Post-insult exposure to (±) kavain potentiates N-methyl-D-aspartate toxicity in the developing hippocampus

Patrick J. Mulholland, Mark A. Prendergast

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Kavapyrone extracts of the pepper plant Piper methysticum Forst. have been reported to be pharmacologically active in the brain by modulating the function of several ionotropic receptor systems and voltage-sensitive ion channels. While kavapyrones have previously demonstrated neuroprotective effects against several forms of neurotoxicity, the possibility remains that perturbed function of neuronal ion transport may prove to be neurotoxic in some instances. The present studies were designed to examine the effects of the kavapyrone, (±) kavain, on viability of organotypic hippocampal explants exposed to the excitotoxin N-methyl-D-aspartate (NMDA). Exposure to (±) kavain (1-600 μM) for 24 h did not alter neuronal viability in the CA1, CA3, or dentate gyrus regions of hippocampal explants. However, higher concentrations of (±) kavain (≥300 μM) produced marked neurotoxicity in the lacunosum moleculare layer of the hippocampus. One hour of exposure to NMDA (20 μM) produced significant neuronal death in both the CA3 and CA1 pyramidal cell regions, effects prevented by co-exposure to MK-801 (30 μM). Co-exposure of explants to (±) kavain (1-100 μM) with NMDA did not alter the severity of NMDA-induced neurotoxicity. However, exposure of NMDA-treated explants to (±) kavain (≥10 μM) for 24 h after insult produced significant increases in neurotoxicity in the CA1 and dentate gyrus regions of explants. In conclusion, while the kavapyrone (±) kavain is neurotoxic only at high concentrations when exposed alone to the developing hippocampus, it appears to adversely affect neuronal recovery following excitotoxic insults.

Original languageEnglish
Pages (from-to)106-113
Number of pages8
JournalBrain Research
Issue number1
StatePublished - Jul 26 2002

Bibliographical note

Funding Information:
The authors would like to thank John A. Blanchard II, Robert C. Holley, and D. Alex Gibson for their assistance in completing these studies. This research was supported by the Kentucky Spinal Cord and Head Injury Research Trust.

Copyright 2008 Elsevier B.V., All rights reserved.


  • Kava kava
  • Kavapyrone
  • NMDA
  • Neurotoxicity
  • Piper methysticum

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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