Non-NMDA antagonists protect against kainate more than AMPA toxicity in the rat hippocampus.

Article date: 1991/12/9

PubMed ID: 1816508

Journal name: Neuroscience letters (ISSN: 0304-3940)


Single focal injection of the excitatory amino acids (EAAs) kainic acid (KA, 1.1 nmol/microliters) and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (S)-AMPA, 6 nmol/microliters) into rat dorsal hippocampus resulted in widespread neurodegeneration with 90-100% loss of hippocampal pyramidal cells in CA1, CA2, CA3 and CA4 subfields, and 50-70% loss of dentate granule (DG) cells. Focal injection of NMDA (30 nmol/microliters) under the same conditions resulted in 70-90% loss of CA1 cells with less damage in CA2, CA3, CA4 and DG cells (30-50%, 10-30%, and 30-50%, respectively). The non-NMDA antagonists NBQX (2,3-dihydro-6-nitro-7-sulphamoyl-benzo(f) quinoxaline) and GYKI 52466 (1-(amino)phenyl-4-methyl-7,8-methylendioxy-5H-2,3,benzodiazepine. HCl) co-injected (24 nmol/microliters) with EAAs or given as i.v. infusion (30 mg/kg/3h), protected against KA toxicity in CA1, CA2 and DG cells, with no protection in CA3 and CA4. NBQX i.v. protected against (S)-AMPA toxicity in the DG cells but no protection was observed against (S)-AMPA toxicity in hippocampal subfields (CA1, CA2 and CA4). Intravenous administration of NBQX and GYKI 52466 (30 mg/kg/3 h) also failed to protect against NMDA toxicity in the hippocampus. Systemic injections of D(-)-CPPene, (E)-4-(3-phos-phonoprop-2-enyl)-piperazine-2-carboxylic acid, (10 and 5 mg/kg, i.p., 20 min prior and 3 h post EAA injection) protected against NMDA and KA toxicity in the CA1, CA2 and DG subfield with no protective effect against (S)-AMPA toxicity.

Author List: Moncada C, Arvin B, Le Peillet E, Meldrum B S

Publication Types: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Anti-Anxiety Agents; Neurotoxins; Quinoxalines; GYKI 52466; 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; Benzodiazepines; Ibotenic Acid; N-Methylaspartate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Kainic Acid;

Mesh terms: Animals; Anti-Anxiety Agents; Benzodiazepines/toxicity; Hippocampus/drug effects; Ibotenic Acid/analogs & derivatives; Kainic Acid/toxicity; Male; N-Methylaspartate/antagonists & inhibitors; Nerve Degeneration/drug effects; Neurons/drug effects; Neurotoxins/toxicity; Pyramidal Tracts/drug effects; Quinoxalines/toxicity; Rats; Rats, Inbred Strains; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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