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

Abstract

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. 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 μg 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). 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. 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. 1993 British Pharmacological Society