Effects of metrifonate on radial arm maze acquisition in middle-aged rats

The efficacy of metrifonate, a well-tolerated cholinesterase (ChE) inhibitor, in attenuating the normal aging- and corticosterone-induced impairments of radial maze performance of rats was compared. Middle-aged Fischer 344 rats were screened for their spatial orientation performance in the Morris water escape task. Good and bad performers were selected: good performers (N = 22) were treated with subcutaneous sustained-release corticosterone pellets, resulting in hippocampal cell damage and impaired spatial orientation in the radial maze; age-induced bad performers (N = 20) were tested without additional pharmacological intervention. Metrifonate (MFT), administered daily during radial maze testing, 30 min before training, at a dose of 15 mg/kg p.o., facilitated the acquisition of the task in age-impaired rats, but not in corticosterone-impaired rats. (C) 1997 Elsevier Science B.V.