title: Potential Use of Nicotinic Receptor Agonists for the Treatment of Chemotherapy-Induced Cognitive Deficits.
abstract: Over the past several decades, research in both humans and animals has established the existence of persistent cognitive deficits resulting from exposure to chemotherapeutic agents. Nevertheless, there has been very little research addressing the treatment of chemotherapy-induced cognitive deficits and there is currently no approved treatment for this condition, often referred to as 'chemo-brain.' Several drugs that enhance cholinergic function and/or increase nicotinic acetylcholine receptor (nAChR) activity have been demonstrated to improve cognitive performance and/or reverse cognitive deficits in animals, findings that have led to the use of these compounds to treat the cognitive deficits present in a variety of disorders including attention deficit disorder, Alzheimer's disease, Parkinson's disease and schizophrenia. Although nAChR agonists have not been assessed for their efficacy in treating chemotherapy-induced cognitive deficits, these drugs have been shown to produce measureable increases in performance on several behavioral tasks known to be disrupted by exposure to chemotherapeutic agents. While the processes underlying chemotherapy-induced cognitive deficits may differ from those underlying other disorders, there appears to be a broad spectrum of application for the use of nAChR agonists to improve cognitive function. Therefore, studies examining the use of these drugs in the treatment of chemotherapy-induced cognitive deficits should be conducted as they may be of benefit for the treatment of 'chemo-brain.'
authors: Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Neurosciences, University of South Florida Morsani College of Medicine, 3515 East Fletcher Avenue, Tampa, FL, 33613-4706, USA. rphilpot@health.usf.edu.
authors: Rex M
authors: RM
authors: Philpot
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy*; D006801:Humans; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine
keywords: Chemo-brain; Chemotherapy; Cognition; Cognitive deficit; Nicotine; Nicotinic agonists
references: Lancet. 2002 Nov 2;360(9343):1361-8
references: 12423981
references: Adv Exp Med Biol. 2010;678:1-10
references: 20737999
references: J Natl Med Assoc. 2007 Apr;99(4):319-27
references: 17444420
references: Cancer. 2007 May 1;109(9):1905-13
references: 17351951
references: Environ Health Perspect. 2001 Dec;109(12):1197-206
references: 11748026
references: Curr Opin Neurobiol. 2010 Apr;20(2):150-5
references: 20303255
references: Palliat Med. 2009 Dec;23(8):731-8
references: 19648224
references: Neuron. 2004 Jun 10;42(5):817-29
references: 15182720
references: J Neurosci. 2007 Oct 3;27(40):10870-7
references: 17913920
references: Clin Cancer Res. 2009 Nov 1;15(21):6665-73
references: 19843664
references: Psychosom Med. 1973 Nov-Dec;35(6):464-71
references: 4764539
references: Life Sci. 2013 Oct 17;93(17):605-10
references: 23567806
references: Psychooncology. 2009 Feb;18(2):134-43
references: 18551510
references: Int J Neurosci. 2004 Sep;114(9):1163-79
references: 15370181
references: Psychopharmacology (Berl). 1998 Aug;138(3-4):266-74
references: 9725748
references: Eur J Pharmacol. 2003 Aug 8;474(2-3):227-32
references: 12921867
references: Pharmacol Biochem Behav. 1994 Dec;49(4):807-12
references: 7886091
references: Breast. 2005 Apr;14(2):142-50
references: 15767184
references: Neurobiol Learn Mem. 1997 Mar;67(2):142-9
references: 9075242
references: J Clin Oncol. 2004 Jun 1;22(11):2233-9
references: 15169812
references: Int J Neuropsychopharmacol. 2006 Apr;9(2):135-45
references: 16174427
references: Neurologist. 2004 Nov;10(6):293-310
references: 15518596
references: Am J Rhinol Allergy. 2010 Mar-Apr;24(2):e73-7
references: 20338106
references: Neuroscience. 2010 Feb 17;165(4):1538-45
references: 19945512
references: J Clin Oncol. 2012 Jul 10;30(20):2500-8
references: 22665542
references: Psychopharmacology (Berl). 2008 Apr;197(3):499-508
references: 18265960
references: J Clin Oncol. 2002 Jan 15;20(2):485-93
references: 11786578
references: Am J Respir Cell Mol Biol. 2009 Feb;40(2):135-46
references: 18676776
references: Neurosci Lett. 2010 Jan 18;469(1):88-92
references: 19941937
references: Clin Pharmacol Ther. 2011 Sep;90(3):366-76
references: 21814191
references: Psychopharmacology (Berl). 2015 Jan;232(1):17-37
references: 24894481
references: J Clin Oncol. 2012 Apr 1;30(10):1080-6
references: 22370315
references: Dev Psychobiol. 1989 Apr;22(3):271-94
references: 2707496
references: Biochem Biophys Res Commun. 2013 Jun 21;436(1):104-9
references: 23726916
references: J Support Oncol. 2008 Sep-Oct;6(7):313-21
references: 18847074
references: J Neurosci. 2001 Mar 1;21(5):1720-6
references: 11222661
references: Front Behav Neurosci. 2012 Dec 04;6:84
references: 23316148
references: Cancer. 2004 Aug 1;101(3):466-75
references: 15274059
references: J Biol. 2006;5(7):22
references: 17125495
references: Cereb Cortex. 2007 Sep;17 Suppl 1:i151-60
references: 17725997
references: Hum Brain Mapp. 2011 Aug;32(8):1206-19
references: 20669165
references: J Pharmacol Exp Ther. 1997 Oct;283(1):247-58
references: 9336330
references: Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6332-7
references: 16601104
references: Curr Top Med Chem. 2004;4(3):267-82
references: 14754447
references: J Clin Exp Neuropsychol. 2012;34(5):543-60
references: 22380580
references: Neurotoxicology. 2012 Jan;33(1):44-52
references: 22119111
references: Cell Mol Neurobiol. 1989 Jun;9(2):141-78
references: 2663167
references: Acta Anaesthesiol Scand. 2000 Nov;44(10):1246-51
references: 11065205
references: Neuropharmacology. 2011 Dec;61(8):1222-8
references: 21803055
references: Eur J Neurosci. 2012 Dec;36(11):3521-30
references: 23039863
references: Neurotoxicol Teratol. 2005 May-Jun;27(3):459-64
references: 15939205
references: J Neurosci. 2004 Nov 3;24(44):9811-25
references: 15525766
references: J Clin Oncol. 2003 Nov 15;21(22):4175-83
references: 14615445
references: Behav Brain Res. 2007 Jul 19;181(1):168-72
references: 17509697
references: Cancer. 2004 Jun 1;100(11):2292-9
references: 15160331
references: Behav Brain Res. 1997 Nov;88(2):261-74
references: 9404635
references: Psychooncology. 2009 Feb;18(2):156-61
references: 18561284
references: EXS. 2006;98:185-205
references: 17019889
references: Am J Psychiatry. 1980 May;137(5):597-601
references: 7369406
references: Eur J Neurosci. 2010 Jan;31(1):134-47
references: 20092559
references: J Neural Transm (Vienna). 2007 Jan;114(1):135-47
references: 16906354
references: Int J Neuropsychopharmacol. 2010 Nov;13(10):1343-54
references: 20219155
references: Cancer. 1999 Feb 1;85(3):640-50
references: 10091737
references: Psychopharmacology (Berl). 2011 Oct;217(4):539-48
references: 21537942
references: Cancer. 2009 Jun 15;115(12):2605-16
references: 19309747
references: Nature. 1982 Jun 24;297(5868):681-3
references: 7088155
references: Int J Neuropsychopharmacol. 2008 Feb;11(1):63-70
references: 17295931
references: J Clin Exp Neuropsychol. 2004 Oct;26(7):955-69
references: 15742545
references: Crit Rev Oncol Hematol. 2006 Feb;57(2):175-82
references: 16213740
references: Front Hum Neurosci. 2011 Nov 01;5:122
references: 22053153
references: Neuropharmacology. 2013 Jan;64:191-6
references: 22659472
references: Behav Brain Res. 1999 Jul;102(1-2):31-9
references: 10403013
references: Cancer J. 2008 Nov-Dec;14(6):396-400
references: 19060604
references: Arch Toxicol. 2009 Jan;83(1):87-94
references: 18528683
references: J Neuroendocrinol. 2006 Oct;18(10):787-95
references: 16965297
references: Eur J Neurosci. 2008 Jul;28(2):323-30
references: 18702703
references: Behav Pharmacol. 2010 May;21(3):246-9
references: 20400893
references: J Clin Invest. 2003 Jan;111(1):81-90
references: 12511591
references: Neuroscience. 1997 Oct;80(3):717-30
references: 9276488
references: Behav Biol. 1973 Feb;8(2):173-81
references: 4705970
references: J Psychiatry Neurosci. 2005 Mar;30(2):100-7
