Skip to main content
Log in

Recovery of Memory by the Glutamate NMDA Receptor Agonist D-Cycloserine Depends on the Stage of Development of Amnesia

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

We have previously observed that in common snails trained to an associative skill consisting of refusing a defined foodstuff, impairment of memory reconsolidation by the NMDA receptor antagonist MK-801 evokes amnesia in which the skill can be recovered by retraining at the early stage (<10 days) while retraining at the late stage does not lead to formation of the skill. In the experiments reported here, amnesia was induced with MK-801 and a reminder 24 h after training of snails to conditioned taste aversion, and the antiamnestic effects of D-cycloserine, a partial agonist of the glycine site of the NMDA receptor, were studied in the early (day 3) and late (day 12) stages. Three days after induction of amnesia, injections of D-cycloserine and a reminder of the conditioned food stimulus led to recovery of the memory; administration of D-cycloserine without a subsequent reminder was ineffective. Injection of D-cycloserine and a reminder 12 days after induction of amnesia had no effect on its development and retraining did not lead to recovery of the memory. Thus, this study is the first to show that the NMDA receptor agonist D-cycloserine influences memory recovery processes only at the early stage of development of amnesia induced by lesioning of reconsolidation processes, while the late stage of amnesia was not sensitive to this agonist.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. N. I. Dubrovina, D. R. Zinoviev, and D. V. Zinovieva, “N-methyl-Daspartate receptors and amnesia in mice with a depression-like state,” Byull. Eksperim. Biol. Med., 144, No. 11, 484–486 (2007).

    Google Scholar 

  2. S. A. Kozyrev and V. P. Nikitin, “Neuronal mechanisms of the reactivation of an associative aversive skill to food in the common snail,” Ros. Fiziol. Zh. im. I. M. Sechenova, 95, No. 6, 652–662 (2009).

    CAS  Google Scholar 

  3. S. V. Solntseva and V. P. Nikitin, “Serotonin and NMDA glutamate receptor antagonists selectively impair the reactivation of associative memory in the common snail,” Ros. Fiziol. Zh. im. I. M. Sechenova, 93, No. 10, 1101–1111 (2007).

    CAS  Google Scholar 

  4. S. V. Solntseva and V. P. Nikitin, “The reversible and irreversible stages of the development of amnesia after impairment of the reactivation of an associative memory in snails,” Zh. Vyssh. Nerv. Deyat., 59, No. 2, 232–241 (2009).

    Google Scholar 

  5. S. V. Solntseva and V. P. Nikitin, “Effects of NMDA glutamate and serotonin receptor agonists at different stages of amnesia induced by impairment to the reconsolidation of long-term memory,” Neirokhimiya, 27, No. 3 (2010).

    Google Scholar 

  6. A. Adeleye, F. Shohami, D. Nachman, A. Alexandrovich, V. Trembovler, R. Yaka, Y. Shoshan, J. Dhawan, and A. Biegon, “D-cycloserine improves functional outcome after traumatic brain injury with wide therapeutic window,” Eur. J. Pharmacol., 629, No. 1–3, 25–30 (2010).

    Article  PubMed  CAS  Google Scholar 

  7. K. V. Anokhin, A. A. Tiunova, and S. P. R. Rose, “Reminder effects – reconsolidation or retrieval deficit? Pharmacological dissection with protein synthesis inhibitors following reminder for a passiveavoidance task in young chicks,” Eur. J. Neurosci., 15, No. 11, 1759–1765 (2002).

    Article  PubMed  Google Scholar 

  8. P. M. Balaban, “Declarative and procedural memory in animals with simple nervous systems,” in: Psychology at the Turn of the Millennium, S. Hofsten (ed.), Akad. Press, Stockholm (2002), No. 1, pp. 1–28.

  9. A. Biegon, M. Alvarado, T. F. Budinger, R. Grossman, K. Hensley, M. S. West, Y. Kotake, M. Ono, and R. A. Floyd, “Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain,” J. Neurochem., 82, No. 4, 924–934 (2002).

    Article  PubMed  CAS  Google Scholar 

  10. A. Biegon, P. A. Fry, C. M. Paden, A. Alexandrovich, J. Tsenter, and E. Shohami, “Dynamic changes in N-methyl-d-aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits,” Proc. Natl. Acad. Sci. USA, 101, No. 14, 5117–5122 (2004).

    Article  PubMed  CAS  Google Scholar 

  11. R. A. Davenport and T. A. Houpt, “D-cycloserine enhances shortdelay, but not long-delay, conditioned taste aversion learning in rats,” Pharmacol. Biochem. Behav., 91, No. 4, 596–603 (2009).

    Article  PubMed  CAS  Google Scholar 

  12. J. Dhawan, H. Benveniste, M. Hawrocky, S. D. Smith, and A. Biegon, “Transient focal ischemia results in persistent and widespread neuroinflammation and loss of glutamate NMDA receptors,” Neuroimage, 51, No. 2, 599–605 (2010).

    Article  PubMed  Google Scholar 

  13. L. K. Friedman, M. D. Ginsberg, L. Belayev, R. Busto, O. F. Alonso, B. Lin, and M. Y. Globus, “Intraischemic but not postischemic hypothermia prevents non-selective hippocampal downregulation of AMPA and NMDA receptor gene expression after global ischemia,” Mol. Brain Res., 86, No. 1–2, 34–47 (2001).

