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 chroni cally with either the acetylcholinesterase (AChE) inhibitor ENA713, or the M1 muscarinic agonist AF150(S). Both treatments reversed the spat ial working memory impairment of apoE-deficient mice but they differed in their effects on the levels of brain AChE activity. AF150(S) enhan ced the brain AChE activity of apoE-deficient mice and rendered it sim ilar to that of the untreated controls, whereas ENA713 reduced the bra in AChE activity of control mice but had no effect on that of apoE-def icient mice. These Findings suggest that AChE inhibition and M1 muscar inic activation have similar beneficial cognitive effects on apoE-defi cient mice, but that the cellular end molecular mechanisms underlying these effects differ. ((C)Elsevier, Paris).