ADENOSINE ANTAGONISTS HAVE DIFFERENTIAL-EFFECTS ON INDUCTION OF LONG-TERM POTENTIATION IN HIPPOCAMPAL SLICES

How adenosine leakage and tetanic release might affect long-term potentiation (LTP) was investigated by applying adenosine antagonists 8(p-sulfophenyl)theophylline (8SPT) or 8-cyclopentyl-3,7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX) to slices, while recording CA1 field EPSPs and population spikes. In the first series of experiments, we applied weak double tetani (at 100 Hz, for 1 s) that were subliminal for evoking LTP in initial control runs. in the presence of 8SPT-at concentrations (10-50 mu M) which block both A(1) and A(2) receptors-the same tetani consistently evoked LTP of population spikes but not of excitatory postsynaptic potentials (EPSPs), whereas DPCPX (50 nM), which blocks only A(1) receptors, facilitated LTP of both EPSPs and population spikes. These results are consistent with previous evidence that tetanic adenosine release on the one hand depresses LTP via A(1) receptors but on the other facilitates LTP via A(2) receptors. In a second set of experiments, 8SPT (50-100 mu M) did not prevent the induction of LTP of both EPSPs and population spikes by stronger tetanic stimulation. Therefore A(2) receptor activation is not essential for the induction of LTP when stronger tetani are applied. Overall, the main effect of endogenous adenosine release is to oppose LTP induction. (C) 1995 Wiley-Liss, Inc.