A preliminary study on the mechanism of neurotoxicity
of MDMA - oxidative stress harm
Li SX, Sun AM, Wang X, Li J, Peng ZG, Kuang WH, Huang MS.
Center of Psychology Health, West China Hospital,
Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 Mar;37(2):191-5.
ABSTRACTOBJECTIVE: Establishing a long-term neurotoxic model to explore the mechanism of neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) and the putative protection conferred by Vit C against oxidative stress harm. METHODS: Male Wistar rats were randomly assigned to control group (A) and MDMA treatment groups(B, C, D, E). Rats of group B were given MDMA 20 mg/kg; groups C, D, E were given Vit C 250 mg/kg 30 min before administration of MDMA (Vit C 30 min group) and 3 h (Vit C 3 h group) and 5 h (VitC 5 h group) after administration of MDMA, respectively. Rats of control group were treated with the same volume of saline. Concentrations of ATP and ADP in brain cortex and 5-HT in hippocampus and occipital cortex were measured by high perfor-mance liquid chromatography; the expression of SERT mRNA was detected by in situ hybridization; and the expression of protein GFAP was detected by immunohisto-chemistry. RESULTS: hours after MDMA treatment, the concentration of ATP in brain cortex was lessened, compared with control (P <0.05). On the 7th day after MDMA treatment, the concentration of 5-HT in rat hippocampus and occipital cortex was decreased, compared with control (P<0.05). The expression of SERT mRNA in hippocampus was decreased, whereas the expression of GFAP in brain tissue was increased (P<0.05). The adminstration of Vit C 30 min before MDMA treatment and 3 h after MDMA treatment did not curb the decrease of ATP, 5-HT and the expression of SERT mRNA, but Vit C administrated 5 h after MDMA treatment could curb the decrease of ATP and the functional markers of 5-HT. And Vit C given at three time points did downregulate the GFAP expression. CONCLUSION: MDMA could deplete the direct energetic substance ATP. MDMA could exert neurotoxic effect on 5-HT system. Vit C given 5 h after MDMA administration could provide neuroprotection for ATP and 5-HT system.Club drugs
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