Testylier_1998_J.Neurosci.Methods_81_53

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.