EFFECTS OF EXTRACELLULAR ACETYLCHOLINE ON MUSCARINIC RECEPTOR-BINDINGASSESSED BY [I-125] DEXETIMIDE AND A SIMPLE PROBE

New pharmacologic approaches to enhance brain cholinergic function foc us on increasing intrasynaptic acetylcholine. We examined the usefulne ss of a simple probe and [I-125]dexetimide to evaluate in vivo the eff ects of extracellular acetylcholine on muscarinic receptor binding in the mouse brain. After radiotracer injection continuous time/activity curves were generated over 330 min. [I-125]Dexetimide reached a platea u at 90 min post-injection. To increase extracellular acetylcholine, t he anticholinesterase physostigmine was administered at 120 min, produ cing a reversible decrease in [I-125]dexetimide specific binding (23%) for 30 min. These findings demonstrate that dynamic changes in extrac ellular acetylcholine can be evaluated by displacement of [I-125]dexet imide binding in vivo using a simple probe system. (C) 1998 Elsevier S cience B.V. All rights reserved.