CHOLINESTERASE INHIBITOR EFFECTS ON EXTRACELLULAR ACETYLCHOLINE IN RAT CORTEX

A microdialysis technique was used to sample acetylcholine (ACh) from the cerebral cortex of conscious rats. We thus investigated the effect s of systemically administered cholinesterase inhibitors (ChEI) such a s physostigmine (300 mug/kg), heptylphysostigmine (5 mg/kg) and tetrah ydroaminoacridine (tacrine, 5 mg/kg) on extracellular ACh levels. Base line quantities of extracellular ACh could be detected, even in the ab sence of ChEI. Acetylcholine levels increased to 1100% over baseline w ithin 30 min of physostigmine administration and returned to control l evels after 1.25 hr. Heptylphysostigmine elicited a maximal increase o f 1000% within 1.5 hr, and the effect persisted up to 9.5 hr. A 500% i ncrease was observed 1.5 hr after tacrine administration, and ACh retu rned to control levels after 4 hr. Although the ACh effects observed i n this study correlated with previously determined levels of acetylcho linesterase (AChE) inhibition, we conclude that measures of cortical A ChE activity alone are not sufficient to predict extracellular ACh lev els following systemic ChEI administration.