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

Publication ,  Journal Article
Stafstrom, CE; Tandon, P; Hori, A; Liu, Z; Mikati, MA; Holmes, GL
Published in: Epilepsy Res
January 1997

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.

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Published In

Epilepsy Res

DOI

ISSN

0920-1211

Publication Date

January 1997

Volume

26

Issue

2

Start / End Page

335 / 344

Location

Netherlands

Related Subject Headings

  • Time Factors
  • Seizures
  • Reaction Time
  • Rats, Sprague-Dawley
  • Rats
  • Neurology & Neurosurgery
  • Male
  • Kainic Acid
  • Electroencephalography
  • Dose-Response Relationship, Drug
 

Citation

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Stafstrom, C. E., Tandon, P., Hori, A., Liu, Z., Mikati, M. A., & Holmes, G. L. (1997). Acute effects of MK801 on kainic acid-induced seizures in neonatal rats. Epilepsy Res, 26(2), 335–344. https://doi.org/10.1016/s0920-1211(96)00904-7
Stafstrom, C. E., P. Tandon, A. Hori, Z. Liu, M. A. Mikati, and G. L. Holmes. “Acute effects of MK801 on kainic acid-induced seizures in neonatal rats.Epilepsy Res 26, no. 2 (January 1997): 335–44. https://doi.org/10.1016/s0920-1211(96)00904-7.
Stafstrom CE, Tandon P, Hori A, Liu Z, Mikati MA, Holmes GL. Acute effects of MK801 on kainic acid-induced seizures in neonatal rats. Epilepsy Res. 1997 Jan;26(2):335–44.
Stafstrom, C. E., et al. “Acute effects of MK801 on kainic acid-induced seizures in neonatal rats.Epilepsy Res, vol. 26, no. 2, Jan. 1997, pp. 335–44. Pubmed, doi:10.1016/s0920-1211(96)00904-7.
Stafstrom CE, Tandon P, Hori A, Liu Z, Mikati MA, Holmes GL. Acute effects of MK801 on kainic acid-induced seizures in neonatal rats. Epilepsy Res. 1997 Jan;26(2):335–344.
Journal cover image

Published In

Epilepsy Res

DOI

ISSN

0920-1211

Publication Date

January 1997

Volume

26

Issue

2

Start / End Page

335 / 344

Location

Netherlands

Related Subject Headings

  • Time Factors
  • Seizures
  • Reaction Time
  • Rats, Sprague-Dawley
  • Rats
  • Neurology & Neurosurgery
  • Male
  • Kainic Acid
  • Electroencephalography
  • Dose-Response Relationship, Drug