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.