Effect of neostigmine on concentration and extraction fraction of acetylcholine using quantitative microdialysis

Abstract

A quantitative microdialysis method was used to determine the effect of local perfusion of 0, 100, 200, and 300 nM neostigmine (NEO) on acetylcholine (ACh) extracellular concentration and microdialysis extraction fraction ( E d) in the striatum of the rat. Because of the efficiency of AChE, the inhibition of this enzyme is expected to result in a substantial increase in ACh levels and a decrease in the E d of ACh. The extracellular concentration of ACh increased linearly with increasing concentrations of NEO. The control ACh concentration was determined to be 18.4±11.8 nM ( n=10; mean±S.E.M.) The ACh extracellular concentration for the remaining groups was determined to be 173±14 nM ( n=5), 329±52.5 nM ( n=13), and 581±109 nM ( n=10) for the 100, 200, and 300 nM NEO groups, respectively. Perfusion with 300 nM NEO resulted in a significant reduction in the E d of ACh (64.5±3.5% vs. 43.6±7.5%, P<0.05). In contrast to ACh, perfusion with 0, 1, and 10 μM hemicholinium-3, an inhibitor of high-affinity choline uptake, increased choline levels but did not affect the E d of choline. The effects on E d are consistent with E d being influenced by rapid clearance mechanisms.