N-乙酰半胱氨酸减轻火鼠纹状体甲基苯丙胺神经毒性

目的探讨N-乙酰半胱氨酸（NAC）对甲基苯丙胺（METH）中毒大鼠模型纹状体神经毒性的影响及作用机制。方法制备大鼠中毒模型,在METH前30min腹腔注射（ip）NAC,应用二氯荧光乙酰乙酸盐作为荧光指标检测纹状体ROS的含量,高效液相色谱方法检测DA浓度,TUNEL方法观察神经元损害情况,并计算神经元的凋亡率。结果NAC预处理能降低纹状体内ROS的含量,减轻DA浓度的下降程度,减少神经细胞的凋亡。结论NAC通过抑制METH诱导纹状体的氧化应激,减轻METH多巴胺能神经毒性。     

N-乙酰半胱氨酸对甲基苯丙胺中毒大鼠行为改变的影响

目的:探讨N-乙酰半胱氨酸(NAC)对甲基苯丙胺(METH)引起中毒大鼠模型行为改变的保护性作用机制。方法:制备大鼠中毒模型,在METH注射前30min腹腔注射NAC,应用二氯荧光乙酰乙酸盐(DCFH)作为荧光指标检测大鼠纹状体ROS的含量,以紫外分光光度计检测NOS的活性,以Sams-Dodd的方法给大鼠刻板行为评分,并计算不同组大鼠评分之间的差异。结果:NAC预处理能降低纹状体内ROS的含量(P<0.001)及NOS的活性(P<0.001),减轻METH中毒大鼠精神行为改变,降低了中毒大鼠的刻板行为评分(P<0.001)。结论:NAC可能通过逆转METH诱导大鼠纹状体区的氧化失衡状态,减轻氧化应激诱导的精神行为异常改变,产生保护性作用。     

甲基苯丙胺所致的大鼠神经毒性损伤及nNOS抑制剂的保护作用

目的探讨神经元型一氧化氮合酶(nNOS)在甲基苯丙胺(METH)所致大鼠中枢神经系统氧化应激损伤中的作用机制。方法建立METH中毒动物模型,并给予nNOS抑制剂7硝基吲唑(7-NI)预处理,观察各组间动物行为学的变化,并检测nNOS表达、多巴胺(DA)含量、硝基化蛋白表达及凋亡等指标。结果 METH组大鼠纹状体中nNOS蛋白表达水平明显升高,而METH+7-NI组nNOS表达水平较METH组明显降低。METH组DA明显降低(P<0.01),而METH+7-NI组、7-NI组与对照组比较,DA无差异(P>0.05)。METH组硝基化蛋白含量明显升高(P<0.01),而METH+7-NI组硝基化蛋白表达较METH组明显降低(P<0.05)。METH组与对照组相比,凋亡细胞数明显升高(P<0.01),而7-NI对凋亡的增高表现出明显的保护作用(与METH组相比P<0.01)。METH组和METH+7-NI组的动物刻板行为评分均明显高于7-NI和对照组(P<0.01),METH、METH+7-NI组间差异无显著性(P>0.05)。结论METH可导致大鼠大脑纹状体nNOS蛋白表达水平增高、DA含量的降低、硝基化蛋白水平升高及细胞凋亡增多等多种神经毒性表现,7-NI能部分减轻其神经毒性作用。METH明显增加大鼠的不自主刻板运动,而应用7-NI预处理后,对刻板行为的改善并不明显。     

头孢曲松对甲基苯丙胺致大鼠行为及纹状体氨基酸等递质含量改变的影响

目的观察甲基苯丙胺(METH)急性处理时致神经损伤情况,以及纹状体中氨基酸类神经递质谷氨酸(glutamate,Glu)、单胺类神经递质多巴胺(dopamine,DA)及其代谢产物DOPAC的变化。方法建立METH急性毒性模型,同时利用药物头孢曲松进行干预,利用清醒动物脑微透析技术检测神经递质含量的变化。结果 METH急性给药组与盐水对照组相比,刻板行为明显增加(P<0.01);急性给予METH后,胞外Glu浓度持续增加,在本试验检测时间(0～6 h)范围内,与基础平衡值相比,在给药5.5 h时Glu浓度已增加450%。胞外DA水平在1 h达峰值,与基础平衡值相比,浓度增加1248.6%。与METH组相比,头孢曲松预防给药可明显降低大鼠纹状体胞外Glu浓度(P<0.05)。结论 METH急性处理能引起纹状体中胞外谷氨酸的含量明显增加,导致神经损伤;METH的神经毒性与兴奋性氨基酸的过度释放密切相关。     

DDAH/NOS途径参与甲基苯丙胺大鼠纹状体的神经毒性研究

目的 探讨二甲基精氨酸二甲基氨基水解酶(DDAH)/一氧化氮合酶(NOS)途径在甲基苯丙胺(METH)神经毒性中发挥的作用及其相关调控机制.方法 将20只♂ Wistar大鼠,随机分为NS对照组和METH组,分别ip生理盐水或METH 15mg·kg-1,bid,用药4 d.采用HE染色光镜观察大鼠脑组织的病理学改变,Western蛋白印迹法检测大鼠纹状体区的DDAH1蛋白表达水平,以紫外分光光度计检测NOS的活性.结果 METH组大鼠脑组织中出现神经元水肿和明显的噬神经细胞现象,与NS组相比,METH组大鼠纹状体区的DDAH 1蛋白表达水平显著性升高(P＜0.05),NOS的活性显著性升高(P＜0.01).结论 DDAH/NOS途径可能参与METH引起的大鼠纹状体区的神经损伤.     

雷公藤氯内酯醇对帕金森病大鼠多巴胺神经元的保护作用

目的探讨雷公藤氯内酯醇(T₄)对帕金森病(PD)大鼠多巴胺(DA)神经元的保护作用。方法采用线刀损毁大鼠内侧前脑束(MFB)制备部分损伤性PD模型,应用旋转行为测试行为学改变,HPLC-ECD检测纹状体DA含量,酪氨酸羟化酶(TH)免疫组化检测DA神经元的存活率,双抗夹心ELISA法检测损毁侧脑组织中细胞因子含量。结果T₄在较低剂量下(1 μg·kg^-1)能够改善安非他明(AMPH)诱发的PD大鼠异常旋转行为,其损伤侧纹状体DA含量和黑质致密部DA神经元存活率均比对照组增加,并能抑制脑内TNF-α和IL-2的异常升高。结论免疫抑制剂T₄对PD大鼠具有肯定的神经保护作用,其作用的发挥与T₄抵抗细胞因子在脑内过度升高而产生的毒性作用有关。     

NGF对烧伤大鼠血清引起纹状体神经元细胞毒性的影响

目的　观察NGF对烧伤大鼠血清引起神经毒性的影响 ,初步探讨NGF对烧伤后神经元损伤的保护作用及其机制。方法　测定烧伤大鼠纹状体组织NO和LDH含量 ;给予原代培养纹状体神经元不同浓度NGF 2 4h后 ,加入不同浓度烧伤大鼠血清 ,测定细胞存活率及培养液中NO含量。结果　大鼠烧伤后 ,纹状体组织NO和LDH含量明显升高 ,烧伤大鼠血清可引起培养的纹状体神经元存活率下降 ,培养液中NO含量升高。NGF能降低纹状体组织中NO和LDH的含量 ,提高培养的纹状体神经元的存活率 ,减少培养液中NO含量 ,其作用呈剂量依赖性 ,NGF对神经元存活率的影响与NO含量呈显著负相关。结论　NGF对烧伤大鼠血清引起的纹状体神经元损伤有保护作用 ,其作用机制可能是通过抑制NO的神经毒性。     

