TY - JOUR
T1 - A long-acting cholinesterase inhibitor reverses spatial memory deficits in mice
AU - Sweeney, Joanne E.
AU - Höhmann, Christine F.
AU - Moran, Timothy H.
AU - Coyle, Joseph T.
N1 - Funding Information:
We gratefully acknowledge Dr. David S. Olton for valuable advice, Drs. Gianluigi Forloni, Masaomi Miyamoto, Robert G. Struble and Lary C. Walker for critically reviewing the manuscript, Mr. John Bowersox and Ms. Chris Kwiterovich for excellent technical support, and Ms. Alice Trawinski for excellent secretarial and editorial assistance. This research was supported by PHS grants NS-18414 (J.T.C.), NS-13584 (J.T.C.), and HD-19920 (J.T.C. and T.H.M.), by NIEHS doctoral training grant T32ES07141 (J.E.S.), and by the Mc Knight Foundation (J.T.C.). Galanthamine was a gift of B. Davis, M.D.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1988/9
Y1 - 1988/9
N2 - 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.
AB - 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.
KW - Acetylcholinesterase
KW - Animal models for Alzheimer's disease
KW - Galanthamine
KW - Mice
KW - Nucleus basalis lesions
KW - Spatial memory
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U2 - 10.1016/0091-3057(88)90325-5
DO - 10.1016/0091-3057(88)90325-5
M3 - Article
C2 - 3252244
AN - SCOPUS:0024162715
SN - 0091-3057
VL - 31
SP - 141
EP - 147
JO - Pharmacology, Biochemistry and Behavior
JF - Pharmacology, Biochemistry and Behavior
IS - 1
ER -