对氨基水杨酸钠对氯化锰染毒大鼠脑单胺递质的影响

本文报道了对氨基水杨酸钠(PAS-Na)对氯化锰腹腔注射染毒大鼠脑单胺递质水平的影响。PAS-Na能使锰染毒所降低了的脑多巴胺(DA)水平逆转;锰使脑去甲肾上腺素(NE)含量增加,染毒后以PAS-Na治疗则使之进一步升高;锰染毒和染毒后治疗组的5-羟色胺(5-HT)及5-羟吲哚醋酸(5-HIAA)的变化与DA相似,但PAS-Na使5-HT、5-HIAA水平升高的幅度大都较NE和DA的要小,提示5-HT能神经元对PAS-Na治疗作用的敏感性低于儿茶酚胺(CA)能神经元。     

模拟高原梭曼中毒大鼠脑单胺递质含量变化

模拟高原梭曼中毒大鼠脑单胺递质含量变化刘勇吕宏宇欧阳子倩赵清（第三军医大学预防医学系毒理学教研室，重庆６３００３８）梭曼是一种难防难治的有机磷神经性毒剂，由于中枢及周围神经系统的胆碱酯酶活性被抑制而导致乙酰胆碱蓄积，进而诱发一系列胆碱能神经亢奋的症状...     

尼莫地平对小鼠脑内单胺递质含量的影响

目的：探讨尼莫地平增强学习记忆的作用机制。方法：采用高效液相色谱－电化学法测定脑内单胺递质及其代谢物的含量。结果：尼莫地平组去甲肾上腺素（NE）,多巴胺（DA）,5－羟色胺（5－HT）及它们的主要代谢产物高香草酸（HVA）,3,4－双羟苯乙酸（DOPAC）含量增加,结论：尼莫地平增强学习记忆的作用可能与单胺递质有关。     

海人草酸损伤大鼠苍白球后脑内单胺递质水平的变化

用海人草酸毁损大鼠苍白球造成老年性痴呆模型并在海马，额皮层、纹状体及延髓脑桥部四个不同脑区测定了单胺递质水平的变化。在此模型中，大鼠海马和额皮层的去甲肾上腺素（NE）水平在四个脑区均有所降低，其中在额皮层和纹状体降低显著，同时在大脑额皮层，纹状体和延髓脑桥部，DA转化率均显著降低。结果提示，在此模型中，DA代谢可能出现紊乱。5羟色胺水平和多巴胺－β－羟化酶（DBH）活性（用NE／DA）的比率表示）同正常对照组相比无显著性差异。结果显示此模型基本上反映了老年性痴呆病人脑中单胺递质水平的变化。可以作为老年性痴呆模型用于基础医学与治疗研究。     

不同阶段海洛因成瘾大鼠脑内单胺递质的变化

目的:观察不同阶段海洛因成瘾大鼠脑内去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)及5-羟吲哚乙酸(5-HIAA)的变化.方法:模拟人类吸毒成瘾、治疗;复吸成瘾,再治疗周而复始的模式.按递增法给大鼠染毒,造成动物海洛因成瘾.剖取不同阶段的鼠脑,以荧光分光光度法检测单胺类递质含量.结果:各阶段海洛因成瘾鼠脑单胺类递质含量明显增高,5-HT代谢物亦明显增高.α-银环蛇毒素和美沙酮等治疗均能显著降低单胺递质.结论:海洛因成瘾的大鼠,不同阶段的脑内单胺递质明显升高,两种治疗方案均可显著降低单胺类递质、缓解戒断症状.     

903与901影响小鼠脑区单胺递质及其代谢产物含量的比较

９０３与９０１影响小鼠脑区单胺递质及其代谢产物含量的比较孙晓红袁淑兰乔建忠苏俊峰（军事医学科学院毒物药物研究所，北京１００８５０）９０３是９０１结构类似的化合物．其毒性强于９０１，９０１是近年来新发现的一种ＤＡ神经元毒素，并已作为帕金森病模型的工具药...     

丙咪嗪单用及与尼莫地平合用对小鼠脑内单胺递质含量的影响

目的：通过测定小鼠脑内单胺递质含量变化探讨丙咪嗪（Ｉｍｉ）单用及与尼莫地平（Ｎｉｍ）合用与单胺递质的关系。方法：采用高效液相色谱－电化学法测定脑内单胺递质及其代谢物的含量。结果：单用及合用组多巴胺含量均增加,去甲肾上腺素和５－羟色胺含量单用组明显增高,且以７ｄ合用组变化明显。结论：７ｄ组Ｉｍｉ与Ｎｉｍ合用对单胺递质水平有一定影响。     

千金藤啶碱对大鼠脑内单胺代谢的影响

1-千金藤啶碱(1-SPD 15～120 mg/kg)能增加大鼠纹状体和边缘区的多巴胺代谢物DOPAC和HVA(+150～300%),并有剂量相关关系。此作用于给药后60 min达峰值,给药后4 h虽有恢复趋势,但仍明显高于对照值。SPD还能中等度地降低上述两个脑区的DA和NA(-18～48%)。DA转换率(表现为代谢物增加)的升高支持SPD为DA受体阻断剂。但DA和NA下降表明,除有受体阻断作用外,不能排除药物对单胺递质的贮存、释放或再摄取的影响。纹状体内的5-HIAA含量亦有明显升高。     

Effects of butorphanol and its metabolites on the levels of monoamines and their metabolites in the rat brain

The effects of butorphanol and its main metabolites, norbutorphanol and hydroxybutorphanol, on the contents of monoamines and their metabolites in various regions of the rat brain were compared with those of morphine and pentazocine using the HPLC-ECD method. The administrations of morphine and pentazocine increased dopamine turnover in the striatum and hypothalamus in a drug dose-dependent manner. The stimulative effects of butorphanol on the dopamine system were weaker than those of morphine and pentazocine, and there were no dose-dependencies in these effects of butorphanol. Butorphanol, morphine and pentazocine increased 5-HT turnover, but there was no drug dose-dependent effect in the case of butorphanol. These differences for the effects of butorphanol from those of morphine and pentazocine seemed to result from the antagonist-agonist property of butorphanol and from a different manner of interaction with the opioid receptor. The effects of butorphanol on the levels of the norepinephrine system were weak. It was considered that the effects of butorphanol on monoamine turnover were produced by the action of butorphanol itself, because norbutorphanol and hydroxybutorphanol showed little change on the level of monoamines and their metabolites.     

Effect of trazodone (KB-831) and its metabolites on brain monoamines in rat

The effects of trazodone (KB-831) and its metabolites on the uptake, turnover and contents of monoamines in rats were studied in comparison with those of imipramine and mianserin. Trazodone exhibited a more potent inhibitory effect on the uptake of [3H] 5-hydroxytryptamine (5-HT) into brain synaptosomes than on the uptake of [3H]norepinephrine (NE). Trazodone at 10-30 mg/kg, p.o., also inhibited the p-chloramphetamine-induced depletion of 5-HT in rat brain, but not the 6-hydroxydopamine-induced NE depletion in rat heart. Trazodone was the most selective 5-HT uptake inhibitor among the drugs tested in vitro. Its metabolite, m-chlorophenyl-piperazine (m-CPP), inhibited 5-HT and NE uptake in vitro, but not in vivo. Trazodone (100 mg/kg) and imipramine (30-100 mg/kg) inhibited the depletion of NE induced by alpha-methyl-p-tyrosine, whereas mianserin (100 mg/kg) facilitated it. At 1 hr after a single administration of each drug, an increase in 5-HT content and a decrease in 5-hydroxyindole-3-acetic acid (5-HIAA) content were observed when 30 mg/kg trazodone was used. At 100 mg/kg, trazodone increased the levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and decreased the NE content. m-CPP (10-30 mg/kg) produced similar effects on monoamine contents to those of trazodone. Imipramine and mianserin had no effect on monoamine contents even at a dose of 100 mg/kg. After 3 weeks of successive administration, an increase in 5-HT and a decrease in 5-HIAA were induced by trazodone and m-CPP at 1 hr, but not at 17 hr, after the final administration. Imipramine decreased the contents of NE and 5-HIAA, and its effects lasted for 17 hr. These results suggest that trazodone is a selective 5-HT uptake inhibitor and that its neurochemical profile is different from those of imipramine and mianserin.     

地佐环平马来酸盐对大鼠甲基苯丙胺辨别效应的影响(英文)

目的:研究兴奋性氨基酸NMDA受体拮抗剂地佐环平马来酸盐对甲基苯丙胺辨别行为的作用。方法:采用双杆、固定比率食物强化型辨别实验程序。结果:大鼠对甲基苯丙胺(1.0mg/kg,sc)可以产生辨别行为,并稳定地维持该行为。在用地佐环平马来酸盐(0.1mg/kg,sc)的替代实验中,1只大鼠的行为表明地佐环平马来酸盐无替代作用,其余6只均表明该剂量下地佐环平马来酸盐具有不同程度的替代甲基苯丙胺的辨别效应;但是地佐环平马来酸盐(0.025,0.05mg/kg,sc)均没有替代作用。在拮抗实验中,地佐环平马来酸盐(0.10mg/kg,sc)不同程度地拮抗甲基苯丙胺的辨别效应(P<0.01);而地佐环平马来酸盐(0.025,0.05mg/kg,sc)均没有拮抗甲基苯丙胺的辨别效应的作用。结论:NMDA受体可能与甲基苯丙胺精神依赖性有关。     

Analysis by HPLC-EC of metabolites of monoamines in fetal and postnatal rat brain

High performance liquid chromatography with electrochemical detection (HPLC-EC) was adapted for the analysis of metabolites of monoamines (MA) in the developing brain of the rat. 3-Methoxy-4-hydroxy-phenyl-ethylene glycol (MOPEG), dihydroxy phenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxy-3-indoleacetic acid (5-HIAA) were found in significant amounts in forebrain of the foetal rat from gestational day (GD) 17. The development pattern of the four metabolites was essentially similar in male and female animals. Except for transient fluctuations at around birth, concentrations of metabolites increased gradually throughout late gestation and early postnatal life. In late gestation and at birth the absolute amounts were small, while the concentrations were comparable to adult levels.     

Effect of carbidine, sulpiride and haloperidol on levels of monoamines and their metabolites in the brain structures of rats

Haloperidol (1 mg/kg) was shown to increase significantly the dopamine (DA) turnover in n. accumbens and striatum and to a lesser degree in frontal cortex and hypothalamus of the rat brain; to decrease the noradrenaline content in hypothalamus. Sulpiride (50 mg/kg) slightly increased DA turnover in striatum and hypothalamus and lowered the serotonin (5-HT) content in frontal cortex. Carbidine (25 mg/kg) was found to increase DA turnover in frontal cortex, striatum and hypothalamus to a greater degree than haloperidol; 5-HT turnover was increased in all the cerebral regions. The results obtained indicated that the atypical neuroleptic drug carbidine exerts the predominant effect on the frontal cortex, the serotoninergic component being clearly pronounced.     

Effect of amperozide on the synthesis and turnover of monoamines in rat brain

The effects of amperozide on the synthesis and the turnover of monoamines in different brain regions of the rat were determined using both ex vivo and in vivo biochemical techniques (i.e. post-mortem measurements of the tissue levels by HPLC-EC, and direct measurements with the in vivo voltammetry technique). It was found that amperozide slightly increased the DOPA accumulation and the DOPAC content in limbic brain areas but not in the striatum. The DOPA accumulation was also slightly increased in the noradrenaline rich cortical region indicating increased synthesis of noradrenaline. Furthermore, amperozide increased the utilization of noradrenaline after tyrosine hydroxylase inhibition by α-methyl-p-tyrosine. The synthesis of 5-HT was not significantly altered by amperozide. In conclusion, the biochemical data obtained in this study suggest that amperozide produces preferential effects on the mesolimbic dopaminergic system. In addition, amperozide also interacts with the noradrenergic system.     

Effect of antidepressants on the balance of biogenic amines and their metabolites in the rat brain

A study was made of changes in the balance of neuromediator monoamines and metabolistes in rat brain, induced by a single administration of pyrazidol, imipramine and norzimelidine. It was revealed that pyrazidal in a dose of 50 mg/kg increased the level of noradrenaline (NA) and serotonin (5-HT), particularly in the hypothalamus and raphe-nucleus of rat brain. In the same brain regions, imipramine (30 mg/kg) raised the NA content and lowered the concentration of 5-HT and dopamine (DA) metabolites. Norzimelidine (60 mg/kg) elevated the levels of NA and DA in the hypothalamus and reduced the 5-HT content in the raphe nucleus of rat brain. It is suggested that the topography of changes in the balance of biogenic amines in the brain induced by different antidepressants reflects the pharmacological features of their action.     

Effect of pentobarbitone and diethyl ether on the synthesis of monoamines in rat brain

Summary Rats were injected i.p. with pentobarbitone sodium 40 mg/kg or were exposed to diethyl ether anaesthesia for 15 to 60 min. Monoamine synthesis in vivo was measured in various brain regions by determining the accumulation of dopa and 5-hydroxytryptophan (5-HTP) during 15 or 30 min after the i.p. injection of NSD 1015 (3-hydroxybenzylhydrazine HCl, 100 mg/kg), an inhibitor of the aromatic amino acid decarboxylase.Pentobarbitone retarded the formation of dopa and 5-HTP by about 25% in most brain regions but had no effect on striatal dopa formation.Ether accelerated the formation of dopa and 5-HTP in most brain regions, the action on striatal dopa being most pronounced (to 250% of control). The effect was generally somewhat less marked during the second than during the first half-hour of anaesthesia. A postanaesthetic inhibition of dopa formation was found in the striatum and of 5-HTP formation in whole brain.If hypothermia was allowed to develop, the stimulating action of ether on dopa and 5-HTP formation tended to be partly antagonized. A complex interaction between NSD 1015 and the hypothermic response to ether was observed.     

Effect of copper loading on various tissue enzymes and brain monoamines in the rat

Three-week-old 50-g rats were injected with 3.75 mg Cu/kg ip. daily for 2, 4 or 6 weeks. Controls received physiological saline. Copper-treated animals showed an increased mortality, and, in survivors, a decrease in body weight. Hepatic copper concentrations increased 17-, 45- and 89-fold after 2,4 and 6 weeks of copper loading, respectively. Dopa decarboxylase (DDC) and monoamine oxidase (MAO) showed a 40% and 14.7% decrease in activity, respectively, after 4 weeks of copper loading but no inhibition after 2 weeks. There was no effect on hepatic succinate dehydrogenase (SDH) or oxidative phosphorylation after 4 weeks of copper administration. After 6 weeks of copper loading, lactate dehydrogenase (LDH), MAO, SDH, and DDC activity were decreased by 15%,25%,29% and 40%, respectively. Malate dehydrogenase (MDH) was unaffected.After 6 weeks of copper loading renal copper concentration increased 14-fold but there was no effect on LDH, SDH, MDH, DDC or MAO.Brain copper increased 35.6% after 6 weeks of copper administration but there was no effect on DDC, MAO, or on concentrations of dopamine, norepinephrine or serotonin (5HT) in this organ. However, the 5-hydroxyindoleacetic acid concentration, an index of the rate of 5HT turnover in the brain, was significantly reduced; this may have been secondary to the stress of copper loading.The adrenal glands of copper-treated rats were markedly increased in weight after 6 weeks; DDC activity was unchanged. The total 5HT content of the small intestine was unchanged after copper treatment.The present results indicate that copper loading can affect enzymes involved in monoamine metabolism and other thiol-containing enzymes, at least in the liver, but only at very high hepatic copper concentrations. The relative protection of liver enzymes and the absence of any effect on renal enzymes from copper may be related to the intracellular distribution and binding of the metal, the localization of the enzymes themselves, and the presence of various protective cellular mechanisms.