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Rationale and prospects for drugs that target nicotinic acetylcholine receptors

  • Andrea Wevers
  • Diana S. Woodruff-Pak
Part of the Milestones in Drug Therapy MDT book series (MDT)

Abstract

Nicotinic acetylcholine receptors (nAChRs) are implicated in a variety of disorders of the human central nervous system including addiction to nicotine, Alzheimer’s disease, anxiety, autism, depression, epilepsy, Parkinson’s disease, schizophrenia, and Tourette’s syndrome [ 1,2]. Mechanisms of nAChR impairment in this disparate group of syndromes are poorly understood. Additionally, in healthy organisms nAChRs play a significant role in a number of cognitive processes including learning and memory [ 3,4]. Because nAChRs are involved in normal cognitive processes as well as a complex range of central nervous system disorders, it is important to define the means by which these receptors exert their action in the brain and interact with disease-related neuropathology. It is also imperative to explore the prospects of therapeutic manipulations of nAChRs in human central nervous systems disorders.

Keywords

Unconditioned Stimulus Nicotinic Receptor Nicotinic Acetylcholine Receptor Eyeblink Conditioning Young Rabbit 
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.

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References

  1. 1.
    Newhouse PA, Kelton M (2000) Clinical aspects of nicotinic agents: Therapeutic application in central nervous system disorders. In: F Clementi, D Fornasari, C Gotti (eds): Neuronal nicotinic receptors: Experimental pharmacology. Springer, Berlin, 779–812CrossRefGoogle Scholar
  2. 2.
    Weiland S, Bertrand D, Leonard S (2000) Neuronal nicotinic acetylcholine receptors: From gene to disease. Behav Brain Res 113: 43–56PubMedCrossRefGoogle Scholar
  3. 3.
    Gould TJ, Wehner JM (1999) Nicotine enhancement of contextual fear conditioning. Behav Brain Res 102: 31–39PubMedCrossRefGoogle Scholar
  4. 4.
    Levin ED (1992) Nicotinic systems and cognitive function. Psychopharmacol 108: 417–431CrossRefGoogle Scholar
  5. 5.
    Conroy WG, Vernallis AB, Berg DK (1992) The a5 gene product assembles with multiple acetyl-choline receptor subunits to form distinctive receptor subtypes in brain. Neuron 9: 679–691PubMedCrossRefGoogle Scholar
  6. 6.
    Lindstrom J, Schoepfer R, Conroy W, Whiting P, Das M, Saedi M, Anand R (1991) The nicotinic acetylcholine receptor gene family: Structure of nicotinic receptors from muscle and neurons and neuronal a-bungarotoxin-binding proteins. Adv Exp Med Biol 287: 255–278PubMedCrossRefGoogle Scholar
  7. 7.
    Flores CM, Rogers SW, Pabreza LA, Wolfe BB, Kellar KJ (1992) A subtype of nicotinic cholinergic receptor in rat brain is composed of α4 and β2 subunits and is up-regulated by chronic nicotine treatment. Mol Pharmacol 41: 31–37PubMedGoogle Scholar
  8. 8.
    Couturier S, Bertrand D, Matter JM, Hernandez MC, Bertrand S, Millar N, Valera S, Barkas T, Ballivet M (1990) A neuronal nicotinic acetylcholine receptor subunit (α7) is developmentally regulated and forms a homo-oligomcric channel blocked by a-BTX. Neuron 5: 847–856PubMedCrossRefGoogle Scholar
  9. 9.
    Schoepfer R, Conroy W, Whiting P, Gore M, Lindstrom J (1990) Brain a-bungarotoxin binding protein cDNAs and mAbs reveal subtypes of this branch of the ligand-gated ion channel gene superfamily. Neuron 5: 35–48PubMedCrossRefGoogle Scholar
  10. 10.
    McGehee DS, Heath MJ, Gelber S, Devay P, Role LW (1995) Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. Science 269: 1692–1696CrossRefGoogle Scholar
  11. 11.
    Frazier CJ, Buhler AV, Weiner JL, Dunwiddie TV (1998) Synaptic potentials mediated via a-bungarotoxin-sensitive nicotinic acetylcholine receptors in rat hippocampal interneurons. J Neurosci 18: 8228–8235PubMedGoogle Scholar
  12. 12.
