Long-term potentiation observed upon blockade of adenosine A 1 receptors in rat hippocampus is N-methyl- d-aspartate receptor-dependent

Abstract

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, 50 nM, 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 (50 nM) plus the selective NMDA receptor antagonist, dl-2-amino-5-phosphonopentanoate (AP5, 50 μM, −3.3±7.0% change). In contrast, LTD was induced by low-frequency stimulation in the presence of DPCPX (50 nM), even in experiments performed in AP5 (50 μM). Thus LTP, but not LTD, observed upon blockade of adenosine A 1 receptors is dependent upon NMDA receptor activation.