title: The sensitivity of hippocampal long-term potentiation to nitric oxide synthase inhibitors is dependent upon the pattern of conditioning stimulation.
abstract: Inhibition of nitric oxide synthase prior to conditioning has been previously found to reduce levels of hippocampal long-term potentiation. In the present experiments in the rat, the reduction of long-term potentiation by nitric oxide synthase inhibitors was highly conditioning-dependent. We have characterized the relative importance of the number of conditioning stimulus trains, pulse number, intensity, and pattern in the reduction of long-term potentiation by nitric oxide synthase inhibitors. Long-term potentiation was reduced relative to control values only when multiple conditioning stimulus trains were presented at maximal stimulus intensity; potentiation produced by an equivalent number and intensity of stimuli presented in a single conditioning train was not reduced by nitric oxide synthase inhibitors, and multiple-train-induced potentiation was sensitive to nitric oxide synthase inhibitors only when maximal stimulation intensity was employed. Another form of synaptic potentiation, primed-burst potentiation, was reduced by nitric oxide synthase inhibition, while homosynaptic and heterosynaptic depression were unaffected. Our results support the hypothesis that conditioning-dependent release of nitric oxide can contribute to long-term potentiation, but also show that its blockade by nitric oxide synthase inhibitors is dependent on the nature of the conditioning stimulus, and that long-term potentiation can be generated that is apparently resistant to the effects of these drugs.
authors.affiliation: Central Nervous System Biophysics and Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492.
authors.forename: J T
authors.initials: JT
authors.lastname: Lum-Ragan
authors.forename: V K
authors.initials: VK
authors.lastname: Gribkoff
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013569:Synapses / Q000502:physiology
chemical_list: D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D015763:2-Amino-5-phosphonovalerate; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases