Long-term effects of excitatory amino acid antagonists NBQX and MK-801 on the developing brain

Pushpa Tandon, Zhao Liu, Carl E. Stafstrom, Matthew Sarkisian, Suzanne J. Werner, Mohamad Mikati, Yili Yang, Gregory L. Holmes

Research output: Contribution to journalArticlepeer-review

Abstract

Because of the critical role of excitatory amino acids (EAAs) in epileptogenesis and seizure-induced brain damage, EAA antagonists are now being considered as a possible therapy for seizures. However, during development EAAs play a pivotal role in learning, memory, and brain plasticity. To evaluate the long-term effects of a short course of EAA antagonists on the developing brain, a non-NMDA antagonist, NBQX, or a NMDA antagonist, MK-801, were administered over 7 days by osmotic pumps stereotaxically implanted into the lateral ventricles of normal 10 day old rats. Alternatively, 10 and 20 day old rats received a 7 day course of intraperitoneal (i.p.) NBQX. One month later, the NBQX-, MK-801-treated rats, and controls underwent a series of behavioral studies: handling test, open field, and Morris water maze. Flurothyl inhalation was used to test seizure susceptibility in all groups. Although all of the rats treated with NBQX via osmotic pumps had spontaneous seizures, rats surviving infusion of EAAs had no deficits in learning, memory, or behavior and did not differ from controls in seizure susceptibility with flurothyl. In the developing animal, a short-term course of EAA antagonists leads to no long-term adverse effects on behavior or seizure susceptibility.

Original languageEnglish (US)
Pages (from-to)256-262
Number of pages7
JournalDevelopmental Brain Research
Volume95
Issue number2
DOIs
StatePublished - Sep 2 1996
Externally publishedYes

Keywords

  • Animal model
  • Behavioral test
  • Brain damage
  • Epilepsy
  • Pilocarpine
  • Seizure
  • Status epilepticus

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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