钙蛋白酶抑制剂Ⅲ MDL 28170对大鼠甲基汞急性神经毒性的拮抗作用

目的为寻找治疗甲基汞急性中毒作用药物新靶点,探讨钙蛋白酶抑制剂ⅢMDL28170对甲基汞急性神经毒性的拮抗作用。方法大鼠随机分为正常对照组、MDL28170(50mg.kg-1,ip)对照组、甲基汞(10mg.kg-1,ig)中毒模型组与MDL28170干预组(同时ig甲基汞和ip MDL28170)。Morris水迷宫检测大鼠学习记忆能力,免疫组织化学法观察脑μ-钙蛋白酶免疫阳性神经元,Western蛋白印迹法检测脑μ-钙蛋白酶表达,TUNEL法观察脑神经元凋亡,免疫荧光染色法观察脑皮质神经元微管相关蛋白2(MAP2)含量。结果大鼠ig给予甲基汞3或7d,中毒模型组出现神经系统损害行为学表现,水迷宫逃避潜伏期明显延长(P<0.01);脑皮质神经元内μ-钙蛋白酶的表达和活性明显升高(P<0.01);脑皮质神经元凋亡显著增加(P<0.01);神经元MAP2含量明显降低。同时给予MDL28170可明显减轻上述改变。结论μ-钙蛋白酶可能参与甲基汞中毒导致的神经细胞凋亡。MDL28170可明显抑制甲基汞的神经毒性损害,可能对甲基汞中毒具有治疗作用。     

N-乙酰半胱氨酸对活性氧诱导的大鼠心肌细胞凋亡的作用

目的探讨N-乙酰半胱氨酸(NAC)对活性氧(ROS)介导的大鼠H9c2心肌细胞凋亡的抑制作用。方法用过氧化氢(H2O2)诱导H9c2心肌细胞,建立氧化损伤凋亡模型,并用NAC进行干预。四甲基偶氮唑蓝(MTT)法检测细胞存活率,应用流式细胞仪分析H9c2心肌细胞内ROS水平及凋亡率。结果不同剂量H2O2(0、2、4mmol/L)作用于H9c2细胞8h后,随着H2O2剂量的增高,细胞存活率降低,ROS水平及凋亡率升高(P<0.01),5mmol/L NAC有效提高了细胞存活率,明显抑制细胞内ROS水平及凋亡的发生(P<0.01)。结论 NAC通过减少自由基的产生,拮抗了ROS介导的大鼠H9c2心肌细胞凋亡。     

甲基苯丙胺急性处理对大鼠纹状体中神经元和谷氨酸转运体的影响

目的:观察甲基苯丙胺(METH)急性处理致神经损伤情况,以及纹状体中谷氨酸转运体1(GLT1)与囊泡型谷氨酸转运体1(VGLUT1)的变化。方法:建立METH急性毒性模型,同时利用谷氨酸转运体激动剂头孢曲松调控谷氨酸转运体的表达,尼氏染色实验观测神经元中尼氏小体的变化,利用Western blot实验检测其谷氨酸转运体蛋白表达的变化。结果:与盐水对照组相比,METH给药组刻板行为明显增加(P<0.01),尼氏小体显著减少,纹状体中GLT1和VGLUT1的表达增加分别为23.1%和66.1%(P<0.05);与METH组相比,头孢曲松预防给药组大鼠刻板行为明显减少,纹状体中GLT1的表达增加15.2%(P<0.05),VGLUT1的表达降低,但没有统计学意义(P>0.05)。结论:METH急性处理能导致神经损伤,引起纹状体中谷氨酸转运体的表达变化;头孢曲松能激活谷氨酸转运体的表达,缓解METH引起的神经损伤。     

Impairment in consolidation of learned place preference following dopaminergic neurotoxicity in mice is ameliorated by N-acetylcysteine but not D1 and D2 dopamine receptor agonists.

Some of the major concerns related to methamphetamine (METH) abuse are the neuronal damage inflicted at dopamine (DA) nerve terminals and the cognitive deficits observed in human METH abusers. We have shown that a high dose of METH selectively depleted dopaminergic markers in striatum, frontal cortex and amygdala of Swiss Webster mice, and impaired learned place preference. In this study, we investigated whether deficits in consolidation of place learning, as a consequence of METH neurotoxicity, underlie the underperformance of cocaine conditioned place preference (CPP). Administration of METH (5 mg/kg x 3) to Swiss Webster mice decreased striatal tyrosine hydroxylase (TH) immunoreactive neurons and significantly increased glial fibrillary acidic protein (GFAP) expression, confirming the neurotoxic potential of METH in mice. This treatment significantly attenuated the establishment of cocaine (15 mg/kg) CPP compared to control. To investigate whether manipulation of the consolidation phase improves learned place preference, mice were trained by cocaine and received daily post-training injections of DA receptor agonists or N-acetylcysteine (NAC). As memory consolidation occurs shortly after training, drugs were administered either immediately or 2 h post-training. Immediate post-training administration of the D1 DA receptor agonist SKF38393 (5, 10, and 20 mg/kg) or the D2 DA receptor agonist quinpirole (0.25, 0.5, and 1.0 mg/kg) did not improve the establishment of CPP following METH neurotoxicity. However, immediate but not delayed NAC administration (50 and 100 mg/kg) enhanced cocaine CPP following METH neurotoxicity and had no effect on control CPP. The levels of the reduced form of glutathione (GSH) in striatum, amygdala, hippocampus and frontal cortex were significantly lower in METH-treated mice compared to control during the period of CPP training. Acute and repeated administration of NAC to METH-treated mice restored the decreased brain GSH but had no effect on controls. Results suggest that METH-induced dopaminergic neurotoxicity is associated with impairment of consolidation of learned place preference, and that this impairment is improved by immediate post-training administration of the glutathione precursor NAC and not by D1 or D2 DA receptor agonists. Restoration of brain glutathione levels immediately post-training may facilitate the consolidation process.     

A recent trend in methamphetamine-induced neurotoxicity]

The neurotoxic damage caused by methamphetamine (METH) is characterized by nerve terminal destruction and/or degeneration of the dopaminergic and serotonergic systems in striatum and hippocampus. It has been hypothesized that intraneural dopamine (DA) redistribution from synaptic vesicles to cytoplasmic compartments produced by METH is an important factor for its neurotoxicity. The METH-induced redistribution of DA is thought to occur after an increased production of DA-based reactive oxygen species (ROS) (e.g., oxygen radicals and hydroxyl radicals) by auto-oxidation or enzymatic degradation, and METH-induced ROS produces an oxidative stress and depletion of energy stores. Furthermore, the glutamatergic system and nitric oxide (NO) may also contribute to METH-induced neurotoxicity. Recently, studies using several knockout strains of mice lacking the DA transporter, the monoamine vesicle transporter-2, c-fos, or neuronal NO synthase confirm a possible role of these factors in METH-induced neurotoxicity. Moreover, it has been proposed that METH causes the apoptosis and activation of cell-death-related genes. For example, METH-induced neurotoxicity is reduced in bcl-2-over expressing neural cell and p53 knockout mice and also induces the activation of caspase 3. Therefore in this review, we discuss the relationship between ROS formation, oxidative stress, and apoptosis in METH-induced neurotoxicity.     

Differential effects of amphetamines-induced neurotoxicity on appetitive and aversive Pavlovian conditioning in mice.

The abuse of substituted amphetamines such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy) can result in neurotoxicity, manifested as the depletion of dopamine (DA) and 5-hydroxytriptamine (5-HT; serotonin) axon terminal markers in humans and animal models. Human METH and MDMA users exhibit impairments in memory and executive functions, which may be a direct consequence of the neurotoxic potential of amphetamines. The objective of this study was to investigate the influence of amphetamines-induced neurotoxicity on Pavlovian learning. Using mouse models of selective DA neurotoxicity (METH; 5 mg/kg x 3), selective 5-HT neurotoxicity (fenfluramine /FEN; 25 mg/kg x 4) and dual DA and 5-HT neurotoxicity (MDMA; 15 mg/kg x 4), appetitive and aversive conditioning were investigated. Dopaminergic neurotoxicity significantly impaired METH and cocaine conditioned place preference (CPP), but had no effect on LiCl-induced conditioned place aversion (CPA). In contrast, serotonergic neurotoxicity significantly enhanced CPP, and had no effect on CPA. Dual dopaminergic/serotonergic neurotoxicity had no apparent effect on CPP; however, CPA was significantly attenuated. Postmortem analysis revealed that significantly diminished levels of DA and 5-HT markers persisted in the striatum, frontal cortex, hippocampus, and amygdala. These findings suggest that amphetamines-induced dopaminergic and serotonergic neurotoxicity exert opposing influences on the affective state produced by subsequent drug reward, while dual dopaminergic/serotonergic neurotoxicity impairs associative learning of aversive conditioning. Furthermore, results revealed that amphetamines-induced DA and 5-HT neurotoxicity modulates appetitive Pavlovian conditioning similar to other DA and 5-HT neurotoxins. Modulation of Pavlovian conditioning by amphetamines-induced neurotoxicity may be relevant to compulsive drug-seeking behavior in METH and MDMA abusers.     

Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption

Methamphetamine (METH)-induced neurotoxicity is characterized by a long-lasting depletion of striatal dopamine (DA) and serotonin as well as damage to striatal dopaminergic and serotonergic nerve terminals. Several hypotheses regarding the mechanism underlying METH-induced neurotoxicity have been proposed. In particular, it is thought that endogenous DA in the striatum may play an important role in mediating METH-induced neuronal damage. This hypothesis is based on the observation of free radical formation and oxidative stress produced by auto-oxidation of DA consequent to its displacement from synaptic vesicles to cytoplasm. In addition, METH-induced neurotoxicity may be linked to the glutamate and nitric oxide systems within the striatum. Moreover, using knockout mice lacking the DA transporter, the vesicular monoamine transporter 2, c-fos, or nitric oxide synthetase, it was determined that these factors may be connected in some way to METH-induced neurotoxicity. Finally a role for apoptosis in METH-induced neurotoxicity has also been established including evidence of protection of bcl-2, expression of p53 protein, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), activity of caspase-3. The neuronal damage induced by METH may reflect neurological disorders such as autism and Parkinson's disease.     

Effects of alpha-phenyl-N-tert-butyl nitrone and N-acetylcysteine on hydroxyl radical formation and dopamine depletion in the rat striatum produced by d-amphetamine.

Previous studies have shown that treatment with free radical scavengers attenuated the D-amphetamine (AMPH) neurotoxicity. But several of these agents also prevent AMPH-induced elevation of body temperature in the rat. Thus, further studies are needed to determine if blockade of the production of free radical or hypothermia are related to the neuroprotective mechanism of the free radical scavengers for AMPH neurotoxicity. In the present study, we examined the effects of the free radical scavengers alpha-phenyl-N-tert-butyl nitrone (PBN) and N-acetylcysteine (NAC) on long-term depletion of striatal dopamine (DA) and lipid peroxidation formation and on hyperthermia induced by AMPH. We also determined their effects on acute hydroxyl radical formation after direct intrastriatal infusion of AMPH. The results showed that both significantly attenuated long-term DA depletion and lipid peroxidation formation in the rat striatum at the dose range that did not block hyperthermia induced by AMPH. These agents also completely inhibited the production of hydroxyl radical after AMPH infusion into the striatum. Our results suggest that free radical scavengers such as PBN and NAC could protect against AMPH-induced oxidative stress and DAergic terminal toxicity via their free radical removing property independent of lowering the core body temperature of rats, and imply that supplement with antioxidants is a potential strategy in the treatment of AMPH neurotoxicity.     

Protective effects of N-acetyl-L-cysteine on the reduction of dopamine transporters in the striatum of monkeys treated with methamphetamine.

Several lines of evidence suggest that oxidative stress might contribute to neurotoxicity in the dopaminergic nerve terminals after administration of methamphetamine (MAP). We undertook the present study to determine whether intravenous administration of N-acetyl-L-cysteine (NAC), a potent antioxidant drug, could attenuate the reduction of dopamine transporter (DAT) in the striatum of monkey brain after administration of MAP. Positron emission tomography studies demonstrated that repeated administration of MAP (2 mg/kg as a salt, four times at 2-h intervals) significantly decreased the accumulation of radioactivity in the striatum after intravenous administration of [11C]beta-CFT. In contrast, the binding of [11C]SCH 23390 to dopamine D1 receptors in the monkey striatum was not altered after the administration of MAP. A bolus injection of NAC (150 mg/kg, i.v.) 30 min before MAP administration and a subsequent continuous infusion of NAC (12 mg/kg/h, i.v.) over 8.5 h significantly attenuated the reduction of DAT in the monkey striatum 3 weeks after the administration of MAP. These results suggest that NAC could attenuate the reduction of DAT in the monkey striatum after repeated administration of MAP. Therefore, it is likely that NAC would be a suitable drug for treatment of neurotoxicity in dopaminergic nerve terminals related to chronic use of MAP in humans.     

