1. Systemically administered kainic acid causes a dose dependent increase in the amount of peripheral benzodiazepine receptor in the rat hippocampus, as assessed by [3H]PK11195 binding. 2. This increase in binding is due to an increase in Bmax and not K0. The increase in PK11195 binding indicates that reactive gliosis has occurred and, by inference, neuronal loss. 3. The kainic acid induced elevation in binding is blocked by the non-NMDA antagonist GYKI 52466 and the NMDA antagonists MK801 and CPP. 4. The adenosine A1 receptor agonist R-phenylisopropyladenosine (R-PIA) is able to attenuate the kainic acid induced neuronal loss in a dose dependent and time dependent manner. 5. The R-PIA response is blocked by 8-cyclopentyl,-l ,3- dipropylxanthine (DPCPX) in a dose dependent manner, although DPCPX is unable to potentiate kainate induced neurotoxicity. 6. 8-p-sulfophenyltheophylline (8-SPT), is unable to cross the blood-brain barrier, and is unable to block the R-PIA induced neuroprotection indicating that the R-PIA effect is centrally mediated. 7. Kynurenine, but not kynurenic acid or tryptophan is able to attenuate kainic acid induced neurotoxicity in a dose dependent manner. 8. Kainic acid and potassium chloride (KCl) are able to release [3H] glutamate from hippocampal slices in a dose dependent manner. 9. The kainic acid induced elevation induces a period of heightened release after the first, but not second or third stimulations, and this is not seen after either KCl or kainic acid/KCl stimulations. 10. The adenosine A1 agonist 2-chloroadenosine (5muM) is unable to block the kainic acid induced release of [3H] glutamate. 11. DPCPX (5nM) is able to induce a significant decrease in KCl stimulated release of [3H] glutamate but not the kainic acid induced release. 12. In conclusion, kainic acid is causing neurotoxicity in a dose dependent manner that is mediated through both non-NMDA and NMD A receptors, and can be attenuated by R-PIA, and ascorbate.
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