Skip to main content

Advertisement

SpringerLink
Log in

Nicotine Significantly Improves Chronic Stress-Induced Impairments of Cognition and Synaptic Plasticity in Mice

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The aim of this study was to examine if nicotine was able to improve cognition deficits in a mouse model of chronic mild stress. Twenty-four male C57BL/6 mice were divided into three groups: control, stress, and stress with nicotine treatment. The animal model was established by combining chronic unpredictable mild stress (CUMS) and isolated feeding. Mice were exposed to CUMS continued for 28 days, while nicotine (0.2 mg/kg) was also administrated for 28 days. Weight and sucrose consumption were measured during model establishing period. The anxiety and behavioral despair were analyzed using the forced swim test (FST) and open-field test (OFT). Spatial cognition was evaluated using Morris water maze (MWM) test. Following behavioral assessment, both long-term potentiation (LTP) and depotentiation (DEP) were recorded in the hippocampal dentate gyrus (DG) region. Both synaptic and Notch1 proteins were measured by Western. Nicotine increased stressed mouse’s sucrose consumption. The MWM test showed that spatial learning and reversal learning in stressed animals were remarkably affected relative to controls, whereas nicotine partially rescued cognitive functions. Additionally, nicotine considerably alleviated the level of anxiety and the degree of behavioral despair in stressed mice. It effectively mitigated the depression-induced impairment of hippocampal synaptic plasticity, in which both the LTP and DEP were significantly inhibited in stressed mice. Moreover, nicotine enhanced the expression of synaptic and Notch1 proteins in stressed animals. The results suggest that nicotine ameliorates the depression-like symptoms and improves the hippocampal synaptic plasticity closely associated with activating transmembrane ion channel receptors and Notch signaling components.

ᅟ

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Darcet F, Mendez-David I, Tritschler L, Gardier AM, Guilloux JP, David DJ (2014) Learning and memory impairments in a neuroendocrine mouse model of anxiety/depression. Front Behav Neurosci 8:136. doi:10.3389/fnbeh.2014.00136

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rotheneichner P, Lange S, O’Sullivan A, Marschallinger J, Zaunmair P, Geretsegger C, Aigner L, Couillard-Despres S (2014) Hippocampal neurogenesis and antidepressive therapy: shocking relations. Neural Plasticity. doi:10.1155/2014/723915

  3. Yu T, Guo M, Garza J, Rendon S, Sun XL, Zhang W, Lu XY (2011) Cognitive and neural correlates of depression-like behaviour in socially defeated mice: an animal model of depression with cognitive dysfunction. Int J Neuropsychopharmacol / Off Sci J Collegium Int Neuropsychopharmacol 14(3):303–317. doi:10.1017/S1461145710000945

    Google Scholar 

  4. Santos T, Baungratz MM, Haskel SP, de Lima DD, da Cruz JN, Dal Magro DD, da Cruz JGP (2012) Behavioral interactions of simvastatin and fluoxetine in tests of anxiety and depression. Neuropsychiatr Dis Treat 8:413–422. doi:10.2147/Ndt.S31714

  5. Sadaghiani MS, Javadi-Paydar M, Gharedaghi MH, Fard YY, Dehpour AR (2011) Antidepressant-like effect of pioglitazone in the forced swimming test in mice: the role of PPAR-gamma receptor and nitric oxide pathway. Behav Brain Res 224(2):336–343. doi:10.1016/j.bbr.2011.06.011

    Article  CAS  PubMed  Google Scholar 

  6. Berrendero F, Plaza-Zabala A, Galeote L, Flores A, Bura SA, Kieffer BL, Maldonado R (2012) Influence of delta-opioid receptors in the behavioral effects of nicotine. Neuropsychopharmacol: Off Publ Am Coll Neuropsychopharmacol 37(10):2332–2344. doi:10.1038/npp.2012.88

    Article  CAS  Google Scholar 

  7. Knott V, Thompson A, Shah D, Ilivitsky V (2012) Neural expression of nicotine’s antidepressant properties during tryptophan depletion: an EEG study in healthy volunteers at risk for depression. Biol Psychol 91(2):190–200. doi:10.1016/j.biopsycho.2012.06.002

    Article  PubMed  Google Scholar 

  8. Suemaru K, Yasuda K, Cui RJ, Li BJ, Umeda K, Amano M, Mitsuhashi H, Takeuchi N, Inoue T, Gomita Y, Araki H (2006) Antidepressant-like action of nicotine in forced swimming test and brain serotonin in mice. Physiol Behav 88(4–5):545–549. doi:10.1016/j.physbeh.2006.05.007

    Article  CAS  PubMed  Google Scholar 

  9. Tizabi Y, Overstreet DH, Rezvani AH, Louis VA, Clark E, Janowsky DS, Kling MA (1999) Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology 142(2):193–199. doi:10.1007/s002130050879

    Article  CAS  PubMed  Google Scholar 

  10. Vazquez-Palacios G, Bonilla-Jaime H, Velazquez-Moctezuma J (2004) Antidepressant-like effects of the acute and chronic administration of nicotine in the rat forced swimming test and its interaction with fluoxetine [correction of flouxetine]. Pharmacol Biochem Behav 78(1):165–169. doi:10.1016/j.pbb.2004.03.002

    Article  CAS  PubMed  Google Scholar 

  11. Levin ED, Simon BB (1998) Nicotinic acetylcholine involvement in cognitive function in animals. Psychopharmacology 138(3–4):217–230. doi:10.1007/s002130050667

    Article  CAS  PubMed  Google Scholar 

  12. Vazquez-Palacios G, Bonilla-Jaime H, Velazquez-Moctezuma J (2005) Antidepressant effects of nicotine and fluoxetine in an animal model of depression induced by neonatal treatment with clomipramine. Prog Neuro-Psychopharmacol Biol Psychiatry 29(1):39–46. doi:10.1016/j.pnpbp.2004.08.008

    Article  CAS  Google Scholar 

  13. Nakamura K, Tanaka Y (2001) Antidepressant-like effects of aniracetam in aged rats and its mode of action. Psychopharmacology 158(2):205–212. doi:10.1007/s002130100849

    Article  CAS  PubMed  Google Scholar 

  14. Popik P, Krawczyk M, Kos T, Nalepa I, Kowalska M, Witarski T, Antkiewicz-Michaluk L, Vetulani J (2005) Nicotine produces antidepressant-like actions: behavioral and neurochemical evidence. Eur J Pharmacol 515(1–3):128–133. doi:10.1016/j.ejphar.2005.04.009

    Article  CAS  PubMed  Google Scholar 

  15. Matsuyama S, Matsumoto A (2003) Epibatidine induces long-term potentiation (LTP) via activation of α4β 2 nicotinic acetylcholine receptors (nAChRs) in vivo in the intact mouse dentate gyrus: both α 7 and α4β 2 nAChRs essential to nicotinic LTP. J Pharmacol Sci 93(2):180–187. doi:10.1254/jphs.93.180

    Article  CAS  PubMed  Google Scholar 

  16. Aleisa AM, Alzoubi KH, Gerges NZ, Alkadhi KA (2006) Nicotine blocks stress-induced impairment of spatial memory and long-term potentiation of the hippocampal CA1 region. Int J Neuropsychopharmacol 9(4):417–426. doi:10.1017/S1461145705005912

    Article  CAS  PubMed  Google Scholar 

  17. Weiss S, Nosten-Bertrand M, McIntosh JM, Giros B, Martres MP (2007) Nicotine improves cognitive deficits of dopamine transporter knockout mice without long-term tolerance. Neuropsychopharmacol: Off Publ Am Coll Neuropsychopharmacol 32(12):2465–2478. doi:10.1038/sj.npp.1301385

    Article  CAS  Google Scholar 

  18. Hajszan T, Milner TA, Leranth C (2007) Sex steroids and the dentate gyrus. Prog Brain Res 163:399-+. doi:10.1016/S0079-6123(07)63023-4

    Article  CAS  PubMed  Google Scholar 

  19. Parducz A, Hajszan T, MacLusky NJ, Hoyk Z, Csakvari E, Kurunczi A, Prange-Kiel J, Leranth C (2006) Synaptic remodeling induced by gonadal hormones: neuronal plasticity as a mediator of neuroendocrine and behavioral responses to steroids. Neuroscience 138(3):977–985. doi:10.1016/j.neuroscience.2005.07.008

    Article  CAS  PubMed  Google Scholar 

  20. Sawada S, Yamamoto C, Ohno-Shosaku T (1994) Long-term potentiation and depression in the dentate gyrus, and effects of nicotine. Neurosci Res 20(4):323–329. doi:10.1016/0168-0102(94)90054-X

    Article  CAS  PubMed  Google Scholar 

  21. Nakauchi S, Sumikawa K (2014) Endogenous ACh suppresses LTD induction and nicotine relieves the suppression via different nicotinic ACh receptor subtypes in the mouse hippocampus. Life Sci 111(1–2):62–68. doi:10.1016/j.lfs.2014.07.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gross M, Sheinin A, Nesher E, Tikhonov T, Baranes D, Pinhasov A, Michaelevski I (2015) Early onset of cognitive impairment is associated with altered synaptic plasticity and enhanced hippocampal GluA1 expression in a mouse model of depression. Neurobiol Aging 36(5):1938–1952. doi:10.1016/j.neurobiolaging.2015.02.015

    Article  CAS  PubMed  Google Scholar 

  23. Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284(5415):770–776. doi:10.1126/science.284.5415.770

    Article  CAS  PubMed  Google Scholar 

  24. Lindsell CE, Boulter J, diSibio G, Gossler A, Weinmaster G (1996) Expression patterns of jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand–receptor pairs that may function in neural development. Mol Cell Neurosci 8(1):14–27. doi:10.1006/mcne.1996.0040

    Article  CAS  PubMed  Google Scholar 

  25. Kageyama R, Ohtsuka T, Hatakeyama J, Ohsawa R (2005) Roles of bHLH genes in neural stem cell differentiation. Exp Cell Res 306(2):343–348. doi:10.1016/j.yexcr.2005.03.015

    Article  CAS  PubMed  Google Scholar 

  26. Le Borgne R, Bardin A, Schweisguth F (2005) The roles of receptor and ligand endocytosis in regulating Notch signaling. Development 132(8):1751–1762. doi:10.1242/dev.01789

    Article  PubMed  Google Scholar 

  27. de Bivort BL, Guo HF, Zhong Y (2009) Notch signaling is required for activity-dependent synaptic plasticity at the drosophila neuromuscular junction. J Neurogenet 23(4):395–404. doi:10.3109/01677060902878481

    Article  PubMed  PubMed Central  Google Scholar 

  28. Matsuno M, Horiuchi J, Tully T, Saitoe M (2009) The drosophila cell adhesion molecule Klingon is required for long-term memory formation and is regulated by notch. Proc Natl Acad Sci U S A 106(1):310–315. doi:10.1073/pnas.0807665106

    Article  CAS  PubMed  Google Scholar 

  29. Wang Y, Chan SL, Miele L, Yao PJ, Mackes J, Ingram DK, Mattson MP, Furukawa K (2004) Involvement of notch signaling in hippocampal synaptic plasticity. Proc Natl Acad Sci U S A 101(25):9458–9462. doi:10.1073/pnas.0308126101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang S, Yuan Y, Xia W, Li F, Huang Y, Zhou Y, Guo Y (2012) Neuronal apoptosis and synaptic density in the dentate gyrus of ischemic rats’ response to chronic mild stress and the effects of Notch signaling. PLoS One 7(8):e42828. doi:10.1371/journal.pone.0042828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Guo YJ, Zhang ZJ, Wang SH, Sui YX, Sun Y (2009) Notch1 signaling, hippocampal neurogenesis and behavioral responses to chronic unpredicted mild stress in adult ischemic rats. Prog Neuro-Psychopharmacol Biol Psychiatry 33(4):688–694. doi:10.1016/j.pnpbp.2009.03.022

    Article  Google Scholar 

  32. Hirata N, Sekino Y, Kanda Y (2010) Nicotine increases cancer stem cell population in MCF-7 cells. Biochem Biophys Res Commun 403(1):138–143. doi:10.1016/j.bbrc.2010.10.134

    Article  CAS  PubMed  Google Scholar 

  33. Manda VK, Mittapalli RK, Geldenhuys WJ, Lockman PR (2010) Chronic exposure to nicotine and saquinavir decreases endothelial Notch-4 expression and disrupts blood-brain barrier integrity. J Neurochem 115(2):515–525. doi:10.1111/j.1471-4159.2010.06948.x

    Article  CAS  PubMed  Google Scholar 

  34. Nouri-Shirazi M, Kahlden C, Nishino P, Guinet E (2015) Nicotine exposure alters the mRNA expression of Notch ligands in dendritic cells and their response to Th1-/Th2-promoting stimuli. Scand J Immunol 81(2):110–120. doi:10.1111/sji.12254

    Article  CAS  PubMed  Google Scholar 

  35. Matta SG, Balfour DJ, Benowitz NL, Boyd RT, Buccafusco JJ, Caggiula AR, Craig CR, Collins AC, Damaj MI, Donny EC, Gardiner PS, Grady SR, Heberlein U, Leonard SS, Levin ED, Lukas RJ, Markou A, Marks MJ, McCallum SE, Parameswaran N, Perkins KA, Picciotto MR, Quik M, Rose JE, Rothenfluh A, Schafer WR, Stolerman IP, Tyndale RF, Wehner JM, Zirger JM (2007) Guidelines on nicotine dose selection for in vivo research. Psychopharmacology 190(3):269–319. doi:10.1007/s00213-006-0441-0

    Article  CAS  PubMed  Google Scholar 

  36. Peng YL, Liu YN, Liu L, Wang X, Jiang CL, Wang YX (2012) Inducible nitric oxide synthase is involved in the modulation of depressive behaviors induced by unpredictable chronic mild stress. J Neuroinflammation 9:1–12. doi:10.1186/1742-2094-9-75

    Article  CAS  Google Scholar 

  37. Willner P (2005) Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 52(2):90–110. doi:10.1159/000087097

    Article  CAS  PubMed  Google Scholar 

  38. Dhingra D, Bhankher A (2014) Behavioral and biochemical evidences for antidepressant-like activity of palmatine in mice subjected to chronic unpredictable mild stress. Pharmacol Rep: PR 66(1):1–9. doi:10.1016/j.pharep.2013.06.001

    Article  CAS  PubMed  Google Scholar 

  39. Quan MN, Zhang N, Wang YY, Zhang T, Yang Z (2011) Possible antidepressant effects and mechanisms of memantine in behaviors and synaptic plasticity of a depression rat model. Neuroscience 182:88–97. doi:10.1016/j.neuroscience.2011.03.026

    Article  CAS  PubMed  Google Scholar 

  40. Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229(2):327–336

    CAS  PubMed  Google Scholar 

  41. Harro J, Haidkind R, Harro M, Modiri AR, Gillberg PG, Pahkla R, Matto V, Oreland L (1999) Chronic mild unpredictable stress after noradrenergic denervation: attenuation of behavioural and biochemical effects of DSP-4 treatment. Eur Neuropsychopharm 10(1):5–16. doi:10.1016/S0924-977x(99)00043-7

  42. Xie Y, Wang Y, Zhang T, Ren G, Yang Z (2012) Effects of nanoparticle zinc oxide on spatial cognition and synaptic plasticity in mice with depressive-like behaviors. J Biomed Sci 19(14):1–11. doi:10.1186/1423-0127-19-14

    Google Scholar 

  43. Wang H, Gao N, Li Z, Yang Z, Zhang T (2015) Autophagy alleviates melamine-induced cell death in PC12 cells via decreasing ROS level. Mol Neurobiol:1–12. doi:10.1007/s12035-014-9073-2

  44. Yu M, Zhang Y, Chen XY, Zhang T (2016) Antidepressant-like effects and possible mechanisms of amantadine on cognitive and synaptic deficits in a rat model of chronic stress. Stress-Int J Biol Stress 19(1):104–113. doi:10.3109/10253890.2015.1108302

    Article  CAS  Google Scholar 

  45. Andreasen J, Redrobe J (2009) Nicotine, but not mecamylamine, enhances antidepressant-like effects of citalopram and reboxetine in the mouse forced swim and tail suspension tests. Behav Brain Res 197(1):150–156. doi:10.1016/j.bbr.2008.08.016

    Article  CAS  PubMed  Google Scholar 

  46. Cryan JF, Mombereau C, Vassout A (2005) The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev 29(4–5):571–625. doi:10.1016/j.neubiorev.2005.03.009

    Article  CAS  PubMed  Google Scholar 

  47. Lino-De-Oliveira C, De Lima TCM, Carobrez AD (2005) Structure of the rat behaviour in the forced swimming test. Behav Brain Res 158(2):243–250. doi:10.1016/j.bbr.2004.09.004

    Article  PubMed  Google Scholar 

  48. Haj-Mirzaian A, Kordjazy N, Haj-Mirzaian A, Ostadhadi S, Ghasemi M, Amiri S, Faizi M, Dehpour A (2015) Evidence for the involvement of NMDA receptors in the antidepressant-like effect of nicotine in mouse forced swimming and tail suspension tests. Psychopharmacology 232(19):3551–3561. doi:10.1007/s00213-015-4004-0

    Article  CAS  PubMed  Google Scholar 

  49. Tizabi Y, Rezvani AH, Russell LT, Tyler KY, Overstreet DH (2000) Depressive characteristics of FSL rats: involvement of central nicotinic receptors. Pharmacol Biochem Behav 66(1):73–77. doi:10.1016/S0091-3057(00)00236-7

    Article  CAS  PubMed  Google Scholar 

  50. Bian Y, Pan Z, Hou Z, Huang C, Li W, Zhao B (2012) Learning, memory, and glial cell changes following recovery from chronic unpredictable stress. Brain Res Bull 88(5):471–476. doi:10.1016/j.brainresbull.2012.04.008

    Article  PubMed  Google Scholar 

  51. Socci DJ, Sanberg PR, Arendash GW (1995) Nicotine enhances Morris water maze performance of young and aged rats. Neurobiol Aging 16(5):857–860. doi:10.1016/0197-4580(95)00091-R

    Article  CAS  PubMed  Google Scholar 

  52. Fu J, Wang H, Gao J, Yu M, Wang R, Yang Z, Zhang T (2016) Rapamycin effectively impedes melamine-induced impairments of cognition and synaptic plasticity in Wistar rats. Mol Neurobiol:1–14. doi:10.1007/s12035-016-9687-7

  53. Qi YJ, NW H, Rowan MJ (2013) Switching off LTP: mGlu and NMDA receptor-dependent novelty exploration-induced depotentiation in the rat hippocampus. Cereb Cortex 23(4):932–939. doi:10.1093/cercor/bhs086

    Article  PubMed  Google Scholar 

  54. An L, Yang Z, Zhang T (2013) Imbalanced synaptic plasticity induced spatial cognition impairment in male offspring rats treated with chronic prenatal ethanol exposure. Alcohol-Clin Exp Res 37(5):763–770. doi:10.1111/acer.12040

    Article  CAS  PubMed  Google Scholar 

  55. Ramoa AS, Alkondon M, Aracava Y, Irons J, Lunt GG, Deshpande SS, Wonnacott S, Aronstam RS, Albuquerque EX (1990) The anticonvulsant MK-801 interacts with peripheral and central nicotinic acetylcholine receptor ion channels. J Pharmacol Exp Ther 254(1):71–82

    CAS  PubMed  Google Scholar 

  56. O’Dell TJ, Christensen BN (1988) Mecamylamine is a selective non-competitive antagonist of N-methyl-d-aspartate- and aspartate-induced currents in horizontal cells dissociated from the catfish retina. Neurosci Lett 94(1):93–98. doi:10.1016/0304-3940(88)90276-5

    Article  PubMed  Google Scholar 

  57. Aramakis VB, Metherate R (1998) Nicotine selectively enhances NMDA receptor-mediated synaptic transmission during postnatal development in sensory neocortex. J Neurosci 18(20):8485–8495

