2165/00002512-199711030-00005

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