Skip to main content
SpringerLink
Log in

Anesthetic ketamine counteracts repetitive mechanical stress-induced learning and memory impairment in developing mice

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The aim of this study is to investigate whether ketamine, a noncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist, had an influence on learning and memory in developing mice. Fifty Kunming mice aged 21 days were randomly divided into 5 subgroups (n = 10 for each) to receive intraperitoneal injection of equal volume of saline (S group) or ketamine (25, 50 or 100 mg/kg of body weight/day) for 7 consecutive days, or to be left untreated (C group). A step-down passive avoidance test was performed to evaluate learning and memory in these mice on days 8 and 9. Additionally, the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus was determined. Rats receiving saline or sub-anesthetic dose of ketamine (25 mg/kg) showed significantly decreased abilities of learning and memory and reduced expression of BDNF, compared to the normal controls (P < 0.05). In contrast, comparable abilities of learning and memory and expression of BDNF were found for anesthetic doses of ketamine (50 or 100 mg/kg)-treated rats and controls (P > 0.05). Repetitive mechanical stress impairs learning and memory performance in developing mice, which may be associated with decreased BDNF expression. The stress-induced learning and memory impairment can be prevented by anesthetic doses of ketamine.

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

Similar content being viewed by others

References

  1. Riedel G, Platt B, Micheau J (2003) Glutamate receptor function in learning and memory. Behav Brain Res 140(1–2):1–47

    Article  PubMed  CAS  Google Scholar 

  2. Li F, Tsien JZ (2009) Memory and the NMDA receptors. N Engl J Med 361(3):302–303

    Article  PubMed  CAS  Google Scholar 

  3. Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44(1):5–21

    Article  PubMed  CAS  Google Scholar 

  4. Tsien JZ (2000) Linking Hebb’s coincidence-detection to memory formation. Curr Opin Neurobiol 10(2):266–273

    Article  PubMed  CAS  Google Scholar 

  5. Sakimura K, Kutsuwada T, Ito I, Manabe T, Takayama C, Kushiya E, Yagi T, Aizawa S, Inoue Y, Sugiyama H et al (1995) Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon 1 subunit. Nature 373(6510):151–155

    Article  PubMed  CAS  Google Scholar 

  6. Shimizu E, Tang YP, Rampon C, Tsien JZ (2000) NMDA receptor-dependent synaptic reinforcement as a crucial process for memory consolidation. Science 290(5494):1170–1174

    Article  PubMed  CAS  Google Scholar 

  7. Tang YP, Shimizu E, Dube GR, Rampon C, Kerchner GA, Zhuo M, Liu G, Tsien JZ (1999) Genetic enhancement of learning and memory in mice. Nature 401(6748):63–69

    Article  PubMed  CAS  Google Scholar 

  8. Tang YP, Wang H, Feng R, Kyin M, Tsien JZ (2001) Differential effects of enrichment on learning and memory function in NR2B transgenic mice. Neuropharmacology 41(6):779–790

    Article  PubMed  CAS  Google Scholar 

  9. Okon T (2007) Ketamine: an introduction for the pain and palliative medicine physician. Pain Physician 10(3):493–500

    PubMed  Google Scholar 

  10. Hetem LA, Danion JM, Diemunsch P, Brandt C (2000) Effect of a subanesthetic dose of ketamine on memory and conscious awareness in healthy volunteers. Psychopharmacology (Berl) 152(3):283–288

    Article  CAS  Google Scholar 

  11. Krystal JH, Bennett A, Abi-Saab D, Belger A, Karper LP, D’Souza DC, Lipschitz D, Abi-Dargham A, Charney DS (2000) Dissociation of ketamine effects on rule acquisition and rule implementation: possible relevance to NMDA receptor contributions to executive cognitive functions. Biol Psychiatry 47(2):137–143

    Article  PubMed  CAS  Google Scholar 

  12. Zhang DX, Levy WB (1992) Ketamine blocks the induction of LTP at the lateral entorhinal cortex-dentate gyrus synapses. Brain Res 593(1):124–127

    Article  PubMed  CAS  Google Scholar 

  13. Haugan F, Rygh LJ, Tjølsen A (2008) Ketamine blocks enhancement of spinal long-term potentiation in chronic opioid treated rats. Acta Anaesthesiol Scand 52(5):681–687

    Article  PubMed  CAS  Google Scholar 

  14. Tsumoto T, Hagihara K, Sato H, Hata Y (1987) NMDA receptors in the visual cortex of young kittens are more effective than those of adult cats. Nature 327(6122):513–514

    Article  PubMed  CAS  Google Scholar 

  15. Miller KD, Chapman B, Stryker MP (1989) Visual responses in adult cat visual cortex depend on N-methyl-d-aspartate receptors. Proceedings of the National Academy of Sciences of the USA 86(13):5183–5187

    Google Scholar 

  16. Yamada K, Nabeshima T (2003) Brain-derived neurotrophic factor/TrkB signaling in memory processes. J Pharmacol Sci 91(4):267–270

    Article  PubMed  CAS  Google Scholar 

  17. Mizuno M, Yamada K, He J, Nakajima A, Nabeshima T (2003) Involvement of BDNF receptor TrkB in spatial memory formation. Learn Mem 10(2):108–115

    Article  PubMed  Google Scholar 

  18. Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A, Izquierdo I, Medina JH (2008) BDNF is essential to promote persistence of long-term memory storage. Proceedings of the National Academy of Sciences of the USA 105(7):2711–2716

    Google Scholar 

  19. Bekinschtein P, Cammarota M, Igaz LM, Bevilaqua LR, Izquierdo I, Medina JH (2007) Persistence of long-term memory storage requires a late protein synthesis- and BDNF-dependent phase in the hippocampus. Neuron 53(2):261–277

    Article  PubMed  CAS  Google Scholar 

  20. Yang J, Zhao X, Zhou Q, Jiang Q (2003) Effects of nimodipine and fructose-1, 6-diphosphate on cerebral damage in carbon monoxide poisoning mice. Chin Med J (Engl) 116(12):1911–1915

    CAS  Google Scholar 

  21. Domino EF, Chodoff P, Corssen G (1965) Pharmacologic effects of ci-581, a new dissociative anesthetic, in man. Clin Pharmacol Ther 6:279–291

    PubMed  CAS  Google Scholar 

  22. Bergman SA (1999) Ketamine: review of its pharmacology and its use in pediatric anesthesia. Anesth Prog 46(1):10–20

    PubMed  CAS  Google Scholar 

  23. Glickman A (1995) Ketamine: the dissociative anesthetic and the development of a policy for its safe administration in the pediatric emergency department. J Emerg Nurs 21(2):116–124

    Article  PubMed  CAS  Google Scholar 

  24. Parwani A, Weiler MA, Blaxton TA, Warfel D, Hardin M, Frey K, Lahti AC (2005) The effects of a subanesthetic dose of ketamine on verbal memory in normal volunteers. Psychopharmacology (Berl) 183(3):265–274

    Article  CAS  Google Scholar 

  25. Jeong YH, Park CH, Yoo J, Shin KY, Ahn SM, Kim HS, Lee SH, Emson PC, Suh YH (2006) Chronic stress accelerates learning and memory impairments and increases amyloid deposition in APPV717I-CT100 transgenic mice, an Alzheimer’s disease model. FASEB J 20(6):729–731

    PubMed  CAS  Google Scholar 

  26. Li XH, Liu NB, Zhang MH, Zhou YL, Liao JW, Liu XQ, Chen HW (2007) Effects of chronic multiple stress on learning and memory and the expression of Fyn, BDNF, TrkB in the hippocampus of rats. Chin Med J (Engl) 120(8):669–674

    CAS  Google Scholar 

  27. Fujioka T, Fujioka A, Tan N, Chowdhury GM, Mouri H, Sakata Y, Nakamura S (2001) Mild prenatal stress enhances learning performance in the non-adopted rat offspring. Neuroscience 103(2):301–307

    Article  PubMed  CAS  Google Scholar 

  28. Garcia R (2001) Stress, hippocampal plasticity, and spatial learning. Synapse 40(3):180–183

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Medical Science Research Foundation of Jiangsu Province, China (Grant No. H200645) and Science Foundation of the Health Bureau of Wuxi City, China (Grant No. XM0805).

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Affiliated No.4 Hospital of Soochow University, Wuxi, 214062, China

    Sheng Peng, Yan Zhang, Hua Wang, Bingxu Ren & Jiannan Zhang

Authors
  1. Sheng Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bingxu Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiannan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yan Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peng, S., Zhang, Y., Wang, H. et al. Anesthetic ketamine counteracts repetitive mechanical stress-induced learning and memory impairment in developing mice. Mol Biol Rep 38, 4347–4351 (2011). https://doi.org/10.1007/s11033-010-0561-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-010-0561-9

Keywords

Search

Navigation