MEDIATION OF THE NEUROPROTECTIVE ACTION OF R-PHENYLISOPROPYL-ADENOSINE THROUGH A CENTRALLY LOCATED ADENOSINE-A(1) RECEPTOR

1. Systemic injections of kainic acid, 10 mg kg-1, into adult rats resulted in lesions in the hippocampus, as assessed by peripheral benzodiazepine ligand binding. Co-administration of clonazepam at 1 mg kg-1 or 0.2 mg kg-1 prevented major seizures associated with kainate injections, but did not alter significantly the production of hippocampal damage. 2 The co-administration of the adenosine A1 agonist R-phenylisopropyladenosine (R-PIA, 25 mug kg-1, i.p.) abolished the lesions induced by kainic acid. 3 The presence of the selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (250 or 50 mug kg-1, i.p.) abolished the R-PIA neuroprotective action. 4 The A1/A2 antagonist, 8-(p-sulphophenyl)theophylline (20 mg kg-1, i.p.) which cannot cross the blood brain barrier, did not alter significantly the neuroprotective action of R-PIA, indicating that the neuroprotective action of the purine may be predominantly central. 5 The time course of the neuroprotection was also examined. R-PIA was effective when administered 2 h before or after kainate administration. 6 The results emphasise the potential utility of systemically active adenosine A1 receptor ligands in reducing CNS gliosis induced by the activation of excitatory amino acid receptors.