N-methyl-D-aspartate receptor antagonists are less effective in blocking long-term potentiation at apical than basal dendrites in hippocampal CA1 of awake rats

Long-term potentiation (LTP) of field excitatory postsynaptic potentials (f EPSPs) at the apical or basal dendrites of CA1 pyramidal cells was induced by stimulation with a 1-s train of 200-Hz pulses in awake rats, with or wit hout the presence of various doses of an N-methyl-D-aspartate (NMDA) recept or antagonist. Apical LTP was blocked by an intracerebroventricular (i.c.v. ) dose of 40 mu g D-2-amino-5-phosphonopentanoic acid (D-APS) or 20 mg/kg i .p. D-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP-40116), whereas ba sal LTP was blocked by half the dose of D-APS or CGP-40116. The noncompetit ive antagonist MK-801 (< 1 mg/kg i.p.) had no significant effect on apical LTP. Apical LTP was not blocked by i.c.v. nifedipine. The effect of an NMDA receptor antagonist alone on apical and basal fEPSPs was also evaluated, t o assess the net effect of the NMDA receptor antagonist in blocking LTP. MK -801 (0.5-1 mg/kg i.p.) or CGP-40116 (10-20 mg/kg i.p.) but not D-APS suppr essed apical fEPSPs for several hours and confounded the expression of apic al LTP during this time. We concluded that hippocampal LTP at different syn apses has different sensitivity to NMDA receptor antagonists and that a gen eral blockade of hippocampal NMDA receptor functions cannot be inferred by a single hippocampal LTP measure. (C) 1999 Wiley-Liss, Inc.