Free radical production induced by methamphetamine in rat striatal synaptosomes

The pro-oxidative effect of methamphetamine (METH) in dopamine terminals was studied in rat striatal synaptosomes. Flow cytometry analysis showed increased production of reactive oxygen species (ROS) in METH-treated synaptosomes, without reduction in the density of dopamine transporters. In synaptosomes from dopamine (DA)-depleted animals, METH did not induce ROS production. Reserpine, in vitro, completely inhibited METH-induced ROS production. These results point to endogenous DA as the main source of ROS induced by METH. Antioxidants and inhibitors of neuronal nitric oxide synthase and protein kinase C (PKC) prevented the METH-induced oxidative effect. EGTA and the specific antagonist methyllycaconitine (MLA, 50 microM) prevented METH-induced ROS production, thus implicating calcium and alpha7 nicotinic receptors in such effect. Higher concentrations of MLA (>100 microM) showed nonspecific antioxidant effect. Preincubation of synaptosomes with METH (1 microM) for 30 min reduced [(3)H]DA uptake by 0%. The METH effect was attenuated by MLA and EGTA and potentiated by nicotine, indicating that activation of alpha(7) nicotinic receptors and Ca(2+) entry are necessary and take place before DAT inhibition. From these findings, it can be postulated that, in our model, METH induces DA release from synaptic vesicles to the cytosol. Simultaneously, METH activates alpha(7) nicotinic receptors, probably inducing depolarization and an increase in intrasynaptosomal Ca(2+). This would lead to DAT inhibition and NOS and PKC activation, initiating oxidation of cytosolic DA.     

New perspectives on the mechanism of methamphetamine-induced neurotoxicity

Various hypotheses have been proposed concerning the mechanisms responsible for methamphetamine (METH)-induced neurotoxicity including reactive oxygen species (ROS), dopamine quinones, glutamatergic activity, apoptosis, etc. Recently, new factors regarding glial cell line-derived neurotorophic factor, tumor necrosis factor-alpha, and alpha-synuclein contained in striatal interneural inclusions have also been associated with METH-induced neurotoxicity. In addition, METH-induced self-injurious behavior (SIB) has been proposed to be an acute or immediate behavioral marker predicting the long-lasting neurotoxicity induced by METH. Specifically, it has been proposed that the SIB response may accurately reflect the underlying mechanistic changes occurring in the neuron that eventually result in the long-lasting damage. Several studies have demonstrated that endogenous dopamine (DA) plays an important role in mediating METH-induced neuronal damage. DA release and redistribution from synaptic vesicles to cytoplasmic compartments is thought to involve METH-induced changes in both the vesicular monoamine transporter-2 and DA transporter function. In turn, the consequent elevation of cytosolic auto-oxidizable DA concentrations is thought generate ROS such as superoxide and hydroxyl radicals and cause the DA terminal injury. Finally, the inflammatory response of microglia and glutamatergic toxicity in astrocytes have been related to the METH-induced neurotoxicity. The objective of the present review will be to consolidate the new perspectives in an attempt to formulate a more cohesive explanation of the underlying mechanism responsible for METH-induced DA damage and its early biological markers.     

Baicalein attenuates methamphetamine-induced loss of dopamine transporter in mouse striatum

Methamphetamine (METH) has been shown to cause dopaminergic neurotoxicity. By using the loss of dopamine transporter (DAT) as a marker of neurotoxicity, this study was aimed to investigate the neuroprotective effect of baicalein against METH-induced striatal damages in mice. Results from Western blotting showed that repeated METH administration (5 mg/kg, i.p., four injections at 2-h interval) caused 40% decrease of DAT level in mouse striatum measured at 72h after the last injection. Despite of the ineffectiveness at high dose (3.0 mg/kg, i.p.), pretreatment with lower doses of baicalein (0.3-1.0 mg/kg, i.p.) significantly attenuated the METH-induced striatal DAT loss in a dose-dependent manner. Furthermore, baicalein diminished METH-induced increase in striatal malondialdehyde content and myeloperoxidase activity, markers for lipid peroxidation and neutrophil increase, respectively. In addition, the present study also revealed that baicalein effectively diminished the ROS production by leukocytes stimulated with METH or PMA, a phorbol ester used as a positive control of stimulant. Surprisingly, we found that METH-induced nNOS overexpression was further increased by the pretreatment with baicalein while the level of nNOS was not altered significantly by baicalein treatment alone. These results suggested that baicalein may attenuate methamphetamine-induced DAT loss by inhibiting the neutrophil increase and the lipid peroxidation caused by neutrophil-derived reactive oxygen species in striatum.