Beta-amyloid induced reduction in synaptic transmission is reversed by inhibitors of nitric oxide synthase.

beta-Amyloid has been shown to be neurotoxic in vivo and in vitro. Free radical production and subsequent lipid oxidation after beta-amyloid application have been observed in vitro and are considered to be factors that contribute to the neurotoxicity. Field recordings in the area CA1 for 3 weeks showed a dose-dependent effect on amplitude after intracerebroventricular (i.c.v.) injections of 1, 5 or 10 nmol beta-amyloid (25-35). The nitric oxide synthase inhibitors 7-nitro indazole (30 mg/kg, i.p.) and 1-(2-trifluoromethylphenyl)imidazole (150 nmol, i.c.v.) which preferentially inhibit the neuronal isoform prevented this beta-amyloid-induced decay of synaptic transmission. The protective effect of these inhibitors was reversed by L-arginine (200 mg/kg, i.p.). The results support the theory that nitric oxide production contributes to beta-amyloid-induced neuronal degeneration or reduction of neurotransmission.