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 (fEPSPs) 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 without the presence of various doses of an N-methyl-D-aspartate (NMDA) receptor antagonist. Apical LTP was blocked by an intracerebroventricular (i.c.v.) dose of 40 microg D-2-amino-5-phosphonopentanoic acid (D-AP5) or 20 mg/kg i.p. D-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP-40116), whereas basal LTP was blocked by half the dose of D-AP5 or CGP-40116. The noncompetitive antagonist MK-801 (< or =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, to 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-AP5 suppressed apical fEPSPs for several hours and confounded the expression of apical LTP during this time. We concluded that hippocampal LTP at different synapses has different sensitivity to NMDA receptor antagonists and that a general blockade of hippocampal NMDA receptor functions cannot be inferred by a single hippocampal LTP measure.
Leung
L S
LS
Department of Physiology and Clinical Neurological Sciences, University of Western Ontario, London, Canada. sleung@julian.uwo.ca
Shen
B
B
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003712:Dendrites / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014851:Wakefulness / Q000502:physiology
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D009543:Nifedipine