Cholinesterase inhibitor effects on extracellular acetylcholine in rat striatum

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.