The Preliminary Study On The Neurotoxicity And Behavioral Effects Of MDMA

Part â…  A Study on the Acute Behavioral Effects of the Neurotoxicity of MDMAObjective To investigate the neurotoxicity of MDMA,by single injectioni.p of different doses of MDMA. Acute behavioral effect were recorded, the GFAP protein and morphology of neuron terminal were studied.Methods Male wistar rats were randomly assigned to control group(A)and MDMA group(B, D,E).Rats of MDMA group were single injected i.p with different doses (3, 5, 10,20mg/kg) of MDMA, rats of control group were injected i.p with the same volume of saline instead. Open field test, elevated plus-maze test, social interaction test were performed at once and morris water-maze test was performed 7 days after MDMA.1 week after observation of behavioral test, the protein expression of GFAP was detected by immunohistochemistry, the degeneration of terminal was demonstrated by Bielschowsky and Glee Marsland silver staining.Results 1.After single administration different doses of MDMA, amarked increase in total locomotion , a significantly reduced in rearing and a significantly increase in serotonin syndrome behaviors were observed in open field test, compared with saline group(P<0.05).2. After single administration different doses of MDMA, the anxiety-related behaviours were not observed in open field test, elevated plus-maze test, social interaction test, compared with saline group (P>0. 05)3. 7 days after single administration different doses of MDMA, Morris water-maze test was performed,there was no signiffcant statistical differences in escape latencies and the times of crossing the exact position of the former platform between the studied groups and the control group(P> 0. 05).4. 2 weeks after single administration different doses of MDMA, the expression of GFAP in rat brain was increased and neuron terminals in cortex was significant reduced in 5 , 10, 20mg/kg MDMA groups, compared with control group (P<0. 05).conclusion 1.MDMA produce behavioral toxicity, results inhyperlocomotion , decreasing of explorative behavior , increasing of serotonin syndrome behaviors, the lowest dose of MDMA is 3mg/kg.2.The neurotoxicity of MDMA results in the changing of tisse structure,the lowest dose of MDMA is 5mg/kg.3.The acute neurotoxicity of MDMA is not affect on spatial learning and memory function and anxiety-related behaviors of rats.part IIA Study on the Chronic Behavioral Effects of the Neurotoxicity of MDMAObjectives To investigate the1 neurotoxicity of MDMA, byrepeatedly administrating MDMA in short time, and observing behavioral effects through multiple behavioral devices at different time, and detecting the expression of related gene and protein , changing of morphology .Methods Male wistar rats were randomly assigned to controlgroup (A) and MDMA group (B). Rats of MDMA group were administrated MDMA lOmg/kg once per hour total 40mg/kg ; rats of control group were treated with the same volume of saline. Open field test, elevated plus-maze test, social interaction test and morris water maze test were performed at 2th, 8th, 26th, 32th week after MDMA, respectively.The expression of SERTmRNA and DBImRNA were detected by in situ hybridization ; the protein expression of GFAP was detected by immunohistochemistry , and the degeneration of neuron terminal was demonstrated by Bielschowsky and Glee Marsland silver staining, after abservation of behavioral test . Results 1. Anxiety-related behaviors were not increased inopen field tes^ elevated plus-maze test,, social interaction test at 2th> 8th week after repeatedly administrating MDMA (p>0. 05), but they were significantly increased at 26th > 32th week , respectively ( p<0. 05), compared with control group.2. There was no signiffcant statistical differences in escape latencies and the times of crossing the exact position of the former platform between the studied groups and the control group(P>0. 05) in morris water maze test at 2t1k 8tlK26tlu32th week after repeatedly administrating MDMA, compared with control group.3. The expression of SERTmRNA in hippocampus was decreased, while expression of DBImRNA in neocortex was increased, compared with control group (p<0.05) .4.The expression of GFAP in the brain tissue was increased (p< 0.05), while neuron terminal in neocortex was significantly reduced demonstrated by silver staining, compared with control group.Conclusion l.The long-term effect of neurotoxicity of MDMA exhibitsan anxiogenic-like activity, while no effect on spatial learning and memory function.2. The mechanism of the anxiogenic effect of MDMA is related to the increasing of the expression of the DBI, at the same time it also may be related to the decreasing of the SERT.3. The neurotoxicity of MDMA results in sustainedly the changing of CNS structure , further results in the disorder of the brain function.(Part III) A Study on the Neurotoxicity and Protection ofVitCofMDMAObjectives To explore the neurotoxicity and its mechanism of MDMA and the protection with antioxidant VitC, by establishing long-term neurotoxic model with single injection of MDMA, measuring the change of the concentration of AT? and the functional markers of 5-HT, and detecting the expression of related protein of brain tissue.Methods Male wistar rats were randomly assigned to control group(A)and MDMA group(B> C\ D> E). Rats of group B were administrated MDMA 20mg/kg ; group C% D> E were treated with VitC 250mg/kg 30min before MDMA> 3h and 5h after MDMA , respectively, rats of control group were treated with the same volume of saline.Concentrations of ATP in brain cortex and of 5-HT in hippocampus and occipital cortex were mearsured by high performance liquid chromatography; the expression of SERTmRNA was detected by in situ hybridization; and the protein expression of GFAP was studied by immunohistochemistryResults (1) 12 hours after MDMA, the concentration of ATP in braincortex was depleted, compared with control group(p<0.05).(2) On the 7th day post-treatment of MDMA, the concentration of 5-HT in rat hippocampus and occipital cortex was decreased, compared with control group(p<0.05).(3)The expression of SERTmRNA in hippocampus wasdecreased, while expression of GFAP in brain tissue was increased (p<0.05). (4) The adminstration of VitC 30min before and 3h after MDMA could not attenuate the decrease of ATP, 5-HT and the expression of SERTmRNA, while 5h after MDMA protect the decrease of ATP and functional marker of 5-HT. As to the expression of GFAP , VitC treated at three time point downregulate GFAP expression.Conclusion (1) MDMA could deplete the direct energic substnce: ATP.(2) MDMA could cause neurotoxicity to 5-HT system. (3) VitC treated 5h after MDMA could have protection to ATP and 5-HT system.