BACKGROUND： 3, 4-methylenedioxymethamphetamine （MDMA, also known as ＂ecstasy＂） has been shown to exhibit neurotoxic effects on the hippocampus. However, exposure to sub-lethal insults of MDMA has been reported to...BACKGROUND： 3, 4-methylenedioxymethamphetamine （MDMA, also known as ＂ecstasy＂） has been shown to exhibit neurotoxic effects on the hippocampus. However, exposure to sub-lethal insults of MDMA has been reported to result in neuroprotection. OBJECTIVE： To investigate the effects of MDMA on hippocampal neuronal viability, caspase-3 activity, and mRNA expression of the N-methyI-D-aspartate （NMDA） receptor 2B （NR2B） subunit. DESIGN, TIME AND SETTING： A cytological, in vitro experiment was performed at the Department of Anatomy, School of Medicine, and Department of Toxicology-Pharmacology, Faculty of Pharmacy Tehran University of Medical Sciences in 2008. MATERIALS： MDMA was extracted from ecstasy tablets, which were kindly supplied by the Pharmacology-Toxicology Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran. METHODS： Hippocampal neurons were isolated from Wistar rats at gestational day 18. Following primary culture, hippocampal neuronal viability was detected by MTT assay. Varying concentrations of MDMA （100-5 000 μmol/L） were used to determine lethal concentration 50 （LC50）, which was around 1 500 μmol/L. Five concentrations of MDMA below 1 500 μmol/L （100, 200, 400, 800, and 1 050 μmol/L） were used for the remaining experiments. After 24 hours of MDMA treatment, NR2B mRNA expression was detected by RT-PCR, and caspase-3 relative activity was determined by colorimetric assay. MAIN OUTCOME MEASURES： Hippocampal neuronal viability, caspase-3 activity, and NR2B mRNA expression. RESULTS： MDMA-induced neurotoxicity in hippocampal neuronal cultures was dose-dependent. In high concentrations （1 000-5 000μmol/L） of MDMA, neuronal viability was decreased. However, with a 500 μmol/L dose of MDMA, neuronal viability was significantly increased （P 〈 0.01）. Low concentrations of MDMA （200 and 400μmol/L） significantly decreased caspase-3 activity （P 〈 0.01）, whereas high concentrations of MDMA significantly increased caspase-3 activity （P 〈 0.01）. NR2B subunit mRNA expression was not significantly altered after 100 -1 050 μmol/L MDMA exposure. CONCLUSION： MDMA exhibits dual effects on hippocampal neuronal viability and caspase-3 activity. These effects are independent from NR2B subunit expression levels.展开更多
Objective To investigate whether 3,4-methylenedioxymethamphetamine (MDMA) abuse produces another neurotoxicity which may significantly inhibit the acetylcholinesterase activity and result in severe oxidative damage an...Objective To investigate whether 3,4-methylenedioxymethamphetamine (MDMA) abuse produces another neurotoxicity which may significantly inhibit the acetylcholinesterase activity and result in severe oxidative damage and liperoxidative damage to MDMA abusers. Methods 120 MDMA abusers (MA) and 120 healthy volunteers (HV) were enrolled in an independent sample control design, in which the levels of lipoperoxide (LPO) in plasma and erythrocytes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and acetylcholinesterase (AChE) in erythrocytes were determined by spectrophotometric methods. Results Compared with the average values of biochemical parameters in the HV group, those of LPO in plasma and erythrocytes in the MA group were significantly increased (P<0.0001), while those of SOD, CAT, GPX and AChE in erythrocytes in the MA group were significantly decreased (P<0.0001). The Pearson product-moment correlation analysis between the values of AChE and biochemical parameters in 120 MDMA abusers showed that significant linear negative correlation was present between the activity of AChE and the levels of LPO in plasma and erythrocytes (P<0.0005-0.0001), while significant linear positive correlation was observed between the activity of AchE and the activities of SOD, CAT and GPX (P<0.0001). The reliability analysis for the above biochemical parameters reflecting oxidative and lipoperoxidative damages in MDMA abusers suggested that the reliability coefficient (alpha) was 0.8124, and that the standardized item alpha was 0.9453. Conclusion The findings in the present study suggest that MDMA abuse can induce another neurotoxicity that significantly inhibits acetylcholinesterase activity and aggravates a series of free radical chain reactions and oxidative stress in the bodies of MDMA abusers, thereby resulting in severe neural, oxidative and lipoperoxidative damages in MDMA abusers.展开更多