    CAS  PubMed  Google Scholar 

  58. Shim I, Kim HT, Kim YH, Chun BG, Hahm DH, Lee EH, Kim SE, Lee HJ (2002) Role of nitric oxide synthase inhibitors and NMDA receptor antagonist in nicotine-induced behavioral sensitization in the rat. Eur J Pharmacol 443(1–3):119–124. doi:10.1016/S0014-2999(02)01582-0

    Article  CAS  PubMed  Google Scholar 

  59. Elizalde N, Garcia-Garcia AL, Totterdell S, Gendive N, Venzala E, Ramirez MJ, Del Rio J, Tordera RM (2010) Sustained stress-induced changes in mice as a model for chronic depression. Psychopharmacology 210(3):393–406. doi:10.1007/s00213-010-1835-6

    Article  CAS  PubMed  Google Scholar 

  60. Gilabert-Juan J, Castillo-Gomez E, Guirado R, Molto MD, Nacher J (2013) Chronic stress alters inhibitory networks in the medial prefrontal cortex of adult mice. Brain Struct Funct 218(6):1591–1605. doi:10.1007/s00429-012-0479-1

    Article  CAS  PubMed  Google Scholar 

  61. Romano E, Fuso A, Laviola G (2013) Nicotine restores Wt-like levels of reelin and GAD67 gene expression in brain of heterozygous reeler mice. Neurotox Res 24(2):205–215. doi:10.1007/s12640-013-9378-3

    Article  CAS  PubMed  Google Scholar 

  62. Alberi L, Liu S, Wang Y, Badie R, Smith-Hicks C, Wu J, Pierfelice TJ, Abazyan B, Mattson MP, Kuhl D, Pletnikov M, Worley PF, Gaiano N (2011) Activity-induced Notch signaling in neurons requires Arc/Arg3.1 and is essential for synaptic plasticity in hippocampal networks. Neuron 69(3):437–444. doi:10.1016/j.neuron.2011.01.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Brai E, Marathe S, Astori S, Fredj NB, Perry E, Lamy C, Scotti A, Alberi L (2015) Notch1 regulates hippocampal plasticity through interaction with the reelin pathway, glutamatergic transmission and CREB signaling. Front Cell Neurosci 9:447. doi:10.3389/fncel.2015.00447

    Article  PubMed  PubMed Central  Google Scholar 

  64. Carlson G, Wang Y, Alger BE (2002) Endocannabinoids facilitate the induction of LTP in the hippocampus. Nat Neurosci 5(8):723–724. doi:10.1038/nn879

    CAS  PubMed  Google Scholar 

  65. Cheng P, Gabrilovich D (2008) Notch signaling in differentiation and function of dendritic cells. Immunol Res 41(1):1–14. doi:10.1007/s12026-007-8011-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Nickoloff BJ, Qin JZ, Chaturvedi V, Denning MF, Bonish B, Miele L (2002) Jagged1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-κB and PPARγ. Cell Death Differ 9(8):842–855. doi:10.1038/sj.cdd.4401036

    Article  CAS  PubMed  Google Scholar 

  67. Furukawa K, Mattson MP (1998) The transcription factor NF-kappaB mediates increases in calcium currents and decreases in NMDA- and AMPA/kainate-induced currents induced by tumor necrosis factor-alpha in hippocampal neurons. J Neurochem 70(5):1876–1886. doi:10.1046/j.1471-4159.1998.70051876.x

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (11232005 & 31171053 to TZ) and 111 Project (B08011 to TZ).

Author information

Authors and Affiliations

  1. College of Life Sciences and State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071, Tianjin, People’s Republic of China

    Xueliang Shang, Yingchun Shang, Jingxuan Fu & Tao Zhang

Authors
  1. Xueliang Shang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yingchun Shang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jingxuan Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tao Zhang.

Ethics declarations

Competing Interests

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shang, X., Shang, Y., Fu, J. et al. Nicotine Significantly Improves Chronic Stress-Induced Impairments of Cognition and Synaptic Plasticity in Mice. Mol Neurobiol 54, 4644–4658 (2017). https://doi.org/10.1007/s12035-016-0012-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-016-0012-2

Keywords

Search

Navigation