Eptastigmine restores the aged rat's normal cortical spectral power pattern.
We studied the ability of eptastigmine, a second-generation acetylcholinesterase inhibitor (AChEI), to reverse the age-related increase of electroencephalogram (EEG) mean cortical spectral power in slow-wave delta activity and decrease in fast-wave alpha and beta activity. The relative basal spectral power profile evaluated for 50 min of the old (27-30 months) in comparison to young (4-6 months) awake rats was consistently different, showing a significant increase in delta(0.2-4.0 Hz) frequency and a significant decrease of alpha(8.2-13.0 Hz) and beta(13.2-25.0) bands. When 0.5, 1, 2, 4 mg kg(-1)of eptastigmine were administered orally as single increasing doses for old and young rats 2 h prior to the EEG recordings, lasting 2 h, the relative mean spectral power difference (Delta%) showed a linear log dose-related decrease in delta activity and a progressive increase in alpha and beta activity in old rats. Compared to vehicle, in young rats, the eptastigmine dose of 0.5 mg kg(-1)produced a significant decrease in delta activity and an increase in beta activity. The spontaneous motor activity, evaluated through cumulative horizontal and vertical counts for 30 min in old rats was significantly decreased when compared to young rats. Single oral treatment with eptastigmine (0.5 mg kg(-1)for young and 2 mg kg(-1)for old rats) given 2 h before the test did not significantly change motor activity in comparison to vehicle group of the same age. These results suggest a possible strategy to alleviate the severe slowing of neocortical EEG accompanying the cognitive decline.
Braida
D
D
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Via Vanvitelli 32, Milano, 20129, Italy.
Ottonello
F
F
Sala
M
M
D000284:Administration, Oral; D000375:Aging / Q000502:physiology; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; 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