title: Interactions between excitotoxins and the Na+/K+-ATPase inhibitor ouabain in causing neuronal lesions in the rat hippocampus.
abstract: A possible indirect role of glutamate in causing the neuronal death found after intracerebral administration of a low dose of ouabain (0.1 nmol) has been evaluated. This dose of ouabain produces a more extensive neuronal lesion than those caused by glutamate receptor agonists (kainate at an equimolar dose, or NMDA (N-methyl-D-aspartate) at a 50-fold higher dose). The selective glutamate receptor antagonists, dizocilpine (MK-801) and NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline), in doses which blocked the direct toxicity of glutamate receptor agonists acting on either the NMDA and non-NMDA classes of glutamate receptor, failed to provide more than a minor protection against ouabain-induced neuronal death in the rat dorsal hippocampus. In contrast, the non-selective glutamate receptor antagonist, kynurenate (100 nmol) reduced the damage by around 70%. The difference in neuroprotection found between the glutamate receptor antagonists suggests that kynurenate may protect by a non-glutamatergic mechanism. Co-administration of ouabain and glutamate receptor agonists (kainate, NMDA or glutamate) resulted in additive rather than synergistic damage to hippocampal neurons. The results suggest that in vivo, ouabain and excitotoxins probably cause neuronal death by independent mechanisms.
authors.affiliation: Department of Psychiatry and Behavioural Science, School of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: G J
authors.initials: GJ
authors.lastname: Lees
authors.forename: W
authors.initials: W
authors.lastname: Leong
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects*
chemical_list: D009498:Neurotoxins; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase