Bejar_1999_Eur.J.Pharmacol_383_231

The effect of rivastigmine on memory impairments induced in rats by scopolamine (0.5 mg/kg) was assessed in the Morris water maze and passive avoidance tests and compared with that of tacrine (2.5-17.7 mg/kg). Rivastigmine, (0.5-2.5 mg/kg) inhibited cholinesterase in the cortex and hippocampus by 21-60% and antagonised the deficits in working and reference memory. Tacrine (12.5 and 17.7 mg/kg) produced significantly less inhibition of cholinesterase in the hippocampus but more in the striatum than rivastigmine (0.75 and 1.5 mg/kg) and only antagonised the deficit in reference memory. Rivastigmine (1.5 and 2.5 mg/kg) or tacrine (12.5 mg/kg), injected immediately after completion of the acquisition trial in the passive avoidance test, antagonised the deficit induced by scopolamine (1 mg/kg) in memory retention. The inability of higher doses of the cholinesterase inhibitors to antagonise memory deficits induced by scopolamine may be related to excessive cholinergic stimulation in the central nervous system.