Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia

Biochemical Pharmacology

Volumn 86, Issue 8, 2013, Pages 1122-1132

  Young, Jared W ^a,b   Geyer, Mark A ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b San Diego Veterans Healthcare Administration   (United States)

Author keywords

Cognition; Positron emission tomography; Translational research

Indexed keywords

EID: 84885577258     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2013.06.031     Document Type: Review

References (200)

1. Kraepelin E. Dementia Praecox; 1896.
2. Andreasen NC, Flaum M, Schultz S, Duzyurek S, Miller D. Diagnosis, methodology and subtypes of schizophrenia. Neuropsychobiology 1997;35:61-3. (Pubitemid 27117212)
3. Pearlson GD. Neurobiology of schizophrenia. Ann Neurol 2000;48:556-66.
4. Ellenbroek BA, Cools AR. Animal models for the negative symptoms of schizophrenia. Behav Pharmacol 2000;11:223-33. (Pubitemid 30449754)
5. Green MF.What are the functional consequences of neurocognitive deficits in schizophrenia. Am J Psychiatry 1996;153:321-30. (Pubitemid 26074706)
6. Green MF. Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry 2006;67(Suppl. 9):3-8 [discussion 36-42]. (Pubitemid 44369648)
7. Carter CS. Applying new approaches from cognitive neuroscience to enhance drug development for the treatment of impaired cognition in schizophrenia. Schizophr Bull 2005;31:810-5. (Pubitemid 41437774)
8. Harvey PD, Keefe RS. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry 2001;158:176-84. (Pubitemid 32116511)
9. Keefe RS, Bilder RM, Davis SM, Harvey PD, Palmer BW, Gold JM, et al. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 2007;64:633-47. (Pubitemid 46878665)
10. Mintz J, Kopelowicz A. CUtLASS confirms CATIE. Arch Gen Psychiatry 2007;64:978 [author reply 79-80].
11. Floresco SB, Geyer MA, Gold LH, Grace AA. Developing predictive animal models and establishing a preclinical trials network for assessing treatment effects on cognition in schizophrenia. Schizophr Bull 2005;31: 888-94. (Pubitemid 41437783)
12. Dolan SL, Sacco KA, Termine A, Seyal AA, Dudas MM, Vessicchio JC, et al. Neuropsychological deficits are associated with smoking cessation treatment failure in patients with schizophrenia. Schizophr Res 2004;70:263-75. (Pubitemid 39141104)
13. D'Souza MS, Markou A. Schizophrenia and tobacco smoking comorbidity: nAChR agonists in the treatment of schizophrenia-Associated cognitive deficits. Neuropharmacology 2012;62:1564-73.
14. Dwoskin LP, Pivavarchyk M, Joyce BM, Neugebauer NM, Zheng G, Zhang Z, et al. Targeting reward-relevant nicotinic receptors in the discovery of novel pharmacotherapeutic agents to treat tobacco dependence. Nebr Symp Motiv 2009;55:31-63.
15. Adams CE, Stevens KE. Evidence for a role of nicotinic acetylcholine receptors in schizophrenia. Front Biosci 2007;12:4755-72.
16. Gilbert DG, Gilbert BO. Personality, psychopathology, and nicotine response as mediators of the genetics of smoking. Behav Genet 1995;25:133-47.
17. Leonard S, Gault J, Adams C, Breese CR, Rollins Y, Adler LE, et al. Nicotinic receptors, smoking and schizophrenia. Restor Neurol Neurosci 1998;12: 195-201. (Pubitemid 28368301)
18. Taiminen TJ, Salokangas RK, Saarijarvi S, Niemi H, Lehto H, Ahola V, et al. Smoking and cognitive deficits in schizophrenia: a pilot study. Addict Behav 1998;23:263-6. (Pubitemid 28136015)
19. Levin ED, Conners CK, Silva D, Hinton SC, Meck WH, March J, et al. Transdermal nicotine effects on attention. Psychopharmacology (Berl) 1998;140: 135-41. (Pubitemid 28538472)
20. Rezvani AH, Levin ED. Cognitive effects of nicotine. Biol Psychiatry 2001;49: 258-67. (Pubitemid 32178435)
21. Heishman SJ, Kleykamp BA, Singleton EG. Meta-Analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology (Berl) 2010;210:453-69.
22. Smith RC, Warner-Cohen J, Matute M, Butler E, Kelly E, Vaidhyanathaswamy S, et al. Effects of nicotine nasal spray on cognitive function in schizophrenia. Neuropsychopharmacology 2006;31:637-43. (Pubitemid 43276979)
23. Newhouse P, Singh A, Potter A. Nicotine and nicotinic receptor involvement in neuropsychiatric disorders. Curr Top Med Chem 2004;4:267-82. (Pubitemid 38842571)
24. Newhouse PA, Potter AS, Dumas JA, Thiel CM. Functional brain imaging of nicotinic effects on higher cognitive processes. Biochem Pharmacol 2011;82: 943-51.
25. Zammit S, Allebeck P, Dalman C, Lundberg I, Hemmingsson T, Lewis G. Investigating the association between cigarette smoking and schizophrenia in a cohort study. Am J Psychiatry 2003;160:2216-21. (Pubitemid 39619616)
26. Ma X, Li C, Meng H, Du L, Wang Q, Wang Y, et al. Premorbid tobacco smoking is associated with later age at onset in schizophrenia. Psychiatry Res 2010;178:461-6.
