Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 May 23;92(11):5047–5051. doi: 10.1073/pnas.92.11.5047

Memory enhancement by intrahippocampal, intraamygdala, or intraentorhinal infusion of platelet-activating factor measured in an inhibitory avoidance task.

I Izquierdo 1, C Fin 1, P K Schmitz 1, R C Da Silva 1, D Jerusalinsky 1, J A Quillfeldt 1, M B Ferreira 1, J H Medina 1, N G Bazan 1
PMCID: PMC41845  PMID: 7761446

Abstract

Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), which is thought to be a retrograde messenger in long-term potentiation (LTP), enhances glutamate release and LTP through an action on presynaptic nerve endings. The PAF antagonist BN 52021 blocks CA1 LTP in hippocampal slices, and, when infused into rat dorsal hippocampus pre- or posttraining, blocks retention of inhibitory avoidance. Here we report that memory is affected by pre- or posttraining infusion of the PAF analog 1-O-hexadecyl-2-N-methylcarbamoyl-sn-glycerol-3-phosphocholine (mc-PAF) into either rat dorsal hippocampus, amygdala, or entorhinal cortex. Male Wistar rats were implanted bilaterally with cannulae in these brain regions. After recovery from surgery, the animals were trained in step-down inhibitory avoidance or in a spatial habituation task and tested for retention 24 h later. mc-PAF (1.0 microgram per side) enhanced retention test performance of the two tasks when infused into the hippocampus before training without altering training session performance. In addition, mc-PAF enhanced retention test performance of the avoidance task when infused into (i) the hippocampus 0 but not 60 min after training; (ii) the amygdala immediately after training; and (iii) the entorhinal cortex 100 but not 0 or 300 min after training. In confirmation of previous findings, BN 52021 (0.5 microgram per side) was found to be amnestic for the avoidance task when infused into the hippocampus or the amygdala immediately but not 30 or more minutes after training or into the entorhinal cortex 100 but not 0 or 300 min after training. These findings support the hypothesis that memory involves PAF-regulated events, possibly LTP, generated at the time of training in hippocampus and amygdala and 100 min later in the entorhinal cortex.

