Involvement of serotonergic neuronal systems in the anti-amnesic action of naftidrofuryl oxalate

The effects of naftidrofuryl oxalate on cycloheximide- and 5-hydroxytryptophan (5-HTP)-induced amnesia were investigated using a passive avoidance task in mice. Naftidrofuryl oxalate significantly improved the cycloheximide-induced amnesia. This effect of naftidrofuryl oxalate was antagonized by 5-HTP, a serotonin (5-HT) precursor, and by p-chloroamphetamine (PCA), a 5-HT releaser. Single administration of 5-HTP in combination with pargyline, a monoamine oxidase inhibitor, induced amnesia (5-HTP-induced amnesia). This amnesia was attenuated by ritanserin, a 5-HT₂-selective antagonist, but not by pindolol a 5-HT₁-selective antagonist. Naftidrofuryl oxalate also attenuated the 5-HTP-induced amnesia. A binding study reveaied that naftidrofuryl oxalate inhibited the binding of [³H]ketanserin to 5-HT₂ receptors in mouse brain synaptic membrane in a dose-dependent fashion (IC₅₀ = 1.42 × 10^-7 M), but did not inhibit that of [³H]serotonin to 5-HT₁ receptors. These resu suggest that naftidrofuryl oxalate may attenuate cycloheximide- and 5-HTP-induced amnesia by blocking 5-HT₂ receptor subtypes.