Eptastigmine improves eight-arm radial maze performance in aged rats.
Eptastigmine, a potent and long-lasting cholinesterase inhibitor on age-related memory deficits, was studied. Four groups of 3-, 18-, 23- and 27-month-old Wistar rats were first submitted to spontaneous motor activity evaluation and then trained in an eight-arm radial maze until they reached the criterion. The effect of introducing a 2-h delay between the fourth and fifth choices was then evaluated under the influence of acute oral dose of eptastigmine (0.5 mgkg(-1)) 120 min before the test. Eptastigmine reversed the impairment observed in vehicle-treated rats at all the tested ages. Two naive groups of 3- and 18-month-old rats were treated twice a day for 30 days with eptastigmine ( 0.25 mgkg(-1)p.o.) or vehicle and trained daily in the maze. Subchronic administration did not affect the performance in young rats, while in 18-month-old rats, the mean number of days needed to reach the criterion decreased and the percentage of animals reaching the criterion increased when compared to the vehicle group. The 18-month-old rats (ex-eptastigmine and ex-vehicle) were then allowed to age in their home cage without any further treatment for an additional 5 and 9 months, until they reached 23 and 27 months. The ex-eptastigmine rats tested at 23 months, without any treatment, showed better performance than that observed in ex-vehicle rats. When the same rats were tested again at 27 months of age, no difference was seen in comparison with ex-vehicle rats. Eptastigmine might, therefore, be helpful for correcting age-related memory impairment attributed to cholinergic hypofunction.
Braida
D
D
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Via Vanvitelli 32, Milan, 20129, Italy.
Ottonello
F
F
Sala
M
M
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002800:Cholinesterase Inhibitors; C052450:physostigmine heptyl; D010830:Physostigmine