Uridine is released by depolarization and inhibits unit activity in the rat hippocampus

Perfusion of 5 microM kainate through microdialysis probes induced >2-fold elevation of extracellular uridine and adenosine concentrations in the hippocampus and in the thalamus of anaesthetized rats. Administration of uridine via this route produced an estimated uridine concentration of 50-100 microM around the electrode surface. This markedly decreased the average firing rate of neurones in the hippocampus, but not in the thalamus. Activity of separated single hippocampal pyramidal cells was completely inhibited by uridine. The same amount of adenosine completely blocked neuronal activity in both hippocampus and thalamus. Uridine administration had no effect on extracellular adenosine concentration. These findings suggest an important neuromodulatory role for depolarization-released uridine in the CNS.