Effect of two different routes of administration of R-PIA on glutamate release during ischemia

Considering that adenosine decreases glutamate release from brain slices by stimulating presynaptic A1 receptors, we have attempted to modulate glutamate release in vivo during global ischemia with an agonist (R-phenylisopropyladenosine, R-PIA) of A1 receptors. Extracellular hippocampal glutamate was sampled by microdialysis and measured by HPLC. Conscious rats were submitted to transient global ischemia for 20 min. Ischemia induced a significant increase (10 fold) in extracellular glutamate. R-PIA (20 micrograms/kg) administered i.p. 30 min before ischemia significantly reduced (-64%) glutamate release. Conversely, R-PIA (100 microM) continuously infused through the hippocampal dialysis probe did not significantly modify glutamate efflux. The efficiency of infused R-PIA was evidenced by the decrease (-47%) of glutamate release induced by veratridine depolarization. These results indicate that the depressive action of R-PIA during ischemia results from various effects which are not restricted to a local action on the hippocampus.