Skip to main content

Advertisement

SpringerLink
Log in

Potential Use of Nicotinic Receptor Agonists for the Treatment of Chemotherapy-Induced Cognitive Deficits

  • Overview
  • Published:
Neurochemical Research Aims and scope Submit manuscript

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.’

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ahles TA, Saykin AJ (2002) Breast cancer chemotherapy-related cognitive dysfunction. Clin Breast Cancer 3(Suppl 3):S84–S90

    Article  CAS  PubMed  Google Scholar 

  2. Ferguson RJ, Ahles TA (2003) Low neuropsychologic performance among adult cancer survivors treated with chemotherapy. Curr Neurol Neurosci Rep 3:215–222

    Article  PubMed  Google Scholar 

  3. Raffa RB, Duong PV, Finney J, Garber DA, Lam LM, Mathew SS, Patel NN, Plaskett KC, Shah M, Jen Weng HF (2006) Is ‘chemo-fog’/‘chemo-brain’ caused by cancer chemotherapy? J Clin Pharm Ther 31:129–138. doi:10.1111/j.1365-2710.2006.00726.x

    Article  CAS  PubMed  Google Scholar 

  4. Raffa RB (2010) Short introduction and history. Adv Exp Med Biol 678:1–10

    Article  CAS  PubMed  Google Scholar 

  5. Ahles TA, Saykin AJ (2007) Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer 7:192–201. doi:10.1038/nrc2073

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Shilling V, Jenkins V, Morris R, Deutsch G, Bloomfield D (2005) The effects of adjuvant chemotherapy on cognition in women with breast cancer—preliminary results of an observational longitudinal study. Breast 14:142–150. doi:10.1016/j.breast.2004.10.004

    Article  CAS  PubMed  Google Scholar 

  7. Tannock IF, Ahles TA, Ganz PA, Van Dam FS (2004) Cognitive impairment associated with chemotherapy for cancer: report of a workshop. J Clin Oncol 22:2233–2239. doi:10.1200/JCO.2004.08.094

    Article  PubMed  Google Scholar 

  8. Davies RK, Quinlan DM, McKegney FP, Kimball CP (1973) Organic factors and psychological adjustment in advanced cancer patients. Psychosom Med 35:464–471

    Article  CAS  PubMed  Google Scholar 

  9. Silberfarb PM (1983) Chemotherapy and cognitive defects in cancer patients. Annu Rev Med 34:35–46. doi:10.1146/annurev.me.34.020183.000343

    Article  CAS  PubMed  Google Scholar 

  10. Silberfarb PM, Philibert D, Levine PM (1980) Psychosocial aspects of neoplastic disease: II. Affective and cognitive effects of chemotherapy in cancer patients. Am J Psychiatry 137:597–601

    Article  CAS  PubMed  Google Scholar 

  11. Kaasa S, Olsnes BT, Mastekaasa A (1988) Neuropsychological evaluation of patients with inoperable non-small cell lung cancer treated with combination chemotherapy or radiotherapy. Acta Oncol 27:241–246

    Article  CAS  PubMed  Google Scholar 

  12. Oxman TE, Silberfarb PM (1980) Serial cognitive testing in cancer patients receiving chemotherapy. Am J Psychiatry 137:1263–1265

    Article  CAS  PubMed  Google Scholar 

  13. Donovan KA, Small BJ, Andrykowski MA, Schmitt FA, Munster P, Jacobsen PB (2005) Cognitive functioning after adjuvant chemotherapy and/or radiotherapy for early-stage breast carcinoma. Cancer 104:2499–2507. doi:10.1002/cncr.21482

    Article  PubMed Central  PubMed  Google Scholar 

  14. Jenkins V, Shilling V, Deutsch G, Bloomfield D, Morris R, Allan S, Bishop H, Hodson N, Mitra S, Sadler G, Shah E, Stein R, Whitehead S, Winstanley J (2006) A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer. Br J Cancer 94:828–834. doi:10.1038/sj.bjc.6603029

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Scherwath A, Mehnert A, Schleimer B, Schirmer L, Fehlauer F, Kreienberg R, Metzner B, Thiel E, Zander AR, Schulz-Kindermann F, Koch U (2006) Neuropsychological function in high-risk breast cancer survivors after stem-cell supported high-dose therapy versus standard-dose chemotherapy: evaluation of long-term treatment effects. Ann Oncol 17:415–423. doi:10.1093/annonc/mdj108

    Article  CAS  PubMed  Google Scholar 

  16. Hermelink K, Untch M, Lux MP, Kreienberg R, Beck T, Bauerfeind I, Munzel K (2007) Cognitive function during neoadjuvant chemotherapy for breast cancer: results of a prospective, multicenter, longitudinal study. Cancer 109:1905–1913. doi:10.1002/cncr.22610

    Article  CAS  PubMed  Google Scholar 

  17. Ahles TA, Saykin AJ, Furstenberg CT, Cole B, Mott LA, Skalla K, Whedon MB, Bivens S, Mitchell T, Greenberg ER, Silberfarb PM (2002) Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. J Clin Oncol 20:485–493

    Article  CAS  PubMed  Google Scholar 

  18. Bender CM (2006) Chemotherapy may have small to moderate negative effects on cognitive functioning. Cancer Treat Rev 32:316–319. doi:10.1016/j.ctrv.2006.02.006

    Article  CAS  PubMed  Google Scholar 

  19. Bender CM, Sereika SM, Berga SL, Vogel VG, Brufsky AM, Paraska KK, Ryan CM (2006) Cognitive impairment associated with adjuvant therapy in breast cancer. Psychooncology 15:422–430. doi:10.1002/pon.964

    Article  PubMed  Google Scholar 

  20. Bender S, Dittmann-Balcar A, Schall U, Wolstein J, Klimke A, Riedel M, Vorbach EU, Kuhn KU, Lambert M, Dittmann RW, Naber D (2006) Influence of atypical neuroleptics on executive functioning in patients with schizophrenia: a randomized, double-blind comparison of olanzapine vs. clozapine. Int J Neuropsychopharmacol 9:135–145. doi:10.1017/S1461145705005924

    Article  CAS  PubMed  Google Scholar 

  21. Brezden CB, Phillips KA, Abdolell M, Bunston T, Tannock IF (2000) Cognitive function in breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol 18:2695–2701

    CAS  PubMed  Google Scholar 

  22. Castellon SA, Ganz PA, Bower JE, Petersen L, Abraham L, Greendale GA (2004) Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol 26:955–969. doi:10.1080/13803390490510905

    Article  PubMed  Google Scholar 

  23. Schagen SB, van Dam FS, Muller MJ, Boogerd W, Lindeboom J, Bruning PF (1999) Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer 85:640–650

    Article  CAS  PubMed  Google Scholar 

  24. Stewart A, Collins B, Mackenzie J, Tomiak E, Verma S, Bielajew C (2008) The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a prospective study. Psychooncology 17:122–130. doi:10.1002/pon.1210

    Article  PubMed  Google Scholar 

  25. Tchen N, Juffs HG, Downie FP, Yi QL, Hu H, Chemerynsky I, Clemons M, Crump M, Goss PE, Warr D, Tweedale ME, Tannock IF (2003) Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer. J Clin Oncol 21:4175–4183. doi:10.1200/JCO.2003.01.119