    Court JA, Perry EK (1995) Distribution of nicotinic receptors in the CNS. In: TW Stone (ed.): CNS neurotransmitters and neuromodulators. CRC Press, London, 85–104Google Scholar
  13. 13.
    Lindstrom J (1997) Nicotinic acetylcholine receptors in health and disease. Mol Neurobiol 15: 193–222PubMedCrossRefGoogle Scholar
  14. 14.
    Wevers A, Schrtider H (1999) Nicotinic acetylcholine receptors in Alzheimer’s disease. J Alzheimer’s Disease 1: 207–219Google Scholar
  15. 15.
    Auld DS, Kar S, Quirion R (1998) β-Amyloid peptides as direct cholinergic neuromodulators: a missing link? TINS 21: 43–49PubMedGoogle Scholar
  16. 16.
    Zeng H, Zhang Y, Peng L, Shao H, Menon NK, Yang J, Salomon AR, Freidland RP, Zagorski MG (2001) Nicotine and amyloid formation. Biol Psychiatry 49: 248–257PubMedCrossRefGoogle Scholar
  17. 17.
    Ono K, Hasegawa K, Yamada M, Naiki H (2002) Nicotine breaks down preformed Alzheimer’s β-amyloid fibrils in vitro. Biol Psychiatry 52: 880–886PubMedCrossRefGoogle Scholar
  18. 18.
    Lee PN (1994) Smoking and Alzheimer’s disease: a review of epidemiological evidence. Neuroepidemiology 13: 131–144PubMedCrossRefGoogle Scholar
  19. 19.
    Merchant C, Tang MX, Albert S, Manly J, Stern Y, Mayeux R (1999) The influence of smoking on the risk of Alzheimer’s disease. Neurology 52: 1408–1412PubMedCrossRefGoogle Scholar
  20. 20.
    Ulrich J, Johannson-Locher G, Seiler WO, Stahelin HB (1997) Does smoking protect from Alzheimer’s disease? Alzheimer-type changes in 301 unselected brains from patients with known smoking history. Acta Neuropathol (Berlin) 94: 450–454CrossRefGoogle Scholar
  21. 21.
    Perry E, Martin-Ruiz C, Lee M, Griffiths M, Johnson M, Piggott M, Haroutunian V, Buxbaum JD, Nasland J, Davis K et al. (2000) Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body disease. Eur J Pharmacol 393: 215–222PubMedCrossRefGoogle Scholar
  22. 22.
    Kihara T, Shimohama S, Sawada H, Kimura J, Kume T, Kochiyama H, Maeda T, Akaike A (1997) Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity. Ann Neurol 42: 159–163PubMedCrossRefGoogle Scholar
  23. 23.
    Kihara T, Shimohama S, Urushitani M, Sawada H, Kimura J, Kume T, Maeda T, Akaike A (1998) Stimulation of alpha4beta2 nicotinic acetylcholine receptors inhibits beta-amyloid toxicity. Brain Res 792: 331–334Google Scholar
  24. 24.
    Shimohama S, Kihara T (2001) Nicotinic receptor-mediated protection against β-amyloid neurotoxicity. Biol Psychiatry 49: 233–239PubMedCrossRefGoogle Scholar
  25. 25.
    Zamani MR, Allen S (2001) Nicotine and its interaction with β-amyloid protein: A short review. Biol Psychiatry 49: 221–232PubMedCrossRefGoogle Scholar
  26. 26.
    Marutle A, Warpman U, Bogdanovic N, Lannfelt L, Nordberg A (1999) Neuronal nicotinic receptor deficits in Alzheimer patients with the Swedish amyloid precursor protein 670/671 mutation. J Neurochem 72: 1161–1169PubMedCrossRefGoogle Scholar
  27. 27.
    Wevers A, Monteggia L, Nowacki S, Bloch W, Schutz U, Lindstrom J, Pereira EFR, Eisenberg H, Giacobini E, de Vos RAI et al. (1999) Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer’s disease — Histotopographical correlation with amyloid plaques and hyperphosphorylated tau-protein. Eur J Neurosci 11: 2551–2565PubMedCrossRefGoogle Scholar
  28. 28.
