Elsevier

Neuropharmacology

Volume 32, Issue 3, March 1993, Pages 291-296
Neuropharmacology

Cholinesterase inhibitor effects on extracellular acetylcholine in rat striatum

https://doi.org/10.1016/0028-3908(93)90114-IGet rights and content

Abstract

The effects of inhibition of cholinesterase on levels of extracellular acetylcholine in the striatum of freely moving rats, were investigated with a microdialysis technique. Acetylcholine could not be detected under basal conditions. However, local administration of the cholinesterase inhibitors neostigmine, physostigmine or heptyl-physostigmine through the dialysis probe elevated acetylcholine above the detection limit. Complex interactions between the effects of local and systemic cholinesterase inhibitors were observed. Whereas systemic administration of physostigmine or heptylphysostigmine alone increased the extracellular concentration of acetylcholine, they also caused acetylcholine to fall below baseline levels, which had been established by perfusing physostigmine through the microdialysis probe. These studies demonstrate the ability of local inhibition of cholinesterase to affect the observation of effects of systemically-administered drugs.

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    Secondly, we used doses that have been proven to inhibit PREP by 60–80% for 5 h. Most importantly, Toide and co-workers used an extremely high concentration (10 μM) of the AChE inhibitor physostigmine in the perfusate in order to obtain detectable quantities of ACh. Physostigmine is known to elevate brain ACh efflux especially at higher concentrations (Messamore et al., 1993), and this manipulation could well account for the differences between the present report and that of Toide et al. (1995a). In recent years, many improvements in the sensitivity of HPLC/MS assays for ACh have been introduced, thus permitting a reduction of the perfusate concentrations of the AChE inhibitors from the micromolar to the present nanomolar range.

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