references: 15798785
references: Eur J Pharmacol. 2007 Oct 31;572(2-3):151-9
references: 17659275
references: Brain Res Bull. 1978 Sep-Oct;3(5):509-18
references: 122716
references: Psychooncology. 2006 May;15(5):422-30
references: 16097037
references: Brain Res Bull. 2008 Nov 25;77(5):237-40
references: 18755251
references: J Clin Pharm Ther. 2006 Apr;31(2):129-38
references: 16635046
references: Behav Neurosci. 2003 Dec;117(6):1276-82
references: 14674846
references: Psychopharmacology (Berl). 2008 Sep;199(4):527-38
references: 18463849
references: J Neurosci. 2000 Dec 1;20(23):8853-60
references: 11102494
references: Biochem Pharmacol. 2009 Oct 1;78(7):668-76
references: 19426718
references: Psychopharmacology (Berl). 1999 May;144(2):175-82
references: 10394999
references: Neuropsychopharmacology. 2007 Jun;32(6):1261-71
references: 17133263
references: Pharmacol Biochem Behav. 2006 Sep;85(1):66-75
references: 16935324
references: Jpn J Pharmacol. 1998 Jan;76(1):23-9
references: 9517401
references: Biochem Pharmacol. 2013 Oct 15;86(8):1145-52
references: 23928190
references: Cell Commun Signal. 2009 Aug 27;7:20
references: 19712465
references: Neurosci Lett. 2011 Jan 10;487(3):368-71
references: 21035521
references: Neurosci Biobehav Rev. 2011 Jan;35(3):729-41
references: 20869395
references: J Clin Exp Neuropsychol. 2010 Mar;32(3):324-31
references: 19642048
references: Hippocampus. 2001;11(1):8-17
references: 11261775
references: Brain Res. 2004 Feb 27;999(1):142-7
references: 14746932
references: Behav Pharmacol. 1992 Aug;3(4):359-73
references: 11224138
references: Cancer. 2005 Dec 1;104(11):2499-507
references: 16247788
references: Curr Opin Neurobiol. 2010 Apr;20(2):143-9
references: 20181475
references: Breast Cancer Res Treat. 2007 Jul;103(3):303-11
references: 17009108
references: Eur J Pharmacol. 2009 Jan 5;602(1):58-65
references: 18848931
references: Psychooncology. 2008 Feb;17(2):122-30
references: 17518411
references: Neuropsychol Rev. 2008 Jun;18(2):121-31
references: 18415683
references: Hum Brain Mapp. 2012 Dec;33(12):2971-83
references: 22095746
references: Ann Oncol. 2006 Mar;17(3):415-23
references: 16357023
references: Neuroscience. 1991;45(3):609-23
references: 1775236
references: Psychopharmacology (Berl). 2006 Mar;184(3-4):292-305
references: 16001117
references: Neurobiol Aging. 2011 May;32(5):834-44
references: 19464074
references: Med Oncol. 2012 Mar;29(1):364-73
references: 21267677
references: Cancer Treat Rev. 2006 Jun;32(4):316-9
references: 16616991
references: Clin Cancer Res. 2012 Jun 1;18(11):3112-21
references: 22467680
references: Clin Breast Cancer. 2008 Feb;8(1):88-91
references: 18501063
references: Eur J Pharmacol. 2013 Feb 28;702(1-3):269-74
references: 23399762
references: Psychooncology. 2014 Dec;23(12):1382-90
references: 24789331
references: Arch Neurol. 2011 Nov;68(11):1447-53
references: 22084128
references: Eur Neuropsychopharmacol. 1999 Jun;9(4):323-7
references: 10422893
references: Behav Neurosci. 2009 Feb;123(1):115-24
references: 19170436
references: J Clin Oncol. 2012 Jan 20;30(3):274-81
references: 22184379
references: Support Care Cancer. 2008 Jun;16(6):577-83
references: 17972110
references: J Pain Symptom Manage. 2009 Nov;38(5):650-62
references: 19896571
references: Pharmacol Biochem Behav. 2010 Dec;97(2):333-9
references: 20828582
references: J Natl Cancer Inst. 1998 Feb 4;90(3):210-8
references: 9462678
references: Bull Exp Biol Med. 2006 Dec;142(6):700-2
references: 17603674
references: Neurobiol Learn Mem. 2010 May;93(4):487-94
references: 20109567
references: J Physiol. 2003 Dec 15;553(Pt 3):857-71
references: 14555718
references: Semin Clin Neuropsychiatry. 2003 Oct;8(4):201-16
references: 14613048
references: Behav Genet. 2012 Jan;42(1):133-50
references: 21822688
references: Brain Res Cogn Brain Res. 1999 Jan;7(3):405-10
references: 9838204
references: Behav Pharmacol. 1999 May;10(3):333-6
references: 10780248
references: Psychopharmacology (Berl). 2006 Mar;184(3-4):523-39
references: 16220335
references: J Neurosci. 2000 Jun 1;20(11):4320-4
references: 10818167
references: J Clin Pharm Ther. 2010 Feb;35(1):1-9
references: 20175809
references: Can J Exp Psychol. 2008 Dec;62(4):247-60
references: 19071993
references: Am J Psychiatry. 1980 Oct;137(10):1263-5
references: 7416282
references: Br J Cancer. 2006 Mar 27;94(6):828-34
references: 16523200
references: J Clin Oncol. 2007 Sep 1;25(25):3866-70
references: 17761972
references: AJNR Am J Neuroradiol. 1998 Feb;19(2):217-21
references: 9504468
references: Eur J Pharmacol. 2003 Mar 28;465(1-2):83-90
references: 12650836
references: Psychopharmacology (Berl). 2010 Jul;210(4):453-69
references: 20414766
references: Clin Cancer Res. 2006 Aug 15;12(16):5000; author reply 5000-1
references: 16914590
references: Neurosci Lett. 2011 Jul 15;499(1):28-31
references: 21624432
references: Int J Oral Maxillofac Surg. 2007 Aug;36(8):739-44
references: 17611077
references: Brain Res Cogn Brain Res. 1993 Oct;1(3):137-43
references: 8257869
references: Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21371-6
references: 19940240
references: J Neurosci Res. 2010 Jun;88(8):1784-94
references: 20127813
references: Clin Cancer Res. 2012 Apr 1;18(7):1954-65
references: 22338017
references: Metab Brain Dis. 2008 Sep;23(3):325-33
references: 18690526
references: Pharmacol Biochem Behav. 1994 Nov;49(3):769-72
references: 7862736
references: Hum Brain Mapp. 2011 Mar;32(3):480-93
references: 20725909
references: Behav Brain Res. 2011 Jan 1;216(1):341-8
references: 20728474
references: J Pharmacol Exp Ther. 2002 Jul;302(1):95-100
references: 12065705
references: Curr Neurol Neurosci Rep. 2003 May;3(3):215-22
references: 12691626
references: Eur Neuropsychopharmacol. 2011 Apr;21(4):333-43
references: 20630711
references: Behav Pharmacol. 1999 Nov;10 (6-7):675-80
references: 10780509
references: Breast Cancer Res Treat. 2010 Oct;123(3):819-28
references: 20690040
references: Curr Opin Neurobiol. 1999 Apr;9(2):195-202
references: 10322181
references: Behav Brain Res. 2008 Jan 25;186(2):168-75
references: 17854921
references: J Exp Psychol Gen. 1996 Dec;125(4):370-86
references: 8945788
references: Clin Breast Cancer. 2002 Dec;3 Suppl 3:S84-90
references: 12533268
references: Eur J Neurosci. 2010 Jun;31(12):2292-307
references: 20550571
references: Clin Breast Cancer. 2005 Feb;5(6):439-46
references: 15748464
references: Brain Res. 1997 Sep 12;768(1-2):49-56
references: 9369300
references: J Neurooncol. 1996 Oct;30(1):61-9
references: 8865004
references: Psychopharmacology (Berl). 2012 Mar;220(1):183-93
references: 21894483
references: Neuropharmacology. 2012 Apr;62(5-6):2096-105
references: 22280876
references: Behav Brain Res. 2003 Aug 14;143(2):159-67
references: 12900042
references: Pharmacol Rep. 2014 Aug;66(4):638-46
references: 24948066
references: J Int Neuropsychol Soc. 2009 Nov;15(6):951-62
references: 19709455
references: Annu Rev Med. 1983;34:35-46
references: 6344764
references: Cancer. 2007 Jan 1;109(1):146-56
references: 17131349
references: Pharmacol Rev. 2009 Mar;61(1):39-61
references: 19293145
references: Anticancer Res. 2000 Jan-Feb;20(1B):563-8
references: 10769726
references: Hippocampus. 2011 Aug;21(8):899-909
references: 20865738
references: Med Pediatr Oncol. 1989;17(3):216-21
references: 2787469
references: Addict Biol. 2009 Jan;14(1):32-42
references: 18855804
references: Neurol Sci. 2013 Jun;34(6):891-7
references: 22773025
references: J Clin Oncol. 2000 Jul;18(14):2695-701
references: 10894868
references: Mol Cell Neurosci. 2010 Nov;45(3):289-96
references: 20624465
references: Acta Oncol. 1988;27(3):241-6
references: 3415853
references: Nat Rev Cancer. 2007 Mar;7(3):192-201
references: 17318212
references: J Pharmacol Exp Ther. 1996 Dec;279(3):1422-9
references: 8968367
references: Psychopharmacology (Berl). 2012 Apr;220(3):627-37
references: 22038535
references: Eur J Pharmacol. 2000 Mar 30;393(1-3):147-54
references: 10771008
references: Behav Brain Res. 2011 Nov 20;225(1):222-9
references: 21820013