Evidence for nitric oxide synthase inhibitor-sensitive and insensitive hippocampal synaptic potentiation.
1. Nitric oxide (NO) has been proposed as a retrograde messenger, mediating the postsynaptic to presynaptic transfer of the effects of conditioning stimulation, responsible for the initiation of hippocampal long-term potentiation (LTP). To further test this hypothesis, we inhibited nitric oxide synthase (NOS) to determine whether synaptic potentiation produced by different conditioning stimulus patterns and intensities was differentially affected by reduction of stimulation-dependent NO production. 2. Synaptic potentiation was produced in hippocampal slices from young F-344 rats by two different conditioning stimulation protocols. Conditioning stimuli were delivered to the Schaffer-collateral commissural system, and moderate levels of potentiation of the population excitatory postsynaptic potential (EPSP) in area CA1 were produced by a single 100 Hz, 1-s conditioning train delivered at half-maximal stimulus intensity. Higher levels of potentiation of the population EPSP were obtained by delivering two 100 Hz, 1-s conditioning stimulus trains, with a 60-s intertrain interval, at high stimulus currents. 3. Application of the nitric oxide synthase inhibitors NG-nitro-L-arginine (NOARG; 0.1-200 microM) and NG-monomethyl-L-arginine (NMMA; 100 microM) produced no significant direct effects on synaptic responses. 4. In slices that received a single conditioning stimulus train, both NOARG and NMMA were ineffective in blocking or reducing potentiation at concentrations between 0.1 and 200 microM. In slices receiving the more intense pair of conditioning stimulus trains, levels of potentiation in control slices were higher, and there was a very significant reduction by both NOARG (50 and 100 microM) and NMMA (100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
Gribkoff
V K
VK
Department of Neuropharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492.
Lum-Ragan
J T
JT
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D011916:Rats, Inbred F344; D013569:Synapses / Q000187:drug effects* / Q000201:enzymology; D019323:omega-N-Methylarginine
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases