Objective To explore the effects of dehydroepiandrosterone (DHEA) on learning and memory ability and activities of choline acetyltransferase (ChAT),acetylcholinesterase (AchE),acetylcholine (Ach) in the frontal,temporal,hippocampal area of the aged rat.Methods Forty 24-month-old male SD rats were randomly divided into 4 groups (n=10,each group):control group,solvent group (intraperitoneal injection with equal volumes of DMSO),low-dose group (intraperitoneal injection with equal volumes of DHEA,1 mg/kg),and high-dose group (intraperitoneal injection with equal volumes of DHEA,5 mg/kg).The activities of ChAT,AchE,and Ach were measured by enzyme linked immunosorbent assay (ELISA) method.Learning and memory ability was detected by Morris water maze test.Results The levels of ChAT in frontal,temporal and hippocampal area were (118.5±1.3) U/mg,(120.6±1.5) U/mg,(130.8±1.5) U/mg,respectively in control group,(i39.5±1.6) U/mg,(137.4±1.4) U/mg,(141.46±1.9) U/mg,respectively in high-dose group,(131.8±1.9) U/mg,(132.4±1.2) U/mg,(139.9±1.3) U/mg,respectively in low-dose group.The levels of AchE in frontal,temporal and hippocampal area were (0.5±0.0) U/mg,(0.4±0.0) U/mg,(0.5±0.0) U/mg,respectively in control group,(0.4±0.0) U/mg,(0.4±0.0) U/mg,(0.4±0.0) U/mg,respectively in high-dose group,and (0.4±0.0) U/mg,(0.4±0.0) U/mg,(0.4±0.0) U/mg,respectively in low-dose group,and (0.5±0.0)U/mg.The Ach levels in frontal,temporal and hippocampal area were (26.0±0.8) U/mg,(24.5±1.4) U/mg,(30.1±0.8) U/mg respectively in control group,(28.7±0.9) U/mg,(28.9±1.3) U/mg,(35.9±1.4) U/mg,respectively in high-dose group,and (27.6±0.1) U/mg,(28.0±1.1) U/mg,(34.2± 1.0) U/mg,rcspectively in low dose group.The activities of ChAT in frontal,temporal and hippocampal area were higher in DHEA treatment group than in control group (P＜0.05).The activities of AchE in frontal,temporal and hippocampal area were much lower in DHEA treatment group than in control group (P＜ 0.05).The Ach levels in frontal,temporal and hippocampal area were much higher in DHEA treatment group than in control group (P＜0.05).There were significant differences in the activities of ChAT and AchE and Ach levels between low-dose group and high-dose group (P＜0.05).Compared with control group,the activities of ChAT and AchE and Ach levels had no significant differences in solvent group (P＞0.05).The escape latency was shorter in low-dose group and high-dose group than in control group (P＜0.05,P＜0.01,respectively),and there was a significant difference in escape latency between low-dose group and high dose group (P＜ 0.05).Conclusions DHEA administration can significantly increase the activity of cholinergic system,and improve the learning and memory ability in aged SD rats.