Full text

PDF
5047

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arai Amy, Lynch Gary. Antagonists of the Platelet-activating Factor Receptor Block Long-term Potentiation in Hippocampal Slices. Eur J Neurosci. 1992;4(5):411–419. doi: 10.1111/j.1460-9568.1992.tb00890.x. [DOI] [PubMed] [Google Scholar]
  2. Bazan N. G., Allan G., Rodriguez de Turco E. B. Role of phospholipase A2 and membrane-derived lipid second messengers in membrane function and transcriptional activation of genes: implications in cerebral ischemia and neuronal excitability. Prog Brain Res. 1993;96:247–257. doi: 10.1016/s0079-6123(08)63271-9. [DOI] [PubMed] [Google Scholar]
  3. Bazan N. G. Arachidonic acid in the modulation of excitable membrane function and at the onset of brain damage. Ann N Y Acad Sci. 1989;559:1–16. doi: 10.1111/j.1749-6632.1989.tb22594.x. [DOI] [PubMed] [Google Scholar]
  4. Bazan N. G., Zorumski C. F., Clark G. D. The activation of phospholipase A2 and release of arachidonic acid and other lipid mediators at the synapse: the role of platelet-activating factor. J Lipid Mediat. 1993 Mar-Apr;6(1-3):421–427. [PubMed] [Google Scholar]
  5. Bazán N. G., Jr Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim Biophys Acta. 1970 Oct 6;218(1):1–10. doi: 10.1016/0005-2760(70)90086-x. [DOI] [PubMed] [Google Scholar]
  6. Bianchin M., Walz R., Ruschel A. C., Zanatta M. S., Da Silva R. C., Bueno e Silva M., Paczko N., Medina J. H., Izquierdo I. Memory expression is blocked by the infusion of CNQX into the hippocampus and/or the amygdala up to 20 days after training. Behav Neural Biol. 1993 Mar;59(2):83–86. doi: 10.1016/0163-1047(93)90782-d. [DOI] [PubMed] [Google Scholar]
  7. Bito H., Nakamura M., Honda Z., Izumi T., Iwatsubo T., Seyama Y., Ogura A., Kudo Y., Shimizu T. Platelet-activating factor (PAF) receptor in rat brain: PAF mobilizes intracellular Ca2+ in hippocampal neurons. Neuron. 1992 Aug;9(2):285–294. doi: 10.1016/0896-6273(92)90167-c. [DOI] [PubMed] [Google Scholar]
  8. Bliss T. V., Collingridge G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993 Jan 7;361(6407):31–39. doi: 10.1038/361031a0. [DOI] [PubMed] [Google Scholar]
  9. Bliss T. V., Lomo T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol. 1973 Jul;232(2):331–356. doi: 10.1113/jphysiol.1973.sp010273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Clark G. D., Happel L. T., Zorumski C. F., Bazan N. G. Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor. Neuron. 1992 Dec;9(6):1211–1216. doi: 10.1016/0896-6273(92)90078-r. [DOI] [PubMed] [Google Scholar]
  11. Ferreira M. B., Da Silva R. C., Medina J. H., Izquierdo I. Late posttraining memory processing by entorhinal cortex: involvement of NMDA and GABAergic receptors. Pharmacol Biochem Behav. 1992 Apr;41(4):767–771. doi: 10.1016/0091-3057(92)90225-5. [DOI] [PubMed] [Google Scholar]
  12. Izquierdo I., Medina J. H., Bianchin M., Walz R., Zanatta M. S., Da Silva R. C., Bueno e Silva M., Ruschel A. C., Paczko N. Memory processing by the limbic system: role of specific neurotransmitter systems. Behav Brain Res. 1993 Dec 20;58(1-2):91–98. doi: 10.1016/0166-4328(93)90093-6. [DOI] [PubMed] [Google Scholar]
  13. Izquierdo I., da Cunha C., Rosat R., Jerusalinsky D., Ferreira M. B., Medina J. H. Neurotransmitter receptors involved in post-training memory processing by the amygdala, medial septum, and hippocampus of the rat. Behav Neural Biol. 1992 Jul;58(1):16–26. doi: 10.1016/0163-1047(92)90847-w. [DOI] [PubMed] [Google Scholar]
  14. Jerusalinsky D., Quillfeldt J. A., Walz R., Da Silva R. C., Bueno e Silva M., Bianchin M., Schmitz P., Zanatta M. S., Ruschel A. C., Paczko N. Effect of the infusion of the GABA-A receptor agonist, muscimol, on the role of the entorhinal cortex, amygdala, and hippocampus in memory processes. Behav Neural Biol. 1994 Mar;61(2):132–138. doi: 10.1016/s0163-1047(05)80066-4. [DOI] [PubMed] [Google Scholar]
  15. Kandel E. R., O'Dell T. J. Are adult learning mechanisms also used for development? Science. 1992 Oct 9;258(5080):243–245. doi: 10.1126/science.1411522. [DOI] [PubMed] [Google Scholar]
  16. Kato K., Clark G. D., Bazan N. G., Zorumski C. F. Platelet-activating factor as a potential retrograde messenger in CA1 hippocampal long-term potentiation. Nature. 1994 Jan 13;367(6459):175–179. doi: 10.1038/367175a0. [DOI] [PubMed] [Google Scholar]
  17. Kumar R., Harvey S. A., Kester M., Hanahan D. J., Olson M. S. Production and effects of platelet-activating factor in the rat brain. Biochim Biophys Acta. 1988 Nov 25;963(2):375–383. doi: 10.1016/0005-2760(88)90304-9. [DOI] [PubMed] [Google Scholar]
  18. Marcheselli V. L., Rossowska M. J., Domingo M. T., Braquet P., Bazan N. G. Distinct platelet-activating factor binding sites in synaptic endings and in intracellular membranes of rat cerebral cortex. J Biol Chem. 1990 Jun 5;265(16):9140–9145. [PubMed] [Google Scholar]
  19. Martin J. H. Autoradiographic estimation of the extent of reversible inactivation produced by microinjection of lidocaine and muscimol in the rat. Neurosci Lett. 1991 Jun 24;127(2):160–164. doi: 10.1016/0304-3940(91)90784-q. [DOI] [PubMed] [Google Scholar]
  20. O'Dell T. J., Hawkins R. D., Kandel E. R., Arancio O. Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11285–11289. doi: 10.1073/pnas.88.24.11285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. O'Flaherty J. T., Redman J. F., Jr, Schmitt J. D., Ellis J. M., Surles J. R., Marx M. H., Piantadosi C., Wykle R. L. 1-O-alkyl-2-N-methylcarbamyl-glycerophosphocholine: a biologically potent, non-metabolizable analog of platelet-activating factor. Biochem Biophys Res Commun. 1987 Aug 31;147(1):18–24. doi: 10.1016/s0006-291x(87)80081-5. [DOI] [PubMed] [Google Scholar]
  22. Panetta T., Marcheselli V. L., Braquet P., Spinnewyn B., Bazan N. G. Effects of a platelet activating factor antagonist (BN 52021) on free fatty acids, diacylglycerols, polyphosphoinositides and blood flow in the gerbil brain: inhibition of ischemia-reperfusion induced cerebral injury. Biochem Biophys Res Commun. 1987 Dec 16;149(2):580–587. doi: 10.1016/0006-291x(87)90407-4. [DOI] [PubMed] [Google Scholar]
  23. Prescott S. M., Zimmerman G. A., McIntyre T. M. Platelet-activating factor. J Biol Chem. 1990 Oct 15;265(29):17381–17384. [PubMed] [Google Scholar]
  24. Squire L. R. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev. 1992 Apr;99(2):195–231. doi: 10.1037/0033-295x.99.2.195. [DOI] [PubMed] [Google Scholar]
  25. Wieraszko A., Li G., Kornecki E., Hogan M. V., Ehrlich Y. H. Long-term potentiation in the hippocampus induced by platelet-activating factor. Neuron. 1993 Mar;10(3):553–557. doi: 10.1016/0896-6273(93)90342-o. [DOI] [PubMed] [Google Scholar]
  26. Williams J. H., Errington M. L., Lynch M. A., Bliss T. V. Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus. Nature. 1989 Oct 26;341(6244):739–742. doi: 10.1038/341739a0. [DOI] [PubMed] [Google Scholar]
  27. Yasuhara H., Hobson R. W., 2nd, Durán W. N. Platelet-activating factor causes venular constriction in the microcirculation. Microvasc Res. 1994 Mar;47(2):279–284. doi: 10.1006/mvre.1994.1021. [DOI] [PubMed] [Google Scholar]
  28. del Cerro S., Arai A., Lynch G. Inhibition of long-term potentiation by an antagonist of platelet-activating factor receptors. Behav Neural Biol. 1990 Nov;54(3):213–217. doi: 10.1016/0163-1047(90)90595-w. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES