ADENOSINE-A2 RECEPTOR ANTAGONIST FACILITATES THE REVERSAL OF LONG-TERM POTENTIATION (DEPOTENTIATION) OF EVOKED POSTSYNAPTIC POTENTIALS BUT INHIBITS THAT OF POPULATION SPIKES IN HIPPOCAMPAL CA1 NEURONS

The effects of the adenosine A2 receptor antagonist CP-66713 on the reversal of long-term potentiation (LTP) were studied in CA1 neurons of guinea pig hippocampal slices. Reduction of LTP (depotentiation, DP) was effected by delivering a train of low-frequency afferent stimuli (depotentiation stimulation, DPS) which was given 20 min after tetanus (100 Hz, 100 pulses). DPS (I Hz, 1000 pulses) was applied during perfusion of CP-66713 (10 muM). In the presence of CP-66713, DPS reduced the potentiated component of the slope of the field EPSP (S-EPSP) and the amplitude of the population spike (A-PS) by 101.7% and 19.1% of the potentiated amount, respectively (mean, n = 8). The reduction of LTP of the S-EPSP was significantly larger than the control (68.5% (mean, n = 6)) while that of the A-PS was significantly smaller than the control (80.1% (mean, n = 6)). Based on these results, we conclude that the inhibition of DP in the EPSP, the facilitation of DP in the PS, and the consequent attenuation in the EPSP-PS relationship follow from activation of adenosine A2 receptors.