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.
Centre de Recherches du Service de Santé des Armées, La Tronche, France.
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G
Testylier
N
N
Micoud
S
S
Martinez
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G
Lallement
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