We investigated the effects of
FR121196 N-(4-acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide on the performance of rats in the Morris water maze using a two-trial-per-day regimen. Escape latency to find the platform was significantly prolonged in young rats subjected to
scopolamine (1 mg/kg) treatment or to nucleus basalis magnocellularis (NBM) or fimbria-fornix (FF) lesioning compared with the respective control animals. Similar
memory deficit was observed in aged rats (24-26 months old) compared with young rats. Daily treatment with
FR121196 (0.1-1.0 mg/kg i.p.) ameliorated all the
memory deficits except in the FF-lesioned rats, whereas
physostigmine (0.032-0.32 mg/kg) ameliorated the
memory deficits in
scopolamine-treated rats but not in the NBM-lesioned, FF-lesioned or aged rats.
Methamphetamine (0.32-3.2 mg/kg) hardly ameliorated the
memory deficits and, rather, aggravated those in the
scopolamine-treated, NBM-lesioned and aged rats. Neurochemical analysis of the brain showed that
dopamine,
norepinephrine and
serotonin levels were significantly reduced in the hippocampus of the FF-lesioned rats compared with the
sham control, and a significant reduction of
dopamine level in the cortex was also observed in the aged rats compared with young rats. None of these parameters were changed after NBM lesioning. We concluded that
FR121196 ameliorates the
memory deficits of rats with
cholinergic dysfunction through the action on the hippocampal monoaminergic (possibly serotonergic) neurons.