Effects of clausenamide on anisodine-induced acetylcholine decrease and memory deficits in the mouse brain

Objectives. To study the action mechanism of a new cognition enhancer clausenamide and the effect of clausenamide on regional acetylcholine (ACh) levels, and to examine anisodine-induced ACh decrease in mice of memory deficits, and to compare the effect of (-) clausenamide on ACh with that of (+) clausenamide. Methods. Animal amnesia model was induced by i.p. anisodine and brain ACh content was measured by high performance liquid chromatography with electrochemical detection. Results. Single administration of (-) clausenamide or (+) clausenamide (10, 20, 50 mg/kg, i.g.) had no effect on the ACh level in the frontal cortex, hippocampus and striatum. However, pretreatment with (-) clausenamide (10, 20, 50 mg/kg, i.g.) significantly ameliorated the reduction of ACh induced by anisodine (10 mg/kg, i.p.) in a dose-dependent manner. Physostigmine (0.2 mg/kg, s.c.), as a cholinesterase inhibitor significantly increased the ACh levels and reversed the anisodine- induced ACh decrease. In contrast, (+)clausenamide had no effect on ACh decrease in all examined brain regions. (-) Clausenamide ameliorated anisodine-induced memory deficits in step-through test in mice. Conclusion. There is significant difference in the action of (-) clausenamide and (+) clausenamide. The protective action of (-) clausenamide against anisodine- induced amnesia is due to its ability to reverse the ACh reduction.