Inhibition by the adenosine analogue, (R-)-N6-phenylisopropyladenosine, of kainic acid neurotoxicity in rat hippocampus after systemic administration.

摘要

1. Binding of the peripheral benzodiazepine receptor ligand, [3H]-PK 11195, to rat hippocampal membranes has been used to quantify the reactive gliosis resulting from neuronal death induced by intraperitoneally administered kainic acid. 2. Intraperitoneal administration of kainic acid (10 mg kg-1) caused a 350-500% increase in [3H]-PK 11195 binding measured in rat hippocampal P2 membranes 7 days later. Co-treatment with the adenosine derivative R-phenylisopropyladenosine (R-PIA) (100, 25 or 10 micrograms kg-1, i.p.) abolished this elevation. The protective action of R-PIA could itself be abolished by co-treatment with 8-phenyltheophylline (1 mg kg-1). 3. Body temperatures were recorded in the antagonist experiments and no significant changes were recorded, suggesting that the protective action of R-PIA was not mediated by hypothermia. 4. Since systemic kainic acid-induced neurotoxicity has been claimed as a good model of neuronal death in temporal lobe epilepsy, the results suggest that the systemic administration of purines in low doses may provide protection against certain neurodegenerative insults.