27. de Leon J, Tracy J, McCann E, McGrory A, Diaz FJ. Schizophrenia and tobacco smoking: a replication study in another US psychiatric hospital. Schizophr Res 2002;56:55-65. (Pubitemid 34655468)
28. Masterson E, O'Shea B. Smoking and malignancy in schizophrenia. Br J Psychiatry 1984;145:429-32. (Pubitemid 14044932)
29. Wing VC, Wass CE, Soh DW, George TP. A review of neurobiological vulnerability factors and treatment implications for comorbid tobacco dependence in schizophrenia. Ann N Y Acad Sci 2012;1248:89-106.
30. White HK, Levin ED. Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer's disease. Psychopharmacology (Berl) 1999;143:158-65. (Pubitemid 29187640)
31. Conners CK, Levin ED, Sparrow E, Hinton SC, Erhardt D, Meck WH, et al. Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD). Psychopharmacol Bull 1996;32:67-73. (Pubitemid 26176204)
32. Wu J, Lukas RJ. Naturally-expressed nicotinic acetylcholine receptor subtypes. Biochem Pharmacol 2011;82:800-7.
33. Changeux JP. Nicotine addiction and nicotinic receptors: lessons from genetically modified mice. Nat Rev Neurosci 2010;11:389-401.
34. Marks MJ, Stitzel JA, Romm E, Wehner JM, Collins AC. Nicotinic binding sites in rat and mouse brain: comparison of acetylcholine, nicotine, and alphabungarotoxin. Mol Pharmacol 1986;30:427-36. (Pubitemid 17202420)
35. Clarke PB. Chronic central nicotinic blockade after a single administration of the bisquaternary ganglion-blocking drug chlorisondamine. Br J Pharmacol 1984;83:527-35. (Pubitemid 14012660)
36. Mamede M, Ishizu K, Ueda M, Mukai T, Iida Y, Fukuyama H, et al. Quantification of human nicotinic acetylcholine receptors with 123I-5IA SPECT. J Nucl Med 2004;45:1458-70. (Pubitemid 47618499)
37. Marks MJ, Stitzel JA, Collins AC. Genetic influences on nicotine responses. Pharmacol Biochem Behav 1989;33:667-78. (Pubitemid 19237546)
38. Picciotto MR, Zoli M, Rimondini R, Lena C, Marubio LM, Pich EM, et al. Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature 1998;391:173-7. (Pubitemid 28092475)
39. Levin ED, Rezvani AH. Nicotinic-Antipsychotic drug interactions and cognitive function. EXS 2006;98:185-205.
40. Martin LF, Kem WR, Freedman R. Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia. Psychopharmacology (Berl) 2004;174:54-64. (Pubitemid 38925091)
41. Adler LE, Hoffer LD, Wiser A, Freedman R. Normalization of auditory physiology by cigarette smoking in schizophrenic patients. Am J Psychiatry 1993;150:1856-61. (Pubitemid 23356580)
42. Brunzell DH, McIntosh JM. Alpha7 nicotinic acetylcholine receptors modulate motivation to self-Administer nicotine: implications for smoking and schizophrenia. Neuropsychopharmacology 2012;37:1134-43.
43. Geerts H. alpha7 Nicotinic receptor modulators for cognitive deficits in schizophrenia and Alzheimer's disease. Expert Opin Investig Drugs 2012;21: 59-65.
44. Brody AL, Mandelkern MA, London ED, Olmstead RE, Farahi J, Scheibal D, et al. Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors. Arch Gen Psychiatry 2006;63:907-15. (Pubitemid 44192334)
45. Marutle A, Zhang X, Court J, Piggott M, Johnson M, Perry R, et al. Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia. J Chem Neuroanat 2001;22:115-26. (Pubitemid 32695514)
46. Cannon M, F Jones P. Schizophrenia. J Neurol Neurosurg Psychiatry 1996;60: 604-13. (Pubitemid 26237110)
47. Klaning U. Greater occurrence of schizophrenia in dizygotic but not monozygotic twins. Register-based study. Br J Psychiatry 1999;175:407-9.
48. van Os J, McGuffin P. Can the social environment cause schizophrenia. Br J Psychiatry 2003;182:291-2. (Pubitemid 36408278)
49. Allen NC, Bagade S, McQueen MB, Ioannidis JPA, Kavvoura FK, Khoury MJ, et al. Systemic meta-Analyses and field synopsis of genetic association studies in schizophrenia: the SZGene database. Nat Genet 2008;40:827-34. (Pubitemid 351913655)
50. Wallace TL, Bertrand D. Alpha7 neuronal nicotinic receptors as a drug target in schizophrenia. Expert Opin Ther Targets 2013;17:139-55.
51. Stefansson H, Rujescu D, Cichon S, Pietilainen OP, Ingason A, Steinberg S, et al. Large recurrent microdeletions associatedwith schizophrenia. Nature 2008;455: 232-6.
52. Mathew SV, Law AJ, Lipska BK, Davila-Garcia MI, Zamora ED, Mitkus SN, et al. Alpha7 nicotinic acetylcholine receptor mRNA expression and binding in postmortem human brain are associated with genetic variation in neuregulin 1. Hum Mol Genet 2007;16:2921-32. (Pubitemid 350048389)
53. Stefansson H, Sarginson J, Kong A, Yates P, Steinthorsdottir V, Gudfinnsson E, et al. Association of neuregulin 1 with schizophrenia confirmed in a Scottish population. Am J Hum Genet 2003;72:83-7. (Pubitemid 36056844)
54. Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S, et al. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 2002;71:877-92. (Pubitemid 135750519)
55. Harrison PJ, Law AJ. Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology. Biol Psychiatry 2006;60:132-40.
56. Law AJ, Lipska BK, Weickert CS, Hyde TM, Straub RE, Hashimoto R, et al. Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 50 SNPs associated with the disease. Proc Natl Acad Sci USA 2006;103:6747-52.
57. Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A, et al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 1997;94:587-92. (Pubitemid 27053677)
58. Leonard KE, Roberts LJ. The effects of alcohol on the marital interactions of aggressive and nonaggressive husbands and their wives. J Abnorm Psychol 1998;107:602-15. (Pubitemid 28527574)
59. Tsuang DW, Skol AD, Faraone SV, Bingham S, Young KA, Prabhudesai S, et al. Examination of genetic linkage of chromosome 15 to schizophrenia in a large Veterans Affairs Cooperative Study sample. Am J Med Genet 2001;105:662-8. (Pubitemid 33101464)
60. Curtis L, Blouin JL, Radhakrishna U, Gehrig C, Lasseter VK, Wolyniec P, et al. No evidence for linkage between schizophrenia and markers at chromosome 15q13-14. Am J Med Genet 1999;88:109-12. (Pubitemid 29156443)
61. Martin LF, Freedman R. Schizophrenia and the alpha7 nicotinic acetylcholine receptor. Int Rev Neurobiol 2007;78:225-46.
62. Amann LC, Gandal MJ, Halene TB, Ehrlichman RS, White SL, McCarren HS, et al. Mouse behavioral endophenotypes for schizophrenia. Brain Res Bull 2010;83:147-61.
63. Stevens KE, Kem WR, Mahnir VM, Freedman R. Selective alpha7-nicotinic agonists normalize inhibition of auditory response in DBA mice. Psychopharmacology (Berl) 1998;136:320-7. (Pubitemid 28189660)
64. Simosky JK, Stevens KE, Kem WR, Freedman R. Intragastric DMXB-A, an alpha7 nicotinic agonist, improves deficient sensory inhibition in DBA/2 mice. Biol Psychiatry 2001;50:493-500. (Pubitemid 32971880)
65. Hashimoto K, Iyo M, Freedman R, Stevens KE. Tropisetron improves deficient inhibitory auditory processing in DBA/2 mice: role of alpha 7 nicotinic acetylcholine receptors. Psychopharmacology (Berl) 2005;183:13-9. (Pubitemid 41484178)
66. Wildeboer-Andrud KM, Stevens KE. The smoking cessation drug varenicline improves deficient P20-N40 inhibition in DBA/2 mice. Pharmacol Biochem Behav 2011;100:17-24.
67. Hajos M, Rogers BN. Targeting alpha7 nicotinic acetylcholine receptors in the treatment of schizophrenia. Curr Pharm Des 2010;16:538-54.
68. Thomsen MS, Hansen HH, Timmerman DB, Mikkelsen JD. Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology. Curr Pharm Des 2010;16:323-43.
69. Martin-Ruiz CM, Haroutunian VH, Long P, Young AH, Davis KL, Perry EK, et al. Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia. Biol Psychiatry 2003;54:1222-33. (Pubitemid 37464868)
70. Court J, Spurden D, Lloyd S, McKeith I, Ballard C, Cairns N, et al. Neuronal nicotinic receptors in dementia with Lewy bodies and schizophrenia: alphabungarotoxin and nicotine binding in the thalamus. J Neurochem 1999;73: 1590-7. (Pubitemid 29440161)
71. Freedman R, Hall M, Adler LE, Leonard S. Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia. Biol Psychiatry 1995;38:22-33.
72. Guan ZZ, Zhang X, Blennow K, Nordberg A. Decreased protein level of nicotinic receptor alpha7 subunit in the frontal cortex from schizophrenic brain. Neuroreport 1999;10:1779-82. (Pubitemid 29354310)
73. Thomsen MS, Weyn A, Mikkelsen JD. Hippocampal alpha7 nicotinic acetylcholine receptor levels in patients with schizophrenia, bipolar disorder, or major depressive disorder. Bipolar Disord 2011;13:701-7.
74. Terry Jr. AV, Gearhart DA, Mahadik SP, Warsi S, Davis LW, Waller JL. Chronic exposure to typical or atypical antipsychotics in rodents: temporal effects on central alpha7 nicotinic acetylcholine receptors. Neuroscience 2005;136: 519-29. (Pubitemid 41607900)
75. Marder SR. Drug initiatives to improve cognitive function. J Clin Psychiatry 2006;67(Suppl. 9):31-5 [discussion 6-42]. (Pubitemid 44369653)
76. Marder SR, Fenton W. Measurement and Treatment Research to Improve Cognition in Schizophrenia: NIMH MATRICS initiative to support the development of agents for improving cognition in schizophrenia. Schizophr Res 2004;72:5-9. (Pubitemid 39452900)
77. Carter CS, Barch DM. Cognitive neuroscience-based approaches to measuring and improving treatment effects on cognition in schizophrenia: the CNTRICS initiative. Schizophr Bull 2007;33:1131-7. (Pubitemid 47347921)
78. Toyohara J, Wu J, Hashimoto K. Recent development of radioligands for imaging alpha7 nicotinic acetylcholine receptors in the brain. Curr Top Med Chem 2010;10:1544-57.
79. Horti AG, Ravert HT, Gao Y, Holt DP, Bunnelle WH, Schrimpf MR, et al. Synthesis and evaluation of new radioligands [(11)C]A-833834 and [(11)C]A-752274 for positron-emission tomography of alpha7-nicotinic acetylcholine receptors. Nucl Med Biol 2013;40:395-402.
80. Breese CR, Lee MJ, Adams CE, Sullivan B, Logel J, Gillen KM, et al. Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology 2000;23:351-64.
