Endogenous adenosine attenuates long-term depression and depotentiation in the CA1 region of the rat hippocampus.

This study tested the hypothesis that endogenous adenosine, a neuromodulator which is known to modify long-term potentiation (LTP), might also affect other forms of long-lasting synaptic plasticity, namely long-term depression (LTD) and depotentiation, in the hippocampus. Long-term depression was induced by applying low-frequency stimulation (LFS; 1 Hz, 900 stimuli, test intensity) to the Schaffer collateral-commissural fibres in hippocampal slices taken from young (12-14-day old) animals. Depotentiation was induced by delivering LFS to a pathway in which LTP had previously been saturated. Under control conditions, LTD induced in two distinct pathways was similar. However, low-frequency stimulation, applied in either pathway in the presence of the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 10 nM), resulted in LTD which was larger than in control conditions. In a similar way, while under control conditions depotentiation induced in two distinct pathways was similar, when LFS was applied in the presence of DPCPX (10 nM) facilitation of depotentiation was observed. These results suggest that endogenous adenosine, acting through adenosine A1 receptors, is able to attenuate long-term depression and depotentiation in the hippocampus.