头孢曲松对甲基苯丙胺致大鼠伏隔核神经元和谷氨酸转运体改变的影响

目的观察头孢曲松对甲基苯丙胺(METH)急性、亚急性处理时致神经损伤情况的影响,以及对伏隔核中谷氨酸转运体1(GLT1)与囊泡型谷氨酸转运体1(VGLUT1)的变化的影响。方法建立METH急性毒性模型,同时利用谷氨酸转运体调节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 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),尼氏小体明显减少;伏隔核中GLT1和VGLUT1的表达增加分别为53.7%和102%(P<0.05);头孢曲松预防给药组与METH组相比,大鼠刻板行为明显减少,伏隔核中GLT1的表达增加36%(P<0.05);VGLUT1的表达下调56%(P<0.05);METH亚急性处理后,与盐水对照组相比,伏隔核中GLT1的蛋白表达增加40.9%,VGLUT1蛋白表达增加52.9%;预防给予头孢曲松后,头孢曲松预防给药组与METH组相比,GLT1和VGLUT1蛋白表达差异没有显著性。结论 METH处理导致神经损伤,引起伏隔核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。     

甲基苯丙胺对大鼠行为和脑组织多巴胺及其代谢产物含量的影响

甲基苯丙胺（methamphetamine，MA）属于苯丙胺类兴奋剂，其盐酸盐为无色透明的晶体，状如冰，俗称“冰毒”。MA最初是作为减肥药、抗疲劳剂使用，随后发现其具有精神依赖性。上世纪50年代，欧美国家出现MA滥用。近年国际上的滥用呈上升趋势，国内大中城市的滥用情况也十分严峻。MA除对心、肝、肺、肾和骨骼肌等有毒性作用外，还有较强的神经毒性。     

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。     

SNP、GLU及GABA对纹状体神经元活动的影响

目的　探讨一氧化氮(NO)在纹状体(STR)信息传递中的作用,对帕金森综合征(PD)的发病机制有更深入的了解,对PD的临床诊断及治疗有更深远的帮助。方法　本实验采用多管玻璃微电极微电泳方法观察了微电泳硝普钠(SNP)、谷氨酸(GLU)及γ- 氨基丁酸(GABA)对大鼠STR神经元自发放电的影响。同时观察了NO对GLU及GABA神经传递的影响。结果　实验观察到微电泳SNP可使77%(51 /66)受试神经元放电频率加快,其兴奋作用可被单硝基L -精氨酸甲酯(L NAME)所拮抗。在微电泳GLU或GABA过程中,给予SNP可增强GLU的兴奋作用,拮抗GABA的抑制作用。给予NOS抑制剂L- NAME可拮抗GLU的兴奋作用。结论　实验结果表明NO、GABA、GLU等神经递质活动在STR的同一神经元有会聚作用,NO、GLU对STR神经元有兴奋作用,而GABA对STR神经元有紧张性抑制作用。     

深部电刺激诱导6-OHDA损伤鼠纹状体神经介质和KATP通道亚单位mRNA的改变

目的探索深部电刺激（deep brain stimulation,DBS）对6-OHDA损伤鼠纹状体神经介质的影响及其对纹状体KATP通道亚单位mRNA的改变。方法采用立体定向的方法将电极置于6-OHDA损伤鼠右侧脑丘脑底核（subthalamic nucleus,STN）进行深部电刺激,分离出大鼠脑纹状体后用高效液相法测定DA、Glu、GABA的浓度,并用RT-PCR检测KATP通道亚单位mRNA的改变。结果DBS显著增加6-OHDA损伤鼠纹状体中DA、Glu、GABA的浓度,同时RT-PCR检测也发现,DBS增强Kir6.1,Kir6.2mRNA的表达。结论DBS可能通过增强Kir6.1,Kir6.2 mRNA的表达而影响大鼠脑纹状体中DA、Glu、GABA的浓度。     

甲基苯丙胺致大鼠神经毒性及纹状体硝化作用的改变

目的探讨甲基苯丙胺(methamphetamine,MA)所导致的大鼠神经毒性及纹状体硝化作用的改变。方法建立MA给药模型,对照组给予等量生理盐水;观察两组大鼠的行为学改变,体温变化,纹状体中NO含量,NOS活性和蛋白质硝化水平的变化情况。结果MA组大鼠刻板行为评分和体温均高于对照组(P<0.01);与对照组相比,MA组大鼠纹状体NO含量及NOS活性增加(P<0.01);纹状体蛋白硝化水平明显增加(P<0.01),差异有显著性。结论MA可导致大鼠行为学改变和体温变化,大鼠脑组织NO含量、NOS活性及蛋白硝化水平的增高可能是MA中枢神经系统损伤的重要机制。     

褪黑素对睡眠的调节作用及与脑内氨基酸递质的关系

目的 :研究褪黑素促眠、昼夜节律作用及其与脑内氨基酸递质的关系。方法 :以翻正反射为指标研究褪黑素对小鼠睡眠及其昼夜节律的影响。采用纸电泳 双波长扫描法 ,测定褪黑素对小鼠不同脑区中γ 氨基丁酸 (GABA)和谷氨酸 (Glu)含量的影响。结果 :褪黑素能明显促进小鼠睡眠 ,其药效强度依赖于给药的时辰。褪黑素可使小鼠下丘脑内γ 氨基丁酸含量明显升高。但对谷氨酸水平无明显影响。结论 :褪黑素促眠作用可能与小鼠下丘脑中γ 氨基丁酸含量升高有关     

孕酮对大鼠大脑皮质神经元氨基酸类神经递质释放的影响

目的研究孕酮对大鼠大脑皮质神经元GLU和GABA释放的影响。方法孕酮(10μmol.L-1)处理原代培养的大鼠大脑皮质神经元,采用OPA-巯基乙醇柱前衍生,荧光检测-高效液相色谱法测定处理后不同时间点(0.5、1、1.5、2、24、36、48、72)细胞培养液中GLU和GABA的水平。结果与对照组相比,孕酮处理组1、1.5、2、24、36、48、72h GLU水平均下降(P<0.01);孕酮处理组0.5、1、1.5、2、24、36、48、72h GABA水平均升高(P<0.05或P<0.01)。结论孕酮通过抑制神经元GLU的释放,促进GABA的释放来调节氨基酸类递质系统,进而影响神经系统的兴奋性。     

锰对不同年龄大鼠脑黑质纹状体多巴胺含量的影响

锰是人体必需微量元素之一,然而长期过量接触可引起中枢神经系统损伤,其临床表现类似帕金森综合征[1]。帕金森病以选择性的黑质纹状体部位多巴胺能神经元损伤和多巴胺含量下降为特征。本实验初步探讨锰对大鼠多巴胺含量影响的毒性特征。1材料与方法1·1试剂与仪器MnCl2和dopami     

N-乙酰半胱氨酸减轻大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。     

The effect of methamphetamine on the release of acetylcholine in the rat striatum

We examined the effect of methamphetamine on the release of acetylcholine in the striatum of freely moving rats, using an in vivo microdialysis method. The basal level of acetylcholine was 3.67±0.47 pmol/30 μl per 15 min in the presence of neostigmine (10 μM). Tetrodotoxin (1 μM), a selective blocker of voltage-dependent Na⁺ channels, markedly inhibited the release of acetylcholine in the striatal perfusates. Apomorphine (1.0 mg/kg, i.p.), a dopamine receptor agonist, also significantly attenuated acetylcholine release. Methamphetamine (0.1 and 0.5 mg/kg, i.p.) did not immediately affect acetylcholine release in the striatum, but a dose of 1.0 mg/kg (i.p.) induced an increase of acetylcholine release in the striatum at 15–60 min. Striatal infusion of methamphetamine (5 and 10 μM) did not influence acetylcholine release. The increase following intraperitoneal administration of methamphetamine was slightly diminished by haloperidol (0.5 mg/kg). After microinjection of the neurotoxin, 6-hydroxydopamine (6 μg/3 μl), in the substantia nigra 7 days before, the increase of acetylcholine induced by the administration of methamphetamine (1.0 mg/kg) was slightly attenuated, whereas the administration of reserpine (2 mg/kg, i.p.) 24 h before, combined with -methyl-p-tyrosine (300 mg/kg, i.p.) 2.5 h before, completely blocked the increase in release of acetylcholine. These findings suggest that methamphetamine exerts an excitatory influence on striatal acetylcholine release in freely moving rats, and that this excitatory effect involves the dopaminergic system and the catecholaminergic system.     

Inhibitory role of oxytocin in psychostimulant-induced psychological dependence and its effects on dopaminergic and glutaminergic transmission

Psychostimulants are frequently abused as a result of their stimulatory effects on several neurotransmitter systems within the central nervous system. Both dopaminergic and glutaminergic neurotransmissions have been closely associated with psychostimulant dependence. In addition to its classical endocrine function in the periphery, oxytocin, an important neurohypophyseal neuropeptide in the central nervous system, has a wide range of behavioral effects, including regulating drug abuse. The present paper reviews the progress of research into the role of oxytocin in reducing psychostimulant-induced psychological dependence and the mechanisms by which oxytocin mediates its effects.     

纹状体中神经元活动的多巴胺调节

纹状体参与机体各种不同的行为活动 ,这些活动主要依赖于完整的多巴胺能神经支配 ,最近的电生理研究表明多巴胺通过改变电压依赖性的通道传导和突触传递来调节靶细胞的活动。该文对多巴胺如何调节纹状体神经元的活动作简要综述     

Bilateral lesions of the striatum induced with 6-hydroxydopamine abolish apomorphine-induced yawning in rats

The subcutaneous injection of 0.1 mg/kg apomorphine induced a syndrome consisting of yawning, chewing and sexual arousal in male rats. Bilateral lesions of the striatum induced with 6-hydroxydopamine abolished the drug-induced yawning, chewing and sexual arousal and produced a 58% depletion of the concentrations of dopamine in the striatum. These data suggest that apomorphine-induced yawning is mediated by presynaptic dopamine receptors (which may be autoreceptors). Furthermore, it appears that dopaminergic innervation of the striatum may play an important role in the production of yawning elicited by small doses of dopamine agonists.     

Effect of methamphetamine on rat spinal cord. Dopamine receptor-mediated depression of monosynaptic reflex

The experiments were performed on spinal rats transected at Cl. Intravenous administration of methamphetamine-HCl (MA-HCl, 2 mg/kg) and apomorphine-HCl (5 mg/kg) reduced the amplitude of the monosynaptic reflex (MSR), while the polysynaptic reflex was increased by methamphetamine. Depression of the monosynaptic reflex by both drugs was antagonized by haloperidol, but not by phentolamine. Depression of the monosynaptic reflex by methamphetamine was not antagonized by pretreatment with reserpine; however, the result was explained by the assumption that methamphetamine releases newly-synthesized dopamine or that methamphetamine may act directly on dopamine receptors. Depression of the monosynaptic reflex induced by methamphetamine was independent of peripheral changes in blood pressure. Oxygen tension in the spinal cord was slightly reduced by methamphetamine in rats treated with phentolamine and a change of pO2 in the spinal cord was ruled out as a possible mechanism of action. These results suggest that dopaminergic neurons in the spinal cord of the rat depress the transmission of monosynaptic spinal reflexes.     

Reduction of endogenous level, uptake and release of taurine after intrastriatal kainic acid injection.

Rats received single unilateral stereotaxic injections of 2 μg of kainic acid into the left caudate nucleus 10 days before sacrifice. On the lesioned side, a significant reduction of endogenous taurine levels and high affinity uptake of ³H-taurine into crude synaptosomal (P₂) fractions to about 75% of control values was found. In agreement with previous reports on the neurotoxic action of kainic acid, a marked reduction of endogenous GABA levels and ¹⁴C-GABA uptake into P₂-fractions was observed, while ³H-dopamine uptake was not significantly changed. In superfusion experiments with prelabeled P₂-fractions prepared from lesioned striata, K⁺(56 mM)-induced release of ³H-taurine and ¹⁴C-GABA, but not of ³H-dopamine, was reduced. The results are compatible with the hypothesis that taurine in the striatum of the rat is partially localized in interneurones.     

氯胺酮麻醉期间大鼠脑内氨基酸递质水平的变化

氨基酸类递质是主要的中枢神经递质之一 ,对于精神意识活动的调整起着关键作用。现认为全麻药 (尤吸入全麻药 )可通过抑制突触前谷氨酸 (Ｇｌｕ)的释放、增强谷氨酸的再摄取及阻滞突触后兴奋性氨基酸受体而发挥全麻作用[1] 。药物对于天冬氨酸 (Ａｓｐ)、γ 氨基丁酸 (ＧＡＢＡ)和甘氨酸(Ｇｌｙ)的突触前作用则较为复杂 ,不如谷氨酸明显和统一[2 ] ,可能不是全麻药的主要作用部位。有些学者认为氯胺酮对各类氨基酸类递质的摄取与释放过程无明显影响[2 ] ,这些都是离体实验的结论 ,活体动物在麻醉状态下 ,中枢神经系统中的氨基酸类递质水平是…     

Effects of flurazepam on amino acid-evoked responses recorded from the lobster muscle and the frog spinal cord.

The effects of flurazepam hydrochloride on GABA- or glutamate-evoked responses recorded from the lobster muscle fibre and the frog isolated spinal cord were studied using electrophysiological techniques. On lobster muscle flurazepam (up to 100 μM) reversibly antagonized responses to bath-applied or iontophoretically-applied glutamate without any effect on GABA responses. Higher concentrations of flurazepam (>200 μM) sometimes increased the resting membrane conductance, an effect different from that of GABA in being insensitive to picrotoxin (0.5 μM). In the tetrodotoxin (TTX)-treated frog spinal cord flurazepam (5 μM) reversibly antagonized both glutamate- and GABA-evoked dorsal root depolarizations although a smaller dose (2.5 μM) clearly potentiated the action of GABA. Spontaneous fluctuations of the dorsal root d.c. level in the presence of flurazepam were also observed. It is suggested that flurazepam antagonized amino acid responses by blocking receptor-activated Na⁺ channels on the postsynaptic membranes. However, the potentiation of GABA action on the frog spinal cord may have involved either release of endogenous GABA or “sensitization” of spinal receptors to GABA, an action easily obscured by the predominant antagonistic effect of flurazepam at higher concentrations.