BACKGROUND： The long-term neurotoxicity of 3,4-methylenedioxymethamphetamine （MDMA） mainly caused by repeated exposure to MDMA or a single big dose of MDMA, which results in degeneration of serotonin terminal of ce...BACKGROUND： The long-term neurotoxicity of 3,4-methylenedioxymethamphetamine （MDMA） mainly caused by repeated exposure to MDMA or a single big dose of MDMA, which results in degeneration of serotonin terminal of central nervous system, and someone believe that the great release of serotonin transmitter in central nervous system will lead to anxious mood. OBJECTIVE： To observe the changes of anxiety related behaviors in rats after single administration of different doses of MDMA. DESIGN： A randomized control study SETTING： Laboratory of Psychopharmacology of the Mental Health Center, West China Hospital of Sichuan University. MATERIALS： Thirty male adult Wistar rats, weighing （251.3＋18.34） g, were used, MDMA were obtained from the National Institute for the Control of Pharmaceutical and Biological Products, and dissolved in saline. All the doses of the drug were administered in a volume of 1 mg/kg. METHODS ： The experiment was carried out in the Laboratory of Psychopharmacology of the Mental Health Center, West China Hospital of Sichuan University in July 2003. ①The rats were randomly divided into control group （n=6） and experimental group （n=24）, and then those in the latter were randomly assigned into four subgroups of MDMA 3, 5, 10 and 20 mg/kg groups, with 6 rats in each, which were administrated by single intraperitoneal injection of MDMA 3, 5, 10 and 20 mg/kg respectively, and those in the control group were administrated by single intraperitoneal injection of saline of the same volume. ② The open field test, elevated plus-maze test and social interaction test were performed immediately after administration. For the open field test, the apparatus was situated in a darkened room, illuminated by a single 60 W white light bulb located approximately 60 cm above the center of the open field. Before administration, all the rats were placed into the open field to be familiar with the open field for 5 minutes. They were observed for 45 minutes after administration. The locomotion （number of squares the rat passes）, rearing response, time spent in central squares and defecation were observed, 1 minute for each time for a total of 9 times. For the elevated plus-maze test, the maze was situated in a quiet darkened room, illuminated by a single 60 W white light bulb located approximately 50 cm above the center of the maze. Arm entries were only counted when all the four paws had entered either a closed or an open arm within 5 minutes, and the time spent in the arms were observed. For the social interaction test, the matched rats were put into the arena head-to-head in opposite direction, and aggressive-type behaviors, avoidance, passive and exploration were observed. ③ The one-way analysis of variance was performed with the SPSS 10.0 software. MAIN OUTCOME MEASURES： The results of open field test, elevated plus-maze test and social interaction test were observed. RESULTS： All the 30 rats were involved in the analysis of results. ① Results of open field test： After single administration of MDMA of 5, 10 and 20 mg/kg, the dose-dependent Iocomotors （number of squares the rat passes） in the experimental groups were obviously higher than those in the control group [（21.67±17,55）, （34.44±19.47）, （33.48±23.34）, （7.31 ±6,02） s; P 〈 0.05], and the rearing responses were markedly lower than those in the control group [（0.70±1.71）, （0.96±1.68）, （0.39±0.88）, （1.37±1.59） s, P 〈 0.05]. ② Results of the elevated plus-maze test： After acute administration of MDMA, there were no differences between the MDMA subgroups and saline group in the number of open-arms entries, the open-arms time, the percent of number of open arm entries/total arm entries, and the percent of time spent on the open arms/total time （P 〉 0.05）.③ Results of the social international test： After acute administration of MDMA, there were no differences between the MDMA subgroups and saline group in the aggressive-type behaviors, avoidance, passive, exploration and total time of interaction （P 〉 0.05） CONCLUSION： The acute administration of MDMA has no obvious influence on the anxiety-related behaviors of rats.展开更多
3, 4-methylenedioxymethamphetamine （MDMA; also known as ＇ecstasy＇） has been shown to impair learning and spatial memory in adult and neonatal rats. Many studies have focused on the acute effects of MDMA on memory....3, 4-methylenedioxymethamphetamine （MDMA; also known as ＇ecstasy＇） has been shown to impair learning and spatial memory in adult and neonatal rats. Many studies have focused on the acute effects of MDMA on memory. In the present study, we intraperitoneally administered MDMA （0, 5, 10, 20 mg/kg） to adult male rats to investigate the effects of different doses on rat spatial memory in the Morris water maze, body temperature, and mortality, twice a day, for 7 successive days. The results indicated that MDMA impaired spatial memory dose-dependently, with the highest dose （20 mg/kg） exerting the strongest effects. In addition, MDMA also caused hyperthermia and increased mortality in rats展开更多
[目的]3-(3′,4′-次甲二氧苯基)-N-正丙基丙烯酰胺是具有广谱抑菌活性的化合物,将其研制成优良环保剂型悬浮剂,可为实现田间应用提供技术依据。[方法]采用湿法研磨制备了12种不同配方的悬浮剂,通过质量指标检测确定最佳配方,测定其表...[目的]3-(3′,4′-次甲二氧苯基)-N-正丙基丙烯酰胺是具有广谱抑菌活性的化合物,将其研制成优良环保剂型悬浮剂,可为实现田间应用提供技术依据。[方法]采用湿法研磨制备了12种不同配方的悬浮剂,通过质量指标检测确定最佳配方,测定其表面张力及其在黄瓜叶面的动态接触角,并开展了防治黄瓜白粉病田间药效试验。[结果]最佳配方为3-(3′,4′-次甲二氧苯基)-N-正丙基丙烯酰胺40%(折百)、S043%、D4252%、W071%、乙二醇3%、硅酸镁铝0.4%、黄原胶0.12%、B150.12%、消泡剂X600.3%、水补足。此悬浮剂在有效成分0.27 g a.i./L时的表面张力以及在黄瓜叶面的动态接触角均小于对照药剂40%苯醚甲环唑SC,表明其具有良好的润湿性能。在有效成分0.27 g a.i./L下的防效为88.38%,与对照药剂25%嘧菌酯SC 0.20 g a.i./L相当,且对黄瓜安全。[结论]制备悬浮剂为类白色均匀悬浮液,流动性好,粒径合格,悬浮率稳定在98.5%左右,pH为4.09,黏度为452 mPa·s,入水分散性合格,热储、低温及冻融稳定性良好,未出现沉淀,各项指标均达标,对黄瓜白粉病防效优良,具有良好的开发应用前景。展开更多
基金Supported by: the Deputy of Research in Tehran University of Medical Sciences
文摘BACKGROUND： 3, 4-methylenedioxymethamphetamine （MDMA, also known as ＂ecstasy＂） has been shown to exhibit neurotoxic effects on the hippocampus. However, exposure to sub-lethal insults of MDMA has been reported to result in neuroprotection. OBJECTIVE： To investigate the effects of MDMA on hippocampal neuronal viability, caspase-3 activity, and mRNA expression of the N-methyI-D-aspartate （NMDA） receptor 2B （NR2B） subunit. DESIGN, TIME AND SETTING： A cytological, in vitro experiment was performed at the Department of Anatomy, School of Medicine, and Department of Toxicology-Pharmacology, Faculty of Pharmacy Tehran University of Medical Sciences in 2008. MATERIALS： MDMA was extracted from ecstasy tablets, which were kindly supplied by the Pharmacology-Toxicology Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran. METHODS： Hippocampal neurons were isolated from Wistar rats at gestational day 18. Following primary culture, hippocampal neuronal viability was detected by MTT assay. Varying concentrations of MDMA （100-5 000 μmol/L） were used to determine lethal concentration 50 （LC50）, which was around 1 500 μmol/L. Five concentrations of MDMA below 1 500 μmol/L （100, 200, 400, 800, and 1 050 μmol/L） were used for the remaining experiments. After 24 hours of MDMA treatment, NR2B mRNA expression was detected by RT-PCR, and caspase-3 relative activity was determined by colorimetric assay. MAIN OUTCOME MEASURES： Hippocampal neuronal viability, caspase-3 activity, and NR2B mRNA expression. RESULTS： MDMA-induced neurotoxicity in hippocampal neuronal cultures was dose-dependent. In high concentrations （1 000-5 000μmol/L） of MDMA, neuronal viability was decreased. However, with a 500 μmol/L dose of MDMA, neuronal viability was significantly increased （P 〈 0.01）. Low concentrations of MDMA （200 and 400μmol/L） significantly decreased caspase-3 activity （P 〈 0.01）, whereas high concentrations of MDMA significantly increased caspase-3 activity （P 〈 0.01）. NR2B subunit mRNA expression was not significantly altered after 100 -1 050 μmol/L MDMA exposure. CONCLUSION： MDMA exhibits dual effects on hippocampal neuronal viability and caspase-3 activity. These effects are independent from NR2B subunit expression levels.
文摘Objective To investigate whether 3,4-methylenedioxymethamphetamine (MDMA) abuse produces another neurotoxicity which may significantly inhibit the acetylcholinesterase activity and result in severe oxidative damage and liperoxidative damage to MDMA abusers. Methods 120 MDMA abusers (MA) and 120 healthy volunteers (HV) were enrolled in an independent sample control design, in which the levels of lipoperoxide (LPO) in plasma and erythrocytes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and acetylcholinesterase (AChE) in erythrocytes were determined by spectrophotometric methods. Results Compared with the average values of biochemical parameters in the HV group, those of LPO in plasma and erythrocytes in the MA group were significantly increased (P<0.0001), while those of SOD, CAT, GPX and AChE in erythrocytes in the MA group were significantly decreased (P<0.0001). The Pearson product-moment correlation analysis between the values of AChE and biochemical parameters in 120 MDMA abusers showed that significant linear negative correlation was present between the activity of AChE and the levels of LPO in plasma and erythrocytes (P<0.0005-0.0001), while significant linear positive correlation was observed between the activity of AchE and the activities of SOD, CAT and GPX (P<0.0001). The reliability analysis for the above biochemical parameters reflecting oxidative and lipoperoxidative damages in MDMA abusers suggested that the reliability coefficient (alpha) was 0.8124, and that the standardized item alpha was 0.9453. Conclusion The findings in the present study suggest that MDMA abuse can induce another neurotoxicity that significantly inhibits acetylcholinesterase activity and aggravates a series of free radical chain reactions and oxidative stress in the bodies of MDMA abusers, thereby resulting in severe neural, oxidative and lipoperoxidative damages in MDMA abusers.
文摘BACKGROUND： The long-term neurotoxicity of 3,4-methylenedioxymethamphetamine （MDMA） mainly caused by repeated exposure to MDMA or a single big dose of MDMA, which results in degeneration of serotonin terminal of central nervous system, and someone believe that the great release of serotonin transmitter in central nervous system will lead to anxious mood. OBJECTIVE： To observe the changes of anxiety related behaviors in rats after single administration of different doses of MDMA. DESIGN： A randomized control study SETTING： Laboratory of Psychopharmacology of the Mental Health Center, West China Hospital of Sichuan University. MATERIALS： Thirty male adult Wistar rats, weighing （251.3＋18.34） g, were used, MDMA were obtained from the National Institute for the Control of Pharmaceutical and Biological Products, and dissolved in saline. All the doses of the drug were administered in a volume of 1 mg/kg. METHODS ： The experiment was carried out in the Laboratory of Psychopharmacology of the Mental Health Center, West China Hospital of Sichuan University in July 2003. ①The rats were randomly divided into control group （n=6） and experimental group （n=24）, and then those in the latter were randomly assigned into four subgroups of MDMA 3, 5, 10 and 20 mg/kg groups, with 6 rats in each, which were administrated by single intraperitoneal injection of MDMA 3, 5, 10 and 20 mg/kg respectively, and those in the control group were administrated by single intraperitoneal injection of saline of the same volume. ② The open field test, elevated plus-maze test and social interaction test were performed immediately after administration. For the open field test, the apparatus was situated in a darkened room, illuminated by a single 60 W white light bulb located approximately 60 cm above the center of the open