Nicotinic Receptors and Attention

  • Britta HahnEmail author
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 23)


Facilitation of different attentional functions by nicotinic acetylcholine receptor (nAChR) agonists may be of therapeutic potential in disease conditions such as Alzheimer’s disease or schizophrenia. For this reason, the neuronal mechanisms underlying these effects have been the focus of research in humans and in preclinical models. Attention-enhancing effects of the nonselective nAChR agonist nicotine can be observed in human nonsmokers and in laboratory animals, suggesting that benefits go beyond a reversal of withdrawal deficits in smokers. The ultimate aim is to develop compounds acting with greater selectivity than nicotine at a subset of nAChRs, with an effects profile narrowly matching the targeted cognitive deficits and minimizing unwanted effects. To date, compounds tested clinically target the nAChR subtypes most abundant in the brain. To help pinpoint more selectively expressed subtypes critical for attention, studies have aimed at identifying the secondary neurotransmitter systems whose stimulation mediates the attention-enhancing properties of nicotine. Evidence indicates that noradrenaline and glutamate, but not dopamine release, are critical mediators. Thus, attention -enhancing nAChR agents could spare the system central to nicotine dependence. Neuroimaging studies suggest that nAChR agonists act on a variety of brain systems by enhancing activation, reducing activation, and enhancing deactivation by attention tasks. This supports the notion that effects on different attentional functions may be mediated by distinct central mechanisms, consistent with the fact that nAChRs interact with a multitude of brain sites and neurotransmitter systems. The challenge will be to achieve the optimal tone at the right subset of nAChR subtypes to modulate specific attentional functions, employing not just direct agonist properties, but also positive allosteric modulation and low-dose antagonism.


Nicotinic acetylcholine receptor Attention Nicotine Subtypes Animal models Neuroimaging 


  1. Adams CE, Stevens KE (2007) Evidence for a role of nicotinic acetylcholine receptors in schizophrenia. Front Biosci 12:4755–4772PubMedGoogle Scholar
  2. Adcock RA, Dale C, Fisher M, Aldebot S, Genevsky A, Simpson GV et al (2009) When top-down meets bottom-up: auditory training enhances verbal memory in schizophrenia. Schizophr Bull 35:1132–1141PubMedCentralPubMedGoogle Scholar
  3. Alkondon M, Albuquerque EX (2004) The nicotinic acetylcholine receptor subtypes and their function in the hippocampus and cerebral cortex. Prog Brain Res 145:109–120PubMedGoogle Scholar
  4. Allison C, Shoaib M (2013) Nicotine improves performance in an attentional set shifting task in rats. Neuropharmacology 64:314–320PubMedGoogle Scholar
  5. Andersson K, Hockey GR (1977) Effects of cigarette smoking on incidental memory. Psychopharmacology 52:223–226PubMedGoogle Scholar
  6. Arneric SP, Sullivan JP, Briggs CA, Donnelly-Roberts D, Anderson DJ, Raszkiewicz JL et al (1994) (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: I. In vitro characterization. J Pharmacol Exp Ther 270:310–318PubMedGoogle Scholar
  7. Ashare RL, Valdez JN, Ruparel K, Albelda B, Hopson RD, Keefe JR et al (2013) Association of abstinence-induced alterations in working memory function and COMT genotype in smokers. Psychopharmacology 230:653–662PubMedGoogle Scholar
  8. Barr RS, Culhane MA, Jubelt LE, Mufti RS, Dyer MA, Weiss AP et al (2008) The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls. Neuropsychopharmacology 33:480–490PubMedGoogle Scholar
  9. Bates T, Mangan G, Stough C, Corballis P (1995) Smoking, processing speed and attention in a choice reaction time task. Psychopharmacology 120:209–212PubMedGoogle Scholar
  10. Bentley P, Husain M, Dolan RJ (2004) Effects of cholinergic enhancement on visual stimulation, spatial attention, and spatial working memory. Neuron 41:969–982PubMedGoogle Scholar
  11. Bizarro L, Stolerman IP (2003) Attentional effects of nicotine and amphetamine in rats at different levels of motivation. Psychopharmacology 170:271–277PubMedGoogle Scholar
  12. Blondel A, Simon H, Sanger DJ, Moser P (1999) The effect of repeated nicotine administration on the performance of drug-naive rats in a five-choice serial reaction time task. Behav Pharmacol 10:665–673PubMedGoogle Scholar
  13. 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. Psychopharmacology 149:293–305PubMedGoogle Scholar
  14. Boorman JP, Groot-Kormelink PJ, Sivilotti LG (2000) Stoichiometry of human recombinant neuronal nicotinic receptors containing the b3 subunit expressed in Xenopus oocytes. J Physiol 529:565–577PubMedCentralPubMedGoogle Scholar
  15. Buccafusco JJ, Jackson WJ, Gattu M, Terry AV Jr (1995a) Isoarecolone-induced enhancement of delayed matching to sample performance in monkeys: role of nicotinic receptors. Neuroreport 6:1223–1227PubMedGoogle Scholar
  16. Buccafusco JJ, Jackson WJ, Terry AV Jr, Marsh KC, Decker MW, Arneric SP (1995b) Improvement in performance of a delayed matching-to-sample task by monkeys following ABT-418: a novel cholinergic channel activator for memory enhancement. Psychopharmacology 120:256–266PubMedGoogle Scholar
  17. Buccafusco JJ, Beach JW, Terry AV (2009) Desensitization of nicotinic acetylcholine receptors as a strategy for drug development. J Pharmacol Exp Ther 328:364–370PubMedCentralPubMedGoogle Scholar
  18. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann NY Acad Sci 1124:1–38PubMedGoogle Scholar
  19. Bushnell PJ, Oshiro WM, Padnos BK (1997) Detection of visual signals by rats: effects of chlordiazepoxide and cholinergic and adrenergic drugs on sustained attention. Psychopharmacology 134:230–241PubMedGoogle Scholar