81. Mamede M, Ishizu K, Ueda M, Mukai T, Iida Y, Kawashima H, et al. Temporal change in human nicotinic acetylcholine receptor after smoking cessation: 5IA SPECT study. J Nucl Med 2007;48:1829-35. (Pubitemid 350099329)
82. Staley JK, Krishnan-Sarin S, Cosgrove KP, Krantzler E, Frohlich E, Perry E, et al. Human tobacco smokers in early abstinence have higher levels of beta2* nicotinic acetylcholine receptors than nonsmokers. J Neurosci 2006;26: 8707-14. (Pubitemid 44319406)
83. D'Souza DC, Esterlis I, Carbuto M, Krasenics M, Seibyl J, Bois F, et al. Lower ss2* -nicotinic acetylcholine receptor availability in smokers with schizophrenia. Am J Psychiatry 2012;169:326-34.
84. Terry Jr. AV, Gearhart DA, Mahadik SP, Warsi S, Waller JL. Chronic treatment with first or second generation antipsychotics in rodents: effects on high affinity nicotinic and muscarinic acetylcholine receptors in the brain. Neuroscience 2006;140:1277-87. (Pubitemid 43928280)
85. Bencherif M, Stachowiak MK, Kucinski AJ, Lippiello PM. Alpha7 nicotinic cholinergic neuromodulation may reconcile multiple neurotransmitter hypotheses of schizophrenia. Med Hypotheses 2012;78:594-600.
86. Dani JA, Bertrand D. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu Rev Pharmacol Toxicol 2007;47:699-729.
87. Quik M, Polonskaya Y, Gillespie A, Jakowec M, Lloyd GK, Langston JW. Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization. J Comp Neurol 2000;425:58-69.
88. Nirogi R, Kandikere V, Bhyrapuneni G, Saralaya R, Muddana N, Komarneni P. Methyllycaconitine: a non-radiolabeled ligand for mapping alpha7 neuronal nicotinic acetylcholine receptors -in vivo target localization and biodistribution in rat brain. J Pharmacol Toxicol Methods 2012;66:22-8.
89. Machaalani R, Kashi PK, Waters KA. Distribution of nicotinic acetylcholine receptor subunits alpha7 and beta2 in the human brainstem and hippocampal formation. J Chem Neuroanat 2010;40:223-31.
90. Sydserff S, Sutton EJ, Song D, Quirk MC, Maciag C, Li C, et al. Selective alpha7 nicotinic receptor activation by AZD0328 enhances cortical dopamine release and improves learning and attentional processes. Biochem Pharmacol 2009;78:880-8.
91. Thomsen MS, Hay-Schmidt A, Hansen HH, Mikkelsen JD. Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain. Cereb Cortex 2010;20:2092-102.
92. Castner SA, Smagin GN, Piser TM, Wang Y, Smith JS, Christian EP, et al. Immediate and sustained improvements in working memory after selective stimulation of alpha7 nicotinic acetylcholine receptors. Biol Psychiatry 2011;69:12-8.
93. Quarta D, Naylor CG, Barik J, Fernandes C, Wonnacott S, Stolerman IP. Drug discrimination and neurochemical studies in alpha7 null mutant mice: tests for the role of nicotinic alpha7 receptors in dopamine release. Psychopharmacology (Berl) 2009;203:399-410.
94. Mansvelder HD, Keath JR, McGehee DS. Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas. Neuron 2002;33: 905-19. (Pubitemid 34246356)
95. Jones IW, Wonnacott S. Precise localization of alpha7 nicotinic acetylcholine receptors on glutamatergic axon terminals in the rat ventral tegmental area. J Neurosci 2004;24:11244-52.
96. Dickinson JA, Kew JN, Wonnacott S. Presynaptic alpha 7-And beta 2-containing nicotinic acetylcholine receptors modulate excitatory amino acid release from rat prefrontal cortex nerve terminals via distinct cellular mechanisms. Mol Pharmacol 2008;74:348-59.
97. Ji D, Lape R, Dani JA. Timing and location of nicotinic activity enhances or depresses hippocampal synaptic plasticity. Neuron 2001;31:131-41. (Pubitemid 32757094)
98. Maggi L, Le Magueresse C, Changeux JP, Cherubini E. Nicotine activates immature silent connections in the developing hippocampus. Proc Natl Acad Sci USA 2003;100:2059-64. (Pubitemid 36254573)
99. Aramakis VB, Metherate R. Nicotine selectively enhances NMDA receptormediated synaptic transmission during postnatal development in sensory neocortex. J Neurosci 1998;18:8485-95. (Pubitemid 28465023)
100. Albuquerque EX, Pereira EF, Braga MF, Matsubayashi H, Alkondon M. Neuronal nicotinic receptors modulate synaptic function in the hippocampus and are sensitive to blockade by the convulsant strychnine and by the anti-Parkinson drug amantadine. Toxicol Lett 1998;102/103:211-8. (Pubitemid 29021223)
101. Frazier CJ, Rollins YD, Breese CR, Leonard S, Freedman R, Dunwiddie TV. Acetylcholine activates an alpha-bungarotoxin-sensitive nicotinic current in rat hippocampal interneurons, but not pyramidal cells. J Neurosci 1998;18:1187-95. (Pubitemid 28082405)
102. Konradsson-Geuken A, Gash CR, Alexander K, Pomerleau F, Huettl P, Gerhardt GA, et al. Second-by-second analysis of alpha 7 nicotine receptor regulation of glutamate release in the prefrontal cortex of awake rats. Synapse 2009;63:1069-82.
103. Nilsson LK, Linderholm KR, Engberg G, Paulson L, Blennow K, Lindstrom LH, et al. Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia. Schizophr Res 2005;80:315-22. (Pubitemid 41713657)
104. Erhardt S, Schwieler L, Engberg G. Kynurenic acid and schizophrenia. Adv Exp Med Biol 2003;527:155-65. (Pubitemid 38197640)
105. Erhardt S, Schwieler L, Emanuelsson C, Geyer M. Endogenous kynurenic acid disrupts prepulse inhibition. Biol Psychiatry 2004;56:255-60. (Pubitemid 39092940)
106. Braff DL, Geyer MA. Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry 1990;47:181-8. (Pubitemid 20058094)
107. Geyer MA, Braff DL. Startle habituation and sensorimotor gating in schizophrenia and related animal models. Schizophr Bull 1987;13:643-68. (Pubitemid 18037659)
108. Swerdlow NR, Braff DL, Taaid N, Geyer MA. Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry 1994;51:139-54. (Pubitemid 24985903)
109. Gu Z, Yakel JL. Timing-dependent septal cholinergic induction of dynamic hippocampal synaptic plasticity. Neuron 2011;71:155-65.
110. Hunter BE, de Fiebre CM, Papke RL, Kem WR, Meyer EM. A novel nicotinic agonist facilitates induction of long-Term potentiation in the rat hippocampus. Neurosci Lett 1994;168:130-4.
111. Dziewczapolski G, Glogowski CM, Masliah E, Heinemann SF. Deletion of the alpha 7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer's disease. J Neurosci 2009;29:8805-15.
112. Hasan A, Nitsche MA, Rein B, Schneider-Axmann T, Guse B, Gruber O, et al. Dysfunctional long-Term potentiation-like plasticity in schizophrenia revealed by transcranial direct current stimulation. Behav Brain Res 2011;224: 15-22.
113. Surmeier DJ, Plotkin J, Shen W. Dopamine and synaptic plasticity in dorsal striatal circuits controlling action selection. Curr Opin Neurobiol 2009;19: 621-8.
114. Tobler PN, O'Doherty JP, Dolan RJ, Schultz W. Human neural learning depends on reward prediction errors in the blocking paradigm. J Neurophysiol 2006;95:301-10. (Pubitemid 44698936)
115. Montague PR, McClure SM, Baldwin PR, Phillips PE, Budygin EA, Stuber GD, et al. Dynamic gain control of dopamine delivery in freely moving animals. J Neurosci 2004;24:1754-9. (Pubitemid 38240973)
116. Schultz W. Getting formal with dopamine and reward. Neuron 2002;36: 241-63. (Pubitemid 35217890)
117. Enomoto K, Matsumoto N, Nakai S, Satoh T, Sato TK, Ueda Y, et al. Dopamine neurons learn to encode the long-Term value of multiple future rewards. Proc Natl Acad Sci USA 2011;108:15462-67.
118. Glimcher PW. Understanding dopamine and reinforcement learning: the dopamine reward prediction error hypothesis. Proc Natl Acad Sci USA 2011;108(Suppl. 3):15647-54.
119. Waltz JA, Frank MJ, Robinson BM, Gold JM. Selective reinforcement learning deficits in schizophrenia support predictions from computational models of striatal-cortical dysfunction. Biol Psychiatry 2007;62:756-64. (Pubitemid 47374640)
120. Waltz JA, Frank MJ, Wiecki TV, Gold JM. Altered probabilistic learning and response biases in schizophrenia: behavioral evidence and neurocomputational modeling. Neuropsychology 2011;25:86-97.
121. Weiler JA, Bellebaum C, Brune M, Juckel G, Daum I. Impairment of probabilistic reward-based learning in schizophrenia. Neuropsychology 2009;23: 571-80.
122. Juckel G, Schlagenhauf F, Koslowski M, Wustenberg T, Villringer A, Knutson B, et al. Dysfunction of ventral striatal reward prediction in schizophrenia. Neuroimage 2006;29:409-16. (Pubitemid 43063297)
123. Keefe RS, Vinogradov S, Medalia A, Silverstein SM, Bell MD, Dickinson D, et al. Report from the working group conference on multisite trial design for cognitive remediation in schizophrenia. Schizophr Bull 2011;37: 1057-65.
124. Strauss GP, Frank MJ, Waltz JA, Kasanova Z, Herbener ES, Gold JM. Deficits in positive reinforcement learning and uncertainty-driven exploration are associated with distinct aspects of negative symptoms in schizophrenia. Biol Psychiatry 2011;69:424-31.
125. Gerfen CR, Engber TM. Molecular neuroanatomic mechanisms of Parkinson's disease: a proposed therapeutic approach. Neurol Clin 1992;10:435-49.
126. Morris G, Schmidt R, Bergman H. Striatal action-learning based on dopamine concentration. Exp Brain Res 2010;200:307-17.
127. Kravitz AV, Tye LD, Kreitzer AC. Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat Neurosci 2012;15:816-8.
128. Wolf ME, Sun X, Mangiavacchi S, Chao SZ. Psychomotor stimulants and neuronal plasticity. Neuropharmacology 2004;47(Suppl. 1):61-79. (Pubitemid 39298253)
129. Ortiz O, Delgado-Garcia JM, Espadas I, Bahi A, Trullas R, Dreyer JL, et al. Associative learning and CA3-CA1 synaptic plasticity are impaired in D1R null, Drd1a mice and in hippocampal siRNA silenced Drd1a mice. J Neurosci 2010;30:12288-300.
130. Granado N, Ortiz O, Suarez LM, Martin ED, Cena V, Solis JM, et al. D1 but not D5 dopamine receptors are critical for LTP, spatial learning, and LTP-Induced arc and zif268 expression in the hippocampus. Cereb Cortex 2008;18:1-12. (Pubitemid 350233047)
131. Matthies H, Becker A, Schroeder H, Kraus J, Hollt V, Krug M. Dopamine D1-deficient mutant mice do not express the late phase of hippocampal longterm potentiation. Neuroreport 1997;8:3533-5. (Pubitemid 27497478)
132. Young JW, Finlayson K, Spratt C, Marston HM, Crawford N, Kelly JS, et al. Nicotine improves sustained attention in mice: evidence for involvement of the alpha7 nicotinic acetylcholine receptor. Neuropsychopharmacology 2004;29:891-900. (Pubitemid 38526789)
133. Young JW, Kerr LE, Kelly JS, Marston HM, Spratt C, Finlayson K, et al. The odour span task: a novel paradigm for assessing working memory in mice. Neuropharmacology 2007;52:634-45. (Pubitemid 46137979)
134. Young JW, Meves JM, Tarantino IS, Caldwell S, Geyer MA. Delayed procedural learning in alpha7-nicotinic acetylcholine receptor knockout mice. Genes Brain Behav 2011;10:720-33.
135. Levin ED, Petro A, Rezvani AH, Pollard N, Christopher NC, Strauss M, et al. Nicotinic alpha7-or beta2-containing receptor knockout: effects on radialarm maze learning and long-Term nicotine consumption in mice. Behav Brain Res 2009;196:207-13.
136. Paylor R, Nguyen M, Crawley JN, Patrick J, Beaudet A, Orr-Urtreger A. Alpha7 nicotinic receptor subunits are not necessary for hippocampal-dependent learning or sensorimotor gating: a behavioral characterization of Acra7-deficient mice. Learn Mem 1998;5:302-16. (Pubitemid 29115261)
137. Harms LR, Turner KM, Eyles DW, Young JW,McGrath JJ, Burne TH. Attentional processing in C57BL/6J mice exposed to developmental vitamin D deficiency. PLoS ONE 2012;7:e35896.
138. Turner KM, Young JW, McGrath JJ, Eyles DW, Burne TH. Cognitive performance and response inhibition in developmentally vitamin D (DVD)-deficient rats. Behav Brain Res 2013;242:47-53.
139. Connor CM, Dincer A, Straubhaar J, Galler JR, Houston IB, Akbarian S. Maternal immune activation alters behavior in adult offspring, with subtle changes in the cortical transcriptome and epigenome. Schizophr Res 2012;140:175-84.
140. Lendvai B, Vizi ES. Nonsynaptic chemical transmission through nicotinic acetylcholine receptors. Physiol Rev 2008;88:333-49. (Pubitemid 351520082)
141. Vizi ES, Lendvai B. Modulatory role of presynaptic nicotinic receptors in synaptic and non-synaptic chemical communication in the central nervous system. Brain Res Brain Res Rev 1999;30:219-35. (Pubitemid 29531485)
142. Werkheiser JL, Sydserff S, Hubbs SJ, Ding M, Eisman MS, Perry D, et al. Ultralow exposure to alpha-7 nicotinic acetylcholine receptor partial agonists elicits an improvement in cognition that corresponds with an increase in alpha-7 receptor expression in rodents: implications for low dose clinical efficacy. Neuroscience 2011;186:76-87.
143. Zwart R, De Filippi G, Broad LM, McPhie GI, Pearson KH, Baldwinson T, et al. 5-Hydroxyindole potentiates human alpha 7 nicotinic receptor-mediated responses and enhances acetylcholine-induced glutamate release in cerebellar slices. Neuropharmacology 2002;43:374-84. (Pubitemid 35257929)
144. Ng HJ, Whittemore ER, Tran MB, Hogenkamp DJ, Broide RS, Johnstone TB, et al. Nootropic alpha7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators. Proc Natl Acad Sci USA 2007;104:8059-64. (Pubitemid 47185875)
145. Christopoulos A. Allosteric binding sites on cell-surface receptors: novel targets for drug discovery. Nat Rev Drug Discov 2002;1:198-210. (Pubitemid 37361423)
146. Williams DK, Wang J, Papke RL. Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-Targeted therapeutics: advantages and limitations. Biochem Pharmacol 2011;82:915-30.
147. Gronlien JH, Hakerud M, Ween H, Thorin-Hagene K, Briggs CA, Gopalakrishnan M, et al. Distinct profiles of alpha7 nAChR positive allosteric modulation revealed by structurally diverse chemotypes. Mol Pharmacol 2007;72: 715-24. (Pubitemid 47347306)
148. Thomsen MS, El-Sayed M, Mikkelsen JD. Differential immediate and sustained memory enhancing effects of alpha7 nicotinic receptor agonists and allosteric modulators in rats. PLoS ONE 2011;6:e27014.
149. Timmermann DB, Gronlien JH, Kohlhaas KL, Nielsen EO, Dam E, Jorgensen TD, et al. An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J Pharmacol Exp Ther 2007;323:294-307. (Pubitemid 47443280)
150. Hurst RS, Hajos M, Raggenbass M, Wall TM, Higdon NR, Lawson JA, et al. A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. J Neurosci 2005;25: 4396-405. (Pubitemid 40628784)
151. Malysz J, Gronlien JH, Timmermann DB, Hakerud M, Thorin-Hagene K, Ween H,
152. Dinklo T, Shaban H, Thuring JW, Lavreysen H, Stevens KE, Zheng L, et al. Characterization of 2-[[4-fluoro-3-(trifluoromethyl)phenyl]amino]-4-(4- pyridinyl)-5-Thiazolemethanol (JNJ-1930942), a novel positive allosteric modulator of the {alpha}7 nicotinic acetylcholine receptor. J Pharmacol Exp Ther 2011;336:560-74.