field. Before administration, all the rats were placed into the open field to be familiar with the open field for 5 minutes. They were observed for 45 minutes after administration. The locomotion （number of squares the rat passes）, rearing response, time spent in central squares and defecation were observed, 1 minute for each time for a total of 9 times. For the elevated plus-maze test, the maze was situated in a quiet darkened room, illuminated by a single 60 W white light bulb located approximately 50 cm above the center of the maze. Arm entries were only counted when all the four paws had entered either a closed or an open arm within 5 minutes, and the time spent in the arms were observed. For the social interaction test, the matched rats were put into the arena head-to-head in opposite direction, and aggressive-type behaviors, avoidance, passive and exploration were observed. ③ The one-way analysis of variance was performed with the SPSS 10.0 software. MAIN OUTCOME MEASURES： The results of open field test, elevated plus-maze test and social interaction test were observed. RESULTS： All the 30 rats were involved in the analysis of results. ① Results of open field test： After single administration of MDMA of 5, 10 and 20 mg/kg, the dose-dependent Iocomotors （number of squares the rat passes） in the experimental groups were obviously higher than those in the control group [（21.67±17,55）, （34.44±19.47）, （33.48±23.34）, （7.31 ±6,02） s; P 〈 0.05], and the rearing responses were markedly lower than those in the control group [（0.70±1.71）, （0.96±1.68）, （0.39±0.88）, （1.37±1.59） s, P 〈 0.05]. ② Results of the elevated plus-maze test： After acute administration of MDMA, there were no differences between the MDMA subgroups and saline group in the number of open-arms entries, the open-arms time, the percent of number of open arm entries/total arm entries, and the percent of time spent on the open arms/total time （P 〉 0.05）.③ Results of the social international test： After acute administration of MDMA, there were no differences between the MDMA subgroups and saline group in the aggressive-type behaviors, avoidance, passive, exploration and total time of interaction （P 〉 0.05） CONCLUSION： The acute administration of MDMA has no obvious influence on the anxiety-related behaviors of rats.
基金a grant from the Substance Abuse and Dependence Research Center University of Social Welfare and Rehabilitation Sciences, No. 313-126417Tehran University of Medical Sciences, No. P/664
文摘3, 4-methylenedioxymethamphetamine （MDMA; also known as ＇ecstasy＇） has been shown to impair learning and spatial memory in adult and neonatal rats. Many studies have focused on the acute effects of MDMA on memory. In the present study, we intraperitoneally administered MDMA （0, 5, 10, 20 mg/kg） to adult male rats to investigate the effects of different doses on rat spatial memory in the Morris water maze, body temperature, and mortality, twice a day, for 7 successive days. The results indicated that MDMA impaired spatial memory dose-dependently, with the highest dose （20 mg/kg） exerting the strongest effects. In addition, MDMA also caused hyperthermia and increased mortality in rats
文摘[目的]3-(3′,4′-次甲二氧苯基)-N-正丙基丙烯酰胺是具有广谱抑菌活性的化合物,将其研制成优良环保剂型悬浮剂,可为实现田间应用提供技术依据。[方法]采用湿法研磨制备了12种不同配方的悬浮剂,通过质量指标检测确定最佳配方,测定其表面张力及其在黄瓜叶面的动态接触角,并开展了防治黄瓜白粉病田间药效试验。[结果]最佳配方为3-(3′,4′-次甲二氧苯基)-N-正丙基丙烯酰胺40%(折百)、S043%、D4252%、W071%、乙二醇3%、硅酸镁铝0.4%、黄原胶0.12%、B150.12%、消泡剂X600.3%、水补足。此悬浮剂在有效成分0.27 g a.i./L时的表面张力以及在黄瓜叶面的动态接触角均小于对照药剂40%苯醚甲环唑SC,表明其具有良好的润湿性能。在有效成分0.27 g a.i./L下的防效为88.38%,与对照药剂25%嘧菌酯SC 0.20 g a.i./L相当,且对黄瓜安全。[结论]制备悬浮剂为类白色均匀悬浮液,流动性好,粒径合格,悬浮率稳定在98.5%左右,pH为4.09,黏度为452 mPa·s,入水分散性合格,热储、低温及冻融稳定性良好,未出现沉淀,各项指标均达标,对黄瓜白粉病防效优良,具有良好的开发应用前景。
