A long-acting cholinesterase inhibitor reverses spatial memory deficits in mice.
The effects of the long-acting acetylcholinesterase (AChE) inhibitor, galanthamine, on spatial memory were investigated in mice. Mice received ibotenic acid or sham lesions to the nucleus basalis magnocellularis (nBM). Groups of nBM-lesioned and control mice were then trained on a modified Morris swim maze task. Each mouse was first placed on a platform and then into quadrants of the swim tank in a random order. Time required to find the hidden platform was measured. In different phases of testing, the animal had to find a platform that either remained in the same quadrant (reference memory component) or was moved daily (working memory component). The nBM-lesioned mice took significantly longer to find the platform as compared to controls on the working, but not on the reference, memory component of the task. Galanthamine (5.0 mg/kg, IP), given 3.5 hours before testing, improved performance on the working memory task in nBM-lesioned mice by 70% and strikingly impaired performance in controls. Galanthamine's ability to reverse cognitive deficits induced by nBM lesions and its comparatively long half-life suggest that it may be effective in treating the central cholinergic deficits in Alzheimer's disease patients.
Sweeney
J E
JE
Department of Environmental Health Sciences, Johns Hopkins University School of Public Health, Baltimore, MD 21205.
Höhmann
C F
CF
Moran
T H
TH
Coyle
J T
JT
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000032:analysis; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005702:Galantamine / Q000494:pharmacology*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C
D002800:Cholinesterase Inhibitors; D005702:Galantamine; D002795:Choline O-Acetyltransferase