Long-term potentiation in the dentate gyrus: induction and increased glutamate release are blocked by D(-)aminophosphonovalerate.
D(-)Aminophosphonovalerate, a specific antagonist of the N-methyl-D-aspartate subtype of glutamate receptor, was perfused through a push-pull cannula into the dentate gyrus of rats anaesthetized with urethan in order to observe its effect on the induction and maintenance of long-term potentiation and on the increase in release of endogenous glutamate associated with long-term potentiation. The amplitude of the population spike evoked by single test shocks to the perforant path was significantly depressed by 100 microM D(-)aminophosphonovalerate, but there was a minimal effect on the slope of the population excitatory postsynaptic potential, or on the concentration of glutamate released into the perfusate. A brief high-intensity tetanus given to the perforant path while D(-)aminophosphono-valerate was being perfused failed to induce long-term potentiation or the sustained increase in glutamate release associated with long-term potentiation. Short-term post-tetanic potentiation was not affected. After wash-out of D(-)aminophosphonovalerate, a second high-frequency train produced both long-term potentiation and an increase in glutamate release which was sustained for the subsequent 1 h period of observation. D(-)Aminophosphonovalerate did not suppress long-term potentiation once it had been induced. D(-)Aminophosphonovalerate (100 microM) did not itself affect in vivo release of glutamate. However, in a separate series of in vitro experiments, D(-)aminophosphonovalerate at concentrations of 50 microM and above was found to depress the Ca2+ -dependent, K+-stimulated release of preloaded [14C]-glutamate from dentate slices.(ABSTRACT TRUNCATED AT 250 WORDS)
D015763:2-Amino-5-phosphonovalerate; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D003864:Depression, Chemical; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000596:Amino Acids; D005971:Glutamates; D001224:Aspartic Acid; D018698:Glutamic Acid; D015763:2-Amino-5-phosphonovalerate; D014633:Valine