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BACKGROUND: Many researches have indicated that the imbalances of various amino acid transmitters and neurotransmitters in brain are involved in the formation of alcohol withdrawal, especially that glutamic acid is one of the important transmitters for alcohol tolerance in central nervous system.OBJECTIVE: To observe the changes of excitatory amino acids in hippocampal dentate gyrus in rats with long-term alcohol drinking after withdrawal under consciousness, and investigate the therapeutic effect of topiramate on alcohol withdrawal.DESIGN: A randomized control animal experiment.SETTING: Department of Neurology, Affiliated Hospital of Yanbian University.MATERIALS: Thirty male Wistar rats of 4 months old, weighing 300-350 g, were purchased from the Experimental Animal Department, Medical College of Yanbian University. Topiramate was produced by Swish Cilag Company, and the batch number was 02CS063.METHODS: The experiments were carried out in the Department of Physiology, Medical College of Yanbian University from August 2005 to February 2006. ① The rats were divided randomly into three groups: control group (n=10), alcohol group (n=10) and topiramate-treated group (n=10). Rats in the alcohol group and topiramate-treated group were given intragastric perfusion of 500 g/L alcohol (10 mL/kg), once a day for 4 weeks successively, and then those in the topiramate-treated group were treated with 80 mg/kg topiramate at 24 hours after the last perfusion of alcohol, once a day for 3 days successively. Rats in the control group were intragastricly given isovolume saline. ② The withdrawal symptoms were assessed at 6, 30, 48 and 72 hours after the last perfusion of alcohol by using the withdrawal rating scale set by Erden et al,which had four observational indexes of stereotyped behaviors, agitation, tail stiffness and abnormal posture,each index was scored by 5 points, the higher the score, the more obvious the symptoms. ③ The contents of aspartic acid and glutamic acid in hippocampal dentate gyrus were detected with microdialysis technique and high-performance liquid chromatograpy (HPLC) respectively at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the three groups.MAIN OUTCOME MEASURES: ① Scoring results of alcohol withdrawal symptoms; ② Changes of the contents of aspartic acid and glutamic acid in hippocampal dentate gyrus at the alcohol withdrawal symptoms, and the effects of topiramate.RESULTS: Seven rats were excluded due to inaccurate localization and natural death, and 23 rats were involved in the analysis of results. ① In the alcohol group, the scores of alcohol withdrawal symptoms at 30 and 48 hours after the last perfusion of alcohol were obviously higher than those in the control group (10.50±0.96, 14.17±1.25; 3.50±0.92, 3.16±0.31; P＜ 0.01). In the topiramate-treated group, the scores at 30 hours after the last perfusion of alcohol (6.06±0.82, 3.50±0.92, P ＜ 0.05), and the withdrawal scores at 48 and 72 hours were close to those in the control group (4.57±0.58, 3.30±0.71; 3.16±0.31, 3.66±0.67; P＞ 0.05). ② Changes of the contents of glutamic acid in hippocampal dentate gyrus: In the alcohol group,the content of glutamic acid at 48 hours after the last perfusion of alcohol was significantly increased as compared with that at 6 hours [(143.32±11.42)%, (99.12±0.69)%; P ＜ 0.05], and that at 72 hours was close to that at 6 hours [(78.50±16.40)%, (99.12±0.69)%; P ＞ 0.05]. The contents of glutamic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [(100.30±0.37)%, (118.91±10.40)%, (99.55±12.81)%, (99.08±11.42)%; P ＞ 0.05]. The content of glutamic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group (P ＜ 0.05), and those at 30 and 72 hours were close (P ＞ 0.05). ③ Changes of the contents of aspartic acid in hippocampal dentate gyrus: In the alcohol group, the contents of aspartic acid at 30 and 48 hours after the last perfusion of alcohol were significantly increased as compared with that at 6 hours [(126.60±8.67)%, (129.17±10.40)%, (99.25±0.87)%; P ＜ 0.05], and that at 72 hours was close to that at 6 hours [(89.87±9.93)%, (99.25±0.87)%; P ＞ 0.05]. The contents of aspartic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [(100.27±0.32)%, (120.81±12.63)%, (98.91±7.83)%, (85.92±8.07)%; P ＞ 0.05]. The content of aspartic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group (P ＜ 0.05), and those at 30 and 72 hours were close (P ＞ 0.05).CONCLUSION: ① The occurrences of alcohol withdrawal symptoms are correlated with the increased contents of excitatory amino acids in hippocampal dentate gyrus in rats. ② Topiramate can alleviate the alcohol withdrawal symptoms, which may be correlated with the decreased contents of excitatory amino acids in hippocampal dentate gyrus in rats.