都可喜对慢性间断性缺氧大鼠学习记忆能力及脑内单胺类神经递质的影响

目的:探讨都可喜(Duxil,阿米三嗪+萝巴新)对慢性间断性缺氧(EHYP)大鼠学习记忆能力和脑内单胺类神经递质水平的影响。方法:建立EHYP大鼠模型,并给予Duxil(0.03片·350g~(-1)体重,bid)干预。用被动避暗回避反射试验评价大鼠学习记忆能力,潜伏期(STL)越长,学习记忆能力越强;用高效液相色谱电化学检测器法测定大鼠皮层、海马和纹状体内去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)等单胺类神经递质的含量。结果:与对照组相比,EHYP组大鼠STL明显缩短(P<0.01),各脑区单胺类神经递质水平显著降低(P<0.05)。与EHYP组相比,Duxil组大鼠STL显著延长(P<0.01),皮层NE和DA含量、海马NE,DA和5-HT含量以及纹状体NE,DA和5-HT含量显著升高(P<0.05)。结论:Duxil可改善EHYP大鼠学习记忆能力并提高脑内单胺类神经递质水平。     

Cedemex对吗啡依赖性大鼠不同脑区3种单胺类神经递质的影响

目的:观察Cedemex对吗啡依赖性大鼠不同脑区单胺类神经递质的影响.方法:采用反相高效液相色谱-荧光检测法分别测定大鼠腹侧被盖区(VTA)、海马区、大脑皮层和伏隔核(NAe)共4个脑区的多巴胺(DA),去甲肾上腺素(NE)、及5-羟色胺(5-HT)的含量.结果:吗啡依赖大鼠脑内各区的DA,NE及5-HT等单胺类神经递质发生紊乱,其含量均明显高于正常.Cedemex能够促进吗啡依赖戒断后脑区内DA,NE及5-HT等单胺类神经递质含量趋于正常.结论:单胺类递质(DA,NE,5-HT)在吗啡依赖中可能起重要作用,Cedemex改善吗啡依赖性大鼠脑内单胺类神经递质的含量,可能是Cedemex临床治疗的作用机制之一.     

MPTP诱导野生型和A53T转基因型小鼠帕金森病模型纹状体中神经递质变化

目的探究帕金森病(Parkinson’s disease,PD)小鼠模型纹状体中多巴胺等神经递质的变化。方法通过腹腔注射丙磺舒(probenecid)、皮下注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)制备PD野生型小鼠和A53T转基因小鼠急性模型和野生型小鼠慢性模型;通过高效液相色谱法(high-performance liquid chromatography,HPLC)检测小鼠纹状体中神经递质的变化。结果HPLC结果显示,MPTP可以诱导野生型和A53T转基因小鼠纹状体中多巴胺(dopamine,DA)递质水平降低,二羟基苯乙酸(dihydroxyphenylacetic acid,DOPAC)水平降低,高香草酸(homovanillic acid,HVA)的水平降低,二羟基苯乙醛(dihydroxy phenylacetaldehyde,DOPAL)的含量升高,而对5-羟色胺(serotonin,5-HT)和去甲肾上腺素(norepinephrine,NE)无显著影响。结论MPTP诱导能够导致DA递质水平降低,以及其毒性代谢产物DOPAL含量增加,从而会促进PD的发生发展。     

经前平颗粒对愤怒情绪模型大鼠不同脑区单胺类神经递质的影响及分析

目的通过研究愤怒模型大鼠不同脑区单胺类神经递质的含量变化,探讨愤怒发生的微观机制及中药经前平颗粒的可能干预机制。方法采用社会隔离结合居住入侵方法制备愤怒大鼠模型,分别为正常组、愤怒模型组、经前平颗粒给药组;运用高效液相色谱法检测各组大鼠不同脑区单胺类神经递质的含量。结果与正常对照组相比,愤模组大鼠下丘脑NE含量明显下降(P<0.01),给药后愤药组大鼠额叶皮质NE含量异常变化得以纠正(P<0.05);愤模组额叶皮质、顶区皮质、海马DA含量下降(P<0.01,P<0.01,P<0.01),而下丘脑DA含量则上升(P<0.01),给药后下丘脑DA含量恢复至正常水平(P<0.01)。愤模组大鼠下丘脑5-HT含量降低(P<0.01)。结论大鼠愤怒情绪反应与下丘脑NE含量下降,额叶皮质、顶区皮质、海马DA、下丘脑5-HT含量下降,下丘脑DA含量上升有关;干预药物经前平颗粒可能通过纠正上述指标异常变化而发挥药理作用。综上所述,本研究为进一步研究愤怒情绪发病机制及调肝方药治病机制提供理论基础和方向。     

L-四氢巴马汀对羟考酮依赖大鼠不同脑区单胺递质水平的影响

目的：观察L-四氢巴马汀（L-THP）对羟考酮依赖大鼠不同脑区单胺递质含量的影响，探讨L—THP对抗羟考酮依赖的机制。方法：以连续递增给药建立羟考酮依赖大鼠模型，L—THP伴随给药，采用HPLC—ECD法测定大鼠前皮层、海马、纹状体和伏隔核内多巴胺（DA）和5-羟色胺（5-HT）含量的变化。结果：与空白对照组相比，羟考酮依赖的大鼠纳络酮催促戒断后前皮层内DA、高香草酸（HVA）和5-HT含量明显降低，伏隔核内DA、3，4-二羟基苯醋酸（DOPAC）、HVA和5-HT含量明显降低，海马内DA、DOPAC、5-HT含量没有明显变化，而5-吲哚乙酸（5-HIAA）明显升高，纹状体内DA及其代谢产物DOPAC、HVA以及5-HT、5-HIAA含量明显降低；L—THP（10，20，30mg&#183;kg^-1，ig）伴随给药，能不同程度抑制上述变化。结论：L—THP可抑制羟考酮依赖引起的不同脑区内单胺类递质含量的变化，提示LTHP对抗羟考酮依赖可能与调节多巴胺和5-HT系统相关。     

利血平和对氯苯异丙胺诱发小鼠单胺耗竭模型的建立和比较研究

目的建立利血平和对氯苯异丙胺(PCA)诱发小鼠单胺递质耗竭模型,并从自发活动、体温、单胺递质及代谢产物含量等方面探讨两种单胺耗竭模型的异同。方法①利血平诱发小鼠单胺耗竭模型研究:小鼠腹腔注射利血平5 mg·kg-1,18 h后测定自发活动和肛温,断头取脑,高效液相色谱法检测下丘脑组织匀浆5-HT,NE,DA及5-HIAA含量;②PCA诱发小鼠单胺耗竭模型研究:小鼠腹腔注射PCA20 mg·kg-1,6 h后测定自发活动和肛温,断头取脑,高效液相色谱法检测下丘脑组织匀浆5-HT,NE,DA及5-HIAA含量。结果①利血平诱发小鼠单胺耗竭模型研究:与正常对照组相比,利血平组(5 mg·kg-1,ip)小鼠自发活动和肛温显著降低,下丘脑组织匀浆5-HT,NE,DA含量显著降低(分别降低约80%),5-HIAA含量显著升高;②PCA诱发小鼠单胺耗竭模型研究:与正常对照组相比,PCA组(20 mg·kg-1,ip)小鼠自发活动显著增加,肛温显著降低,下丘脑组织匀浆5-HT,NE含量显著降低(分别降低约50%),但PCA对小鼠下丘脑DA及5-HIAA含量无显著影响。结论①利血平和对氯苯异丙胺诱发小鼠单胺耗竭模型建立成功,可用于单胺重摄取抑制剂类抗抑郁剂的靶标和机制研究;②两种模型的相同点:利血平和PCA均可诱发小鼠肛温降低,可并可耗竭5-HT,NE含量;③两种模型的不同点:利血平可同时引起5-HT,NE和DA三种单胺递质耗竭,而PCA仅引起5-HT和NE的含量,且耗竭程度比利血平弱;利血平可引发5-HT代谢产物5-HIAA含量生高,而PCA对5-HIAA含量无影响;利血平对中枢产生抑制作用,而PCA对中枢产生兴奋作用;上述研究表明利血平和PCA引发单胺递质耗竭的作用机制不同。     

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。     

白松片对慢性应激大鼠海马单胺类神经递质含量的影响

目的:观察中药白松片对应激大鼠海马单胺类神经递质含量的影响。方法:健康成年雄性SD大鼠42只,随机分为正常对照组、模型对照组、氟西汀对照组(1.8mg·kg-1)及白松片3个剂量(4.32,13.0,21.6g·kg-1,生药量)组。每只大鼠每日灌胃给药1次,连续14d。给药d6始,通过强迫游泳建立应激大鼠模型。用高效液相色谱-电化学法测定大鼠海马单胺类神经递质及其代谢产物的含量。结果:模型对照组大鼠海马去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)含量及多巴胺/3,4-二羟苯乙酸(DA/DOPAC)和5-羟色胺/5-羟吲哚乙酸(5-HT/5-HIAA)的比值分别为(4.7±s1.3)nmol·g-1,(47±12)nmol·g-1,(0.97±0.22)nmol·g-1,19±4,0.23±0.06,低于正常对照组(P<0.05或P<0.01);NE/5-HT比值(4.9±0.9)高于正常对照组(P<0.01);用白松片预防给药可使模型大鼠海马NE,DA和5-HT含量及NE/5HT,DA/DOPAC和5-HT/5-HIAA的比值恢复至正常水平(P<0.05或P<0.01)。结论:白松片可能通过提高NE,DA及5-HT的含量并降低其代谢率来发挥其抗抑郁作用。     

松果菊苷对帕金森病大鼠纹状体及海马细胞外液中单胺类神经递质的影响

目的研究松果菊苷(echinacoside,ECH)对帕金森病(Parkinson's disease,PD)大鼠纹状体及海马细胞外液中单胺类神经递质的影响,以探讨ECH对脑神经保护作用的可能机制。方法采用双点注射6-羟基多巴胺损毁术制作PD模型,各组大鼠腹腔注射相应的药物或生理盐水连续4周,进行双靶点微透析程序,将透析液注入高效液相-电化学检测器(HPLC-ECD),测定各组大鼠纹状体及海马细胞外液中多巴胺(DA)、3,4-二羟基苯乙酸(DOPAC)、高香草酸(HVA)、去甲肾上腺素(NE)及5-羟色胺(5-HT)的含量。结果与对照组相比,模型组大鼠纹状体及海马细胞外液中NE、DA、DOPAC、HVA、5-HT含量均明显降低(P<0.01);与模型组相比,各给药组大鼠的纹状体及海马细胞外液中5种物质的含量均明显升高(P<0.05,P<0.01);ECH高剂量组与阳性药MD组相差不大。结论 ECH对PD大鼠纹状体及海马细胞外液中的单胺类神经递质的含量减少具有改善作用,对于PD具有一定的治疗作用,这是ECH对PD大鼠脑神经保护作用的可能机制之一。     

钩藤碱对大鼠脑内去甲肾上腺素、5-羟吲哚乙酸的影响

目的 测定钩藤碱对大鼠脑内去甲肾上腺素(norepinephrine，NE)、5-羟吲哚乙酸(5-hydmxyindolea ceticadd，5-HIAA)影响，进一步探讨钩藤碱的镇静作用机制。方法 利用脑微透析方法收集药前及药后纹状体、海马及大脑皮质的细胞外液(透析液)。经反相高效液相电化学法(HPLC-ECD)检测其NE、5-HIAA的变化。结果 Rhy增高正常鼠脑纹状体及海马细胞外液中5-HIAA的含量，降低海马和皮层中NE的含量。结论 钩藤碱的镇静作用，可能与其改变脑内单胺类递质及其代谢产物的含量有关。     

脑缺血再灌注小鼠脑内不同神经核团单胺递质及其代谢产物的变化

目的　测定脑缺血再灌注后小鼠脑内不同神经核团单胺递质及其代谢产物的动态变化。方法　阻断小鼠双侧颈总动脉 (CCAO)进行缺血再灌 ,于术后当天 (d 0 )及d 1、3、5、2 0用HPLC ECD动态检测小鼠海马 ,纹状体 ,皮层的神经递质及其代谢产物的变化。结果　与假手术对照组相比 ,脑缺血再灌注小鼠术后上述神经核团去甲肾上腺素 (NE) ,多巴胺 (DA) ,5 羟色胺 (5 HT)等神经递质及其代谢产物含量降低 ,其中海马表现尤为明显。结论　脑内多个神经系统参与了脑缺血再灌注小鼠的病理过程 ,小鼠海马对缺血损伤最为敏感。提示脑缺血再灌注后海马神经递质异常是其后期行为表现的物质基础 ,是临床治疗中应予以重视的靶点     

原花青素对慢性不可预知性应激小鼠脑内单胺递质的影响

目的 研究原花青素在慢性不可预知性应激（unpredictable chronic mild stress,UCMS）小鼠中的抗抑郁样作用以及对小鼠脑内单胺递质含量的影响。方法 随机将ICR小鼠分为6组：空白对照组,UCMS组,原花青素低、中、高剂量组（UCMS+原花青素12.5,25,50 mg·kg^-1）,氟西汀组（UCMS+氟西汀10 mg·kg^-1）。采用UCMS建立模型组评估小鼠的抑郁和焦虑样行为,采用HPLC测定小鼠海马、额叶皮层和下丘脑中单胺递质的含量。结果 与空白对照组比较,UCMS组小鼠悬尾的不动时间明显增加（P<0.05）,大理石掩埋数目显著增加（P<0.01）;小鼠海马、额叶皮层和下丘脑中的去甲肾上腺素、5-羟色胺和多巴胺的含量均减少;与UCMS组比较,原花青素组能明显逆转上述行为学以及脑内单胺递质含量的改变。结论 UCMS小鼠存在抑郁焦虑样行为学的改变,海马、额叶皮层和下丘脑中单胺递质含量表达异常。原花青素可以改善UCMS小鼠行为学的改变,并调节海马、额叶皮层和下丘脑中单胺递质的表达。     

可乐定加强安定抑制大鼠离体脑片单胺递质释放作用

建立了高K~+去极化诱发离体脑片单胺递质释放及高压液相色谱仪电化学检测器测定释放的微量递质方法。可乐定和安定均可抑制高K~+诱发的皮层、海马、杏仁核和脑干单胺递质释放,并分别为育亨宾和Ro 15-1788所拮抗。将低于最小有效浓度的可乐定和安定合并应用,可显著抑制高K~+诱发四个脑区单胺递质的释放。蝇蕈醇可显著加强安定对高K~+诱发皮层NE和5-HT释放的抑制作用。     

Alpha2-adrenergic drug effects on brain monoamines,locomotion, and body temperature are largely abolished in mice lacking the alpha2A-adrenoceptor subtype

alpha(2)-ARs regulate brain monoaminergic function by inhibiting neuronal firing and release of monoamine neurotransmitters, noradrenaline (NA), serotonin (5-HT) and dopamine (DA). Both alpha(2A)- and alpha(2C)-AR inhibit monoamine release in vitro in brain slices, but the in vivo roles of individual alpha(2)-AR subtypes in modulating monoamine metabolism have not been characterised. Metabolism of brain monoamine neurotransmitters, locomotor activity and body temperature were investigated in mice with targeted inactivation of the gene encoding alpha(2A)-AR (alpha(2A)-knockout, alpha(2A)-KO) and wild-type (WT) mice after treatment with the alpha(2)-AR agonist dexmedetomidine and the antagonist atipamezole. Dexmedetomidine caused profound hypothermia (up to 14.7 degrees C mean reduction in rectal temperature) and locomotor inhibition in WT mice, and inhibited the turnover of NA, 5-HT and DA, but increased NA turnover in alpha(2A)-KO mice. alpha(2)-AR agonist-induced hypothermia and locomotor inhibition were attenuated, but not totally abolished, in alpha(2A)-KO mice. These results suggest that alpha(2A)-ARs are principally responsible for the alpha(2)-AR mediated inhibition of brain monoamine metabolism, but other alpha(2)-ARs, possibly alpha(2C)-ARs, are also involved, especially in the striatum. However, secondary effects of the physiological alterations caused by drug administration, especially hypothermia, may have contributed to the observed neurochemical changes in WT mice.     

Effects of prenatal and postnatal exposure to amitraz on norepinephrine, serotonin and dopamine levels in brain regions of male and female rats

The effects of maternal exposure to amitraz on brain region monoamine levels of male and female offspring rats at 60 days of age were observed. Maternal and offspring body weight, physical and general activity development were unaffected by the exposure of dams to amitraz (20mg/kgbw, orally on days 6-21 of pregnancy and 1-10 of lactation). Male and female offspring were sacrificed at 60 days of age and possible alterations in the content and metabolism of NE, DA and 5-HT were determined in brain regions by HPLC. The results showed that all these neurotransmitter systems were altered in a brain regional-related manner. In male and female offspring, amitraz induced a significant decrease in the prefrontal cortex 5-HT and its metabolite 5-HIAA and DA and its metabolites DOPAC and HVA levels with interaction of sex. Nevertheless, we verified that striatum DA and 5-HT and corresponding metabolite contents decreased in male and female offspring without statistical distinction of sex. In contrast, amitraz did not modify 5-HT content, but caused an increase in 5-HIAA content in the medulla oblongata and hippocampus in male and female offspring. Alterations in the hippocampus DA, DOPAC and HVA levels after amitraz exposure were also observed displaying a sex interaction. NE levels also showed a decrease after amitraz treatment in the prefrontal cortex and striatum without statistical sex interaction, but MHPG levels decreased in both regions with a sex interaction. Amitraz evoked increases in 5-HT turnover in the prefrontal cortex as well as in DA turnover in the striatum and hippocampus but decreases in NE turnover in the hypothalamus, prefrontal cortex and striatum. The present findings indicated that maternal exposure to amitraz altered noradrenergic, serotonergic and dopaminergic neurochemistry in their offspring in the prefrontal cortex, striatum and hippocampus, and those variations could be related to several alterations in the functions in which these brain regions are involved.     

The influence of orally administered docosahexaenoic acid on monoamine neurotransmitter,nerve growth factor,and brain-derived neurotrophic factor in aged mice

In this study we attempt to investigate the new role of docosahexaenoic acid (DHA) supplementation on cognitive ability in aged mice. Kunming-line mice were treated with DHA (200, 400?mg/kg body weight/day) for 30 successive days. The cognitive ability of mice was assessed by learning and memory behavioral test; the levels of DHA were assessed by capillary gas chromatography; the levels of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) were assessed by high-performance liquid chromatography; the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) proteins were assessed by the enzyme-linked immunosorbent assay method. The results showed the cognitive ability of mice were significantly different between the DHA-treated groups and the aged group, and orally administered DHA can increase the levels of DA, NE and 5-HT, the content of BDNF and NGF proteins in hippocampus, frontal cortex and striatum tissues. In addition, aged-related changes in phospholipid DHA content were seen. Decreases in DHA were mostly corrected by DHA supplementation. These novel data suggest that DHA supplementation can improve the cognitive dysfunction due to aging by increasing the levels of BDNF and NGF protein and the levels of DA, NE, 5-HT to some extent. We speculate that the mechanism of DHA on cognitive ability may have a beneficial effect on signaling networks through modulation of monoamine neurotransmitters and neurotrophic factors in brain aging.     

左金丸总生物碱对束缚水浸应激性胃溃疡模型大鼠神经体液调节的影响

目的左金丸是黄连和吴茱萸按6∶1配伍组成,临床常用于胃溃疡的治疗。该文主要探讨左金丸总生物碱(ZJP-TA)对束缚水浸应激性胃溃疡模型大鼠神经体液调节的影响。方法采用束缚水浸法复制大鼠胃溃疡模型,测定ZJP-TA对大鼠胃溃疡指数,胃黏膜TNF-α含量的影响。测定大鼠海马、皮质、下丘脑、纹状体等脑区中单胺类神经递质5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)及其代谢产物5-羟吲哚乙酸(5-HIAA)含量以及肾上腺组织中NE和肾上腺素(E)含量的影响。结果预先口服ZJPTA可明显降低应激性胃溃疡大鼠的溃疡指数,明显降低胃黏膜中TNF-α的含量。各剂量ZJPTA可不同程度降低大鼠脑组织单胺类神经递质的浓度,与模型组比较差异具有显著性(P<0.05或P<0.01)。模型组肾上腺组织NE和E含量明显升高,ZJPTA能明显抑制其升高(P<0.05或P<0.01)。结论 ZJPTA可通过神经体液调节作用,对抗应激性胃溃疡损伤。     

Effects of Panax ginseng root on the vertical and horizontal motor activities and on brain monoamine-related substances in mice

Effects of the Panax ginseng root (PGR) on spontaneous motor activity (vertical and horizontal motor activities), and on monoamine-related substances (tyrosine, DA, DOPAC, 3-MT, HVA, NE, MHPG, tryptophan, 5-HT, and 5-HIAA) in discrete brain areas (cerebral cortex, hippocampus, hypothalamus, corpus striatum, limbic lobe, midbrain, cerebellum, and medulla oblongata) of ddY male mice (weighing 18-22 g) were examined using an infrared photo-cell counter and HPLC with electrochemical detection. PGR (100 mg/kg) was orally administered, twice a day, for 2 successive weeks (2W-group) or 7 successive weeks (7W-group). Vertical and horizontal motor activities increased significantly in the 7W-group but not in the 2W-group when compared to those of the control group. As to brain monoamine-related substances, the metabolism of DA and NE in the cerebral cortex and of 5-HT in the corpus striatum and cerebellum in the 2W-group were facilitated, while metabolism of DA in the corpus striatum and of 5-HT in the hypothalamus and midbrain were inhibited. In the 7W-group, except for a facilitated metabolism of 5-HT in the cerebellum, metabolism of DA, NE and 5-HT in all discrete brain areas were inhibited. These results show that PGR exerts an influence on the CNS.     

香砂六君子汤的抗抑郁活性部位筛选

目的：筛选香砂六君子汤的抗抑郁活性部位.方法：选用小鼠行为绝望模型（小鼠强迫游泳实验）评价抗抑郁作用;用荧光分光光度法测定单胺类神经递质.结果：香砂六君子汤的5个提取部位均可不同程度地降低小鼠的不动时间,其中正丁醇部位的作用最强;各部位第2周效果比第1周强.正丁醇部位,乙醇中、高剂量部位和水高剂量部位均显著提高了5-HT、NA和DA在海马、纹状体两个脑区中的含量;其中正丁醇部位对提高海马内3种神经递质含量的作用最强,乙醇高剂量部位对提高纹状体内3种神经递质含量的作用最强.结论：香砂六君子汤5个提取部位具有不同程度的抗抑郁活性,其活性成分主要分布在正丁醇和乙醇高剂量部位,可能是通过多方面影响单胺类神经递质系统来达到抗抑郁的目的.