It has been hypothesized that high levels of presynaptic activity that fail to activate postsynaptic N-methyl-D-aspartate (NMDA) receptors may lead to long-term depression (LTD). Therefore, we tested the ability of high-frequency (50 Hz) synaptic stimulation in the presence of a blocker of NMDA receptors to elicit homosynaptic LTD at Schaffer collateral-CA1 synapses in hippocampal slices from 15-, 30- and 60-day-old rats. In control slices, there were no developmental differences in the incidence of long-term potentiation (LTP) of either EPSP slope or population spike amplitude. However, while NMDA receptor blockade with the specific antagonist D-2-amino-5-phosphonopentanoic acid (AP5; 25 microM) completely eliminated LTP in 30 and 60-day-olds, a significant number of slices from 15-day-old rats displayed some non-NMDA LTP of synaptic transmission. Moreover, under NMDA receptor blockade, the same high-frequency stimulation now induced homosynaptic LTD of population spike amplitude in a significant number of slices from 15- and 60-day-old rats (47% and 42%, respectively) but not in 30-day-olds (7%). LTD of population spike amplitude was most pronounced in 15-day-old slices (27 +/- 6% of baseline), whereas, in 60-day-old slices, LTD was 81 +/- 3% of baseline. LTD of EPSP slopes occurred in 44% of 15-day-olds, 13% of 30-day-olds, and 33% of slices from 60-day-old rats; the magnitude of EPSP was similar in 15 and 60-day-old slices (70 +/- 9% versus 81 +/- 1% of baseline).(ABSTRACT TRUNCATED AT 250 WORDS)