Acute effects of MK801 on kainic acid-induced seizures in neonatal rats

Carl Stafstrom, Pushpa Tandon, Ariyuki Hori, Zhao Liu, Mohamad A. Mikati, Gregory L. Holmes

Research output: Contribution to journalArticle

Abstract

Kainic acid (KA) causes behavioral and electrographic status epilepticus (SE) in rats of all ages. In adult rats, the noncompetitive N-methyl-D-aspartate (NMDA) channel blocker MK801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten- 5,10-imine) is anticonvulsant against KA-induced seizures: it reduces their severity and protects against neuronal damage, although it may worsen electrographic seizures. Here we examined the effects of MK801 on KA seizures in the immature brain. Neonatal rats (P11-P12) were pretreated with MK801 (0.01, 0.1, 0.5 or 1.0 mg/kg, i.p.) or saline twenty minutes prior to KA (2 mg/kg, i.p.). Clinical seizure behavior was monitored for >6 hrs, and in some rats the EEG was monitored with an intrahippocampal or intracortical electrode. MK801 caused immobility alternating with hyperactivity, ataxia, scratching and sometimes alternate limb cycling, which correlated with the appearance of spikes on the EEG. Compared to KA alone or KA preceded by 0.01 mg/kg MK801, the higher doses of MK801 (0.1, 0.5 and 1.0 mg/kg) significantly lowered the latency to electrographic seizures (P <0.001), ictal scratching (P <0.0001), and status epilepticus (P <0.0001). MK801 pretreatment did not lower significantly the death rate due to KA seizures. No histologic damage was seen after MK801, KA or both agents together. These results suggest that MK801 exacerbates KA-induced seizures in the neonatal brain, and may even cause ictal behavioral and electrographic manifestations by itself. The findings point to an age-dependency of NMDA antagonist action, and suggest caution in considering the use of NMDA antagonists in neonates.

Original languageEnglish (US)
Pages (from-to)335-344
Number of pages10
JournalEpilepsy Research
Volume26
Issue number2
DOIs
StatePublished - Jan 1997
Externally publishedYes

Fingerprint

Kainic Acid
Seizures
N-Methylaspartate
Status Epilepticus
Electroencephalography
Stroke
Imines
Brain
Ataxia
Anticonvulsants
Electrodes
Extremities
Mortality

Keywords

  • Kainic acid
  • MK801
  • NMDA receptor
  • Seizure immature rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Neurology

Cite this

Acute effects of MK801 on kainic acid-induced seizures in neonatal rats. / Stafstrom, Carl; Tandon, Pushpa; Hori, Ariyuki; Liu, Zhao; Mikati, Mohamad A.; Holmes, Gregory L.

In: Epilepsy Research, Vol. 26, No. 2, 01.1997, p. 335-344.

Research output: Contribution to journalArticle

Stafstrom, Carl ; Tandon, Pushpa ; Hori, Ariyuki ; Liu, Zhao ; Mikati, Mohamad A. ; Holmes, Gregory L. / Acute effects of MK801 on kainic acid-induced seizures in neonatal rats. In: Epilepsy Research. 1997 ; Vol. 26, No. 2. pp. 335-344.
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