    Terzano S, Court JA, Fornasari D, Griffiths M, Spurden DP, Lloyd S, Perry RH, Perry EK, Clementi F (1998) Expression of the alpha3 nicotinic receptor subunit mRNA in aging and Alzheimer’s disease. Mol Brain Res 63: 72–78PubMedCrossRefGoogle Scholar
  29. 29.
    Hell strOm-Lindahl E, Mousavi M, Zhang X, Ravid R, Nordberg A (1999) Regional distribution of nicotinic receptor subunit mRNAs in human brain: Comparison between Alzheimer and normal brain. Mol Brain Res 66: 94–103CrossRefGoogle Scholar
  30. 30.
    Wevers A, Witter B, Moser N, Burghaus L, Banerjee C, Steinlein OK, Schutz U, de Vos RAI, Jansen Steur ENH, Lindstrom J et al. (2000) Classical Alzheimer features and cholinergic dysfunction: towards a unifying hypothesis? Acta Neurol Scand Suppl 176: 42–48PubMedCrossRefGoogle Scholar
  31. 31.
    Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, Kholodenko D, Malenka RC, Nicoll RA, Mucke L (1999) Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models. Proc Nati Acad Sci USA 96: 3228–3233CrossRefGoogle Scholar
  32. 32.
    Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L (2000) High-level neuronal expression of AP 1–42 in wild-type human amyloid protein precursor transgenic mice: Synaptotoxicity without plaque formation. J Neurosci 20: 4050–4058PubMedGoogle Scholar
  33. 33.
    Bednar I, Paterson D, Marutle A, Pham TM, Svedberg M, Hellstrom-Lindahl E, Mousavi M, Court J, Morris C, Perry E et al. (2002) Selective nicotinic receptor consequences in APP(SWE) trans-genic mice. Mol Cell Neurosci 20: 354–365PubMedCrossRefGoogle Scholar
  34. 34.
    Apelt J, Kumar A, Schliebs R (2002) Impairment of cholinergic neurotransmission in adult and aged transgenic Tg2576 mouse brain expressing the Swedish mutation of human β-amyloid precursor protein. Brain Res 953: 17–30PubMedCrossRefGoogle Scholar
  35. 35.
    Reid RT, Sabbagh MN, Corey-Bloom J, Tiraboschi P, Thal LJ (2000) Nicotinic receptor losses in dementia with Lewy bodies: Comparisons with Alzheimer’s disease. Neurobiol Aging 21: 741–746CrossRefGoogle Scholar
  36. 36.
    Younkin SG (1998) The role of Aβ42 in Alzheimer’s disease. J Physiol Paris 92: 289–292PubMedCrossRefGoogle Scholar
  37. 37.
    Wang HY, Lee DHS, D’Andrea MR, Peterson PA, Shank RP, Reitz AB (2000) β-amyloid1–42 binds to α7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer’s disease pathology. J Biol Chem 275: 5626–5632PubMedCrossRefGoogle Scholar
  38. 38.
    Wang HY, Lee DH, Davis CB, Shark RR (2000) Amyloid peptide Abeta (1–42) binds selectively and with picomolar affinity to alpha 7 nicotinic acetylcholine receptor. J Neurochem 75: 1155–1161PubMedCrossRefGoogle Scholar
  39. 39.
    Pettit DL, Shao Z, Yakel JL (2001) beta-Amyloid (1–42) peptide directly modulates nicotinic receptors in the rat hippocampal slice. J Neurosci 21: RC120 (1–5)Google Scholar
  40. 40.
    Liu Q, Kawai H, Berg DK (2001) beta -Amyloid peptide blocks the response of alpha 7-containing nicotinic receptors on hippocampal neurons. Proc Natl Acad Sci USA 98: 4734–4739PubMedCrossRefGoogle Scholar
  41. 41.
    Grassi F, Palma E, Tonini R, Amici M, Ballivet M, Eusebi F (2003) Amyloid β1–42 peptide alters the gating of human and mouse a-bungarotoxin-sensitive nicotinic receptors. J Physiol 547: 147–157PubMedCrossRefGoogle Scholar
  42. 42.
    Dineley KT, Bell KA, Bui D, Sweatt JD (2002) β-Amyloid peptide activates α7 nicotinic acetylcholine receptors expressed in Xenopus oocytes. J Biol Chem 277: 25056–25061PubMedCrossRefGoogle Scholar
  43. 43.
    Tozaki H, Matsumoto A, Kanno T, Nagai K, Nagata T, Yamamoto S, Nishizaki T (2002) The inhibitory and facilitatory actions of amyloid-beta peptides on nicotinic ACh receptors and AMPA receptors. Biochem Biophys Res Commun 294: 42–45PubMedCrossRefGoogle Scholar
  44. 44.
    Guan Z-Z, Miao H, Tian J-Y, Unger C, Nordberg A, Zhang X (2001) Suppressed expression of nicotinic acetylcholine receptors by nanomolar β-amyloid peptides in PC12 cells. J Neural Transm 108: 1417–1433PubMedCrossRefGoogle Scholar
  45. 45.
    Gravina S, Ho Libin, Eckman CB, Long KE, Otvos L, Younkin LH, Suzuki N, Younkin SG (1995) Amyloid β protein (Ab) in Alzheimer’s disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at Aβ40 or Aβ42(43). J Biol Chem 270: 7013–7016PubMedCrossRefGoogle Scholar
  46. 46.
    Golde TE (2003) Alzheimer disease therapy: Can amyloid cascade be halted? J Chn Invest 111: 11–18Google Scholar
  47. 47.
    Nagele RG, D’ Andrea MR, Anderson WJ, Wang HY (2002) Intracellular accumulation of β-amyloid1–42in neurons is facilitated by the α7 nicotinic acetylcholine receptor in Alzheimer’s disease. Neuroscience 110: 199–211PubMedCrossRefGoogle Scholar
  48. 48.
    Kihara T, Shimohama S, Sawada H, Honda K, Nakamizo T, Shibasaki H, Kume T, Akaike A (2001) ea nicotinic receptor trancduces signals to phosphatidylinositol 3-kinase to block A beta-amyloid-induced neurotoxicity. J Biol Chem 276: 13541–13546PubMedGoogle Scholar
  49. 49.
    Shaw S, Bencherif M, Marrero B (2002) Janus kinase 2, an early target of α7 nicotinic acetylcholine receptor-mediated neuroprotection against Aβ-(1–42) amyloid. J Biol Chem 277: 44920–44924PubMedCrossRefGoogle Scholar
  50. 50.
    Dineley KT, Westerman M, Bui D, Bell K, Ashe KH, Sweatt JD (2001) Beta-amyloid activates the mitogen-activated protein kinase cascade via hippocampal alpha7 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimer’s disease. J Neurosci 21: 4125–4133PubMedGoogle Scholar
  51. 51.
    Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang I, Johnson-Wood K, Khan K et al. (1999) Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400: 173–177PubMedCrossRefGoogle Scholar
  52. 52.
    Janus C, Pearson J, McLaurin J, Mathews PM, Jiang Y, Schmidt SD, Chishti MA, Home P, Heslin D, French J et al. (2000) Al peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer’s disease. Nature 408: 979–982PubMedCrossRefGoogle Scholar
  53. 53.
    Dodart J-C, Bales KR, Gannon KS, Green SJ, DeMattos RB, Mathis C, DeLong CA, Wu S, Wu X, Holtzman DM et al. (2002) Immunization reverses memory deficits without reducing brain Al burden in Alzheimer’s disease model. Nature Neurosci 5: 452–457PubMedGoogle Scholar
  54. 54.
    Birmingham K, Frantz S (2002) Set back to Alzheimer vaccine studies. Nature Med 8: 199–200PubMedGoogle Scholar
  55. 55.
    Nicoll JAR, Wilkinson D, Holmes C, Stert P, Markham H, Weller RO (2003) Neuropathology of human Alzheimer disease after immunization with amyloid-f3 peptide: A case report. Nature Med 9: 448–452PubMedCrossRefGoogle Scholar
  56. 56.
    Nordberg A, Hellstrom-Lindahl E, Lee M, Johnson M, Mousavi M, Hall R, Perry E, Bednar I, Court J (2002) Chronic nicotine treatment reduces ß-amyloidosis in the brain of a mouse model of Alzheimer’s disease (APPsw). J Neurochem 81: 655–658PubMedCrossRefGoogle Scholar
  57. 57.
    Kern WR, Abbott BC, Coates RM (1971) Isolation and structure of a hoplonemertine toxin. Toxicol 9: 15–22Google Scholar
  58. 58.
    Grottick AJ, Higgins GA (2000) Effect of subtype selective nicotinic compounds on attention as assessed by the five-choice serial reaction time task. Behav Brain Res 117: 197–208PubMedCrossRefGoogle Scholar
  59. 59.
    Jones G, Sahakian B, Levy P, Warburton D, Gray J (1992) Effects of acute subcutaneous nicotine on attention, information processing, and short-term memory. Psychopharmacol (Bed) 108: 485–494CrossRefGoogle Scholar
  60. 60.
    Acri JB, Morse DE, Popke EJ, Grunberg NE (1994) Nicotine increases sensory gating measured as inhibition of the acoustic startle reflex in rats. Psychopharmacol 114: 369–374CrossRefGoogle Scholar
  61. 61.
    Adler LE, Olincy A, Waldo M, Harris JG, Griffith J, Stevens K, Flach K, Nagamoto H, Bickford P, Leonard S et al. (1998) Schizophrenia, sensory gating, and nicotinic receptors. Schizophrenia Bull 24: 189–202Google Scholar
  62. 62.
    Schreiber R, Dalmus M, De Vry J (2002) Effects of alpha4/beta2- and alpha 7-nicotine acetylcholine receptor agonists on prepulse inhibition of the acoustic startle response in rats and mice. Psychopharmacology (Ben) 159: 248–257CrossRefGoogle Scholar
  63. 63.
    Blondel A, Sanger DJ, Moser PC (2000) Characterisation of the effects of nicotine in the five-choice serial reaction time task in rats: Antagonist studies. Psychopharmacol 149: 293–305CrossRefGoogle Scholar
  64. 64.
    Rezvani AH, Bushnell PJ, Levin ED (2002) Effects of nicotine and mecamylamine on choice accuracy in an operant visual signal detection task in female rats. Psychopharmacol (Berl) 164: 369–375CrossRefGoogle Scholar
  65. 65.
    Schildein S, Huston JP, Schwarting RK (2002) Open field habituation learning is improved by nicotine and attenuated by mecamylamine administered post-trial into the nucleus accumbens. Neurobiol Learn Mem 77: 277–290PubMedCrossRefGoogle Scholar
  66. 66.
    Ueno K, Togashi H, Matsumoto M, Ohashi S, Saito H, Yoshioka M (2002) Alpha4beta2 nicotinic acetylcholine receptor activation ameliorates impairment of spontaneous alternation behavior in stroke-prone spontaneously hypertensive rats, an animal model of attention deficit hyperactivity disorder. J Pharmacol Exp Ther 302: 95–100PubMedCrossRefGoogle Scholar
  67. 67.
    Brown RW, Beale KS, Jay Frye GD (2002) Mecamylamine blocks enhancement of reference memory but not working memory produced by post-training injection of nicotine in rats tested on the radial arm maze. Behav Brain Res 134: 259–265PubMedCrossRefGoogle Scholar
  68. 68.
    Brown RW, Gonzalez CL, Whishaw IQ, Kolb B (2001) Nicotine improvement of Morris water task performance after fimbria-fornix lesion is blocked by mecamylamine. Behav Brain Res 119: 185–202PubMedCrossRefGoogle Scholar
  69. 69.
    Bancroft A, Levin ED (2000) Ventral hippocampal alpha4beta2 nicotinic receptors and chronic nicotine effects on memory. Neurophannacol 39: 2770–2778CrossRefGoogle Scholar
  70. 70.
    Bettany JH, Levin ED (2001) Ventral hippocampal alpha 7 nicotinic receptor blockade and chronic nicotine effects on memory performance in the radial-arm maze. Pharmacol Biochem Behav 70: 467–474PubMedCrossRefGoogle Scholar
  71. 71.
    Levin ED, Bradley A, Addy N, Sigurani N (2002) Hippocampal alpha 7 and alpha4 beta 2 nicotinic receptors and working memory. Neurosci 109: 757–765CrossRefGoogle Scholar
  72. 72.
    Levin ED, Rose JE (1990) Anticholinergic sensitivity following chronic nicotine administration as measured by radial-arm maze performance in rats. Behav Pharmacol 1: 511–520PubMedCrossRefGoogle Scholar
  73. 73.
    Levin ED, Briggs SJ, Christopher NC, Rose JE (1993) Chronic nicotinic stimulation and blockade effects on working memory. Behav Pharmacol 4: 179–182PubMedCrossRefGoogle Scholar
  74. 74.
    Papke RL, Sanberg, PR, Shytle, RD (2001) Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes. J Pharmacol Exp Ther 297: 646–656PubMedGoogle Scholar
  75. 75.
    Solomon PR, Levine E, Bein T, Pendlebury WW (1991) Disruption of classical conditioning in patients with Alzheimer’s disease. Neurobiol Aging 12: 283–287PubMedCrossRefGoogle Scholar
  76. 76.
    Woodruff-Pak DS, Finkbiner RG, Sasse DK (1990) Eyeblink conditioning discriminates Alzheimer’s patients from non-demented aged. Neuroreport I: 45–49CrossRefGoogle Scholar
  77. 77.
    Woodruff-Pak DS, Papka M, Romano S, Li Y-T (1996) Eyeblink classical conditioning in Alzheimer’s disease and cerebrovascular dementia. Neurobiol Aging 17: 505–512PubMedGoogle Scholar
  78. 78.
    Myers CE, DeLuca J, Schultheis MT, Schnirman GM, Ermita BR, Diamond B, Warren SG, Gluck MA (2001) Impaired delay eyeblink classical conditioning in individuals with anterograde amnesia resulting from anterior communicating artery aneurysm rupture. Behav Neurosci 115: 560–570PubMedCrossRefGoogle Scholar
  79. 79.
    Fukutani Y, Cairns NJ, Rossor MN, Lantos PL (1996) Purkinje cell loss and astrocytosis in the cerebellum in familial and sporadic Alzheimer’s disease. Neurosci Lett 214: 33–36PubMedCrossRefGoogle Scholar
  80. 80.
    Fukutani Y, Cairns NJ, Rossor MN, Lantos PL (1997) Cerebellar pathology in sporadic and famil-ial Alzheimer’s disease APP 717 (Val—Ile) mutation cases: A morphometric investigation. J Neurol Sci 149: 177–184PubMedCrossRefGoogle Scholar
  81. 81.
    Weiss C, Preston AR, Oh MM, Schwarz RD, Welty D, Disterhoft JD (2000) The M1 muscarinic agonist CI-1017 facilitates trace eyeblink conditioning in aging rabbits and increases the excitability of CAI pyramidal neurons. J Neurosci 20: 783–790PubMedGoogle Scholar
  82. 82.
    Moore JW, Goodell NA, Solomon PR (1976) Central cholinergic blockade by scopolamine and habituation, classical conditioning, and latent inhibition of the rabbit’s nictitating membrane response. Physiolog Psychol 4: 395–399Google Scholar
  83. 83.
    Woodruff-Pak DS, Vogel RW III, Wenk GL (2001) Galantamine: Effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning. PNAS 98: 2089–2094PubMedCrossRefGoogle Scholar
  84. 84.
    Woodruff-Pak DS, Li Y-T, Kazmi A, Kem WR (1994) Nicotinic cholinergic system involvement in eyeblink classical conditioning in rabbits. Behav Neurosci 108: 486–493PubMedCrossRefGoogle Scholar
  85. 85.
    Solomon PR, Solomon SD, van der Schaaf E, Perry HE (1983) Altered activity in the hippocampus is more detrimental to classical conditioning than removing the structure. Science 220: 329–331PubMedCrossRefGoogle Scholar
  86. 86.
    Woodruff-Pak DS, Li Y-T, Hinchliffe RM, Port RL (1997) Hippocampus in delay eyeblink classical conditioning: Essential for nefiracetam amelioration of learning in older rabbits. Brain Res 747: 207–218PubMedCrossRefGoogle Scholar
  87. 87.
