Evidence for involvement of the neuronal isoform of nitric oxide synthase during induction of long-term potentiation and long-term depression in the rat dentate gyrus in vitro.
The possible role of nitric oxide in the induction of long-term potentiation and long-term depression of field excitatory postsynaptic potentials in the dentate gyrus of the hippocampal slice has been investigated, in the rat, using two novel nitric oxide synthase inhibitors, 1-(2-trifluoromethylphenyl)imidazole, which is selective for the neuronal isoform in vitro, and 3-bromo-7-nitro-indazole. Long-term potentiation was induced by a series of high-frequency trains, and long-term depression was induced by prolonged low-frequency stimulation at 1 Hz. The induction of long-term potentiation was inhibited by both 1-(2-trifluoromethylphenyl)imidazole and 3-bromo-7-nitro-indazole at concentrations which did not alter the amplitude of the test excitatory postsynaptic potential. The inhibitory effect of 1-(2-trifluoromethylphenyl)imidazole on the induction of long-term potentiation was prevented by pretreatment with L-arginine, the substrate amino acid used by nitric oxide synthase for nitric oxide production. The induction of long-term depression was inhibited by both 3-bromo-7-nitro-indazole and 1-(2-trifluoromethylphenyl)imidazole at concentrations which did not affect the test excitatory postsynaptic potential. The inhibitory effect of 1-(2-trifluoromethylphenyl)imidazole was prevented by pretreatment with L-arginine. The present experiments provide strong support for the involvement of the neuronal isoform of nitric oxide synthase in the induction of long-term potentation and long-term depression.
Wu
J
J
Department of Physiology, Trinity College, Dublin, Ireland.
Wang
Y
Y
Rowan
M J
MJ
Anwyl
R
R
D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
C106731:3-bromo-7-nitroindazole; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007191:Indazoles; D007527:Isoenzymes; C098186:1-(2-trifluoromethylphenyl)imidazole; D019001:Nitric Oxide Synthase