    Article  PubMed  Google Scholar 

  26. Wefel JS, Lenzi R, Theriault R, Buzdar AU, Cruickshank S, Meyers CA (2004) ‘Chemobrain’ in breast carcinoma?: a prologue. Cancer 101:466–475. doi:10.1002/cncr.20393

    Article  PubMed  Google Scholar 

  27. Wefel JS, Lenzi R, Theriault RL, Davis RN, Meyers CA (2004) The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial. Cancer 100:2292–2299. doi:10.1002/cncr.20272

    Article  CAS  PubMed  Google Scholar 

  28. van Dam FS, Schagen SB, Muller MJ, Boogerd W, vd Wall E, Droogleever Fortuyn ME, Rodenhuis S (1998) Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy. J Natl Cancer Inst 90:210–218

    Article  PubMed  Google Scholar 

  29. Whitney KA, Lysaker PH, Steiner AR, Hook JN, Estes DD, Hanna NH (2008) Is “chemobrain” a transient state? A prospective pilot study among persons with non-small cell lung cancer. J Support Oncol 6:313–321

    PubMed  Google Scholar 

  30. Collins B, Mackenzie J, Stewart A, Bielajew C, Verma S (2009) Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment. Psychooncology 18:134–143. doi:10.1002/pon.1379

    Article  PubMed  Google Scholar 

  31. Wefel JS, Witgert ME, Meyers CA (2008) Neuropsychological sequelae of non-central nervous system cancer and cancer therapy. Neuropsychol Rev 18:121–131. doi:10.1007/s11065-008-9058-x

    Article  PubMed  Google Scholar 

  32. Correa DD, Ahles TA (2008) Neurocognitive changes in cancer survivors. Cancer J 14:396–400. doi:10.1097/PPO.0b013e31818d8769

    Article  PubMed  Google Scholar 

  33. Wieneke MH, Dienst ER (1995) Neuropsychological assessment of cognitive functioning following chemotherapy for breast cancer. Psychooncology 4:61–66

    Article  Google Scholar 

  34. Carlsson M, Strang P, Bjurstrom C (2000) Treatment modality affects long-term quality of life in gynaecological cancer. Anticancer Res 20:563–568

    CAS  PubMed  Google Scholar 

  35. Koppelmans V, Breteler MM, Boogerd W, Seynaeve C, Gundy C, Schagen SB (2012) Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. J Clin Oncol 30:1080–1086. doi:10.1200/JCO.2011.37.0189

    Article  PubMed  Google Scholar 

  36. Skeel RT (2011) Handbook of cancer chemotherapy. Lippincott Williams and Wilkins, Philadelphia

    Google Scholar 

  37. Dietrich J, Han R, Yang Y, Mayer-Proschel M, Noble M (2006) CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo. J Biol 5:22. doi:10.1186/jbiol50

    Article  PubMed Central  PubMed  Google Scholar 

  38. Raffa RB (2010) Is a picture worth a thousand (forgotten) words?: neuroimaging evidence for the cognitive deficits in ‘chemo-fog’/‘chemo-brain’. J Clin Pharm Ther 35:1–9. doi:10.1111/j.1365-2710.2009.01044.x

    Article  CAS  PubMed  Google Scholar 

  39. Brown MS, Stemmer SM, Simon JH, Stears JC, Jones RB, Cagnoni PJ, Sheeder JL (1998) White matter disease induced by high-dose chemotherapy: longitudinal study with MR imaging and proton spectroscopy. AJNR Am J Neuroradiol 19:217–221

    CAS  PubMed  Google Scholar 

  40. Ferguson RJ, McDonald BC, Saykin AJ, Ahles TA (2007) Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy. J Clin Oncol 25:3866–3870. doi:10.1200/JCO.2007.10.8639

    Article  PubMed Central  PubMed  Google Scholar 

  41. Abraham J, Haut MW, Moran MT, Filburn S, Lemiuex S, Kuwabara H (2008) Adjuvant chemotherapy for breast cancer: effects on cerebral white matter seen in diffusion tensor imaging. Clin Breast Cancer 8:88–91. doi:10.3816/CBC.2008.n.007

    Article  PubMed  Google Scholar 

  42. Deprez S, Amant F, Smeets A, Peeters R, Leemans A, Van Hecke W, Verhoeven JS, Christiaens MR, Vandenberghe J, Vandenbulcke M, Sunaert S (2012) Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. J Clin Oncol 30:274–281. doi:10.1200/JCO.2011.36.8571

    Article  PubMed  Google Scholar 

  43. Deprez S, Amant F, Yigit R, Porke K, Verhoeven J, Van den Stock J, Smeets A, Christiaens MR, Leemans A, Van Hecke W, Vandenberghe J, Vandenbulcke M, Sunaert S (2011) Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients. Hum Brain Mapp 32:480–493. doi:10.1002/hbm.21033

    Article  PubMed  Google Scholar 

  44. de Ruiter MB, Reneman L, Boogerd W, Veltman DJ, Caan M, Douaud G, Lavini C, Linn SC, Boven E, van Dam FS, Schagen SB (2012) Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: converging results from multimodal magnetic resonance imaging. Hum Brain Mapp 33:2971–2983. doi:10.1002/hbm.21422

    Article  PubMed  Google Scholar 

  45. Inagaki M, Yoshikawa E, Matsuoka Y, Sugawara Y, Nakano T, Akechi T, Wada N, Imoto S, Murakami K, Uchitomi Y (2007) Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy. Cancer 109:146–156. doi:10.1002/cncr.22368

    Article  PubMed  Google Scholar 

  46. McDonald BC, Conroy SK, Ahles TA, West JD, Saykin AJ (2010) Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. Breast Cancer Res Treat 123:819–828. doi:10.1007/s10549-010-1088-4

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Saykin AJ, Ahles TA, McDonald BC (2003) Mechanisms of chemotherapy-induced cognitive disorders: neuropsychological, pathophysiological, and neuroimaging perspectives. Semin Clin Neuropsychiatry 8:201–216

    Article  PubMed  Google Scholar 

  48. Kesler SR, Bennett FC, Mahaffey ML, Spiegel D (2009) Regional brain activation during verbal declarative memory in metastatic breast cancer. Clin Cancer Res 15:6665–6673. doi:10.1158/1078-0432.CCR-09-1227

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. de Ruiter MB, Reneman L, Boogerd W, Veltman DJ, van Dam FS, Nederveen AJ, Boven E, Schagen SB (2011) Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer. Hum Brain Mapp 32:1206–1219. doi:10.1002/hbm.21102

    Article  PubMed  Google Scholar 

  50. Kesler SR, Kent JS, O’Hara R (2011) Prefrontal cortex and executive function impairments in primary breast cancer. Arch Neurol 68:1447–1453. doi:10.1001/archneurol.2011.245

    Article  PubMed Central  PubMed  Google Scholar 

  51. Silverman DH, Dy CJ, Castellon SA, Lai J, Pio BS, Abraham L, Waddell K, Petersen L, Phelps ME, Ganz PA (2007) Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy. Breast Cancer Res Treat 103:303–311. doi:10.1007/s10549-006-9380-z

    Article  CAS  PubMed  Google Scholar 

  52. Cimprich B, Reuter-Lorenz P, Nelson J, Clark PM, Therrien B, Normolle D, Berman MG, Hayes DF, Noll DC, Peltier S, Welsh RC (2010) Prechemotherapy alterations in brain function in women with breast cancer. J Clin Exp Neuropsychol 32:324–331. doi:10.1080/13803390903032537

    Article  PubMed  Google Scholar 

  53. McDonald BC, Conroy SK, Ahles TA, West JD, Saykin AJ (2012) Alterations in brain activation during working memory processing associated with breast cancer and treatment: a prospective functional magnetic resonance imaging study. J Clin Oncol 30:2500–2508. doi:10.1200/JCO.2011.38.5674

    Article  PubMed Central  PubMed  Google Scholar 

  54. Scherling C, Collins B, Mackenzie J, Bielajew C, Smith A (2011) Pre-chemotherapy differences in visuospatial working memory in breast cancer patients compared to controls: an FMRI study. Front Hum Neurosci 5:122. doi:10.3389/fnhum.2011.00122

    Article  PubMed Central  PubMed  Google Scholar 

  55. Scherling C, Collins B, Mackenzie J, Bielajew C, Smith A (2012) Prechemotherapy differences in response inhibition in breast cancer patients compared to controls: a functional magnetic resonance imaging study. J Clin Exp Neuropsychol 34:543–560. doi:10.1080/13803395.2012.666227

    Article  PubMed  Google Scholar 

  56. Massa E, Madeddu C, Lusso MR, Gramignano G, Mantovani G (2006) Evaluation of the effectiveness of treatment with erythropoietin on anemia, cognitive functioning and functions studied by comprehensive geriatric assessment in elderly cancer patients with anemia related to cancer chemotherapy. Crit Rev Oncol Hematol 57:175–182. doi:10.1016/j.critrevonc.2005.06.001

    Article  PubMed  Google Scholar 

  57. Vearncombe KJ, Rolfe M, Wright M, Pachana NA, Andrew B, Beadle G (2009) Predictors of cognitive decline after chemotherapy in breast cancer patients. J Int Neuropsychol Soc 15:951–962. doi:10.1017/S1355617709990567

    Article  PubMed  Google Scholar 

  58. Fardell JE, Vardy J, Johnston IN, Winocur G (2011) Chemotherapy and cognitive impairment: treatment options. Clin Pharmacol Ther 90:366–376. doi:10.1038/clpt.2011.112

    Article  CAS  PubMed  Google Scholar 

  59. O’Shaughnessy JA, Vukelja SJ, Holmes FA, Savin M, Jones M, Royall D, George M, Von Hoff D (2005) Feasibility of quantifying the effects of epoetin alfa therapy on cognitive function in women with breast cancer undergoing adjuvant or neoadjuvant chemotherapy. Clin Breast Cancer 5:439–446

    Article  PubMed  Google Scholar 

  60. Fan HG, Park A, Xu W, Yi QL, Braganza S, Chang J, Couture F, Tannock IF (2009) The influence of erythropoietin on cognitive function in women following chemotherapy for breast cancer. Psychooncology 18:156–161. doi:10.1002/pon.1372

    Article  PubMed  Google Scholar 

  61. Kohli S, Fisher SG, Tra Y, Adams MJ, Mapstone ME, Wesnes KA, Roscoe JA, Morrow GR (2009) The effect of modafinil on cognitive function in breast cancer survivors. Cancer 115:2605–2616. doi:10.1002/cncr.24287

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Lundorff LE, Jonsson BH, Sjogren P (2009) Modafinil for attentional and psychomotor dysfunction in advanced cancer: a double-blind, randomised, cross-over trial. Palliat Med 23:731–738. doi:10.1177/0269216309106872

    Article  CAS  PubMed  Google Scholar 

  63. Lower EE, Fleishman S, Cooper A, Zeldis J, Faleck H, Yu Z, Manning D (2009) Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. J Pain Symptom Manage 38:650–662. doi:10.1016/j.jpainsymman.2009.03.011

    Article  CAS  PubMed  Google Scholar 

  64. Mar Fan HG, Clemons M, Xu W, Chemerynsky I, Breunis H, Braganza S, Tannock IF (2008) A randomised, placebo-controlled, double-blind trial of the effects of d-methylphenidate on fatigue and cognitive dysfunction in women undergoing adjuvant chemotherapy for breast cancer. Support Care Cancer 16:577–583. doi:10.1007/s00520-007-0341-9

    Article  PubMed  Google Scholar 

  65. Gagnon B, Low G, Schreier G (2005) Methylphenidate hydrochloride improves cognitive function in patients with advanced cancer and hypoactive delirium: a prospective clinical study. J Psychiatry Neurosci 30:100–107

    PubMed Central  PubMed  Google Scholar 

  66. Winocur G, Binns MA, Tannock I (2011) Donepezil reduces cognitive impairment associated with anti-cancer drugs in a mouse model. Neuropharmacology 61:1222–1228. doi:10.1016/j.neuropharm.2011.07.013

    Article  CAS  PubMed  Google Scholar 

  67. Levin ED, McClernon FJ, Rezvani AH (2006) Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. Psychopharmacology Berl 184:523–539. doi:10.1007/s00213-005-0164-7

    Article  CAS  PubMed  Google Scholar 

  68. Mansvelder HD, van Aerde KI, Couey JJ, Brussaard AB (2006) Nicotinic modulation of neuronal networks: from receptors to cognition. Psychopharmacology Berl 184:292–305. doi:10.1007/s00213-005-0070-z

    Article  CAS  PubMed  Google Scholar 

  69. Poorthuis RB, Goriounova NA, Couey JJ, Mansvelder HD (2009) Nicotinic actions on neuronal networks for cognition: general principles and long-term consequences. Biochem Pharmacol 78:668–676. doi:10.1016/j.bcp.2009.04.031

    Article  CAS  PubMed  Google Scholar 

  70. Evans DE, Drobes DJ (2009) Nicotine self-medication of cognitive-attentional processing. Addict Biol 14:32–42. doi:10.1111/j.1369-1600.2008.00130.x

    Article  CAS  PubMed  Google Scholar 

  71. Heishman SJ, Kleykamp BA, Singleton EG (2010) Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology Berl 210:453–469. doi:10.1007/s00213-010-1848-1

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Levin ED, Rezvani AH (2006) Nicotinic-antipsychotic drug interactions and cognitive function. Exs 98:185–205

    CAS  PubMed  Google Scholar 

  73. Newhouse P, Singh A, Potter A (2004) Nicotine and nicotinic receptor involvement in neuropsychiatric disorders. Curr Top Med Chem 4:267–282

    Article  CAS  PubMed  Google Scholar 

  74. Christie LA, Acharya MM, Parihar VK, Nguyen A, Martirosian V, Limoli CL (2012) Impaired cognitive function and hippocampal neurogenesis following cancer chemotherapy. Clin Cancer Res 18:1954–1965. doi:10.1158/1078-0432.CCR-11-2000

    Article  CAS  PubMed  Google Scholar 

  75. Walker EA, Foley JJ, Clark-Vetri R, Raffa RB (2011) Effects of repeated administration of chemotherapeutic agents tamoxifen, methotrexate, and 5-fluorouracil on the acquisition and retention of a learned response in mice. Psychopharmacology Berl 217:539–548. doi:10.1007/s00213-011-2310-8

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Winocur G, Henkelman M, Wojtowicz JM, Zhang H, Binns MA, Tannock IF (2012) The effects of chemotherapy on cognitive function in a mouse model: a prospective study. Clin Cancer Res 18:3112–3121. doi:10.1158/1078-0432.CCR-12-0060

    Article  CAS  PubMed  Google Scholar 

  77. Seigers R, Fardell JE (2011) Neurobiological basis of chemotherapy-induced cognitive impairment: a review of rodent research. Neurosci Biobehav Rev 35:729–741. doi:10.1016/j.neubiorev.2010.09.006

    Article  PubMed  Google Scholar 

  78. Schantz SL, Widholm JJ (2001) Cognitive effects of endocrine-disrupting chemicals in animals. Environ Health Perspect 109:1197–1206

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Galea LA, Uban KA, Epp JR, Brummelte S, Barha CK, Wilson WL, Lieblich SE, Pawluski JL (2008) Endocrine regulation of cognition and neuroplasticity: our pursuit to unveil the complex interaction between hormones, the brain, and behaviour. Can J Exp Psychol 62:247–260. doi:10.1037/a0014501

    Article  PubMed  Google Scholar 

  80. Daniel JM (2006) Effects of oestrogen on cognition: what have we learned from basic research? J Neuroendocrinol 18:787–795. doi:10.1111/j.1365-2826.2006.01471.x

    Article  CAS  PubMed  Google Scholar 

  81. Duffner PK (2004) Long-term effects of radiation therapy on cognitive and endocrine function in children with leukemia and brain tumors. Neurologist 10:293–310. doi:10.1097/01.nrl.0000144287.35993.96

    Article  PubMed  Google Scholar 

  82. Klein M, Heimans JJ, Aaronson NK, van der Ploeg HM, Grit J, Muller M, Postma TJ, Mooij JJ, Boerman RH, Beute GN, Ossenkoppele GJ, van Imhoff GW, Dekker AW, Jolles J, Slotman BJ, Struikmans H, Taphoorn MJ (2002) Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study. Lancet 360:1361–1368

    Article  CAS  PubMed  Google Scholar 

  83. Abildstrom H, Rasmussen LS, Rentowl P, Hanning CD, Rasmussen H, Kristensen PA, Moller JT (2000) Cognitive dysfunction 1-2 years after non-cardiac surgery in the elderly. ISPOCD group. International study of post-operative cognitive dysfunction. Acta Anaesthesiol Scand 44:1246–1251

    Article  CAS  PubMed  Google Scholar 

  84. Scheibel RS, Meyers CA, Levin VA (1996) Cognitive dysfunction following surgery for intracerebral glioma: influence of histopathology, lesion location, and treatment. J Neurooncol 30:61–69

    CAS  PubMed  Google Scholar 

  85. Seigers R, Loos M, Van Tellingen O, Boogerd W, Smit AB, Schagen SB (2014) Cognitive impact of cytotoxic agents in mice. Psychopharmacology Berl. doi:10.1007/s00213-014-3636-9

    PubMed  Google Scholar 

  86. Bennett TL, Hebert PN, Moss DE (1973) Hippocampal theta activity and the attention component of discrimination learning. Behav Biol 8:173–181

    Article  CAS  PubMed  Google Scholar 

  87. Berry SD, Rinaldi PC, Thompson RF, Verzeano M (1978) Analysis of temporal relations among units and slow waves in rabbit hippocampus. Brain Res Bull 3:509–518

    Article  CAS  PubMed  Google Scholar 

  88. Duzel E, Penny WD, Burgess N (2010) Brain oscillations and memory. Curr Opin Neurobiol 20:143–149. doi:10.1016/j.conb.2010.01.004

    Article  PubMed  CAS  Google Scholar 

  89. Hoffmann LC, Berry SD (2009) Cerebellar theta oscillations are synchronized during hippocampal theta-contingent trace conditioning. Proc Natl Acad Sci U.S. A 106:21371–21376. doi:10.1073/pnas.0908403106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Jutras MJ, Buffalo EA (2010) Synchronous neural activity and memory formation. Curr Opin Neurobiol 20:150–155. doi:10.1016/j.conb.2010.02.006

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Wikgren J, Nokia MS, Penttonen M (2010) Hippocampo-cerebellar theta band phase synchrony in rabbits. Neuroscience 165:1538–1545. doi:10.1016/j.neuroscience.2009.11.044

    Article  CAS  PubMed  Google Scholar 

  92. Nokia MS, Anderson ML, Shors TJ (2012) Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain. Eur J Neurosci 36:3521–3530. doi:10.1111/ejn.12007

    Article  PubMed Central  PubMed  Google Scholar 

  93. Helal GK, Helal OK (2009) Metallothionein attenuates carmustine-induced oxidative stress and protects against pulmonary fibrosis in rats. Arch Toxicol 83:87–94. doi:10.1007/s00204-008-0325-7

    Article  CAS  PubMed  Google Scholar 

  94. Winocur G, Vardy J, Binns MA, Kerr L, Tannock I (2006) The effects of the anti-cancer drugs, methotrexate and 5-fluorouracil, on cognitive function in mice. Pharmacol Biochem Behav 85:66–75. doi:10.1016/j.pbb.2006.07.010

    Article  CAS  PubMed  Google Scholar 

  95. Rezvani AH, Levin ED (2003) Nicotinic-glutamatergic interactions and attentional performance on an operant visual signal detection task in female rats. Eur J Pharmacol 465:83–90

    Article  CAS  PubMed  Google Scholar 

  96. Rezvani AH, Kholdebarin E, Dawson E, Levin ED (2008) Nicotine and clozapine effects on attentional performance impaired by the NMDA antagonist dizocilpine in female rats. Int J Neuropsychopharmacol 11:63–70. doi:10.1017/S1461145706007528

    Article  CAS  PubMed  Google Scholar 

  97. Levin ED, Christopher NC, Briggs SJ, Rose JE (1993) Chronic nicotine reverses working memory deficits caused by lesions of the fimbria or medial basalocortical projection. Brain Res Cogn Brain Res 1:137–143

    Article  CAS  PubMed  Google Scholar 

  98. Mirza NR, Stolerman IP (1998) Nicotine enhances sustained attention in the rat under specific task conditions. Psychopharmacology Berl 138:266–274

    Article  CAS  PubMed  Google Scholar 

  99. Stolerman IP, Mirza NR, Hahn B, Shoaib M (2000) Nicotine in an animal model of attention. Eur J Pharmacol 393:147–154

    Article  CAS  PubMed  Google Scholar 

  100. Levin ED, Petro A, Beatty A (2005) Olanzapine interactions with nicotine and mecamylamine in rats: effects on memory function. Neurotoxicol Teratol 27:459–464. doi:10.1016/j.ntt.2005.01.011

    Article  CAS  PubMed  Google Scholar 

  101. Hodges H, Allen Y, Sinden J, Lantos PL, Gray JA (1991) Effects of cholinergic-rich neural grafts on radial maze performance of rats after excitotoxic lesions of the forebrain cholinergic projection system–II. Cholinergic drugs as probes to investigate lesion-induced deficits and transplant-induced functional recovery. Neuroscience 45:609–623

