EFFECT OF OXOTREMORINE, PHYSOSTIGMINE, AND SCOPOLAMINE ON BRAIN ACETYLCHOLINE SYNTHESIS - A STUDY USING HPLC

The synthesis rate of brain acetylcholine (ACh) was estimated in mice following i.v. administration of [H-3]choline (Ch). The measurements were performed 1 min after the tracer injection, using the [H-3]ACh/[H-3]Ch specific radioactivity ratio as an index of ACh synthesis rate. Endogenous and labeled Ch and ACh were quantified using HPLC methodology. Oxotremorine and physostigmine (0.5 mg/kg, i.p.) increased the steady state concentration of brain ACh by + 130% and 84%, respectively and of Ch by + 60% (oxotremorine); they decreased ACh synthesis by 62 and 55%, respectively. By contrast, scopolamine (0.7 mg/kg, i.p.) decreased the cerebral content of Ch by - 26% and of ACh by - 23% without enhancing the synthesis of ACh. The results show the utility of HPLC methodology in the investigation of ACh turnover.