    De Fiebre CM, Meyer EM, Henry JC, Muraskin SI, Kem WR, Papke RL (1995) Characterization of a series of anabaseine-derived compounds reveals that the 3-(4)-dimethylaminocinnamylidine derivative is a selective agonist at neuronal nicotinic a7/125-a-bungarotoxin receptor subtypes. Mol Pharmacol 47: 164–171PubMedGoogle Scholar
  88. 88.
    Kern WR, Mahnir VM, Papke RL, Lingle CJ (1997) Anabaseine is a potent agonist on muscle and neuronal a-bungarotoxin-sensitive nicotinic receptors. Pharmacol Exp Ther 283: 979–992Google Scholar
  89. 89.
    Woodruff-Pak DS, Li Y-T, Kern WR (1994) A nicotinic agonist (GTS-21), eyeblink classical conditioning, and nicotinic receptor binding in rabbit brain. Brain Res 645: 309–317PubMedCrossRefGoogle Scholar
  90. 90.
    Woodruff-Pak DS, Green JT, Coleman-Valencia C, Pak JT (2000) A nicotinic cholinergic drug (GTS-21) and eyeblink classical conditioning: Acquisition, retention, and relearning in older rabbits. Expt Aging Res 26: 323–336CrossRefGoogle Scholar
  91. 91.
    Woodruff-Pak, DS (2003) Mecamylamine reversal by nicotine and by a partial alpha 7 nicotinic acetylcholine receptor agonist (GTS-21) in rabbits tested with delay eyeblink classical conditioning. Behav Brain Res 143: 159–167PubMedCrossRefGoogle Scholar
  92. 92.
    Pereira EFR, Alkondon M, Reinhardt S, Maelicke A, Peng X, Lindstrom J, Whiting P, Albuquerque EX (1994) Physostigmine and galantamine: Probes for a novel binding site on the a4(32 subtype of neuronal nicotinic acetylcholine receptors stably expressed in fibroblast cells. J Pharmacol Exp Ther 270: 768–778PubMedGoogle Scholar
  93. 93.
    Pereira EFR, Reinhardt-Maelicke S, Schrattenholz A, Maelicke A, Albuquerque EX (1993) Identification and functional characterization of a new agonist site on nicotinic acetylcholine receptors of cultured hippocampal neurons. J Pharmacol Exp Ther 265: 1474–1491PubMedGoogle Scholar
  94. 94.
    Storch A, Schrattenholz A, Cooper JC, Abdel Ghani M, Gutbrod 0, Weber K-H, Reinhardt S, Lobron C, Hermsen B, Soskic Vet al. (1995) Physostigmine, galantamine and codeine act as noncompetitive nicotinic agonists on clonal rat pheochromocytoma cells. European J Pharmacol 290: 207–219CrossRefGoogle Scholar
  95. 95.
    Woodruff-Pak DS, Ewers M, Vogel RW, Shiotani T, Watabe S, Tanaka M, Wenk GL (2003) Nefiracetam and physostigmine: Separate and combined effects on learning in older rabbits. Neurobiol Aging; in press Google Scholar
  96. 96.
    Woodruff-Pak DS, Santos I (2000) Nicotinic modulation in an animal model of a form of associative learning impaired in Alzheimer’s disease. Behav Brain Res 113: 11–19PubMedCrossRefGoogle Scholar
  97. 97.
    Woodruff-Pak DS, Vogel RW III, Wenk GL (2003) Mecamylamine interactions with galantamine and donepezil: Effects on learning, acetylcholinesterase, and nicotinic acetylcholine receptors. Neurosci 117: 439–447CrossRefGoogle Scholar

Copyright information

© Springer Basel AG 2004

Authors and Affiliations

  • Andrea Wevers
    • 1
  • Diana S. Woodruff-Pak
    • 2
    • 3
  1. 1.Department II of Anatomy — NeuroanatomyUniversity of CologneCologneGermany
  2. 2.Department of PsychologyTemple UniversityPhiladelphiaUSA
  3. 3.Department of NeurologyAlbert Einstein Healthcare NetworkPhiladelphiaUSA

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