INHIBITION BY THE ADENOSINE ANALOG, (R-)-N(6)-PHENYLISOPROPYL-ADENOSINE, OF KAINIC ACID NEUROTOXICITY IN RAT HIPPOCAMPUS AFTER SYSTEMIC ADMINISTRATION

1 Binding of the peripheral benzodiazepine receptor ligand, [H-3]-PK 1 1195, to rat hippocampal membranes has been used to quantify the react ive 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 [H-3]-PK 11195 binding measured in rat hippocampal P2 membranes 7 days later. Co-treatment w ith the adenosine derivative R-phenylisopropyladenosine (R-PIA) (100, 25 or 10 mug kg-1, i.p.) abolished this elevation. The protective acti on of R-PIA could itself be abolished by co-treatment with 8-phenylthe ophylline (1 mg kg-1). 3 Body temperatures were recorded in the antago nist 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 p rovide protection against certain neurodegenerative insults.