Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Note
  • Published:

Hippocampal long-term potentiation in adult mice after recovery from ketamine anesthesia

Lab Animal volume 43, pages 353–357 (2014)Cite this article

Abstract

Ketamine is frequently used to induce analgesia or anesthesia in laboratory animals, but its effects on learning and memory are poorly characterized. Long-term potentiation (LTP) is considered a cellular mechanism for learning and memory. Ketamine administration immediately abolishes hippocampal LTP in vivo, but whether this effect persists is not known. The authors administered one of two doses of ketamine to adult male C57BL/6 mice and measured LTP in hippocampal slices from the mice 24 h later. Neither LTP induction nor LTP maintenance differed significantly in mice that were administered ketamine compared with mice that were administered saline. The findings suggest that a single intraperitoneal dose of ketamine does not persistently alter LTP in adult male mice.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: LTP induction and maintenance 24 h after ketamine administration.

Similar content being viewed by others

References

  1. Mohammad, F.K., Al-Zubaidy, M.H. & Alias, A.S. Sedative and hypnotic effects of combined administration of metoclopramide and ketamine in chickens. Lab Anim. (NY) 36, 35–39 (2007).

    Article  Google Scholar 

  2. Cruz, J.I., Loste, J.M. & Burzaco, O.H. Observations on the use of medetomidine/ketamine and its reversal with atipamezole for chemical restraint in the mouse. Lab. Anim. 32, 18–22 (1998).

    Article  CAS  Google Scholar 

  3. Arnemo, J.M., Storaas, T., Khadka, C.B. & Wegge, P. Use of medetomidine-ketamine and atipamezole for reversible immobilization of free-ranging hog deer (Axis porcinus) captured in drive nets. J. Wildl. Dis. 41, 467–470 (2005).

    Article  Google Scholar 

  4. Russell, W.M.S. & Burch, R.L. The Principles of Humane Experimental Technique (Methuen, London, 1959).

    Google Scholar 

  5. Brønstad, A. & Berg, A.G. The role of organizational culture in compliance with the principles of the 3Rs. Lab Anim. (NY) 40, 22–26 (2011).

    Article  Google Scholar 

  6. Hahn, N., Eisen, R.J., Eisen, L. & Lane, R.S. Ketamine-medetomidine anesthesia with atipamezole reversal: practical anesthesia for rodents under field conditions. Lab Anim. (NY) 34, 48–51 (2005).

    Article  Google Scholar 

  7. Kuznetsova, O., Marusanov, V.E., Biderman, F.M., Danilevich, E. & Khrushchev, N.V. Ketalar anesthesia in the first-aid stage with the victims of severe injury and traumatic shock [Russian]. Vestn. Khir. Im. I. I. Grek. 132, 88–91 (1984).

    PubMed  Google Scholar 

  8. Adams, H.A. & Hempelmann, G. 20 years of ketamine—a backward look [German]. Anaesthesist 39, 71–76 (1990).

    CAS  PubMed  Google Scholar 

  9. Ikechebelu, J.I., Udigwe, G.O., Obi, R.A., Joe-Ikechebelu, N.N. & Okoye, I.C. The use of simple ketamine anaesthesia for day-case diagnostic laparoscopy. J. Obstet. Gynaecol. 23, 650–652 (2003).

    Article  CAS  Google Scholar 

  10. Copeland, J. & Dillon, P. The health and psycho-social consequences of ketamine use. Int. J. Drug Policy 16, 122–131 (2005).

    Article  Google Scholar 

  11. Erhardt, W., Hebestedt, A., Aschenbrenner, G., Pichotka, B. & Blümel, G. A comparative study with various anesthetics in mice (pentobarbitone, ketamine-xylazine, carfentanyl-etomidate). Res. Exp. Med. (Berl.) 184, 159–169 (1984).

    Article  CAS  Google Scholar 

  12. Liu, D. et al. Comparison of ketamine-pentobarbital anesthesia and fentanyl-pentobarbital anesthesia for open-heart surgery in minipigs. Lab Anim. (NY) 38, 234–240 (2009).

    Article  Google Scholar 

  13. Green, C.J., Knight, J., Precious, S. & Simpkin, S. Ketamine alone and combined with diazepam or xylazine in laboratory animals: a 10 year experience. Lab. Anim. 15, 163–170 (1981).

    Article  CAS  Google Scholar 

  14. Weisbroth, S.H. & Fudens, J.H. Use of ketamine hybrochloride as an anesthetic in laboratory rabbits, rats, mice, and guinea pigs. Lab. Anim. Sci. 22, 904–906 (1972).

    CAS  PubMed  Google Scholar 

  15. Jevtovic-Todorovic, V. et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J. Neurosci. 23, 876–882 (2003).

    Article  CAS  Google Scholar 

  16. Culley, D.J., Baxter, M.G., Crosby, C.A., Yukhananov, R. & Crosby, G. Impaired acquisition of spatial memory 2 weeks after isoflurane and isoflurane-nitrous oxide anesthesia in aged rats. Anesth. Analg. 99, 1393–1397 (2004).

    Article  CAS  Google Scholar 

  17. Bliss, T.V. & Collingridge, G.L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39 (1993).

    Article  CAS  Google Scholar 

  18. Lynch, M.A. Long-term potentiation and memory. Physiol. Rev. 84, 87–136 (2004).

    Article  CAS  Google Scholar 

  19. Davies, S.N., Alford, S.T., Coan, E.J., Lester, R.A. & Collingridge, G.L. Ketamine blocks an NMDA receptor–mediated component of synaptic transmission in rat hippocampus in a voltage-dependent manner. Neurosci. Lett. 92, 213–217 (1988).

    Article  CAS  Google Scholar 

  20. Orser, B.A., Pennefather, P.S. & MacDonald, J.F. Multiple mechanisms of ketamine blockade of N-methyl-D-aspartate receptors. Anesthesiology 86, 903–917 (1997).

    Article  CAS  Google Scholar 

  21. Stringer, J.L. & Guyenet, P.G. Elimination of long-term potentiation in the hippocampus by phencyclidine and ketamine. Brain Res. 258, 159–164 (1983).

    Article  CAS  Google Scholar 

  22. Ribeiro, P.O., Tomé, A.R., Silva, H.B., Cunha, R.A. & Antunes, L.M. Clinically relevant concentrations of ketamine mainly affect long-term potentiation rather than basal excitatory synaptic transmission and do not change paired-pulse facilitation in mouse hippocampal slices. Brain Res. 1560, 10–17 (2014).

    Article  CAS  Google Scholar 

  23. Rammes, G. et al. Isoflurane anaesthesia reversibly improves cognitive function and long-term potentiation (LTP) via an up-regulation in NMDA receptor 2B subunit expression. Neuropharmacology 56, 626–636 (2009).

    Article  CAS  Google Scholar 

  24. FELASA working group on revision of guidelines for health monitoring of rodents and rabbits et al. FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units. Lab. Anim. 48, 178–192 (2014).

  25. Anderson, W.W. & Collingridge, G.L. The LTP Program: a data acquisition program for on-line analysis of long-term potentiation and other synaptic events. J. Neurosci. Methods 108, 71–83 (2001).

    Article  CAS  Google Scholar 

  26. Costenla, A.R. et al. Enhanced role of adenosine A(2A) receptors in the modulation of LTP in the rat hippocampus upon ageing. Eur. J. Neurosci. 34, 12–21 (2011).

    Article  Google Scholar 

  27. Grover, L.M. & Teyler, T.J. Differential effects of NMDA receptor antagonist APV on tetanic stimulation induced and calcium induced potentiation. Neurosci. Lett. 113, 309–314 (1990).

    Article  CAS  Google Scholar 

  28. Tsien, J.Z., Huerta, P.T. & Tonegawa, S. The essential role of hippocampal CA1 NMDA receptor–dependent synaptic plasticity in spatial memory. Cell 87, 1327–1338 (1996).

