Simultaneous in vivo determination of acetylcholinesterase activity and acetylcholine release in the cortex of waking rat by microdialysis. Effects of VX.
We have designed a microdialysis technique to measure acetylcholinesterase (AChE) activity in the cortex of freely moving rats while simultaneously measuring the release of acetylcholine (ACh). Our approach was validated using ethyl S-2-di-isopropylaminoethyl-phosphonothiolate (VX), an irreversible inhibitor of AChE and comparing inhibition measured by this 'in vivo' method with traditional post-mortem assays of AChE activity 120 min after an intraventricular injection of VX. Maximum inhibition of AChE occurred 30 min after injection and was followed by a slow recovery. ACh release reached its maximum 60 min after treatment and then decreased towards normal levels. This method offers a new way to develop medications against poisoning with anticholinesterasic neurotoxic and allows the evaluation of the effects of cholinergic drugs for the treatment of Alzheimer's disease.
Testylier
G
G
Centre de Recherches du Service de Santé des Armées, La Tronche, France.
Micoud
N
N
Martinez
S
S
Lallement
G
G
D000109:Acetylcholine / Q000032:analysis / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D002404:Catheterization; D002540:Cerebral Cortex / Q000737:chemistry* / Q000187:drug effects* / Q000201:enzymology; D002800:Cholinesterase Inhibitors; D004569:Electroencephalography; D004789:Enzyme Activation / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D008839:Microelectrodes; D009388:Neostigmine / Q000494:pharmacology; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
D000109:Acetylcholine; D000110:Acetylcholinesterase; D002800:Cholinesterase Inhibitors; D009388:Neostigmine; D009946:Organothiophosphorus Compounds; C009680:VX-agent