α‐Sialyl cholesterol reverses AF64A‐induced deficit in passive avoidance response and depletion of hippocampal acetylcholine in mice

1 The effect of α‐sialyl cholesterol (α‐SC; α‐ d ‐N‐acethylneuraminyl cholesterol) on disturbances of the central cholinergic system induced by ethylcholine mustard aziridinium ion (AF64A) and by scopolamine were studied by means of a step‐down passive avoidance response and locomotor activities in mice. The levels of acetylcholine (ACh) in certain regions of the brain were measured to assess the neurochemical recovery promoted by α‐SC. 2 Treatment with AF64A (2.5, 5 and 10 nmol, i.c.v.) impaired the 24 h retention latencies of animals in a dose‐dependent manner, and scopolamine (0.5 mg kg −1 , i.p.) also impaired the retention performance. Administration of α‐SC (1 and 4 mg kg −1 , p.o.) once daily for 13 days improved the retention performance in AF64A‐treated animals in a dose‐dependent manner, but not in the scopolamine‐treated animals. 3 Treatment with AF64A (2.5, 5 and 10 nmol, i.c.v.) and scopolamine (0.5 mg kg −1 , i.p.) increased vertical and horizontal locomotor activities. α‐SC dose‐dependently attenuated the increase in locomotor activies induced by 2.5 nmol of AF64A, but not the locomotor activities caused by 5 or 10 nmol of AF64A, or scopolamine (0.5 mg kg −1 , i.p.). 4 The deficit retention performance of AF64A‐treated animals was associated with depletion of ACh levels in the hippocampus, but not in the septum or cerebral cortex. Administration of α‐SC to AF64A‐treated animals dose‐dependently reversed the depletion of ACh levels in the hippocampus. 5 The results indicate that α‐SC had significant effects after oral administration of AF64A‐treated animals. The behavioural recovery promoted by α‐SC may be based on the reversal of ACh depletion in the hippocampus.