Long-term potentiation observed upon blockade of adenosine A1 receptors in rat hippocampus is N-methyl-D-aspartate receptor-dependent.

Endogenous adenosine, acting upon A(1) receptors, attenuates long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission in hippocampal slices. Adenosine might exert these effects by inhibiting the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Theta burst-induced LTP was larger in the presence of the selective adenosine A(1) receptor antagonist, 1, 3-dipropyl-8-cyclopentylxanthine (DPCPX, 50nM, 40.5+/-6.6% increase in fEPSP) than in the control solution (18.2+/-4.7% increase), and was completely prevented in the presence of DPCPX (50nM) plus the selective NMDA receptor antagonist, DL-2-amino-5-phosphonopentanoate (AP5, 50microM, -3.3+/-7.0% change). In contrast, LTD was induced by low-frequency stimulation in the presence of DPCPX (50nM), even in experiments performed in AP5 (50microM). Thus LTP, but not LTD, observed upon blockade of adenosine A(1) receptors is dependent upon NMDA receptor activation.