It has recently been proposed that activation of the NR2A subunit results in Long-term potentiation (LTP) induction, whereas activation of the NR2B subunit results in long-term depression (LTD) induction. The present study undertakes to replicate these findings in vivo to determine if a role for specific subunits in synaptic plasticity can be shown in the intact brain. Field recordings were made from the CA1 subfield of the hippocampus using Schaffer collateral stimulation in anesthetized male Sprague-Dawley rats. Antagonists of the N-methyl-D-aspartate receptors NR2A and NR2B subunits were administered by either intraperitoneal (i.p.) or intrahippocampal (i.h.) injections to assess their involvement in LTP (100 Hz stimuli) and LTD (200 Paired-burst stimuli). i.h. injection of Ro25-6981 (100 microM) significantly attenuated hippocampal LTP expression and completely blocked LTD expression. When administered i.p., Ro25-6981 (6 mg/kg) again blocked LTD, but did not significantly diminish the expression of LTP. When NVP-AAM077 was administered i.h. (80 microM) both LTP and LTD were completely abolished. The administration of this compound i.p. (1.2 mg/kg) also significantly attenuated LTP, but did not affect LTD. These data suggest that both NR2A and NR2B subunits can play roles in LTP and LTD in the hippocampus in vivo.