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 potent iation and long-term depression of field excitatory postsynaptic poten tials in the dentate gyrus of the hippocampal slice has been investiga ted, 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 potentiatio n was induced by a series of high-frequency trains, and long-term depr ession was induced by prolonged low-frequency stimulation at 1 Hz. The induction of long-term potentiation was inhibited by both 1-(2-triflu oromethylphenyl)imidazole and 3-bromo-7-nitro-indazole at concentratio ns which did not alter the amplitude of the test excitatory postsynapt ic potential. The inhibitory effect of 1-(2-trifluoromethylphenyl)imid azole on the induction of long-term potentiation was prevented by pret reatment with L-arginine, the substrate amino acid used by nitric oxid e synthase for nitric oxide production. The induction of long-term dep ression was inhibited by both 3-bromo-7-nitro-indazole and 1-(2-triflu oromethylphenyl)imidazole at concentrations which did not affect the t est excitatory postsynaptic potential. The inhibitory effect of 1-(2-t rifluoromethylphenyl)imidazole was prevented by pretreatment with L-ar ginine. The present experiments provide strong support for the involve ment of the neuronal isoform of nitric oxide synthase in the induction of long-term potentation and long-term depression. (C) 1997 IBRO. Pub lished by Elsevier Science Ltd.