    Article  PubMed  CAS  Google Scholar 

  14. T. H. Gainutdinova, R. R. Tagirova, A. I. Ismailova, L. N. Muranova, E. I. Samarova, K. L. Gainutdinov, and P. M. Balaban, “Reconsolidation of a context long-term memory in the terrestrial snail requires protein synthesis,” Learn. Mem., 12, No. 6, 620–625 (2005).

    Article  PubMed  Google Scholar 

  15. G. J. Golden and T. A. Haupt, “NMDA receptor in conditioned flavor-taste preference learning: blockade by MK-801 and enhancement by D-cycloserine,” Pharmacol. Biochem. Behav., 86, No. 3, 587–596 (2007).

    Article  PubMed  CAS  Google Scholar 

  16. T. J. Ha, A. B. Kohnl, Y. V. Bobkoval, and L. L. Moroz, “Molecular characterization of NMDA-like receptors in Aplysia and Lymnaea: Relevance to memory and mechanisms,” Biol. Bull., 210, No. 3, 255–270 (2006).

    Article  PubMed  CAS  Google Scholar 

  17. J. L. Lee and B. J. Everitt, “Appetitive memory reconsolidation depends on NMDA receptor-mediated neurotransmission,” Neurobiol. Learn. Mem., 90, No. 1, 147–154 (2008).

    Article  PubMed  CAS  Google Scholar 

  18. J. L. C. Lee, A. L. Milton, and B. J. Everitt, “Reconsolidation and extinction of conditioned fear: inhibition and potentiation,” J. Neurosci., 26, No. 39, 10051–10056 (2006).

    Article  PubMed  CAS  Google Scholar 

  19. Y.-S. Lee and A. J. Silva, “The molecular and cellular biology of enhancer recognition,” Nat. Rev. Neurosci., 10, No. 2, 126–140 (2009).

    Article  PubMed  CAS  Google Scholar 

  20. T. Maurice, B. P. Lockhart, T. P. Su, and A. Privat, “Reversion of beta 25-35-amyloid peptide-induced amnesia by NMDA receptor-associated glycine site agonists,” Brain Res., 731, No. 1–2, 249–253 (1996).

    Article  PubMed  CAS  Google Scholar 

  21. K. A. Nader, “A single standard for memory; the case for reconsolidation,” Debates Neuroscience, 1, No. 1, 2–16 (2007).

    Article  Google Scholar 

  22. R. Richardson, L. Ledgerwood, and J. Cranney, “Facilitation of fear extinction by D-cycloserine: Theoretic and clinical implications,” Learn. Mem., 11, No. 5, 510–516 (2004).

    Article  PubMed  Google Scholar 

  23. S. J. Sara and B. Hars, “In memory of consolidation,” Learn. Mem., 13, No. 5, 515–521 (2006).

    Article  PubMed  Google Scholar 

  24. S. Sihver, N. Marklund, L. Hillered, B. Långström, T. Watanabe, and M. Bergström, “Changes in mACh, NMDA and GABA(A) receptor binding after lateral fluid-percussion injury: in vitro autoradiography of rat brain frozen sections,” J. Neurochem., 78, No. 3, 417–423 (2001).

    Article  PubMed  CAS  Google Scholar 

  25. F. A. Stephenson, S. L. Cousins, and A. V. Kenny, “Assembly and forward trafficking of NMDA receptors,” Mol. Membr. Biol., 25, No. 4, 311–320 (2008).

    Article  PubMed  CAS  Google Scholar 

  26. N. C. Tronson and J. R. Taylor, “Molecular mechanisms of memory reconsolidation,” Nat. Rev. Neurosci., 8, No. 4, 262–275 (2007).

    Article  PubMed  CAS  Google Scholar 

  27. D. L. Walker, K. J. Ressler, K. T. Lu, and M. Davis, “Facilitation of conditioned fear extinction by systemic administration of intraamygdalar infusions of D-cycloserine as assessed with fear-potentiated startle in rats,” J. Neurosci., 22, No. 6, 2343–2351 (2002).

    PubMed  CAS  Google Scholar 

  28. H. Wolosker, “NMDA receptor regulation by D-serine: new findings and perspectives,” Mol. Neurobiol., 36, No. 2, 152–164 (2007).

    Article  PubMed  CAS  Google Scholar 

  29. R. Yaka, A. Biegon, N. Grigoriadis, C. Simeonidou, S. Grigoriadis, A. G. Alexandrovich, H. Matzner, J. Scheumann, V. Trembovler, J. Tsenter, and E. Shohami, “D-cycloserine improves functional recovery and reinstates long-term potentiation (LTP) in a mouse model of closed head injury,” FASEB J., 21, No. 9, 2033–2041 (2007).

    Article  PubMed  CAS  Google Scholar 

  30. W. Zajaczkowski and W. Danysz, “Effects of D-cycloserine and aniracetam on spatial learning in rats with entorhinal cortex lesions,” Pharmacol. Biochem. Behav., 56, No. 1, 21–29 (1997).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. P. Nikitin.

Additional information

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 96, No. 12, pp. 1212–1222, December, 2010.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Solntseva, S.V., Nikitin, V.P. Recovery of Memory by the Glutamate NMDA Receptor Agonist D-Cycloserine Depends on the Stage of Development of Amnesia. Neurosci Behav Physi 42, 408–415 (2012). https://doi.org/10.1007/s11055-012-9580-4

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-012-9580-4

Keywords

Navigation