Long-term depression is not modulated by ATP receptors in the rat CA1 hippocampal region

ATP is an important extracellular messenger in the CNS. In the hippocampus, a brain structure relevant for learning and memory processes, it acts both as a modulator and as a mediator of synaptic transmission, with implications for synaptic plasticity phenomena. Recent evidence suggests that ATP modulates activity-dependent long-term potentiation (LTP) of Schaffer collateral-CA1 synapses. However, it remains unclear if ATP also modulates LTP counterpart's phenomenon, long-term depression (LTD), in the rat hippocampus. This study investigated the effect of ATP analogues on homosynaptic LTD, induced by low-frequency stimulation of the Schaffer collaterals (1 Hz; 900 pulses) in the CA1 region of young rat hippocampal slices. The metabolically stable ATP analogues beta,gamma-ImATP (20 microM), a P2 receptor agonist, and alpha,beta-MeATP (20 microM), a preferential P2X(1,3) receptor agonist, did not modify LTD (LTD values of 14.7+/-0.5% and 14.1+/-3% for aCSF controls and of 15.1+/-4% and 19.0+/-5.2% for beta,gamma-ImATP and alpha,beta-MeATP, respectively). The ATP analogue beta,gamma-ImATP (20 microM) did not modify LTD also in the presence of the adenosine A1 receptor antagonist DPCPX (50 nM) (21.5+/-4.2% for DPCPX only and of 23.8+/-8.9% for DPCPX plus beta,gamma-ImATP). Finally, the preferential P2X(1,3) receptor antagonist NF023 (10 microM) had also no effect on LTD (18.6+/-5.2% for aCSF and of 18.7+/-5.2% for NF023). The present results suggest that ATP does not modulate activity-dependent homosynaptic LTD in the rat CA1 hippocampal region by activating P2 receptors.