Effect of MK-801, kynurenate, glycine, dextrorphan and 4-acetylpyridine on striatal toxicity of quinolinate.
Measurements of striatal choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) activities indicated that systemic administration of 4-8 mg/kg of MK-801 to rats completely blocked neuronal damage due to intrastriatal injections of 75-150 nmol of quinolinic acid. Similar experiments with 0-2 mg/kg MK-801 suggested the ED50 might be between 1 and 1.5 mg/kg for protection against 50 nmol of intrastriatal quinolinic acid, and between 2 and 3 mg/kg for 75 nmol. Repeated pretreatment with kynurenate (3 x 300 mg/kg) gave significant but not complete protection against similar doses of quinolinic acid, with the protective effect being greater for GAD than for ChAT. Glycine appeared to potentiate the effect of high doses of quinolinic acid on ChAT and the other pretreatments tested (dextrorphan, dextromethorphan, 4-acetylpyridine) had no significant effect.
Zhu
S G
SG
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
McGeer
E G
EG
McGeer
P L
PL
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003917:Dextrorphan / Q000494:pharmacology; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000494:pharmacology*; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology / Q000633:toxicity*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D003986:Dibenzocycloheptenes; D009498:Neurotoxins; D011725:Pyridines; D011805:Quinolinic Acids; D003917:Dextrorphan; D016291:Dizocilpine Maleate; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D017378:Quinolinic Acid; C055538:4-acetylpyridine; D007736:Kynurenic Acid; D005998:Glycine