Dexamethasone potentiates NMDA receptor-mediated neuronal injury in the postnatal rat

Donna E. Supko, Michael V Johnston

Research output: Contribution to journalArticle

Abstract

The present study investigated the effect of a synthetic glucocorticoid, dexamethasone, on excitatory amino acid receptor-mediated neurotoxicity in the 7-day-old rat. Pretreatment with dexamethasone (0.7 mg/kg i.p.) 1 h prior to unilateral intrastriatal injection of excitotoxin enhanced damage resulting from N-methyl-D-aspartate (NMDA), but not α-amino-3-hydroxy-5- methyl-4-isoxazolepropionate (AMPA), or kainate receptor activation. The glucocorticoid-induced enhancement of NMDA toxicity was dose dependent. The time of dexamethasone administration appeared critical since only treatment 1 h prior to, but not 24 h prior to, simultaneously with, or 1 h after NMDA injection, affected toxicity. The administration of the adrenal mineralocorticoid aldosterone, or the phospholipase A2 inhibitor mepacrine, did not affect excitotoxicity. Quantitative receptor autoradiography was performed to assess the effect of dexamethasone on NMDA-sensitive [3H]glutamate receptor binding. Neither pretreatment in vivo nor the addition of dexamethasone in vitro affected NMDA-sensitive binding in the striatum. Possible explanations for these observations are discussed.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalEuropean Journal of Pharmacology: Environmental Toxicology and
Volume270
Issue number1
DOIs
StatePublished - Jan 3 1994

Fingerprint

N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Dexamethasone
Toxicity
Rats
Wounds and Injuries
Glutamate Receptors
Amino acids
Chemical activation
Glucocorticoids
Kainic Acid Receptors
Quinacrine
Mineralocorticoids
Injections
AMPA Receptors
Neurotoxins
Aldosterone
Autoradiography

Keywords

  • AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropiionate)
  • Dexamethasone
  • Glucocorticoid
  • Neurotoxicity
  • NMDA (N-methyl-D-aspartate)
  • Postnatal

ASJC Scopus subject areas

  • Pollution
  • Pharmacology
  • Toxicology

Cite this

Dexamethasone potentiates NMDA receptor-mediated neuronal injury in the postnatal rat. / Supko, Donna E.; Johnston, Michael V.

In: European Journal of Pharmacology: Environmental Toxicology and, Vol. 270, No. 1, 03.01.1994, p. 105-113.

Research output: Contribution to journalArticle

@article{3bac04c7cbbb4ce6ae4ddb3ee7bd0c2c,
title = "Dexamethasone potentiates NMDA receptor-mediated neuronal injury in the postnatal rat",
abstract = "The present study investigated the effect of a synthetic glucocorticoid, dexamethasone, on excitatory amino acid receptor-mediated neurotoxicity in the 7-day-old rat. Pretreatment with dexamethasone (0.7 mg/kg i.p.) 1 h prior to unilateral intrastriatal injection of excitotoxin enhanced damage resulting from N-methyl-D-aspartate (NMDA), but not α-amino-3-hydroxy-5- methyl-4-isoxazolepropionate (AMPA), or kainate receptor activation. The glucocorticoid-induced enhancement of NMDA toxicity was dose dependent. The time of dexamethasone administration appeared critical since only treatment 1 h prior to, but not 24 h prior to, simultaneously with, or 1 h after NMDA injection, affected toxicity. The administration of the adrenal mineralocorticoid aldosterone, or the phospholipase A2 inhibitor mepacrine, did not affect excitotoxicity. Quantitative receptor autoradiography was performed to assess the effect of dexamethasone on NMDA-sensitive [3H]glutamate receptor binding. Neither pretreatment in vivo nor the addition of dexamethasone in vitro affected NMDA-sensitive binding in the striatum. Possible explanations for these observations are discussed.",
keywords = "AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropiionate), Dexamethasone, Glucocorticoid, Neurotoxicity, NMDA (N-methyl-D-aspartate), Postnatal",
author = "Supko, {Donna E.} and Johnston, {Michael V}",
year = "1994",
month = "1",
day = "3",
doi = "10.1016/0926-6917(94)90086-8",
language = "English (US)",
volume = "270",
pages = "105--113",
journal = "Environmental Toxicology and Pharmacology",
issn = "1382-6689",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Dexamethasone potentiates NMDA receptor-mediated neuronal injury in the postnatal rat

AU - Supko, Donna E.

AU - Johnston, Michael V

PY - 1994/1/3

Y1 - 1994/1/3

N2 - The present study investigated the effect of a synthetic glucocorticoid, dexamethasone, on excitatory amino acid receptor-mediated neurotoxicity in the 7-day-old rat. Pretreatment with dexamethasone (0.7 mg/kg i.p.) 1 h prior to unilateral intrastriatal injection of excitotoxin enhanced damage resulting from N-methyl-D-aspartate (NMDA), but not α-amino-3-hydroxy-5- methyl-4-isoxazolepropionate (AMPA), or kainate receptor activation. The glucocorticoid-induced enhancement of NMDA toxicity was dose dependent. The time of dexamethasone administration appeared critical since only treatment 1 h prior to, but not 24 h prior to, simultaneously with, or 1 h after NMDA injection, affected toxicity. The administration of the adrenal mineralocorticoid aldosterone, or the phospholipase A2 inhibitor mepacrine, did not affect excitotoxicity. Quantitative receptor autoradiography was performed to assess the effect of dexamethasone on NMDA-sensitive [3H]glutamate receptor binding. Neither pretreatment in vivo nor the addition of dexamethasone in vitro affected NMDA-sensitive binding in the striatum. Possible explanations for these observations are discussed.

AB - The present study investigated the effect of a synthetic glucocorticoid, dexamethasone, on excitatory amino acid receptor-mediated neurotoxicity in the 7-day-old rat. Pretreatment with dexamethasone (0.7 mg/kg i.p.) 1 h prior to unilateral intrastriatal injection of excitotoxin enhanced damage resulting from N-methyl-D-aspartate (NMDA), but not α-amino-3-hydroxy-5- methyl-4-isoxazolepropionate (AMPA), or kainate receptor activation. The glucocorticoid-induced enhancement of NMDA toxicity was dose dependent. The time of dexamethasone administration appeared critical since only treatment 1 h prior to, but not 24 h prior to, simultaneously with, or 1 h after NMDA injection, affected toxicity. The administration of the adrenal mineralocorticoid aldosterone, or the phospholipase A2 inhibitor mepacrine, did not affect excitotoxicity. Quantitative receptor autoradiography was performed to assess the effect of dexamethasone on NMDA-sensitive [3H]glutamate receptor binding. Neither pretreatment in vivo nor the addition of dexamethasone in vitro affected NMDA-sensitive binding in the striatum. Possible explanations for these observations are discussed.

KW - AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropiionate)

KW - Dexamethasone

KW - Glucocorticoid

KW - Neurotoxicity

KW - NMDA (N-methyl-D-aspartate)

KW - Postnatal

UR - http://www.scopus.com/inward/record.url?scp=0028177943&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028177943&partnerID=8YFLogxK

U2 - 10.1016/0926-6917(94)90086-8

DO - 10.1016/0926-6917(94)90086-8

M3 - Article

C2 - 7512506

AN - SCOPUS:0028177943

VL - 270

SP - 105

EP - 113

JO - Environmental Toxicology and Pharmacology

JF - Environmental Toxicology and Pharmacology

SN - 1382-6689

IS - 1

ER -