    Article  CAS  Google Scholar 

  29. Irifune, M., Shimizu, T., Nomoto, M. & Fukuda, T. Ketamine-induced anesthesia involves the N-methyl-D-aspartate receptor–channel complex in mice. Brain Res. 596, 1–9 (1992).

    Article  CAS  Google Scholar 

  30. Ribeiro, P.O., Rodrigues, P.C., Valentim, A.M. & Antunes, L.M. A single intraperitoneal injection of ketamine does not affect spatial working, reference memory or neurodegeneration in adult mice: An animal study. Eur. J. Anaesthesiol. 30, 618–626 (2013).

    Article  CAS  Google Scholar 

  31. Ribeiro, P.O., Valentim, A.M., Rodrigues, P., Olsson, I.A. & Antunes, L.M. Apoptotic neurodegeneration and spatial memory are not affected by sedative and anaesthetics doses of ketamine/medetomidine combinations in adult mice. Br. J. Anaesth. 108, 807–814 (2012).

    Article  CAS  Google Scholar 

  32. Valentim, A.M., Ribeiro, P.O., Olsson, I.A. & Antunes, L.M. The memory stages of a spatial Y-maze task are not affected by a low dose of ketamine/midazolam. Eur. J. Pharmacol. 712, 39–47 (2013).

    Article  CAS  Google Scholar 

  33. Valentim, A.M., Olsson, I.A. & Antunes, L.M. The anaesthetic combination of ketamine/midazolam does not alter the acquisition of spatial and motor tasks in adult mice. Lab. Anim. 47, 19–25 (2013).

    Article  CAS  Google Scholar 

  34. Gao, J., Peng, S., Xiang, S., Huang, J. & Chen, P. Repeated exposure to propofol impairs spatial learning, inhibits LTP and reduces CaMKIIα in young rats. Neurosci. Lett. 560, 62–66 (2014).

    Article  CAS  Google Scholar 

  35. Haseneder, R. Sevoflurane anesthesia improves cognitive performance in mice, but does not influence in vitro long-term potentiation in hippocampus CA1 stratum radiatum. PLoS ONE 8, e64732 (2013).

    Article  CAS  Google Scholar 

  36. Fredriksson, A., Archer, T., Alm, H., Gordh, T. & Eriksson, P. Neurofunctional deficits and potentiated apoptosis by neonatal NMDA antagonist administration. Behav. Brain Res. 153, 367–376 (2004).

    Article  CAS  Google Scholar 

  37. Jang, H.S., Choi, H.S., Lee, S.H., Jang, K.H. & Lee, M.G. Evaluation of the anaesthetic effects of medetomidine and ketamine in rats and their reversal with atipamezole. Vet. Anaesth. Analg. 36, 319–327 (2009).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Foundation for Science and Technology (Lisbon, Portugal) and co-funded through post-doctoral fellowship project grants by COMPETE: 01-0124- FEDER-009497 (Lisbon, Portugal) and through a personal doctoral training grant to P.O.R.

Author information

Authors and Affiliations

  1. Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Patrícia O. Ribeiro,  Henrique B. Silva,  Ângelo R. Tomé &  Rodrigo A. Cunha

  2. Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal

    Ângelo R. Tomé

  3. Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Rodrigo A. Cunha

  4. Laboratory Animal Science, Institute for Molecular and Cellular Biology, Porto, Portugal

    Luís M. Antunes

  5. Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal

    Luís M. Antunes

Authors
  1. Patrícia O. Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henrique B. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ângelo R. Tomé
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rodrigo A. Cunha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luís M. Antunes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrícia O. Ribeiro.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ribeiro, P., Silva, H., Tomé, Â. et al. Hippocampal long-term potentiation in adult mice after recovery from ketamine anesthesia. Lab Anim 43, 353–357 (2014). https://doi.org/10.1038/laban.571

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/laban.571

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing