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。     

心肌Na^＋，K^＋-ATP酶在抑郁症时的活性及mRNA表达

目的 探讨Na+,K+-ATP酶在抑郁症发病中的作用及其和单胺类神经递质之间的关系.方法 对SD大鼠进行慢性随机刺激建立抑郁症模型,检测大鼠心肌Na+,K+-ATP酶的活性及mRNA表达,海马组织及血液中去甲肾上腺素(NA)和5-羟色胺代谢物5-羟吲哚乙酸(5-HIAA)水平.结果 抑郁症大鼠心肌Na+,K+-ATP酶的转录水平下调(P＜0.01);酶的活性明显降低(P＜0.01);海马及血浆中的NA及5-HIAA水平显著下降(P＜0.01).结论 推测抑郁症时神经体液因素的变化可能是引起心肌细胞Na+,K+-ATP酶分子变化的原因之一,该酶在抑郁症的发病机制中有一定的生理和病理意义.     

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.     

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。     

山奈酚对乳腺癌抑郁模型大鼠的抗抑郁作用研究

目的 探讨山奈酚对实验性乳腺癌抑郁大鼠的抗抑郁作用。方法 90只大鼠随机分为对照组、乳腺癌组、抑郁组、复合模型组、氟西汀组、山奈酚组,每组15只。通过慢性不可预知性轻度应激方法建立大鼠抑郁模型,以二甲基苯蒽为诱导剂建立乳腺癌大鼠模型。采用旷场实验垂直运动次数及水平活动总路程观察各组大鼠自主活动;液质联检分析各组大鼠脑内海马及前额叶皮质单胺类神经递质,包括去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)和5-羟色胺(5-hydroxytryptamine,5-HT)含量的变化。结果 乳腺癌组自主活动均减少,但与对照组比较无显著性差异;抑郁组和复合模型组自主活动减少,与对照组比较差异均有显著性(P<0.01);与复合模型组相比,山奈酚组与氟西汀组垂直运动次数及水平活动总路程均显著增加(P<0.05或P<0.01)。与复合模型组比较,氟西汀组海马区DA、5-HT含量显著增高(P<0.01),前额叶皮质DA、NE、5-HT浓度均显著性增高(P<0.05);山奈酚组与复合模型组比较,海马部位NE含量明显增高(P<0.05),前额叶皮质部位DA、NE、5-HT浓度均显著性增高(P <0.05或P <0.01)。结论 山奈酚具有显著抗大鼠抑郁作用,可能通过提高前额叶皮质部位NE、DA、5-HT递质水平达到抗抑郁作用。     

柴胡对肝郁证中枢神经递质作用的实验研究

目的探索柴胡对肝郁证大鼠中枢神经递质的作用。方法利用中医证候模型,研究柴胡对单胺类神经递质的作用。结果肝郁证模型组大鼠脑内NE与DA水平与对照组比较下降明显(P<0.05);肝郁证模型加逍遥散组大鼠脑内NE与DA水平与对照组比较无显著性差异(P>0.05);肝郁证模型加柴胡组大鼠脑内NE与DA水平与对照组比较也无显著性差异(P>0.05)。结论肝郁证大鼠脑内NE与DA水平明显降低,柴胡舒肝解郁,有增加肝郁证大鼠脑内NE、DA神经递质的作用。     

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。     

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。     

慢性不可预知应激诱导的抑郁大鼠血清中神经递质含量的动态变化

目的观察慢性不可预知应激(CUS)并配合孤养诱导模型大鼠抑郁样行为过程中神经递质水平的变化,探讨神经递质作为诊断抑郁症的客观、可量化标志物的可能性。方法 利用CUS并配合孤养模型建立抑郁大鼠动物模型,以体质量、糖水偏爱率和旷场实验(穿格数和直立次数等)结果评定大鼠行为学的动态变化;采用高效液相-荧光法(HPLC-FD)测定血清中5-羟色胺(5-HT)、去甲肾上腺素(NE)、肾上腺素(E)、多巴胺(DA)、左旋多巴(L-DOPA)、5-羟基吲哚乙酸(5-HIAA)、高香草酸(HVA)、3,4-二羟基苯乙酸(DOPAC)、酪氨酸(Tyr)和色氨酸(Trp)等10种神经递质的含量;应用SPSS软件对体质量、糖水偏爱率和旷场数据等行为结果进行主成分分析,并采用回归分析方法分析行为学与神经递质变化间的相关性。结果 ①与正常对照组相比,造模期间第14天,模型组直立次数显著降低(P<0.05);造模期间第22天,模型组体质量、糖水偏爱率、穿格数和直立次数均显著降低(P<0.05)。②与正常对照组相比,造模期间第6天,模型组Tyr和5-HIAA的含量显著降低(P<0.05);造模期间第9天,NE的含量显著降低(P<0.05);造模期间第22天,NE和5-HT的含量显著降低(P<0.05);造模期间第15和22天,NE,5-HIAA,HVA和5-HT的含量显著降低(P<0.05)。③NE,HVA和5-HT的变化趋势为降低的程度逐渐增大,与行为学结果变化趋势接近;而Tyr的变化趋势为先升后降,5-HIAA,L-DOPA,DA,DOPAC,Trp和E呈波动性变化。主成分分析结果显示,第一主成分可代表93.47%的信息,结果可靠;相关性分析结果表明,5-HT,NE和HVA与第一主成分的相关性好。结论 血清中神经递质在CUS诱导抑郁样行为过程中呈动态变化,其中NE,5-HT和HVA的变化可以在一定程度上反映大鼠的抑郁状态和程度,可作为诊断抑郁症的临床辅助指标。     

益智五海胶囊对血管性痴呆模型大鼠的海马Ach、AchE及大脑皮层5-HT、NE、DA的影响

目的 研究益智五海胶囊改善血管性痴呆的作用机理.方法 采用缺血再灌注法制作血管性痴呆(VD)大鼠模型,检测益智五海胶囊对VD大鼠模型海马Ach、AchE及大脑皮层5-HT、NE、DA的影响.结果 益智五海胶囊对VD大鼠模型海马Ach、AchE,大脑皮层5-HT、NE、DA具有不同程度的影响.结论 益智五海胶囊改善智能是多途径的,通过改善海马中Ach、AchE和大脑皮质DA、NE、5-HT,改善VD的智力障碍.     

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.     

Effects of ovariectomy on naloxone-modulated hypertension in spontaneously hypertensive rats (SHR)

Ovariectomy was performed at 4 weeks of age (W), and the rats were used when they were 33 and 75 W old. Systolic blood pressure (BP) was measured by the tail-cuff method. Naloxone (10 mg/kg) was given i.p. Catecholamines (CA) were determined with HPLC. Norepinephrine (NE) was not significantly altered in intact rats by naloxone; however, a significant increase in NE appeared in the plasma, hippocampus, thalamus plus mid-brain and hypothalamus in castrated rats following naloxone. With naloxone treatment, dopamine (DA) was significantly increased in the plasma and hypothalamus, but decreased in the cerebral cortex in intact rats; and with castrated rats, there was a tendency to see an increase in plasma DA and significantly increased levels of DA in the thalamus plus mid-brain and hypothalamus. This suggests that in female brain, lack of estrogen in the castrated rats leads to an increase in intrinsic opiate, and this in turn inhibits CA release. On the other hand, when naloxone was administered to castrated rats, intrinsic opiate was blocked, and, consequently, inhibition of CA release was lost and induction of CA release was enhanced.     

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。     

Monoamine neurotransmitters and metabolites during the estrous cycle, pregnancy, and the postpartum period

A wide variety of behavioral changes in the female rat have been associated with the estrous cycle, pregnancy, and the postpartum period and their accompanying hormonal fluctuations. Since monoamine systems have been implicated in the control of these behaviors, the present study examined the tissue concentrations of norepinephrine (NE), dopamine (DA), and serotonin (5HT) and their primary metabolites dihydroxyphenylglycol (DHPG), 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5HIAA) in the anterior cerebral cortex, hippocampus, and cerebellum during the estrous cycle, late pregnancy, and the early postpartum period. Results show no significant differences in neurotransmitter or metabolite levels during the estrous cycle in any of the three brain regions examined. However, profound differences were observed between samples from late pregnancy, early postpartum, and the estrous cycle. In general, NE and 5HT levels in all three brain regions fell from normal values during late pregnancy and rose in the early postpartum period; levels of their metabolites rose in postpartum samples. Conversely, DA levels were elevated in late pregnancy and depressed in the early postpartum period in anterior cortex, while DOPAC levels were depressed in both late pregnancy and the early postpartum period. The finding of changes in monoamine metabolism associated with pregnancy and its termination could be important in understanding the increased susceptibility to affective illness in women during the postpartum period.     

The actions of dopaminergic and noradrenergic antagonists on conditioned avoidance responses in intact and 6-hydroxydopamine-treated rats

The actions of various doses of haloperidol, pimozide, clozapine, and phenoxybenzamine were assessed on a conditioned-avoidance response (CAR) in control and 6-hydroxydopamine-treated rats, using a pole-climbing device. Haloperidol proved to be the most potent in disrupting the CAR. Pimozide was about 1.6 times less potent, and clozapine and phenoxybenzamine were approximately 52 and 155 times less potent than haloperidol, respectively. Prior treatment with 6-hydroxydopamine slightly enhanced the sensitivity to some of the doses of the DA and NE antagonists. Significantly lower levels of responding, however, were observed only after the highest dose of pimozide.Clonidine was not only ineffective in reverting avoidance decrements, but also induced a further decline of the CAR. Apomorphine produced a partial, but significant, reversal of the haloperidol and pimozide-induced depression of conditioned responses. Regarding the clozapine-pretreated animals, a significant antagonism was observed only with the smaller dose of apomorphine. The highest dose induced a further decline of the CAR. The DA agonist was also ineffective in the phenoxybenzamine-injected rats. Amphetamine was effective in antagonizing the avoidance decrements produced by all the CA antagonists.Our results support the suggestion that CAR depends on both DA and NE mechanisms. DA seems to be more significant that NE, however, since the CAR was more depressed when receptors depending on the former neurotransmitter were blocked.     

雌激素对卒中后抑郁大鼠血清单胺类递质的影响

目的:探讨雌激素对卒中后抑郁(PSD)大鼠的血清单胺类递质的影响。方法:选用雌性SD大鼠,经Open-Field行为学评分后随机分成对照组、卒中组、PSD组、药物治疗组和雌激素干预组,所有大鼠均行卵巢切除术。对照组为常规饲养;卒中组去卵巢后7d采用线栓法制备局灶性脑缺血大鼠模型;PSD组为卒中大鼠结合孤养、束缚应激制备PSD大鼠模型;药物治疗组对PSD大鼠模型行帕罗西汀灌胃治疗;雌激素干预组对PSD大鼠模型皮下包埋雌激素释放管。观察雌激素对PSD大鼠自发性行为和外周血去甲肾上腺素(NE)和5-羟色胺(5-HT)的影响。结果:与对照组比较,PSD组大鼠旷场实验水平和垂直得分明显减少,外周血NE和5-HT浓度明显降低,差异有统计学意义(P<0.05)。与PSD组比较,雌激素干预组大鼠旷场实验得分增加,外周血5-HT和NE浓度明显升高,差异有统计学意义(P<0.05)。与药物治疗组相较,雌激素干预组大鼠旷场实验得分、外周血5-HT浓度差异无统计学意义(P>0.05)。结论:雌激素能够改善PSD大鼠的行为学、增加血清5-HT浓度,提示对PSD大鼠有脑保护作用。     

Alterations in brain catecholamines during pregnancy

During pregnancy mice are more susceptible to flurothyl-induced seizures than are non-pregnant controls. The potential role of brain catecholamines in mediating this behavior was examined in the present study. The concentration and turnover of norepinephrine (NE) and dopamine (DA) were measured in hippocampus, striatum, midbrain and cortex in control, pregnant and delivery-day mice. There were no significant changes from control in DA levels during pregnancy and parturition. The turnover of DA was not altered during pregnancy, except for a small increase in turnover rate in the hippocampus. The concentration of NE decreased during pregnancy, and rose at parturition. This effect was most striking in the hippocampus. The turnover of NE was markedly depressed during pregnancy, with the hippocampus again being most affected. These data imply a role for NE, but not DA in the mediation of increased seizure susceptibility during pregnancy.     

Biochemical resistance to development of morphine-dependence in rats: biogenic amines, its receptors and antibodies

The level of norepinephrine (NE), epinephrine (E) and dopamine (DA) in hypothalamus and blood plasma along with antibodies to NE, DA and serotonin (5-HT) and characteristics of ₁−, ₂-adrenergic, D₂-dopaminergic and S₂-serotoninergic receptors in synaptic brain membranes were studied in two groups of rats predisposed or resistant to the formation of physical morphine dependence. The resistant animals were characterized by a significant elevation of DA levels in blood plasma, elevation of antibodies to NE, and by higher concentration of ₂-adrenergic receptors in the brain cortex and of D₂-receptors in striatum. The affinity of D₂-receptors to dopamine in resistant rats also was higher than in predisposed animals. The other parameters studied did not differ significantly between the two groups. These findings suggest that the increased activity of DA and NE neurotransmitter systems can be a cause for the genetic resistance of some individuals among Wistar rats to the formation of physical dependence on morphine.