153. Grottick AJ, Haman M, Wyler R, Higgins GA. Reversal of a vigilance decrement in the aged rat by subtype-selective nicotinic ligands. Neuropsychopharmacology 2003;28:880-7.
154. Grottick AJ, Higgins GA. Effect of subtype selective nicotinic compounds on attention as assessed by the five-choice serial reaction time task. Behav Brain Res 2000;117:197-208.
155. Hahn B, Shoaib M, Stolerman IP. Nicotine-induced enhancement of attention in the five-choice serial reaction time task: the influence of task demands. Psychopharmacology (Berl) 2002;162:129-37. (Pubitemid 34743952)
156. Turek JW, Kang CH, Campbell JE, Arneric SP, Sullivan JP. A sensitive technique for the detection of the alpha 7 neuronal nicotinic acetylcholine receptor antagonist, methyllycaconitine, in rat plasma and brain. J Neurosci Methods 1995;61:113-8.
157. Cilia J, Cluderay JE, Robbins MJ, Reavill C, Southam E, Kew JN, et al. Reversal of isolation-rearing-induced PPI deficits by an alpha7 nicotinic receptor agonist. Psychopharmacology (Berl) 2005;182:214-9. (Pubitemid 41464614)
158. Van Kampen M, Selbach K, Schneider R, Schiegel E, Boess F, Schreiber R AR-R. 17779 improves social recognition in rats by activation of nicotinic alpha7 receptors. Psychopharmacology (Berl) 2004;172:375-83. (Pubitemid 38650972)
159. O'Neill HC, Rieger K, Kem WR, Stevens KE. DMXB, an alpha7 nicotinic agonist, normalizes auditory gating in isolation-reared rats. Psychopharmacology (Berl) 2003;169:332-9. (Pubitemid 37255522)
160. Bitner RS, Bunnelle WH, Decker MW, Drescher KU, Kohlhaas KL, Markosyan S, et al. In vivo pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107: preclinical considerations in Alzheimer's disease. J Pharmacol Exp Ther 2010;334:875-86.
161. Othman AA, Lenz RA, Zhang J, Li J, Awni WM, Dutta S. Single-And multipledose pharmacokinetics, safety, and tolerability of the selective alpha7 neuronal nicotinic receptor agonist, ABT-107, in healthy human volunteers. J Clin Pharmacol 2011;51:512-26.
162. Simpson K, Spencer CM,McClellan KJ. Tropisetron: an update of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs 2000;59: 1297-315. (Pubitemid 30410146)
163. Hashimoto K, Fujita Y, Ishima T, Hagiwara H, Iyo M. Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of tropisetron: role of alpha7 nicotinic receptors. Eur J Pharmacol 2006;553:191-5. (Pubitemid 44779614)
164. Jentsch JD. Pre-clinical models of cognitive dysfunction in schizophrenia: new avenues to addressing unmet needs. Clin Neurosci Res 2003;3:303-13. (Pubitemid 37474036)
165. Neill JC, Barnes S, Cook S, Grayson B, Idris NF, McLean SL, et al. Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism. Pharmacol Ther 2010;128(3):419-32.
166. Kohnomi S, Suemaru K, Goda M, Choshi T, Hibino S, Kawasaki H, et al. Ameliorating effects of tropisetron on dopaminergic disruption of prepulse inhibition via the alpha(7) nicotinic acetylcholine receptor in Wistar rats. Brain Res 2010;1353:152-8.
167. Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR. Pharmacological studies of prepulse inhibitionmodels of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (Berl) 2001;156:117-54. (Pubitemid 32702206)
168. Rezvani AH, Kholdebarin E, Brucato FH, Callahan PM, Lowe DA, Levin ED. Effect of R3487/MEM3454, a novel nicotinic alpha7 receptor partial agonist and 5-HT3 antagonist on sustained attention in rats. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:269-75.
169. Livingstone PD, Srinivasan J, Kew JN, Dawson LA, Gotti C, Moretti M, et al. alpha7 and non-Alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex. Eur J Neurosci 2009;29:539-50.
170. Rushforth SL, Allison C, Wonnacott S, Shoaib M. Subtype-selective nicotinic agonists enhance olfactory working memory in normal rats: a novel use of the odour span task. Neurosci Lett 2010;471:114-8.
171. Hauser TA, Kucinski A, Jordan KG, Gatto GJ,Wersinger SR, Hesse RA, et al. TC-5619: an alpha7 neuronal nicotinic receptor-selective agonist that demonstrates efficacy in animal models of the positive and negative symptoms and cognitive dysfunction of schizophrenia. Biochem Pharmacol 2009;78:803-12.
172. Chan WK, Wong PT, Sheu FS. Frontal cortical alpha7 and alpha4beta2 nicotinic acetylcholine receptors in working and reference memory. Neuropharmacology 2007;52:1641-9. (Pubitemid 46843139)
173. McLean SL, Grayson B, Idris NF, Lesage AS, Pemberton DJ, Mackie C, et al. Activation of alpha7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: implications for therapy of cognitive dysfunction in schizophrenia. Eur Neuropsychopharmacol 2011;21:333-43.
174. Young JW, Meves JM, Geyer MA. Nicotinic agonist-induced improvement of vigilance in mice in the 5-choice continuous performance test. Behav Brain Res 2013;240:119-33.