  20. Chavez-Noriega LE, Crona JH, Washburn MS, Urrutia A, Elliott KJ, Johnson EC (1997) Pharmacological characterization of recombinant human neuronal nicotinic acetylcholine receptors h alpha 2 beta 2, h alpha 2 beta 4, h alpha 3 beta 2, h alpha 3 beta 4, h alpha 4 beta 2, h alpha 4 beta 4 and h alpha 7 expressed in Xenopus oocytes. J Pharmacol Exp Ther 280:346–356PubMedGoogle Scholar
  21. Chen D, Patrick JW (1997) The alpha-bungarotoxin-binding nicotinic acetylcholine receptor from rat brain contains only the alpha7 subunit. J Biol Chem 272:24024–24029PubMedGoogle Scholar
  22. Cinciripini PM (1986) The effects of smoking on electrocortical arousal in coronary prone (Type-A) and noncoronary prone (Type-B) subjects. Psychopharmacology 90:522–527PubMedGoogle Scholar
  23. Clarke PB, Kumar R (1983) Characterization of the locomotor stimulant action of nicotine in tolerant rats. Br J Pharmacol 80:587–594PubMedCentralPubMedGoogle Scholar
  24. Clementi F, Fornasari D, Gotti C (2000) Neuronal nicotinic receptors, important new players in brain function. Eur J Pharmacol 393:3–10PubMedGoogle Scholar
  25. Colrain IM, Mangan GL, Pellett OL, Bates TC (1992) Effects of post-learning smoking on memory consolidation. Psychopharmacology 108:448–451PubMedGoogle Scholar
  26. Damaj MI, Creasy KR, Grove AD, Rosecrans JA, Martin BR (1994) Pharmacological effects of epibatidine optical enantiomers. Brain Res 664:34–40PubMedGoogle Scholar
  27. Damaj MI, Creasy KR, Welch SP, Rosecrans JA, Aceto MD, Martin BR (1995) Comparative pharmacology of nicotine and ABT-418, a new nicotinic agonist. Psychopharmacology 120:483–490PubMedGoogle Scholar
  28. Dani JA, Radcliffe KA, Pidoplichko VI (2000) Variations in desensitization of nicotinic acetylcholine receptors from hippocampus and midbrain dopamine areas. Eur J Pharmacol 393:31–38PubMedGoogle Scholar
  29. Davies AR, Hardick DJ, Blagbrough IS, Potter BV, Wolstenholme AJ, Wonnacott S (1999) Characterisation of the binding of [3H]methyllycaconitine: a new radioligand for labelling alpha 7-type neuronal nicotinic acetylcholine receptors. Neuropharmacology 38:679–690PubMedGoogle Scholar
  30. Decker MW, Brioni JD, Sullivan JP, Buckley MJ, Radek RJ, Raszkiewicz JL et al (1994) (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: II. In vivo characterization. J Pharmacol Exp Ther 270:319–328PubMedGoogle Scholar
  31. Decker MW, Brioni JD, Bannon AW, Arneric SP (1995) Diversity of neuronal nicotinic acetylcholine receptors: lessons from behavior and implications for CNS therapeutics. Life Sci 56:545–570PubMedGoogle Scholar
  32. Di Chiara G (2000) Role of dopamine in the behavioural actions of nicotine related to addiction. Eur J Pharmacol 393:295–314PubMedGoogle Scholar
  33. Domier CP, Monterosso JR, Brody AL, Simon SL, Mendrek A, Olmstead R et al (2007) Effects of cigarette smoking and abstinence on stroop task performance. Psychopharmacology 195:1–9PubMedCentralPubMedGoogle Scholar
  34. Dunbar G, Boeijinga PH, Demazieres A, Cisterni C, Kuchibhatla R, Wesnes K et al (2007) Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers. Psychopharmacology 191:919–929PubMedGoogle Scholar
  35. Ettinger U, Williams SCR, Patel D, Michel TM, Nwaigwe A, Caceres A et al (2009) Effects of acute nicotine on brain function in healthy smokers and non-smokers: estimation of inter-individual response heterogeneity. Neuroimage 45:549–561PubMedGoogle Scholar
  36. Fisher DJ, Scott TL, Shah DK, Prise S, Thompson M, Knott VJ (2010) Light up and see: enhancement of the visual mismatch negativity (vMMN) by nicotine. Brain Res 1313:162–171PubMedGoogle Scholar
  37. Foulds J, Stapleton J, Swettenham J, Bell N, McSorley K, Russell MA (1996) Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers. Psychopharmacology 127:31–38PubMedGoogle Scholar
  38. Freedman R, Coon H, MylesWorsley M, OrrUrtreger A, Olincy A, Davis A et al (1997) Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 94:587–592PubMedCentralPubMedGoogle Scholar
  39. Freedman R, Olincy A, Buchanan RW, Harris JG, Gold JM, Johnson L et al (2008) Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J Psychiatry 165:1040–1047PubMedCentralPubMedGoogle Scholar
  40. Gentry CL, Lukas RJ (2002) Regulation of nicotinic acetylcholine receptor numbers and function by chronic nicotine exposure. Curr Drug Targets CNS Neurol Disord 1:359–385PubMedGoogle Scholar
  41. Gerzanich V, Peng X, Wang F, Wells G, Anand R, Fletcher S et al (1995) Comparative pharmacology of epibatidine: a potent agonist for neuronal nicotinic acetylcholine receptors. Mol Pharmacol 48:774–782PubMedGoogle Scholar
  42. Giessing C, Thiel CM, Rosler F, Fink GR (2006) The modulatory effects of nicotine on parietal cortex activity in a cued target detection task depend on cue reliability. Neuroscience 137:853–864PubMedGoogle Scholar
  43. Gilbert DG, McClernon FJ, Rabinovich NE, Sugai C, Plath LC, Asgaard G et al (2004) Effects of quitting smoking on EEG activation and attention last for more than 31 days and are more severe with stress, dependence, DRD2 A1 allele, and depressive traits. Nicotine Tob Res 6:249–267PubMedGoogle Scholar
  44. Gilbert DG, Izetelny A, Radtke R, Hammersley J, Rabinovich NE, Jameson TR et al (2005) Dopamine receptor (DRD2) genotype-dependent effects of nicotine on attention and distraction during rapid visual information processing. Nicotine Tob Res 7:361–379PubMedGoogle Scholar
  45. Giniatullin R, Nistri A, Yakel JL (2005) Desensitization of nicotinic ACh receptors: shaping cholinergic signaling. Trends Neurosci 28:371–378PubMedGoogle Scholar
  46. Goldberg SR, Risner ME, Stolerman IP, Reavill C, Garcha HS (1989) Nicotine and some related compounds: effects on schedule-controlled behaviour and discriminative properties in rats. Psychopharmacology 97:295–302PubMedGoogle Scholar
  47. Gotti C, Moretti M, Gaimarri A, Zanardi A, Clementi F, Zoli M (2007) Heterogeneity and complexity of native brain nicotinic receptors. Biochem Pharmacol 74:1102–1111PubMedGoogle Scholar
  48. Gotti C, Clementi F, Fornari A, Gaimarri A, Guiducci S, Manfredi I et al (2009) Structural and functional diversity of native brain neuronal nicotinic receptors. Biochem Pharmacol 78:703–711PubMedGoogle Scholar
  49. Griesar WS, Zajdel DP, Oken BS (2002) Nicotine effects on alertness and spatial attention in non-smokers. Nicotine Tob Res 4:185–194PubMedGoogle Scholar
  50. Grilly DM (2000) A verification of psychostimulant-induced improvement in sustained attention in rats: effects of d-amphetamine, nicotine, and pemoline. Exp Clin Psychopharmacol 8:14–21PubMedGoogle Scholar
  51. Grilly DM, Simon BB, Levin ED (2000) Nicotine enhances stimulus detection performance of middle- and old-aged rats: a longitudinal study. Pharmacol Biochem Behav 65:665–670PubMedGoogle Scholar
  52. Grobe JE, Perkins KA, Goettler-Good J, Wilson A (1998) Importance of environmental distractors in the effects of nicotine on short-term memory. Exp Clin Psychopharmacol 6:209–216PubMedGoogle Scholar
  53. 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 117:197–208PubMedGoogle Scholar
  54. Grottick AJ, Trube G, Corrigall WA, Huwyler J, Malherbe P, Wyler R et al (2000) Evidence that nicotinic alpha(7) receptors are not involved in the hyperlocomotor and rewarding effects of nicotine. J Pharmacol Exp Ther 294:1112–1119PubMedGoogle Scholar
  55. Grottick AJ, Wyler R, Higgins GA (2001) A study of the nicotinic agonist SIB-1553A on locomotion, and attention as measured by the five-choice serial reaction time task. Pharmacol Biochem Behav 70:505–513PubMedGoogle Scholar
  56. Grottick AJ, Haman M, Wyler R, Higgins GA (2003) Reversal of a vigilance decrement in the aged rat by subtype-selective nicotinic ligands. Neuropsychopharmacology 28:880–887PubMedGoogle Scholar
  57. Gundisch D, Eibl C (2011) Nicotinic acetylcholine receptor ligands, a patent review (2006–2011). Expert Opin Ther Pat 21:1867–1896PubMedCentralPubMedGoogle Scholar
  58. Gusnard DA, Raichle ME (2001) Searching for a baseline: functional imaging and the resting human brain. Nat Rev Neurosci 2:685–694PubMedGoogle Scholar
  59. Hahn B, Stolerman IP (2002) Nicotine-induced attentional enhancement in rats: effects of chronic exposure to nicotine. Neuropsychopharmacology 27:712–722Google Scholar
  60. Hahn B, Stolerman IP (2005) Modulation of nicotine-induced attentional enhancement in rats by adrenoceptor antagonists. Psychopharmacology 177:438–447PubMedGoogle Scholar
  61. Hahn B, Shoaib M, Stolerman IP (2002a) Effects of dopamine receptor antagonists on nicotine-induced attentional enhancement. Behav Pharmacol 13:621–632PubMedGoogle Scholar
  62. Hahn B, Shoaib M, Stolerman IP (2002b) Nicotine-induced enhancement of attention in the five-choice serial reaction time task: the influence of task-demands. Psychopharmacology 162:129–137PubMedGoogle Scholar
  63. Hahn B, Sharples CG, Wonnacott S, Shoaib M, Stolerman IP (2003) Attentional effects of nicotinic agonists in rats. Neuropharmacology 44:1054–1067PubMedGoogle Scholar
  64. Hahn B, Ross TJ, Yang Y, Kim I, Huestis MA, Stein EA (2007) Nicotine enhances visuospatial attention by deactivating areas of the resting brain default network. J Neurosci 27:3477–3489PubMedCentralPubMedGoogle Scholar
  65. Hahn B, Ross TJ, Wolkenberg FA, Shakleya DM, Huestis MA, Stein EA (2009) Performance effects of nicotine during selective attention, divided attention, and simple stimulus detection: an fMRI study. Cereb Cortex 19:1990–2000PubMedCentralPubMedGoogle Scholar
  66. Hahn B, Shoaib M, Stolerman IP (2011) Selective nicotinic receptor antagonists: effects on attention and nicotine-induced attentional enhancement. Psychopharmacology 217:75–82PubMedGoogle Scholar
  67. Harris JG, Kongs S, Allensworth D, Martin L, Tregellas J, Sullivan B et al (2004) Effects of nicotine on cognitive deficits in schizophrenia. Neuropsychopharmacology 29:1378–1385PubMedGoogle Scholar
  68. Harvey SC, Luetje CW (1996) Determinants of competitive antagonist sensitivity on neuronal nicotinic receptor beta subunits. J Neurosci 16:3798–3806PubMedGoogle Scholar
  69. Harvey SC, Maddox FN, Luetje CW (1996) Multiple determinants of dihydro-beta-erythroidine sensitivity on rat neuronal nicotinic receptor alpha subunits. J Neurochem 67:1953–1959PubMedGoogle Scholar
  70. Hasenfratz M, Battig K (1992) Action profiles of smoking and caffeine: Stroop effect, EEG, and peripheral physiology. Pharmacol Biochem Behav 42:155–161PubMedGoogle Scholar
  71. Hasenfratz M, Michel C, Nil R, Battig K (1989) Can smoking increase attention in rapid information-processing during noise—electrocortical, physiological and behavioral-effects. Psychopharmacology 98:75–80PubMedGoogle Scholar
  72. Hatsukami D, Fletcher L, Morgan S, Keenan R, Amble P (1989) The effects of varying cigarette deprivation duration on cognitive and performance tasks. J Subst Abuse 1:407–416PubMedGoogle Scholar
  73. Haydar SN, Dunlop J (2010) Neuronal nicotinic acetylcholine receptors—targets for the development of drugs to treat cognitive impairment associated with schizophrenia and Alzheimer’s disease. Curr Top Med Chem 10:144–152PubMedGoogle Scholar
  74. Heishman SJ, Henningfield JE (2000) Tolerance to repeated nicotine administration on performance, subjective, and physiological responses in nonsmokers. Psychopharmacology 152:321–333PubMedGoogle Scholar
  75. Heishman SJ, Snyder FR, Henningfield JE (1990) Effect of repeated nicotine administration in nonsmokers. NIDA Res Monogr 105:314–315PubMedGoogle Scholar
  76. Heishman SJ, Snyder FR, Henningfield JE (1993) Performance, subjective, and physiological effects of nicotine in non-smokers. Drug Alcohol Depend 34:11–18PubMedGoogle Scholar
  77. Heishman SJ, Taylor RC, Henningfield JE (1994) Nicotine and smoking: a review of effects on human performance. Exp Clin Psychopharmacol 2:345–395Google Scholar
  78. Heishman SJ, Kleykamp BA, Singleton EG (2010) Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology 210:453–469PubMedCentralPubMedGoogle Scholar
  79. Hong LE, Schroeder M, Ross TJ, Buchholz B, Salmeron BJ, Wonodi I et al (2011) Nicotine enhances but does not normalize visual sustained attention and the associated brain network in schizophrenia. Schizophr Bull 37:416–425PubMedCentralPubMedGoogle Scholar
  80. Howe WM, Ji J, Parikh V, Williams S, Mocaer E, Trocme-Thibierge C et al (2010) Enhancement of attentional performance by selective stimulation of alpha4beta2(*) nAChRs: underlying cholinergic mechanisms. Neuropsychopharmacology 35:1391–1401PubMedCentralPubMedGoogle Scholar
  81. Hoyle E, Genn RF, Fernandes C, Stolerman IP (2006) Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task. Psychopharmacology 189:211–223PubMedCentralPubMedGoogle Scholar
  82. Hurst R, Rollema H, Bertrand D (2013) Nicotinic acetylcholine receptors: from basic science to therapeutics. Pharmacol Ther 137:22–54PubMedGoogle Scholar
  83. Jacobsen LK, Gore JC, Skudlarski P, Lacadie CM, Jatlow P, Krystal JH (2002) Impact of intravenous nicotine on BOLD signal response to photic stimulation. Magn Reson Imaging 20:141–145PubMedGoogle Scholar
  84. Jacobsen LK, D’Souza DC, Mencl WE, Pugh KR, Skudlarski P, Krystal JH (2004) Nicotine effects on brain function and functional connectivity in schizophrenia. Biol Psychiatry 55:850–858PubMedGoogle Scholar
  85. Jones GM, Sahakian BJ, Levy R, Warburton DM, Gray JA (1992) Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer’s disease. Psychopharmacology 108:485–494PubMedGoogle Scholar
  86. Jones KM, McDonald IM, Bourin C, Olson RE, Bristow LJ, Easton A (2014) Effect of alpha7 nicotinic acetylcholine receptor agonists on attentional set-shifting impairment in rats. Psychopharmacology 231:673–683PubMedGoogle Scholar
  87. Juliano LM, Fucito LM, Harrell PT (2011) The Influence of nicotine dose and nicotine dose expectancy on the cognitive and subjective effects of cigarette smoking. Exp Clin Psychopharmacol 19:105–115PubMedCentralPubMedGoogle Scholar
  88. Kelly AM, Uddin LQ, Biswal BB, Castellanos FX, Milham MP (2008) Competition between functional brain networks mediates behavioral variability. Neuroimage 39:527–537PubMedGoogle Scholar
  89. Kendziorra K, Wolf H, Meyer PM, Barthel H, Hesse S, Becker GA et al (2011) Decreased cerebral a4β2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer’s disease assessed with positron emission tomography. Eur J Nucl Med Mol Imaging 38:515–525PubMedGoogle Scholar
  90. Kenney JW, Gould TJ (2008) Modulation of hippocampus-dependent learning and synaptic plasticity by nicotine. Mol Neurobiol 38:101–121PubMedCentralPubMedGoogle Scholar
  91. Knott V, Bosman M, Mahoney C, Ilivitsky V, Quirt K (1999) Transdermal nicotine: Single dose effects on mood, EEG, performance, and event-related potentials. Pharmacol Biochem Behav 63:253–261PubMedGoogle Scholar
  92. Knott V, Millar A, Fisher D, Albert P (2010a) Effects of nicotine on the amplitude and gating of the auditory P50 and its influence by dopamine D2 receptor gene polymorphism. Neuroscience 166:145–156PubMedGoogle Scholar
  93. Knott VJ, Fisher DJ, Millar AM (2010b) Differential effects of nicotine on P50 amplitude, its gating, and their neural sources in low and high suppressors. Neuroscience 170:816–826PubMedGoogle Scholar
  94. Knott VJ, Millar AM, McIntosh JF, Shah DK, Fisher DJ, Blais CM et al (2011) Separate and combined effects of low dose ketamine and nicotine on behavioural and neural correlates of sustained attention. Biol Psychol 88:83–93PubMedGoogle Scholar
  95. Koelega HS (1993) Stimulant drugs and vigilance performance: a review. Psychopharmacology 111:1–16PubMedGoogle Scholar
  96. Kumari V, Gray JA, ffytche DH, Mitterschiffthaler MT, Das M, Zachariah E et al (2003) Cognitive effects of nicotine in humans: an fMRI study. Neuroimage 19:1002–1013PubMedGoogle Scholar
  97. Lawrence NS, Ross TJ, Stein EA (2002) Cognitive mechanisms of nicotine on visual attention. Neuron 36:539–548PubMedGoogle Scholar
  98. Leiser SC, Bowlby MR, Comery TA, Dunlop J (2009) A cog in cognition: how the alpha 7 nicotinic acetylcholine receptor is geared towards improving cognitive deficits. Pharmacol Ther 122:302–311PubMedGoogle Scholar
  99. Leonard S, Gault J, Hopkins J, Logel J, Vianzon R, Short M et al (2002) Association of promoter variants in the alpha 7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia. Arch Gen Psychiatry 59:1085–1096PubMedGoogle Scholar
  100. Lerman C, Audrain J, Tercyak K, Hawk LW Jr, Bush A, Crystal-Mansour S et al (2001) Attention-deficit hyperactivity disorder (ADHD) symptoms and smoking patterns among participants in a smoking-cessation program. Nicotine Tob Res 3:353–359PubMedGoogle Scholar
  101. Levin ED (1992) Nicotinic systems and cognitive function. Psychopharmacology 108:417–431PubMedGoogle Scholar
  102. Levin ED, Caldwell DP (2006) Low-dose mecamylamine improves learning of rats in the radial-arm maze repeated acquisition procedure. Neurobiol Learn Mem 86:117–122PubMedGoogle Scholar
  103. Levin ED, Rezvani AH (2002) Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord 1:423–431PubMedGoogle Scholar
  104. Levin ED, Conners CK, Sparrow E, Hinton SC, Erhardt D, Meck WH et al (1996) Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology 123:55–63PubMedGoogle Scholar
  105. Levin ED, Conners CK, Silva D, Hinton SC, Meck WH, March J et al (1998) Transdermal nicotine effects on attention. Psychopharmacology 140:135–141PubMedGoogle Scholar
  106. Levin ED, Cauley M, Rezvani AH (2013) Improvement of attentional function with antagonism of nicotinic receptors in female rats. Eur J Pharmacol 702:269–274PubMedCentralPubMedGoogle Scholar
  107. Lieberman JA, Dunbar G, Segreti AC, Girgis RR, Seoane F, Beaver JS et al (2013) A randomized exploratory trial of an alpha-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia. Neuropsychopharmacology 38:968–975PubMedCentralPubMedGoogle Scholar
  108. Lindgren M, Stenberg G, Rosen I (1998) Effects of nicotine in a bimodal attention task. Neuropsychobiology 38:42–49PubMedGoogle Scholar
  109. Lopez E, Arce C, Vicente S, Oset-Gasque MJ, Gonzalez MP (2001) Nicotinic receptors mediate the release of amino acid neurotransmitters in cultured cortical neurons. Cereb Cortex 11:158–163PubMedGoogle Scholar
  110. Loughead J, Ray R, Wileyto EP, Ruparel K, Sanborn P, Siegel S et al (2010) Effects of the alpha 4 beta 2 partial agonist varenicline on brain activity and working memory in abstinent smokers. Biol Psychiatry 67:715–721PubMedGoogle Scholar
  111. Lukas RJ, Changeux J-P, Le Novere N, Albuquerque EX, Balfour DJK, Berg DK et al (1999) International union of pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits. Pharmacol Rev 51:397–401PubMedGoogle Scholar
  112. Macallan DR, Lunt GG, Wonnacott S, Swanson KL, Rapoport H, Albuquerque EX (1988) Methyllycaconitine and (+)-anatoxin-a differentiate between nicotinic receptors in vertebrate and invertebrate nervous systems. FEBS Lett 226:357–363PubMedGoogle Scholar
  113. MacDermott AB, Role LW, Siegelbaum SA (1999) Presynaptic ionotropic receptors and the control of transmitter release. Annu Rev Neurosci 22:443–485PubMedGoogle Scholar
  114. Mackworth NH (1950) Researches on the measurement of human performance. Medical Research Council, Special report series 268. His Majesty’s stationary office, London, p 156Google Scholar
  115. Mahncke HW, Bronstone A, Merzenich MM (2006) Brain plasticity and functional losses in the aged: scientific bases for a novel intervention. Reprogram Brain 157:81–109Google Scholar
  116. Mancuso G, Warburton DM, Melen M, Sherwood N, Tirelli E (1999) Selective effects of nicotine on attentional processes. Psychopharmacology 146:199–204PubMedGoogle Scholar
  117. Mancuso G, Lejeune M, Ansseau M (2001) Cigarette smoking and attention: processing speed or specific effects? Psychopharmacology 155:372–378PubMedGoogle Scholar
  118. Mangan GL, Golding JF (1983) The effects of smoking on memory consolidation. J Psychol 115:65–77PubMedGoogle Scholar
  119. Mansvelder HD, Keath JR, McGehee DS (2002) Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas. Neuron 33:905–919PubMedGoogle Scholar
  120. Mansvelder HD, van Aerde KI, Couey JJ, Brussaard AB (2006a) Nicotinic modulation of neuronal networks: from receptors to cognition. Psychopharmacology 184:292–305PubMedGoogle Scholar
  121. Mansvelder HD, van Aerde KI, Couey JJ, Brussaard AB (2006b) Nicotinic modulation of neuronal networks: from receptors to cognition. Psychopharmacology 184:292–305PubMedGoogle Scholar
  122. Martin LF, Freedman R (2007) Schizophrenia and the alpha 7 nicotinic acetylcholine receptor. Integr Neurobiol Schizophr 78:225–246Google Scholar
  123. Martin LF, Kem WR, Freedman R (2004) Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia. Psychopharmacology 174:54–64PubMedGoogle Scholar
  124. Martin LF, Davalos DB, Kisley MA (2009) Nicotine enhances automatic temporal processing as measured by the mismatch negativity waveform. Nicotine Tob Res 11:698–706PubMedGoogle Scholar
  125. McGaughy J, Sarter M (1995) Behavioral vigilance in rats: task validation and effects of age, amphetamine, and benzodiazepine receptor ligands. Psychopharmacology 117:340–357PubMedGoogle Scholar
  126. McGaughy J, Decker MW, Sarter M (1999) Enhancement of sustained attention performance by the nicotinic acetylcholine receptor agonist ABT-418 in intact but not basal forebrain-lesioned rats. Psychopharmacology 144:175–182PubMedGoogle Scholar
  127. McLean SL, Idris NF, Grayson B, Gendle DF, Mackie C, Lesage AS et al (2012) PNU-120596, a positive allosteric modulator of alpha7 nicotinic acetylcholine receptors, reverses a sub-chronic phencyclidine-induced cognitive deficit in the attentional set-shifting task in female rats. J Psychopharmacol 26:1265–1270PubMedGoogle Scholar
  128. Michel C, Hasenfratz M, Nil R, Battig K (1988) Cardiovascular, electrocortical, and behavioral-effects of nicotine chewing gum. Klin Wochenschr 66:72–79PubMedGoogle Scholar
  129. Millar NS, Gotti C (2009) Diversity of vertebrate nicotinic acetylcholine receptors. Neuropharmacology 56:237–246PubMedGoogle Scholar
  130. Mirza NR, Stolerman IP (1998) Nicotine enhances sustained attention in the rat under specific task conditions. Psychopharmacology 138:266–274PubMedGoogle Scholar
  131. Mirza NR, Pei Q, Stolerman IP, Zetterstrom TS (1996) The nicotinic receptor agonists (−)-nicotine and isoarecolone differ in their effects on dopamine release in the nucleus accumbens. Eur J Pharmacol 295:207–210PubMedGoogle Scholar
  132. Morrison CF, Stephenson JA (1973) Effects of stimulants on observed behaviour of rats on six operant schedules. Neuropharmacology 12:297–310PubMedGoogle Scholar
  133. Muir JL, Everitt BJ, Robbins TW (1995) 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 118:82–92PubMedGoogle Scholar
  134. Murphy FC, Klein RM (1998) The effects of nicotine on spatial and non-spatial expectancies in a covert orienting task. Neuropsychologia 36:1103–1114PubMedGoogle Scholar
  135. Nelsen JM, Goldstein L (1972) Improvement of performance on an attention task with chronic nicotine treatment in rats. Psychopharmacology 26:347–360Google Scholar
  136. Nelsen JM, Goldstein L (1973) Chronic nicotine treatment in rats. 1. Acquisition and performance of an attention task. Res Commun Chem Pathol Pharmacol 5:681–693PubMedGoogle Scholar
  137. Newhouse PA, Potter A, Singh A (2004) Effects of nicotinic stimulation on cognitive performance. Curr Opin Pharmacol 4:36–46PubMedGoogle Scholar
  138. Nordberg A, Alafuzoff I, Winblad B (1992) Nicotinic and muscarinic subtypes in the human brain: changes with aging and dementia. J Neurosci Res 31:103–111PubMedGoogle Scholar
  139. Nordberg A, Lundqvist H, Hartvig P, Lilja A, Langstrom B (1995) Kinetic analysis of regional (S)(-)11C-nicotine binding in normal and Alzheimer brains—in vivo assessment using positron emission tomography. Alzheimer Dis Assoc Disord 9:21–27PubMedGoogle Scholar
  140. O’Brien JT, Colloby SJ, Pakrasi S, Perry EK, Pimlott SL, Wyper DJ (2007) alpha4beta2 nicotinic receptor status in Alzheimer’s disease using 123I-5IA-85380 single-photon-emission computed tomography. J Neurol Neurosurg Psychiatry 78:356–362PubMedCentralPubMedGoogle Scholar
  141. Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D et al (2006) Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry 63:630–638PubMedGoogle Scholar
  142. Paolone G, Angelakos CC, Meyer PJ, Robinson TE, Sarter M (2013) Cholinergic control over attention in rats prone to attribute incentive salience to reward cues. J Neurosci 33:8321–8335PubMedCentralPubMedGoogle Scholar
  143. Parasuraman R, Warm JS, Dember WN (1987) Vigilance: taxonomy and utility. In: Mark LS, Warm JS, Houston RL (eds) Ergonomics and human factors. Springer, New YorkGoogle Scholar
  144. Parrott AC, Craig D (1992) Cigarette smoking and nicotine gum (0, 2 and 4 mg): effects upon four visual attention tasks. Neuropsychobiology 25:34–43PubMedGoogle Scholar
  145. Peeke SC, Peeke HV (1984) Attention, memory, and cigarette smoking. Psychopharmacology 84:205–216PubMedGoogle Scholar
  146. Perkins KA, Grobe JE, Fonte C, Goettler J, Caggiula AR, Reynolds WA et al (1994) Chronic and acute tolerance to subjective, behavioral and cardiovascular effects of nicotine in humans. J Pharmacol Exp Ther 270:628–638PubMedGoogle Scholar
  147. Perry E, Martin-Ruiz C, Lee M, Griffiths M, Johnson M, Piggott M et al (2000) Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases. Eur J Pharmacol 393:215–222PubMedGoogle Scholar
  148. Petrovsky N, Quednow BB, Ettinger U, Schmechtig A, Mossner R, Collier DA et al (2010) Sensorimotor gating is associated with CHRNA3 polymorphisms in schizophrenia and healthy volunteers. Neuropsychopharmacology 35:1429–1439PubMedCentralPubMedGoogle Scholar
  149. Phillips JM, McAlonan K, Robb WG, Brown VJ (2000) Cholinergic neurotransmission influences covert orientation of visuospatial attention in the rat. Psychopharmacology 150:112–116PubMedGoogle Scholar
  150. Picciotto MR, Addy NA, Mineur YS, Brunzell DH (2008) It is not “either/or”: activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood. Prog Neurobiol 84:329–342PubMedCentralPubMedGoogle Scholar
  151. Pimlott SL, Piggott M, Owens J, Greally E, Court JA, Jaros E et al (2004) Nicotinic acetylcholine receptor distribution in Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease, and vascular dementia: in vitro binding study using 5-[(125)I]-A-85380. Neuropsychopharmacology 29:108–116PubMedGoogle Scholar
  152. Polli FE, Barton JJ, Cain MS, Thakkar KN, Rauch SL, Manoach DS (2005) Rostral and dorsal anterior cingulate cortex make dissociable contributions during antisaccade error commission. Proc Natl Acad Sci USA 102:15700–15705PubMedCentralPubMedGoogle Scholar
  153. Poltavski DV, Petros T (2006) Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits. Physiol Behav 87:614–624PubMedGoogle Scholar
  154. Potter AS, Ryan KK, Newhouse PA (2009) Effects of acute ultra-low dose mecamylamine on cognition in adult attention-deficit/hyperactivity disorder (ADHD). Hum Psychopharmacol 24:309–317PubMedCentralPubMedGoogle Scholar
  155. Prendergast MA, Jackson WJ, Terry AV Jr, Decker MW, Arneric SP, Buccafusco JJ (1998) Central nicotinic receptor agonists ABT-418, ABT-089, and (−)-nicotine reduce distractibility in adult monkeys. Psychopharmacology 136:50–58PubMedGoogle Scholar
  156. Pritchard WS, Robinson JH, Debethizy JD, Davis RA, Stiles MF (1995) Caffeine and smoking—subjective, performance, and psychophysiological effects. Psychophysiology 32:19–27PubMedGoogle Scholar
  157. Provost SC, Woodward R (1991) Effects of nicotine gum on repeated administration of the Stroop test. Psychopharmacology 104:536–540PubMedGoogle Scholar
  158. Quarta D, Naylor CG, Morris HV, Patel S, Genn RF, Stolerman IP (2007) Different effects of ionotropic and metabotropic glutamate receptor antagonists on attention and the attentional properties of nicotine. Neuropharmacology 53:421–430PubMedGoogle Scholar
  159. Quarta D, Naylor CG, Glennon JC, Stolerman IP (2012) Serotonin antagonists in the five-choice serial reaction time task and their interactions with nicotine. Behav Pharmacol 23:143–152PubMedGoogle Scholar
  160. Radek RJ, Miner HM, Bratcher NA, Decker MW, Gopalakrishnan M, Bitner RS (2006) Alpha(4)beta(2) nicotinic receptor stimulation contributes to the effects of nicotine in the DBA/2 mouse model of sensory gating. Psychopharmacology 187:47–55PubMedGoogle Scholar
  161. Radek RJ, Kohlhaas KL, Rueter LE, Mohler EG (2010) Treating the cognitive deficits of schizophrenia with alpha4beta2 neuronal nicotinic receptor agonists. Curr Pharm Des 16:309–322PubMedGoogle Scholar
  162. Revell AD (1988) Smoking and performance–a puff-by-puff analysis. Psychopharmacology 96:563–565PubMedGoogle Scholar
  163. Rezvani AH, Caldwell DP, Levin ED (2005) Nicotinic-serotonergic drug interactions and attentional performance in rats. Psychopharmacology 179:521–528PubMedGoogle Scholar
  164. Rezvani AH, Kholdebarin E, Brucato FH, Callahan PM, Lowe DA, Levin ED (2009) Effect of R3487/MEM3454, a novel nicotinic alpha7 receptor partial agonist and 5-HT3 antagonist on sustained attention in rats. Prog Neuropsychopharmacol Biol Psychiatry 33:269–275PubMedGoogle Scholar
  165. Role LW, Berg DK (1996) Nicotinic receptors in the development and modulation of CNS synapses. Neuron 16:1077–1085PubMedGoogle Scholar
  166. Rollema H, Hajos M, Seymour PA, Kozak R, Majchrzak MJ, Guanowsky V et al (2009) Preclinical pharmacology of the alpha 4 beta 2 nAChR partial agonist varenicline related to effects on reward, mood and cognition. Biochem Pharmacol 78:813–824PubMedGoogle Scholar
  167. Rose JE, Corrigall WA (1997) Nicotine self-administration in animals and humans: similarities and differences. Psychopharmacology 130:28–40PubMedGoogle Scholar
  168. Rose EJ, Ross TJ, Kurup PK, Stein EA (2010) Nicotine modulation of information processing is not limited to input (attention) but extends to output (intention). Psychopharmacology 209:291–302PubMedCentralPubMedGoogle Scholar
  169. Rusted JM, Warburton DM (1992) Facilitation of memory by post-trial administration of nicotine: evidence for an attentional explanation. Psychopharmacology 108:452–455PubMedGoogle Scholar
  170. Sahakian B, Jones G, Levy R, Gray J, Warburton D (1989) The effects of nicotine on attention, information processing, and short- term memory in patients with dementia of the Alzheimer type. Br J Psychiatry 154:797–800PubMedGoogle Scholar
  171. Salminen O, Whiteaker P, Grady SR, Collins AC, McIntosh JM, Marks MJ (2005) The subunit composition and pharmacology of alpha-conotoxin MII-binding nicotinic acetylcholine receptors studied by a novel membrane-binding assay. Neuropharmacology 48:696–705PubMedGoogle Scholar
  172. Schreiber R, Dalmus M, De Vry J (2002) Effects of alpha(4)/beta(2)- and alpha(7)-nicotine acetylcholine receptor agonists on prepulse inhibition of the acoustic startle response in rats and mice. Psychopharmacology 159:248–257PubMedGoogle Scholar
  173. Seguela P, Wadiche J, Dineley-Miller K, Dani JA, Patrick JW (1993) Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium. J Neurosci 13:596–604PubMedGoogle Scholar
  174. Semenova S, Stolerman IP, Markou A (2007) Chronic nicotine administration improves attention while nicotine withdrawal induces performance deficits in the 5-choice serial reaction time task in rats. Pharmacol Biochem Behav 87:360–368PubMedCentralPubMedGoogle Scholar
  175. Shiina A, Shirayama Y, Niitsu T, Hashimoto T, Yoshida T, Hasegawa T et al (2010) A randomised, double-blind, placebo-controlled trial of tropisetron in patients with schizophrenia. Ann Gen Psychiatry 9:27Google Scholar
  176. Shoaib M (2006) Effects of isoarecolone, a nicotinic receptor agonist in rodent models of nicotine dependence. Psychopharmacology 188:252–257PubMedGoogle Scholar
  177. Singh A, Potter A, Newhouse P (2004) Nicotinic acetylcholine receptor system and neuropsychiatric disorders. IDrugs. 7:1096–1103PubMedGoogle Scholar
  178. Snyder FR, Davis FC, Henningfield JE (1989) The tobacco withdrawal syndrome: performance decrements assessed on a computerized test battery. Drug Alcohol Depend 23:259–266PubMedGoogle Scholar
  179. Spealman RD, Goldberg SR, Gardner ML (1981) Behavioral effects of nicotine: schedule-controlled responding by squirrel monkeys. J Pharmacol Exp Ther 216:484–491PubMedGoogle Scholar
  180. Spilich GJ, June L, Renner J (1992) Cigarette smoking and cognitive performance. Br J Addict 87:1313–1326PubMedGoogle Scholar
  181. Stewart C, Burke S, Marrocco R (2001) Cholinergic modulation of covert attention in the rat. Psychopharmacology 155:210–218PubMedGoogle Scholar
  182. Stolerman IP (1999) Inter-species consistency in the behavioural pharmacology of nicotine dependence. Behav Pharmacol 10:559–580PubMedGoogle Scholar
  183. Stolerman IP, Mirza NR, Shoaib M (1995) Nicotine psychopharmacology: addiction, cognition and neuroadaptation. Med Res Rev 15:47–72PubMedGoogle Scholar
  184. Stolerman IP, Chandler CJ, Garcha HS, Newton JM (1997) Selective antagonism of behavioural effects of nicotine by dihydro-beta-erythroidine in rats. Psychopharmacology 129:390–397PubMedGoogle Scholar
  185. Stolerman IP, Naylor CG, Mesdaghinia A, Morris HV (2009) The duration of nicotine-induced attentional enhancement in the five-choice serial reaction time task: lack of long-lasting cognitive improvement. Behav Pharmacol 20:742–754PubMedGoogle Scholar
  186. Sullivan JP, Decker MW, Brioni JD, Donnelly-Roberts D, Anderson DJ, Bannon AW et al (1994) (±)-Epibatidine elicits a diversity of in vitro and in vivo effects mediated by nicotinic acetylcholine receptors. J Pharmacol Exp Ther 271:624–631PubMedGoogle Scholar
  187. Sweet LH, Mulligan RC, Finnerty CE, Jerskey BA, David SP, Cohen RA et al (2010) Effects of nicotine withdrawal on verbal working memory and associated brain response. Psychiatry Res-Neuroimaging 183:69–74Google Scholar
  188. Tani Y, Saito K, Tsuneyoshi A, Imoto M, Ohno T (1997) Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice. Psychopharmacology 129:225–232PubMedGoogle Scholar
  189. Terriere E, Sharman M, Donaghey C, Herrmann L, Lonie J, Strachan M et al (2008) Alpha4 beta2-nicotinic receptor binding with 5-IA in Alzheimer’s disease: methods of scan analysis. Neurochem Res 33:643–651PubMedGoogle Scholar
  190. Terry AV, Buccafusco JJ, Prendergast MA (1999) Dose-specific improvements in memory-related task performance by rats and aged monkeys administered the nicotinic-cholinergic antagonist mecamylamine. Drug Dev Res 47:127–136Google Scholar
  191. Thiel CM, Zilles K, Fink GR (2005) Nicotine modulates reorienting of visuospatial attention and neural activity in human parietal cortex. Neuropsychopharmacology 30:810–820PubMedGoogle Scholar
  192. Tregellas JR, Tanabe JL, Martin LF, Freedman R (2005) fMRI of response to nicotine during a smooth pursuit eye movement task in schizophrenia. Am J Psychiatry 162:391–393PubMedGoogle Scholar
  193. Tregellas JR, Olincy A, Johnson L, Tanabe J, Shatti S, Martin LF et al (2010) Functional magnetic resonance imaging of effects of a nicotinic agonist in Schizophrenia. Neuropsychopharmacology 35:938–942PubMedCentralPubMedGoogle Scholar
  194. Tregellas JR, Tanabe J, Rojas DC, Shatti S, Olincy A, Johnson L et al (2011) Effects of an alpha 7-nicotinic agonist on default network activity in schizophrenia. Biol Psychiatry 69:7–11PubMedCentralPubMedGoogle Scholar
  195. Tuesta LM, Fowler CD, Kenny PJ (2011) Recent advances in understanding nicotinic receptor signaling mechanisms that regulate drug self-administration behavior. Biochem Pharmacol 82:984–995PubMedCentralPubMedGoogle Scholar
  196. Turchi J, Holley LA, Sarter M (1995) Effects of nicotinic acetylcholine receptor ligands on behavioral vigilance in rats. Psychopharmacology 118:195–205PubMedGoogle Scholar
  197. Turchi J, Holley LA, Sarter M (1996) Effects of benzodiazepine receptor inverse agonists and nicotine on behavioral vigilance in senescent rats. J Gerontol Ser A-Biol Sci Med Sci 51:B225–B231Google Scholar
  198. Umbricht D, Keefe RS, Murray S, Lowe DA, Porter R, Garibaldi G et al (2014) A randomized, placebo-controlled study investigating the nicotinic a7 Agonist, RG3487, for cognitive deficits in schizophrenia. Neuropsychopharmacology 39:1568–1577PubMedGoogle Scholar
  199. Velligan D, Brenner R, Sicuro F, Walling D, Riesenberg R, Sfera A et al (2012) Assessment of the effects of AZD3480 on cognitive function in patients with schizophrenia. Schizophr Res 134:59–64PubMedGoogle Scholar
  200. Volkow ND, Fowler JS, Wang GJ, Telang F, Logan J, Wong C et al (2008) Methylphenidate decreased the amount of glucose needed by the brain to perform a cognitive task. PLoS ONE 3:e2017Google Scholar
  201. Vossel S, Thiel CM, Fink GR (2008) Behavioral and neural effects of nicotine on visuospatial attentional reorienting in non-smoking subjects. Neuropsychopharmacology 33:731–738PubMedGoogle Scholar
  202. Wallace TL, Ballard TM, Pouzet B, Riedel WJ, Wettstein JG (2011a) Drug targets for cognitive enhancement in neuropsychiatric disorders. Pharmacol Biochem Behav 99:130–145PubMedGoogle Scholar
  203. Wallace TL, Callahan PM, Tehim A, Bertrand D, Tombaugh G, Wang SJ et al (2011b) RG3487, a novel nicotinic alpha 7 receptor partial agonist, improves cognition and sensorimotor gating in rodents. J Pharmacol Exp Ther 336:242–253PubMedGoogle Scholar
  204. Warbrick T, Mobascher A, Brinkmeyer J, Musso F, Stoecker T, Shah NJ et al (2011) Direction and magnitude of nicotine effects on the fMRI BOLD response are related to nicotine effects on behavioral performance. Psychopharmacology 215:333–344PubMedCentralPubMedGoogle Scholar
  205. Warburton DM, Arnall C (1994) Improvements in performance without nicotine withdrawal. Psychopharmacology 115:539–542PubMedGoogle Scholar
  206. Warburton DM, Mancuso G (1998) Evaluation of the information processing and mood effects of a transdermal nicotine patch. Psychopharmacology 135:305–310PubMedGoogle Scholar
  207. Warburton DM, Rusted JM, Fowler J (1992a) A comparison of the attentional and consolidation hypotheses for the facilitation of memory by nicotine. Psychopharmacology 108:443–447PubMedGoogle Scholar
  208. Warburton DM, Rusted JM, Muller C (1992b) Patterns of facilitation of memory by nicotine. Behav Pharmacol 3:375–378PubMedGoogle Scholar
  209. Waters AJ (1998) The effects of smoking on performance on the Garner speeded classification task. Hum Psychopharmacol Clin Exp 13:477–491Google Scholar
  210. Weissman DH, Roberts KC, Visscher KM, Woldorff MG (2006) The neural bases of momentary lapses in attention. Nat Neurosci 9:971–978PubMedGoogle Scholar
  211. Wesnes K, Warburton DM (1983) Smoking, nicotine and human performance. Pharmacol Ther 21:189–208PubMedGoogle Scholar
  212. Wesnes K, Warburton DM (1984) Effects of scopolamine and nicotine on human rapid information processing performance. Psychopharmacology 82:147–150PubMedGoogle Scholar
  213. Wesnes K, Warburton DM, Matz B (1983) Effects of nicotine on stimulus sensitivity and response bias in a visual vigilance task. Neuropsychobiology 9:41–44PubMedGoogle Scholar
  214. White HK, Levin ED (1999) Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease. Psychopharmacology 143:158–165PubMedGoogle Scholar
  215. Whiteaker P, Garcha HS, Wonnacott S, Stolerman IP (1995) Locomotor activation and dopamine release produced by nicotine and isoarecolone in rats. Br J Pharmacol 116:2097–2105PubMedCentralPubMedGoogle Scholar
  216. Wildeboer KM, Stevens KE (2008) Stimulation of the alpha 4 beta 2 nicotinic receptor by 5-I A-85380 improves auditory gating in DBA/2 mice. Brain Res 1224:29–36PubMedCentralPubMedGoogle Scholar
  217. Williams G (1980) Effects of cigarette smoking on immediate memory and performance in different kinds of smoker. Br J Psychol 71:83–90PubMedGoogle Scholar
  218. Williams DK, Wang JY, Papke RL (2011) Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations. Biochem Pharmacol 82:915–930PubMedCentralPubMedGoogle Scholar
  219. Witte EA, Davidson MC, Marrocco RT (1997) Effects of altering brain cholinergic activity on covert orienting of attention: comparison of monkey and human performance. Psychopharmacology 132:324–334PubMedGoogle Scholar
  220. Wonnacott S, Barik J, Dickinson J, Jones IW (2006) Nicotinic receptors modulate transmitter cross talk in the CNS. J Mol Neurosci 30:137–140PubMedGoogle Scholar
  221. Wooltorton JR, Pidoplichko VI, Broide RS, Dani JA (2003) Differential desensitization and distribution of nicotinic acetylcholine receptor subtypes in midbrain dopamine areas. J Neurosci 23:3176–3185PubMedGoogle Scholar
  222. Xu JS, Mendrek A, Cohen MS, Monterosso J, Rodriguez P, Simon SL et al (2005) Brain activity in cigarette smokers performing a working memory task: effect of smoking abstinence. Biol Psychiatry 58:143–150PubMedCentralPubMedGoogle Scholar
  223. Young JW, Finlayson K, Spratt C, Marston HM, Crawford N, Kelly JS et al (2004) Nicotine improves sustained attention in mice: evidence for involvement of the alpha7 nicotinic acetylcholine receptor. Neuropsychopharmacology 29:891–900PubMedGoogle Scholar
  224. Zhang XY, Liu L, Liu SW, Hong XH, Chen DC, Xiu MH et al (2012) Short-term tropisetron treatment and cognitive and P50 auditory gating deficits in schizophrenia. Am J Psychiatry 169:974–981PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Maryland Psychiatric Research CenterUniversity of Maryland School of MedicineBaltimoreUSA

Personalised recommendations