, Volume 201, Issue 3, pp 405–411 | Cite as

Arcaine and MK-801 make recall state-dependent in rats

  • Ana Paula Chiapinotto Ceretta
  • Keli Camera
  • Carlos Fernando Mello
  • Maribel Antonello RubinEmail author
Original Investigation



The polyamines putrescine, spermidine, and spermine are a group of aliphatic amines that may act as physiological modulators of the N-methyl-d-aspartate (NMDA) receptor, a glutamate receptor implicated in memory formation and consolidation. Arcaine is a competitive antagonist of the polyamine binding site at the NMDA receptor, the post-training administration of which impairs memory of various tasks.


In this study, we investigated whether the administration of arcaine and MK-801 alters the memory of the step-down inhibitory avoidance task, and whether the effects of these NMDA antagonists involve state-dependency mechanisms, in adult male Wistar rats.


The administration of arcaine (30 mg/kg, i.p.) or MK-801 (0.03 mg/kg, i.p.) immediately after training impaired inhibitory avoidance performance at testing. Arcaine- and MK-801-induced performance impairment was reversed by the administration of arcaine (30 mg/kg, i.p.) and MK-801 (0.03 mg/kg, i.p.), respectively, 30 min before testing. Response transfer also occurred if arcaine substituted MK-801 at testing, and vice-versa.


These results suggest that arcaine and MK-801 induce state-dependent recall and that, probably due to their ability to decrease NMDA receptor function, one drug can substitute for the other at testing, demonstrating a cross-state dependency between arcaine and MK-801.


Polyamines Arcaine NMDA receptor MK-801 Memory State dependence 



The authors thank Dr. Juliano Ferreira for the helpful suggestions, and Paulino Aguiar and Rinaldo Moreira for competent technical support. This study was supported by CNPq (475131/04-5, 477836/2007-0). K Camera is recipient of a CAPES fellowship CF Mello and MA Rubin are recipients of CNPq productivity fellowships (500120/2003-0, 500096/2003-1, 301558/2007-8). All the experiments complied with the current laws of Brazil.


  1. Arenas MC, Vinader-Caerols C, Monleon S, Martos AJ, Everss E, Ferrer-Ano A, Parra A (2006) Are the effects of the antidepressants amitriptyline, maprotiline, and fluoxetine on inhibitory avoidance state-dependent? Behav Brain Res 166:150–158PubMedCrossRefGoogle Scholar
  2. Arkhipov VI (1999) Memory dissociation: the approach to the study of retrieval processes. Behav Brain Res 106:39–46PubMedCrossRefGoogle Scholar
  3. Berlese DB, Sauzem PD, Carati MC, Guerra GP, Stiegemeier JA, Mello CF, Rubin MA (2005) Time-dependent modulation of inhibitory avoidance memory by spermidine in rats. Neurobiol Learn Mem 83:48–53PubMedCrossRefGoogle Scholar
  4. Bruins Slot LA, Colpaert FC (1999) Recall rendered dependent on an opiate state. Behav Neurosci 113:337–344PubMedCrossRefGoogle Scholar
  5. Bruins Slot LA, Koek W, Colpaert FC (1999) Ethanol state dependence involving a lever press response requirement in rats. Behav Pharmacol 10:229–233PubMedCrossRefGoogle Scholar
  6. Camera K, Mello CF, Ceretta AP, Rubin MA (2007) Systemic administration of polyaminergic agents modulate fear conditioning in rats. Psychopharmacology (Berl) 192:457–464CrossRefGoogle Scholar
  7. Carter C (1994) Neuropharmacology of polyamines. Academic, New YorkGoogle Scholar
  8. Guerra GP, Mello CF, Sauzem PD, Berlese DB, Furian AF, Tabarelli Z, Rubin MA (2006) Nitric oxide is involved in the memory facilitation induced by spermidine in rats. Psychopharmacology (Berl) 186:150–158CrossRefGoogle Scholar
  9. Harrod SB, Flint RW, Riccio DC (2001) MK-801 induced retrieval, but not acquisition, deficits for passive avoidance conditioning. Pharmacol Biochem Behav 69:585–593PubMedCrossRefGoogle Scholar
  10. Izquierdo I (1984) Endogenous state dependency: memory depends on the relation between the neurohumoral and hormonal states present after training and the time of testing. In: Lynch G McGaugh JL, Weinberger NM (eds) Neurobiology of learning and memory. Guilford, New York, pp 333–350Google Scholar
  11. Izquierdo I, Netto CA, Dalmaz C, Chaves ML, Pereira ME, Siegfried B (1988) Construction and reconstruction of memories. Braz J Med Biol Res 21:9–25PubMedGoogle Scholar
  12. Jackson A, Koek W, Colpaert FC (1992) NMDA antagonists make learning and recall state-dependent. Behav Pharmacol 3:415–421PubMedCrossRefGoogle Scholar
  13. Jafari-Sabet M, Zarrindast MR, Rezayat M, Rezayof A, Djahanguiri B (2005) The influence of NMDA receptor agonist and antagonist on morphine state-dependent memory of passive avoidance in mice. Life Sci 78:157–163PubMedCrossRefGoogle Scholar
  14. Kim M, McGaugh JL (1992) Effects of intra-amygdala injections of NMDA receptor antagonists on acquisition and retention of inhibitory avoidance. Brain Res 585:35–48PubMedCrossRefGoogle Scholar
  15. McGurk JF, Bennett MVL, Zukin RS (1990) Polyamines potentiate responses of N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Proc Natl Acad Sci U S A 87:9971–9974PubMedCrossRefGoogle Scholar
  16. Nakagawa Y, Iwasaki T (1996) Ethanol-induced state-dependent learning is mediated by 5-hydroxytryptamine3 receptors but not by N-methyl-D-aspartate receptor complex. Brain Res 706:227–232PubMedCrossRefGoogle Scholar
  17. Netto CA, Maltchik M (1991) Retrieval effects of beta-endorphin and naloxone, and the novelty-induced antinociception in the developing rat. Behav Neural Biol 55:366–379PubMedCrossRefGoogle Scholar
  18. Pellegrini-Giampietro DE (2003) An activity-dependent spermine-mediated mechanism that modulates glutamate transmission. Trends Neurosci 26:9–11PubMedCrossRefGoogle Scholar
  19. Ransom RW, Stec NL (1988) Cooperative modulation of [3H]MK-801 binding to the N-methyl-D-aspartate receptor-ion channel complex by L-glutamate, glycine, and polyamines. J Neurochem 51:830–836PubMedCrossRefGoogle Scholar
  20. Reynolds IJ (1990) Arcaine is a competitive antagonist of the polyamine site on the NMDA receptor. Eur J Pharmacol 177:215–216PubMedCrossRefGoogle Scholar
  21. Rock DM, Macdonald RL (1995) Polyamine regulation of N-methyl-D-aspartate receptor channels. Annu Rev Pharmacol Toxicol 35:463–482PubMedCrossRefGoogle Scholar
  22. Rubin MA, Boemo RL, Jurach A, Rojas DB, Zanolla GR, Obregon AD, Souza DO, Mello CF (2000) Intrahippocampal spermidine administration improves inhibitory avoidance performance in rats. Behav Pharmacol 11:57–61PubMedGoogle Scholar
  23. Rubin MA, Stiegemeier JA, Volkweis MA, Oliveira DM, Fenili AC, Boemo RL, Jurach A, Mello CF (2001) Intra-amygdala spermidine administration improves inhibitory avoidance performance in rats. Eur J Pharmacol 423:35–39PubMedCrossRefGoogle Scholar
  24. Rubin MA, Berlese DB, Stiegemeier JA, Volkweis MA, Oliveira DM, dos Santos TL, Fenili AC, Mello CF (2004) Intra-amygdala administration of polyamines modulates fear conditioning in rats. J Neurosci 24:2328–2334PubMedCrossRefGoogle Scholar
  25. Scott RH, Sutton KG, Dolphin AC (1993) Interactions of polyamines with neuronal ion channels. Trends Neurosci 16:153–160PubMedCrossRefGoogle Scholar
  26. Shimada A, Spangler EL, London ED, Ingram DK (1994) Spermidine potentiates dizocilpine-induced impairment of learning performance by rats in a 14-unit T-maze. Eur J Pharmacol 263:293–300PubMedCrossRefGoogle Scholar
  27. Shulz DE, Sosnik R, Ego V, Haidarliu S, Ahissar E (2000) A neuronal analogue of state-dependent learning. Nature 403:549–553PubMedCrossRefGoogle Scholar
  28. Sprosen TS, Woodruff GN (1990) Polyamines potentiate NMDA induced whole-cell currents in cultured striatal neurons. E J Pharmacol 179:477–478CrossRefGoogle Scholar
  29. Williams K (1997) Interactions of polyamines with ion channels. Biochem J 325(Pt 2):289–297PubMedGoogle Scholar
  30. Williams K, Dawson VL, Romano C, Dichter MA, Molinoff PB (1990) Characterization of polyamines having agonist, antagonist, and inverse agonist effects at the polyamine recognition site of the NMDA receptor. Neuron 5:199–208PubMedCrossRefGoogle Scholar
  31. Williams K, Romano C, Dichter MA, Molinoff PB (1991) Modulation of the NMDA receptor by polyamines. Life Sci 48:469–498PubMedCrossRefGoogle Scholar
  32. Zarrindast MR, Shendy MM, Ahmadi S (2007) Nitric oxide modulates state dependency induced by lithium in an inhibitory avoidance task in mice. Behav Pharmacol 18:289–295PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ana Paula Chiapinotto Ceretta
    • 1
  • Keli Camera
    • 1
  • Carlos Fernando Mello
    • 2
  • Maribel Antonello Rubin
    • 1
    Email author
  1. 1.Laboratório de Neurotoxicidade e Psicofarmacologia, Centro de Ciências Naturais e Exatas, Departamento de QuímicaUniversidade Federal de Santa MariaSanta MariaBrazil
  2. 2.Laboratório de Neurotoxicidade e Psicofarmacologia, Centro de Ciências da Saúde, Departamento de Fisiologia e FarmacologiaUniversidade Federal de Santa MariaSanta MariaBrazil

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