    Article  CAS  PubMed  Google Scholar 

  102. Turner JJ, Hodges H, Sinden JD, Gray JA (1992) Comparison of radial maze performance of rats after ibotenate and quisqualate lesions of the forebrain cholinergic projection system: effects of pharmacological challenge and changes in training regime. Behav Pharmacol 3:359–373

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  104. 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 Berl 144:175–182

    Article  CAS  PubMed  Google Scholar 

  105. Levin ED, Christopher NC (2002) Persistence of nicotinic agonist RJR 2403-induced working memory improvement in rats. Drug Dev Res 55:97–103

    Article  CAS  Google Scholar 

  106. Lippiello PM, Bencherif M, Gray JA, Peters S, Grigoryan G, Hodges H, Collins AC (1996) RJR-2403: a nicotinic agonist with CNS selectivity II. In vivo characterization. J Pharmacol Exp Ther 279:1422–1429

    CAS  PubMed  Google Scholar 

  107. Ueno K, Togashi H, Matsumoto M, Ohashi S, Saito H, Yoshioka M (2002) Alpha4beta2 nicotinic acetylcholine receptor activation ameliorates impairment of spontaneous alternation behavior in stroke-prone spontaneously hypertensive rats, an animal model of attention deficit hyperactivity disorder. J Pharmacol Exp Ther 302:95–100

    Article  CAS  PubMed  Google Scholar 

  108. Decker MW, Bannon AW, Curzon P, Gunther KL, Brioni JD, Holladay MW, Lin NH, Li Y, Daanen JF, Buccafusco JJ, Prendergast MA, Jackson WJ, Arneric SP (1997) ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride]: II. A novel cholinergic channel modulator with effects on cognitive performance in rats and monkeys. J Pharmacol Exp Ther 283:247–258

    CAS  PubMed  Google Scholar 

  109. Marighetto A, Valerio S, Desmedt A, Philippin JN, Trocme-Thibierge C, Morain P (2008) Comparative effects of the alpha7 nicotinic partial agonist, S 24795, and the cholinesterase inhibitor, donepezil, against aging-related deficits in declarative and working memory in mice. Psychopharmacology Berl 197:499–508. doi:10.1007/s00213-007-1063-x

    Article  CAS  PubMed  Google Scholar 

  110. Levin ED, Bettegowda C, Blosser J, Gordon J (1999) AR-R17779, and alpha7 nicotinic agonist, improves learning and memory in rats. Behav Pharmacol 10:675–680

    Article  CAS  PubMed  Google Scholar 

  111. McLean SL, Grayson B, Idris NF, Lesage AS, Pemberton DJ, Mackie C, Neill JC (2011) Activation of alpha7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: implications for therapy of cognitive dysfunction in schizophrenia. Eur Neuropsychopharmacol 21:333–343. doi:10.1016/j.euroneuro.2010.06.003

    Article  CAS  PubMed  Google Scholar 

  112. Miller RR, Matute H (1996) Biological significance in forward and backward blocking: resolution of a discrepancy between animal conditioning and human causal judgment. J Exp Psychol Gen 125:370–386

    Article  CAS  PubMed  Google Scholar 

  113. Xiang JZ, Brown MW (2004) Neuronal responses related to long-term recognition memory processes in prefrontal cortex. Neuron 42:817–829. doi:10.1016/j.neuron.2004.05.013

    Article  CAS  PubMed  Google Scholar 

  114. Redrobe JP, Nielsen EO, Christensen JK, Peters D, Timmermann DB, Olsen GM (2009) Alpha7 nicotinic acetylcholine receptor activation ameliorates scopolamine-induced behavioural changes in a modified continuous Y-maze task in mice. Eur J Pharmacol 602:58–65. doi:10.1016/j.ejphar.2008.09.035

    Article  CAS  PubMed  Google Scholar 

  115. Cannon CE, Puri V, Vivian JA, Egbertson MS, Eddins D, Uslaner JM (2013) The nicotinic alpha7 receptor agonist GTS-21 improves cognitive performance in ketamine impaired rhesus monkeys. Neuropharmacology 64:191–196. doi:10.1016/j.neuropharm.2012.05.003

    Article  CAS  PubMed  Google Scholar 

  116. Diamond A, Doar B (1989) The performance of human infants on a measure of frontal cortex function, the delayed response task. Dev Psychobiol 22:271–294. doi:10.1002/dev.420220307

    Article  CAS  PubMed  Google Scholar 

  117. Wilkinson LS, Dias R, Thomas KL, Augood SJ, Everitt BJ, Robbins TW, Roberts AC (1997) Contrasting effects of excitotoxic lesions of the prefrontal cortex on the behavioural response to D-amphetamine and presynaptic and postsynaptic measures of striatal dopamine function in monkeys. Neuroscience 80:717–730

    Article  CAS  PubMed  Google Scholar 

  118. Alexander KS, Wu HQ, Schwarcz R, Bruno JP (2012) Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine. Psychopharmacology Berl 220:627–637. doi:10.1007/s00213-011-2539-2

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  119. Robbins TW, Roberts AC (2007) Differential regulation of fronto-executive function by the monoamines and acetylcholine. Cereb Cortex 17(Suppl 1):i151–i160. doi:10.1093/cercor/bhm066

    Article  PubMed  Google Scholar 

  120. Birrell JM, Brown VJ (2000) Medial frontal cortex mediates perceptual attentional set shifting in the rat. J Neurosci 20:4320–4324

    CAS  PubMed  Google Scholar 

  121. Aggleton JP, O’Mara SM, Vann SD, Wright NF, Tsanov M, Erichsen JT (2010) Hippocampal-anterior thalamic pathways for memory: uncovering a network of direct and indirect actions. Eur J Neurosci 31:2292–2307. doi:10.1111/j.1460-9568.2010.07251.x

    Article  PubMed Central  PubMed  Google Scholar 

  122. Albasser MM, Poirier GL, Aggleton JP (2010) Qualitatively different modes of perirhinal-hippocampal engagement when rats explore novel vs. familiar objects as revealed by c-Fos imaging. Eur J Neurosci 31:134–147. doi:10.1111/j.1460-9568.2009.07042.x

    Article  PubMed Central  PubMed  Google Scholar 

  123. Albasser MM, Davies M, Futter JE, Aggleton JP (2009) Magnitude of the object recognition deficit associated with perirhinal cortex damage in rats: effects of varying the lesion extent and the duration of the sample period. Behav Neurosci 123:115–124. doi:10.1037/a0013829

    Article  CAS  PubMed  Google Scholar 

  124. Buckmaster CA, Eichenbaum H, Amaral DG, Suzuki WA, Rapp PR (2004) Entorhinal cortex lesions disrupt the relational organization of memory in monkeys. J Neurosci 24:9811–9825. doi:10.1523/JNEUROSCI.1532-04.2004

    Article  CAS  PubMed  Google Scholar 

  125. Clark RE, Zola SM, Squire LR (2000) Impaired recognition memory in rats after damage to the hippocampus. J Neurosci 20:8853–8860

    CAS  PubMed  Google Scholar 

  126. Melichercik AM, Elliott KS, Bianchi C, Ernst SM, Winters BD (2012) Nicotinic receptor activation in perirhinal cortex and hippocampus enhances object memory in rats. Neuropharmacology 62:2096–2105. doi:10.1016/j.neuropharm.2012.01.008

    Article  CAS  PubMed  Google Scholar 

  127. Fardell JE, Vardy J, Logge W, Johnston I (2010) Single high dose treatment with methotrexate causes long-lasting cognitive dysfunction in laboratory rodents. Pharmacol Biochem Behav 97:333–339. doi:10.1016/j.pbb.2010.08.019

    Article  CAS  PubMed  Google Scholar 

  128. Mustafa S, Walker A, Bennett G, Wigmore PM (2008) 5-Fluorouracil chemotherapy affects spatial working memory and newborn neurons in the adult rat hippocampus. Eur J Neurosci 28:323–330. doi:10.1111/j.1460-9568.2008.06325.x

    Article  PubMed  Google Scholar 

  129. Seigers R, Schagen SB, Beerling W, Boogerd W, van Tellingen O, van Dam FS, Koolhaas JM, Buwalda B (2008) Long-lasting suppression of hippocampal cell proliferation and impaired cognitive performance by methotrexate in the rat. Behav Brain Res 186:168–175. doi:10.1016/j.bbr.2007.08.004

    Article  CAS  PubMed  Google Scholar 

  130. Yang M, Kim JS, Song MS, Kim SH, Kang SS, Bae CS, Kim JC, Wang H, Shin T, Moon C (2010) Cyclophosphamide impairs hippocampus-dependent learning and memory in adult mice: possible involvement of hippocampal neurogenesis in chemotherapy-induced memory deficits. Neurobiol Learn Mem 93:487–494. doi:10.1016/j.nlm.2010.01.006

    Article  CAS  PubMed  Google Scholar 

  131. Fardell JE, Vardy J, Shah JD, Johnston IN (2012) Cognitive impairments caused by oxaliplatin and 5-fluorouracil chemotherapy are ameliorated by physical activity. Psychopharmacology Berl 220:183–193. doi:10.1007/s00213-011-2466-2

    Article  CAS  PubMed  Google Scholar 

  132. Kruk-Slomka M, Michalak A, Budzynska B, Biala G (2014) A comparison of mecamylamine and bupropion effects on memory-related responses induced by nicotine and scopolamine in the novel object recognition test in mice. Pharmacol Rep 66:638–646. doi:10.1016/j.pharep.2014.02.002

    Article  CAS  PubMed  Google Scholar 

  133. Puma C, Deschaux O, Molimard R, Bizot JC (1999) Nicotine improves memory in an object recognition task in rats. Eur Neuropsychopharmacol 9:323–327

    Article  CAS  PubMed  Google Scholar 

  134. Sambeth A, Riedel WJ, Smits LT, Blokland A (2007) Cholinergic drugs affect novel object recognition in rats: relation with hippocampal EEG? Eur J Pharmacol 572:151–159. doi:10.1016/j.ejphar.2007.06.018

    Article  CAS  PubMed  Google Scholar 

  135. Furukawa-Hibi Y, Alkam T, Nitta A, Matsuyama A, Mizoguchi H, Suzuki K, Moussaoui S, Yu QS, Greig NH, Nagai T, Yamada K (2011) Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-beta peptide in mice. Behav Brain Res 225:222–229. doi:10.1016/j.bbr.2011.07.035

    Article  CAS  PubMed  Google Scholar 

  136. Noda Y, Mouri A, Ando Y, Waki Y, Yamada SN, Yoshimi A, Yamada K, Ozaki N, Wang D, Nabeshima T (2010) Galantamine ameliorates the impairment of recognition memory in mice repeatedly treated with methamphetamine: involvement of allosteric potentiation of nicotinic acetylcholine receptors and dopaminergic-ERK1/2 systems. Int J Neuropsychopharmacol 13:1343–1354. doi:10.1017/S1461145710000222

    Article  CAS  PubMed  Google Scholar 

  137. Wang D, Noda Y, Zhou Y, Mouri A, Mizoguchi H, Nitta A, Chen W, Nabeshima T (2007) The allosteric potentiation of nicotinic acetylcholine receptors by galantamine ameliorates the cognitive dysfunction in beta amyloid25-35 i.c.v.-injected mice: involvement of dopaminergic systems. Neuropsychopharmacology 32:1261–1271. doi:10.1038/sj.npp.1301256

    Article  CAS  PubMed  Google Scholar 

  138. Anagnostaras SG, Gale GD, Fanselow MS (2001) Hippocampus and contextual fear conditioning: recent controversies and advances. Hippocampus 11:8–17. doi:10.1002/1098-1063(2001)11:1<8:AID-HIPO1015>3.0.CO;2-7

    Article  CAS  PubMed  Google Scholar 

  139. Corcoran KA, Maren S (2001) Hippocampal inactivation disrupts contextual retrieval of fear memory after extinction. J Neurosci 21:1720–1726

    CAS  PubMed  Google Scholar 

  140. Holland PC, Bouton ME (1999) Hippocampus and context in classical conditioning. Curr Opin Neurobiol 9:195–202

    Article  CAS  PubMed  Google Scholar 

  141. Maren S, Aharonov G, Fanselow MS (1997) Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats. Behav Brain Res 88:261–274

    Article  CAS  PubMed  Google Scholar 

  142. Maren S, Fanselow MS (1997) Electrolytic lesions of the fimbria/fornix, dorsal hippocampus, or entorhinal cortex produce anterograde deficits in contextual fear conditioning in rats. Neurobiol Learn Mem 67:142–149. doi:10.1006/nlme.1996.3752

    Article  CAS  PubMed  Google Scholar 

  143. Nokia MS, Mikkonen JE, Penttonen M, Wikgren J (2012) Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning. Front Behav Neurosci 6:84. doi:10.3389/fnbeh.2012.00084

    Article  PubMed Central  PubMed  Google Scholar 

  144. Yanovski JA, Packer RJ, Levine JD, Davidson TL, Micalizzi M, D’Angio G (1989) An animal model to detect the neuropsychological toxicity of anticancer agents. Med Pediatr Oncol 17:216–221

    Article  CAS  PubMed  Google Scholar 

  145. Macleod JE, DeLeo JA, Hickey WF, Ahles TA, Saykin AJ, Bucci DJ (2007) Cancer chemotherapy impairs contextual but not cue-specific fear memory. Behav Brain Res 181:168–172. doi:10.1016/j.bbr.2007.04.003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  146. Konat GW, Kraszpulski M, James I, Zhang HT, Abraham J (2008) Cognitive dysfunction induced by chronic administration of common cancer chemotherapeutics in rats. Metab Brain Dis 23:325–333. doi:10.1007/s11011-008-9100-y

    Article  CAS  PubMed  Google Scholar 

  147. Hou JG, Xue JJ, Lee MR, Sun MQ, Zhao XH, Zheng YN, Sung CK (2013) Compound K is able to ameliorate the impaired cognitive function and hippocampal neurogenesis following chemotherapy treatment. Biochem Biophys Res Commun 436:104–109. doi:10.1016/j.bbrc.2013.05.087

    Article  CAS  PubMed  Google Scholar 

  148. Reiriz AB, Reolon GK, Preissler T, Rosado JO, Henriques JA, Roesler R, Schwartsmann G (2006) Cancer chemotherapy and cognitive function in rodent models: memory impairment induced by cyclophosphamide in mice. Clin Cancer Res 12(16):5000–5001. doi:10.1158/1078-0432.CCR-06-0138

    Article  CAS  PubMed  Google Scholar 

  149. Foley JJ, Raffa RB, Walker EA (2008) Effects of chemotherapeutic agents 5-fluorouracil and methotrexate alone and combined in a mouse model of learning and memory. Psychopharmacology Berl 199:527–538. doi:10.1007/s00213-008-1175-y

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  150. Krynetskiy E, Krynetskaia N, Rihawi D, Wieczerzak K, Ciummo V, Walker E (2013) Establishing a model for assessing DNA damage in murine brain cells as a molecular marker of chemotherapy-associated cognitive impairment. Life Sci 93:605–610. doi:10.1016/j.lfs.2013.03.013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  151. Uzum G, Diler AS, Bahcekapili N, Tasyurekli M, Ziylan YZ (2004) Nicotine improves learning and memory in rats: morphological evidence for acetylcholine involvement. Int J Neurosci 114:1163–1179. doi:10.1080/00207450490475652

    Article  CAS  PubMed  Google Scholar 

  152. Meguro K, Yamaguchi S, Arai H, Nakagawa T, Doi C, Yamada M, Ikarashi Y, Maruyama Y, Sasaki H (1994) Nicotine improves cognitive disturbance in senescence-accelerated mice. Pharmacol Biochem Behav 49:769–772

    Article  CAS  PubMed  Google Scholar 

  153. Gould TJ, Lommock JA (2003) Nicotine enhances contextual fear conditioning and ameliorates ethanol-induced deficits in contextual fear conditioning. Behav Neurosci 117:1276–1282. doi:10.1037/0735-7044.117.6.1276

    Article  CAS  PubMed  Google Scholar 

  154. Gould TJ, Wehner JM (1999) Nicotine enhancement of contextual fear conditioning. Behav Brain Res 102:31–39

    Article  CAS  PubMed  Google Scholar 

  155. Portugal GS, Wilkinson DS, Kenney JW, Sullivan C, Gould TJ (2012) Strain-dependent effects of acute, chronic, and withdrawal from chronic nicotine on fear conditioning. Behav Genet 42:133–150. doi:10.1007/s10519-011-9489-7

    Article  PubMed Central  PubMed  Google Scholar 

  156. Tian S, Huang F, Li P, Li Z, Zhou S, Deng H, Yang Y (2011) Nicotine enhances contextual fear memory reconsolidation in rats. Neurosci Lett 487:368–371. doi:10.1016/j.neulet.2010.10.058

    Article  CAS  PubMed  Google Scholar 

  157. Woodruff-Pak DS (2003) Mecamylamine reversal by nicotine and by a partial alpha7 nicotinic acetylcholine receptor agonist (GTS-21) in rabbits tested with delay eyeblink classical conditioning. Behav Brain Res 143:159–167

    Article  CAS  PubMed  Google Scholar 

  158. Davis JA, Kenney JW, Gould TJ (2007) Hippocampal alpha4beta2 nicotinic acetylcholine receptor involvement in the enhancing effect of acute nicotine on contextual fear conditioning. J Neurosci 27:10870–10877. doi:10.1523/JNEUROSCI.3242-07.2007

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  159. Kenney JW, Wilkinson DS, Gould TJ (2010) The enhancement of contextual fear conditioning by ABT-418. Behav Pharmacol 21:246–249. doi:10.1097/FBP.0b013e32833a5b9d

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  160. Nitta A, Katono Y, Itoh A, Hasegawa T, Nabeshima T (1994) Nicotine reverses scopolamine-induced impairment of performance in passive avoidance task in rats through its action on the dopaminergic neuronal system. Pharmacol Biochem Behav 49:807–812

    Article  CAS  PubMed  Google Scholar 

  161. Hefco V, Yamada K, Hefco A, Hritcu L, Tiron A, Olariu A, Nabeshima T (2003) Effects of nicotine on memory impairment induced by blockade of muscarinic, nicotinic and dopamine D2 receptors in rats. Eur J Pharmacol 474:227–232

    Article  CAS  PubMed  Google Scholar 

  162. Sapronov NS, Fedotova YO, Kuznetsova NN (2006) Antiamnestic effect of alpha7-nicotinic receptor agonist RJR-2403 in middle-aged ovariectomized rats with Alzheimer type dementia. Bull Exp Biol Med 142:700–702

    Article  CAS  PubMed  Google Scholar 

  163. Meyer EM, Tay ET, Papke RL, Meyers C, Huang GL, de Fiebre CM (1997) 3-[2,4-Dimethoxybenzylidene]anabaseine (DMXB) selectively activates rat alpha7 receptors and improves memory-related behaviors in a mecamylamine-sensitive manner. Brain Res 768:49–56

    Article  CAS  PubMed  Google Scholar 

  164. Nanri M, Yamamoto J, Miyake H, Watanabe H (1998) Protective effect of GTS-21, a novel nicotinic receptor agonist, on delayed neuronal death induced by ischemia in gerbils. Jpn J Pharmacol 76:23–29

    Article  CAS  PubMed  Google Scholar 

  165. Morris RG, Garrud P, Rawlins JN, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297:681–683

    Article  CAS  PubMed  Google Scholar 

  166. Li CQ, Liu D, Huang L, Wang H, Zhang JY, Luo XG (2008) Cytosine arabinoside treatment impairs the remote spatial memory function and induces dendritic retraction in the anterior cingulate cortex of rats. Brain Res Bull 77:237–240. doi:10.1016/j.brainresbull.2008.07.010

    Article  CAS  PubMed  Google Scholar 

  167. Bernal MC, Vicens P, Carrasco MC, Redolat R (1999) Effects of nicotine on spatial learning in C57BL mice. Behav Pharmacol 10:333–336

    Article  CAS  PubMed  Google Scholar 

  168. Levin ED, Christopher NC, Weaver T, Moore J, Brucato F (1999) Ventral hippocampal ibotenic acid lesions block chronic nicotine-induced spatial working memory improvement in rats. Brain Res Cogn Brain Res 7:405–410

    Article  CAS  PubMed  Google Scholar 

  169. Sultana R, Ameno K, Jamal M, Miki T, Tanaka N, Ono J, Kinoshita H, Nakamura Y (2013) Low-dose nicotine facilitates spatial memory in ApoE-knockout mice in the radial arm maze. Neurol Sci 34:891–897. doi:10.1007/s10072-012-1149-z

    Article  PubMed  Google Scholar 

  170. Aleisa AM, Alzoubi KH, Alkadhi KA (2011) Post-learning REM sleep deprivation impairs long-term memory: reversal by acute nicotine treatment. Neurosci Lett 499:28–31. doi:10.1016/j.neulet.2011.05.025

    Article  CAS  PubMed  Google Scholar 

  171. Aleisa AM, Helal G, Alhaider IA, Alzoubi KH, Srivareerat M, Tran TT, Al-Rejaie SS, Alkadhi KA (2011) Acute nicotine treatment prevents REM sleep deprivation-induced learning and memory impairment in rat. Hippocampus 21:899–909. doi:10.1002/hipo.20806

    CAS  PubMed  Google Scholar 

  172. Alkadhi KA, Srivareerat M, Tran TT (2010) Intensification of long-term memory deficit by chronic stress and prevention by nicotine in a rat model of Alzheimer’s disease. Mol Cell Neurosci 45:289–296. doi:10.1016/j.mcn.2010.06.018

    Article  CAS  PubMed  Google Scholar 

  173. Srivareerat M, Tran TT, Salim S, Aleisa AM, Alkadhi KA (2011) Chronic nicotine restores normal Abeta levels and prevents short-term memory and E-LTP impairment in Abeta rat model of Alzheimer’s disease. Neurobiol Aging 32:834–844. doi:10.1016/j.neurobiolaging.2009.04.015

    Article  CAS  PubMed  Google Scholar 

  174. Zhou M, Suszkiw JB (2004) Nicotine attenuates spatial learning deficits induced in the rat by perinatal lead exposure. Brain Res 999:142–147

    Article  CAS  PubMed  Google Scholar 

  175. Azami K, Tabrizian K, Hosseini R, Seyedabadi M, Shariatpanahi M, Noorbakhsh F, Kebriaeezadeh A, Ostad SN, Sharifzadeh M (2012) Nicotine attenuates spatial learning deficits induced by sodium metavanadate. Neurotoxicology 33:44–52. doi:10.1016/j.neuro.2011.11.004

    Article  CAS  PubMed  Google Scholar 

  176. Yamada K, Furukawa S, Iwasaki T, Ichitani Y (2010) Nicotine improves AF64A-induced spatial memory deficits in Morris water maze in rats. Neurosci Lett 469:88–92. doi:10.1016/j.neulet.2009.11.050

    Article  CAS  PubMed  Google Scholar 

  177. Vicens P, Ribes D, Torrente M, Domingo JL (2011) Behavioral effects of PNU-282987, an alpha7 nicotinic receptor agonist, in mice. Behav Brain Res 216:341–348. doi:10.1016/j.bbr.2010.08.015

    Article  CAS  PubMed  Google Scholar 

  178. Chen L, Wang H, Zhang Z, Li Z, He D, Sokabe M (2010) DMXB (GTS-21) ameliorates the cognitive deficits in beta amyloid(25-35(-)) injected mice through preventing the dysfunction of alpha7 nicotinic receptor. J Neurosci Res 88:1784–1794. doi:10.1002/jnr.22345

    CAS  PubMed  Google Scholar 

  179. Buckingham SD, Jones AK, Brown LA, Sattelle DB (2009) Nicotinic acetylcholine receptor signalling: roles in Alzheimer’s disease and amyloid neuroprotection. Pharmacol Rev 61:39–61. doi:10.1124/pr.108.000562

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  180. Mudo G, Belluardo N, Fuxe K (2007) Nicotinic receptor agonists as neuroprotective/neurotrophic drugs. Progress in molecular mechanisms. J Neural Transm 114:135–147. doi:10.1007/s00702-006-0561-z

    Article  CAS  PubMed  Google Scholar 

  181. Resende RR, Adhikari A (2009) Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation. Cell Commun Signal 7:20. doi:10.1186/1478-811X-7-20

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  182. West KA, Brognard J, Clark AS, Linnoila IR, Yang X, Swain SM, Harris C, Belinsky S, Dennis PA (2003) Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. J Clin Invest 111:81–90. doi:10.1172/JCI16147

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  183. Zhou Y, Gu X, Ashayeri E, Zhang R, Sridhar R (2007) Nicotine decreases the cytotoxicity of doxorubicin towards MCF-7 and KB-3.1 human cancer cells in culture. J Natl Med Assoc 99:319–327

    PubMed Central  PubMed  Google Scholar 

  184. Dasgupta P, Kinkade R, Joshi B, Decook C, Haura E, Chellappan S (2006) Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin. Proc Natl Acad Sci USA 103:6332–6337. doi:10.1073/pnas.0509313103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  185. Zeng F, Li YC, Chen G, Zhang YK, Wang YK, Zhou SQ, Ma LN, Zhou JH, Huang YY, Zhu WY, Liu XG (2012) Nicotine inhibits cisplatin-induced apoptosis in NCI-H446 cells. Med Oncol 29:364–373. doi:10.1007/s12032-010-9792-9

    Article  CAS  PubMed  Google Scholar 

  186. Xu J, Huang H, Pan C, Zhang B, Liu X, Zhang L (2007) Nicotine inhibits apoptosis induced by cisplatin in human oral cancer cells. Int J Oral Maxillofac Surg 36:739–744. doi:10.1016/j.ijom.2007.05.016

    Article  CAS  PubMed  Google Scholar 

  187. Shen T, Le W, Yee A, Kamdar O, Hwang PH, Upadhyay D (2010) Nicotine induces resistance to chemotherapy in nasal epithelial cancer. Am J Rhinol Allergy 24:e73–e77. doi:10.2500/ajra.2010.24.3456

    Article  PubMed  Google Scholar 

  188. Zhang J, Kamdar O, Le W, Rosen GD, Upadhyay D (2009) Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer. Am J Respir Cell Mol Biol 40:135–146. doi:10.1165/rcmb.2007-0277OC

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  189. Ahles TA, Li Y, McDonald BC, Schwartz GN, Kaufman PA, Tsongalis GJ, Moore JH, Saykin AJ (2014) Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: the impact of APOE and smoking. Psychooncology 23:1382–1390. doi:10.1002/pon.3545

    Article  PubMed  PubMed Central  Google Scholar 

  190. Levin ED, Cauley M, Rezvani AH (2013) Improvement of attentional function with antagonism of nicotinic receptors in female rats. Eur J Pharmacol 702:269–274. doi:10.1016/j.ejphar.2013.01.056

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  191. Levin ED (2013) Complex relationships of nicotinic receptor actions and cognitive functions. Biochem Pharmacol 86:1145–1152. doi:10.1016/j.bcp.2013.07.021

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  192. Ochoa EL, Chattopadhyay A, McNamee MG (1989) Desensitization of the nicotinic acetylcholine receptor: molecular mechanisms and effect of modulators. Cell Mol Neurobiol 9:141–178

    Article  CAS  PubMed  Google Scholar 

  193. Paradiso KG, Steinbach JH (2003) Nicotine is highly effective at producing desensitization of rat alpha4beta2 neuronal nicotinic receptors. J Physiol 553:857–871. doi:10.1113/jphysiol.2003.053447

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. 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

    Rex M. Philpot

Authors
  1. Rex M. Philpot
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rex M. Philpot.

Additional information

Special Issue: In honor of Lynn Wecker.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Philpot, R.M. Potential Use of Nicotinic Receptor Agonists for the Treatment of Chemotherapy-Induced Cognitive Deficits. Neurochem Res 40, 2018–2031 (2015). https://doi.org/10.1007/s11064-015-1528-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-015-1528-y

Keywords

Search

Navigation