Endogenous adenosine modulates long-term potentiation in the hippocampus.

The effect of endogenous adenosine on frequency-induced long-term potentiation of the responses evoked by stimulation of the Schaffer fibres and recorded in the CA1 area was studied in hippocampal slices of the rat. Long-term potentiation was facilitated in the presence of the selective A1 adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (10-20 nM), and was reduced in the presence of the adenosine uptake blocker, nitrobenzylthioinosine (5 microM), suggesting that endogenous adenosine exerted a tonic inhibitory role on long-term potentiation, which was mediated through adenosine A1 receptors. We also found that long-term potentiation was increased in the presence of the selective A2 receptor agonist, CGS 21680 (30 nM), suggesting that the activation of adenosine A2 receptors may have excitatory effects on long-term potentiation. We suggest that, endogenous adenosine is able to modulate mechanisms of synaptic plasticity, such as long-term potentiation, in the hippocampus.