Effects of extracellular acetylcholine on muscarinic receptor binding assessed by [125I]dexetimide and a simple probe.
New pharmacologic approaches to enhance brain cholinergic function focus on increasing intrasynaptic acetylcholine. We examined the usefulness of a simple probe and [125I]dexetimide to evaluate in vivo the effects of extracellular acetylcholine on muscarinic receptor binding in the mouse brain. After radiotracer injection continuous time/activity curves were generated over 330 min. [125I]Dexetimide reached a plateau at 90 min post-injection. To increase extracellular acetylcholine, the anticholinesterase physostigmine was administered at 120 min, producing a reversible decrease in [125I]dexetimide specific binding (23%) for 30 min. These findings demonstrate that dynamic changes in extracellular acetylcholine can be evaluated by displacement of [125I]dexetimide binding in vivo using a simple probe system.
Sánchez-Roa
P M
PM
Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD 21205-2179, USA.
Wagner
H N
HN
Villemagne
V L
VL
London
E D
ED
Lever
J R
JR
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003909:Dexetimide / Q000378:metabolism* / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D015902:Gamma Cameras; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000378:metabolism* / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011877:Radionuclide Imaging; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D007457:Iodine Radioisotopes; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; C018580:levetimide; D003909:Dexetimide; D010830:Physostigmine; D000109:Acetylcholine