175. Prickaerts J, van Goethem NP, Chesworth R, Shapiro G, Boess FG, Methfessel C, et al. EVP-6124, a novel and selective alpha7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of alpha7 nicotinic acetylcholine receptors. Neuropharmacology 2012;62:1099-110.
176. O'Donnell CJ, Rogers BN, Bronk BS, Bryce DK, Coe JW, Cook KK, et al. Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2] nonane (CP-810,123), a novel alpha 7 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders in schizophrenia: synthesis, SAR development, and in vivo efficacy in cognition models. J Med Chem 2010;53: 1222-37.
177. Biton B, Bergis OE, Galli F, Nedelec A, Lochead AW, Jegham S, et al. SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (1) binding and functional profile. Neuropsychopharmacology 2007;32:1-16. (Pubitemid 44967780)
178. Thomsen MS, Mikkelsen JD. Type I and II positive allosteric modulators differentially modulate agonist-induced up-regulation of alpha7 nicotinic acetylcholine receptors. J Neurochem 2012;123:73-83.
179. Alexander KS, Wu HQ, Schwarcz R, Bruno JP. Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine. Psychopharmacology (Berl) 2012;220: 627-37.
180. Wu HQ, Pereira EF, Bruno JP, Pellicciari R, Albuquerque EX, Schwarcz R. The astrocyte-derived alpha7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex. J Mol Neurosci 2010;40:204-10.
181. Callahan PM, Hutchings EJ, Kille NJ, Chapman JM, Terry Jr. AV. Positive allosteric modulator of alpha 7 nicotinic-Acetylcholine receptors, PNU-120596 augments the effects of donepezil on learning and memory in aged rodents and non-human primates. Neuropharmacology 2013;67:201-12.
182. McLean SL, Idris NF, Grayson B, Gendle DF, Mackie C, Lesage AS, et al. 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 2012;26: 1265-70.
183. Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, et al. Proofof-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry 2006;63:630-8. (Pubitemid 43848294)
184. Freedman R, Olincy A, Buchanan RW, Harris JG, Gold JM, Johnson L, et al. Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J Psychiatry 2008;165:1040-7.
185. Tregellas JR, Tanabe J, Rojas DC, Shatti S, Olincy A, Johnson L, et al. Effects of an alpha 7-nicotinic agonist on default network activity in schizophrenia. Biol Psychiatry 2011;69:7-11.
186. Lieberman JA, Dunbar G, Segreti AC, Girgis RR, Seoane F, Beaver JS, et al. A randomized exploratory trial of an alpha-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia. Neuropsychopharmacology 2013;38:968-75.
187. Shiina A, Shirayama Y, Niitsu T, Hashimoto T, Yoshida T, Hasegawa T, et al. A randomised, double-blind, placebo-controlled trial of tropisetron in patients with schizophrenia. Ann Gen Psychiatry 2010;9:27.
188. Zhang XY, Liu L, Liu S, Hong X, Chen da C, Xiu MH, et al. Short-Term tropisetron treatment and cognitive and P50 auditory gating deficits in schizophrenia. Am J Psychiatry 2012;169:974-81.
189. Noroozian M, Ghasemi S, Hosseini SM, Modabbernia A, Khodaie-Ardakani MR, Mirshafiee O, et al. A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia. Psychopharmacology (Berl) 2013.
190. EnVivo; 2011, http://www.envivopharma.com/pipeline-nicotinic.php.
191. Winterer G, Gallinat J, Brinkmeyer J, Musso F, Kornhuber J, Thuerauf N, et al. Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study. Neuropharmacology 2013;64: 197-204.
192. Young JW, Amitai N, Geyer MA. Behavioral animal models to assess procognitive treatments for schizophrenia. In: Geyer MA, Gross G, editors. Handbook of experimental pharmacology. Heidelberg: Springer; 2012.
193. Young JW, Jentsch JD, Bussey TJ, Wallace TL, Hutcheson DM. Consideration of species differences in developing novel molecules as cognition enhancers. Neurosci Biobehav Rev 2012. http://dx.doi.org/10.1016/j.neubiorev.2012. 10.002.
194. Wonnacott S, Barik J, Dickinson J, Jones IW. Nicotinic receptors modulate transmitter cross talk in the CNS: nicotinic modulation of transmitters. J Mol Neurosci 2006;30:137-40. (Pubitemid 46035352)
195. Hamada M, Higashi H, Nairn AC, Greengard P, Nishi A. Differential regulation of dopamine D1 and D2 signaling by nicotine in neostriatal neurons. J Neurochem 2004;90:1094-103. (Pubitemid 39167343)
196. Ragland JD, Cools R, Frank M, Pizzagalli DA, Preston A, Ranganath C, et al. CNTRICS final task selection: long-Term memory. Schizophr Bull 2009;35: 197-212.
197. Wickham R, Solecki W, Rathbun L, McIntosh JM, Addy NA. Ventral tegmental area alpha6beta2 nicotinic acetylcholine receptors modulate phasic dopamine release in the nucleus accumbens core. Psychopharmacology (Berl) 2013 [Epub ahead of print].
198. Hahn B, Gold JM, Buchanan RW. The potential of nicotinic enhancement of cognitive remediation training in schizophrenia. Neuropharmacology 2013;64:185-90.
199. Swerdlow NR. Are we studying and treating schizophrenia correctly. Schizophr Res 2011;130:1-10.
200. Young JW, Powell SB, Risbrough V, Marston HM, Geyer MA. Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia. Pharmacol Ther 2009;122:150-202.