Effect of FR121196, a novel cognitive enhancer, on the memory impairment of rats in passive avoidance and radial arm maze tasks

Passive avoidance performance was impaired in young rats by scopolamine (1.0 mg/kg) or by nucleus basalis magnocellularis lesions and in aged rats (24-26 months old). FR121196[N-(4-acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide+ ++], a newly introduced cognitive enhancer, ameliorated the failure in memory retention with bell-shaped dose-response curves in doses ranging from 0.1 to 10 mg/kg. Similar dose-response curves also were obtained with methamphetamine (0.1-10 mg/kg), whereas physostigmine (0.01-1.0 mg/kg) attenuated the amnesia in scopolamine-treated rats, but hardly affected that in nucleus basalis magnocellularis-lesioned or aged rats. In radial arm maze tasks, behavioral indices of spatial memory, such as first correct choices and number of errors, were impaired by an injection of scopolamine (0.5 mg/kg) or by lesions of the medial septum or fimbria-fornix. FR121196 ameliorated the scopolamine-induced memory deficit with a bell-shaped dose-response curve, whereas methamphetamine had the opposite effect. These two drugs had little effect on memory deficits brought about by medial septum or fimbria-fornix lesioning, whereas physostigmine ameliorated these deficits in scopolamine-treated and medial septum-lesioned rats, but not in fimbria-fornix-lesioned rats. Behavioral studies using Animex demonstrated that FR121196, in contrast with methamphetamine, does not increase locomotor activities in rats up to a dose of 10 mg/kg. These results are discussed in relation to the cholinergic and dopaminergic mechanisms of memory.