The effects of the acetylcholinesterase inhibitor ENA713 and the M1 agonist AF150(S) on apolipoprotein E deficient mice.
Apolipoprotein E (apoE)-deficient and control mice were treated chronically with either the acetylcholinesterase (AChE) inhibitor ENA713, or the M1 muscarinic agonist AF150(S). Both treatments reversed the spatial working memory impairment of apoE-deficient mice but they differed in their effects on the levels of brain AChE activity. AF150(S) enhanced the brain AChE activity of apoE-deficient mice and rendered it similar to that of the untreated controls, whereas ENA713 reduced the brain AChE activity of control mice but had no effect on that of apoE-deficient mice. These findings suggest that AChE inhibition and M1 muscarinic activation have similar beneficial cognitive effects on apoE-deficient mice, but that the cellular and molecular mechanisms underlying these effects differ.
Chapman
S
S
Department of Neurobiochemistry, Tel-Aviv University, Israel.
Fisher
A
A
Weinstock
M
M
Brandies
R
R
Shohami
E
E
Michaelson
D M
DM
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D002219:Carbamates / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D006651:Histocytochemistry; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018721:Muscarinic Agonists / Q000494:pharmacology*; D048448:Phenylcarbamates; D010880:Piperidines / Q000494:pharmacology*; D000068836:Rivastigmine; D013844:Thiazoles / Q000494:pharmacology*
C111926:1-methylpiperidine-4-spiro-(2'-methylthiazoline); D001057:Apolipoproteins E; D002219:Carbamates; D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D048448:Phenylcarbamates; D010880:Piperidines; D013844:Thiazoles; D000068836:Rivastigmine