杏仁核亚核群毁损对PCP模型大鼠行为和递质的影响

目的探讨杏仁核亚核群毁损后五氯苯酚(pentachlorophenol,PCP)模型大鼠行为和前额叶单胺类递质含量的变化,为立体定向技术治疗精神病提供参考。方法经腹腔注射PCP制作精神分裂症动物模型,立体定向电极毁损大鼠杏仁核,对其刻板行为进行评分,应用高效液相色谱分析系统检测前额叶多巴胺(DA)、5-羟色胺(5-HT)和去甲肾上腺素(NE)的含量。结果杏仁核内侧核群毁损能减轻PCP模型大鼠的刻板行为和社会行为,与假毁损组之间具有非常显著性差别(P<0.001)。毁损组前额叶DA含量低于假毁损组(P <0.05),5-HT和NE含量均高于假毁损组(P<0.05)。结论PCP模型大鼠前额叶DA含量增高,5-HT和NE含量下降。立体定向毁损杏仁核内侧核群能够改变前额叶单胺类递质的水平,改善模型大鼠精神分裂症症状。     

不同强度脑电场刺激对抑郁大鼠额叶单胺类递质含量的影响

目的:探讨不同强度脑电场刺激对抑郁大鼠额叶单胺类递质含量的影响。方法:建立Wistar大鼠抑郁症模型;分别在模型大鼠双侧颅骨大脑额叶区放置刺激电极(国家发明专利号ZL01103273.1)并固定,应用脑电场刺激仪给予不同强度脑电场刺激,刺激频率30Hz,刺激波形为正弦波,刺激持续时间1h。应用荧光分光光度法分别测定大鼠额叶脑组织内5羟色胺(5-HT)、去甲肾上腺素(NE)和多巴胺(DA)含量。结果:与正常对照组比,模型对照组大鼠5-HT及NE明显下降(分别P<0.001),治疗对照组单胺类递质无明显变化(分别P>0.05)。低强度治疗组治疗1h后,DA、5-HT及NE含量均无明显改变(分别P>0.05),中等强度治疗组及高强度模型治疗组大鼠额叶脑组织内5-HT及NE含量出现显著增高(分别P<0.05,P<0.01)。结论:一定强度的脑电场刺激可显著提高额叶内单胺类递质的含量,对抑郁症可能提示具有治疗作用。     

帕金森病患者立体定向手术前后脑脊液单胺类递质含量的改变

目的　研究帕金森病 (PD)患者脑立体定向手术前后脑脊液 (CSF)中单胺类递质含量的变化。方法测定 2 6例原发性PD患者 (PD组 )脑立体定向术前、后CSF中多巴胺 (DA)、5 羟色胺 (5 HT)、去甲肾上腺素 (NE)及其代谢产物高香草酸 (HVA)、5 羟吲哚乙酸 (5 HIAA)、3 甲氧基 4羟基苯乙二醇 (MHPG)的含量 ,另外测定 2 5例外科疾病腰麻手术患者 (对照组 )CSF中HVA、5 HIAA、MHPG含量。结果　PD组CSF中HVA、5 HIAA、MHPG含量明显低于对照组 (P <0 0 0 1、P <0 0 5、P <0 0 0 1) ;手术后组的CSF中DA、HVA ,、5 HT、5 HIAA、NE、MHPG含量明显高于手术前组 (其中DA、HVA、5 HT、5 HIAA和NE均P <0 0 0 1;MHPGP <0 0 5 )。结论　PD患者CSF单胺类神经递质代谢产物含量明显降低 ,脑立体定向术可提高PD患者脑部单胺类神经递质及其代谢产物的含量 ,其发生机制可能与DA能神经元的保护作用有关     

杏仁核毁损对甲基苯丙胺大鼠刻板行为和额叶皮质多巴胺的影响

目的　探讨立体定向杏仁核毁损对甲基苯丙胺 (methamphetamine ,MAP)大鼠刻板行为和额叶皮质多巴胺 (dopamine ,DA)含量的影响。方法　立体定向射频毁损杏仁核 ,经腹腔注射MAP观察大鼠行为学改变 ,荧光分光光度法测定额叶皮质DA含量。结果　杏仁核毁损组大鼠较假手术组大鼠刻板行为评分显著降低 ;甲基苯丙胺逆耐受持续时间显著缩短 ,潜伏期显著延长。MAP大鼠额叶皮质DA含量显著高于对照组 ;杏仁核毁损组的MAP大鼠额叶皮质DA含量显著低于假毁损组。结论　杏仁核毁损可有效地对抗使用甲基苯丙胺而出现的逆耐受现象 ,对额叶皮质DA增高有明显阻断作用     

产后抑郁症与孤啡肽及单胺类递质的相关性研究

目的　探讨孤啡肽 (OFQ)及单胺类递质与产后抑郁症的关系。方法　采用放射免疫法测定 2 5名健康产妇 (对照组 )及 17例产后抑郁症妇女 (抑郁组 )静脉血中孤啡肽及单胺类递质含量。结果　①抑郁组及对照组血孤啡肽含量分别为 (2 7 39± 6 0 4 )ng/L及 (10 37± 3 6 5 )ng/L ,与对照组相比 ,抑郁组孤啡肽含量显著升高 (P <0 0 1) ;抑郁组及对照组血 5 羟色胺 (5 HT)含量分别为 (0 93± 0 2 1) μmol/L及 (1 4 3± 0 36 ) μmol/L ,二者间有显著差异 (P <0 0 5 ) ;抑郁组血多巴胺 (DA)含量为 (2 15± 0 4 1) μmol/L ,显著低于对照组 (P <0 0 5 )。②抑郁组孤啡肽与5 HT及DA含量呈显著负相关 (r为 0 6 0 1及 0 5 93,P <0 0 5 )。③抑郁组爱丁保产后抑郁量表总分 (EPDS)与OFQ含量呈显著正相关 (r为 0 5 12 ,P <0 0 5 ) ,与 5 HT、DA含量呈显著负相关 (r分别为 - 0 5 71及 - 0 5 2 6 ,P <0 0 5 )。结论　孤啡肽与产后抑郁症的发生发展密切相关。     

中隔核毁损对甲基苯丙胺大鼠颞叶皮质多巴胺受体的影响

目的　探讨立体定向中隔核毁损对甲基苯丙胺 (MAP)大鼠脑颞叶皮质多巴胺D2 受体表达的影响。方法　 4 0只SD大鼠随机分为对照组、MAP组、MAP +毁损组和MAP +假毁损组 ,每组各 10只 ;采用经腹腔注射MAP制备精神分裂症MAP模型 ,立体定向 射频毁损中隔核 ,免疫组织化学ABC法观察颞叶皮质D2 受体的表达。结果　与对照组比较 ,MAP组及MAP +假毁损组大鼠颞叶皮质D2 受体表达有非常显著性差异 (P <0 .0 1) ;MAP+毁损组大鼠颞叶皮质DA受体阳性细胞数目与对照组比较差异无显著性 (P >0 .0 5 )。结论　中隔核毁损可以抑制使用MAP而诱发的颞叶皮质D2 表达的亢进。     

性激素对雌性大鼠缰核单胺类递质含量的影响

用高效液相-荧光检测法分别测定了成年及幼年雌性大鼠缰核(Hb)内单胺类递质的含量.结果表明,成年大鼠动情前期缰核内NE含量明显高于动情期和动情间期,DA、5-HT含量在整个动情期中无明显变化.皮下注射50 μg的雌二醇后,缰核内DA含量明显升高,NE、5-HT含量与对照组相比则无明显改变;在去卵巢给以雌激素的大鼠注射孕酮后,可显著提高缰核内NE含量,DA、5-HT含量与对照组比较则无明显变化;在幼年雌性大鼠皮下注射5、50 μg雌激素后,缰核内DA含量显著减少,NE、5-HT含量与对照组相比则均无明显变化.另外,对照组幼年雌性大鼠DA含量明显高于成年雌性大鼠对照组,成年大鼠NE、5-HT含量明显高于幼年大鼠.以上结果提示,雌、孕激素的水平可改变缰核内单胺类递质含量.     

卒中后抑郁状态患者的血浆、脑脊液单胺类神经递质测定

目的　探讨卒中后抑郁状态与血浆、脑脊液单胺类递质水平的关系。方法　采用高压液相色谱仪 ,测定 32例卒中后抑郁状态患者、30例卒中后无抑郁状态患者及 2 8名正常人的血浆、脑脊液单胺类递质水平 ,进行对照分析。结果　卒中后抑郁状态患者血浆、脑脊液中单胺类递质水平[多巴胺 (DA) =(2 6± 0 4) μmol L ,(2 0± 0 3) μmol L ;去甲肾上腺素 (NE) =(0 19± 0 0 6 ) μmol L ,(0 14± 0 0 6 ) μmol L ;5 羟色胺 (5 HT) =(1 0 9± 0 30 ) μmol L ,(0 6 0± 0 12 ) μmol L]低于卒中后无抑郁组 [DA =(3 2± 0 5 ) μmol L ,(2 6± 0 4) μmol L ;NE =(0 31± 0 12 ) μmol L ,(0 2 8± 0 0 8) μmol L ;5 HT=(1 31± 0 40 ) μmol L ,(1 11± 0 40 ) μmol L]及正常对照组 [DA =(2 9± 0 5 ) μmol L ,(2 2± 0 6 )μmol L ;NE =(0 2 7± 0 70 ) μmol L ,(0 2 3± 0 0 8) μmol L ;5 HT =(1 19± 0 30 ) μmol L ,(0 88± 0 0 7)μmol L],而大脑左侧及前部卒中患者的血浆、脑脊液中单胺类递质水平低于其它卒中部位患者 (P <0 0 5 ) ,脑脊液单胺类递质水平与抑郁程度呈负相关 (P <0 0 5 )。结论　卒中后抑郁状态的发生与血浆、脑脊液中单胺类神经递质的降低有关     

脑梗死后遗症大鼠模型脑组织ATP、ADP及单胺类神经递质含量的变化

目的 研究脑梗死后遗症大鼠模型脑组织ATP、ADP及单胺类神经递质含量的变化。方法 建立脑梗死后遗症大鼠模型，用高效液相色谱（HPLC）法测定大鼠脑组织ATP、ADP及单胺类神经递质含量。结果 刺激组（SG）毛发相对黯淡无光、卷曲，精神萎靡，惊恐，消瘦，肢体无力，摄食减少，饮水减少，手术伤口愈合迟缓，符合中医脑梗死后遗症征候。正常组（NG）大鼠脑组织ATP、ADP含量显著高于SG组、术后不刺激组（SG）（P〈0．01），同时NSG组大鼠脑组织ATP、ADP含量显著高于SG组（P〈0．05）。SG组大鼠脑组织NE、DA和5-HT含量显著低于NG组（P〈0．01），NSG组（P〈0．05）；NSG组大鼠脑组织DA含量显著低于NG组（P〈0．05）。结论 脑梗死后遗症大鼠由于能量代谢障碍而出现脑组织的ATP、ADP含量降低，并且伴有大脑释放单胺类递质增加及脑细胞内的单胺类递质含量减少，单胺类递质分泌增加又加重了脑组织的损伤，加剧ATP、ADP等能量物质代谢障碍，形成恶性循环。     

无先兆偏头痛患者血单胺类递质变化的研究

目的 了解5－羟色胺（5－TH）、5－羟吲哚乙酸（5－HIAA）、多巴胺（DA）、去甲肾上腺素（NE）在无先兆偏头痛发病中的作用。方法 用荧光分光光度法检测35例无先兆偏头痛患者（发作期16例、间歇期19例）和23例正常人血浆及血小板5－HT、5－HIAA、DA、NE含量。结果 无先兆偏头痛患者发作期组血浆5－HT含量低于对照组（P＜0.05),而5－HIAA含量高于对照组（P＜0.01）;间歇期组5－HT含量高于发作期组,而5－HIAA含量低于发作期组（P＜0.01）;发作期组血浆DA、NE含量均低于对照组（P＜0.01）间歇期组血浆DA与发作期组相比亦有显著性差异（P＜0.01）。无先兆偏头痛患者发作期组血小板5－HT含量高于对照组和间歇期组,而5－HIAA含量低于对照组和间歇期组（P＜0.01）;而发作期组血小板NE含量高于对照组和间歇期组（P＜0.01）;DA含量则低于对照组和间歇期组（P＜0.01）。结论 单胺类递质对偏头痛的发生可能有重要意义。     

Influences of cholecystokinin antiserum on the dopamine,norepinephrine and serotonin contents of different brain regions in rats

The effects of intraventricular administration of cholecystokinin antiserum on the dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents of the hypothalamus, mesencephalon, amygdala, septum, striatum and cerebral cortex were tested 24 hr following injection in rats.Cholecystokinin antiserum decreased the DA and NE contents of the hypothalamus, mesencephalon, amygdala and septum, while it increased the DA and decreased the NE content of the striatum. In the cerebral cortex the NE content was decreased. The 5-HT contents decreased in the mesencephalon, amygdala and septum, and increased in the striatum.     

Influence of cholecystokinin octapeptide sulfate ester on brain monoamine metabolism in rats

Summary The effects of intracerebroventricular administration of an 80 pmole dose of cholecystokinin octapeptide sulfate ester (CCK-8-SE) were tested on the dopamine (DA), norepinephrine (NE) and serotonin (5-HT) turnovers of the hypothalamus, mesencephalon, amygdala, septum, striatum and cerebral cortex in rats.CCK-8-SE in an 80 pmole dose decreased the DA turnovers of the hypothalamus, mesencephalon, amygdala and septum, while it increased that of the striatum. The NE turnovers were increased in the hypothalamus and amygdala, but decreased in the striatum. The 5-HT turnover decreased only in the hypothalamus.     

Dramatic brain aminergic deficit in a genetic mouse model of phenylketonuria

Clinical data suggest that brain catecholamines and serotonin are deficient in phenylketonuria (PKU), an inherited metabolic disorder that causes severe mental retardation and neurological disturbances. To test this hypothesis, brain tissue levels of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT) and their metabolites were evaluated in the genetic mouse model of PKU (Pah(enu2)). Results indicated a significant reduction of 5-HT levels and metabolism in prefrontal cortex (pFC), cingulate cortex (Cg), nucleus accumbens (NAc), caudate putamen (CP), hippocampus (HIP) and amygdala (AMY). NE content and metabolism were reduced in pFC, Cg, AMY and HIP. Finally, significantly reduced DA content and metabolism was observed in pFC, NAc, CP and AMY. In pFC, NAc and CP there was also a marked reduction of DA release.     

Site-specific activation of dopamine and serotonin transmission by aniracetam in the mesocorticolimbic pathway of rats

The effects of aniracetam on extracellular levels of dopamine (DA), serotonin (5-HT) and their metabolites were examined in five brain regions in freely moving stroke-prone spontaneously hypertensive rats (SHRSP) using in vivo microdialysis. Basal DA release in SHRSP was uniformly lower in all regions tested than that in age-matched control Wistar Kyoto rats. 3,4-Dihydroxyphenylacetic acid and homovanillic acid levels were altered in the basolateral amygdala, dorsal hippocampus and prefrontal cortex of SHRSP. While basal 5-HT release decreased in the striatum and increased in the basolateral amygdala, there was no associated change in 5-hydroxyindoleacetic acid levels. Systemic administration of aniracetam to SHRSP enhanced both DA and 5-HT release with partly associated change in their metabolite levels in the prefrontal cortex, basolateral amygdala and dorsal hippocampus, but not in the striatum and nucleus accumbens shell, in a dose-dependent manner (30 and/or 100 mg/kg p.o.). Microinjection (1 and 10 ng) of aniracetam or its metabolites (N-anisoyl-GABA and 2-pyrrolidinone) into the nucleus accumbens shell produced no turning behavior. These findings indicate that SHRSP have a dopaminergic hypofunction throughout the brain and that aniracetam elicits a site-specific activation in mesocorticolimbic dopaminergic and serotonergic pathways in SHRSP, possibly via nicotinic acetylcholine receptors in the ventral tegmental area and raphe nuclei. The physiological roles in the aniracetam-sensitive brain regions may closely link with their clinical efficacy towards emotional disturbances appearing after cerebral infarction.     

Evaluation of glycine site antagonists of the NMDA receptor in global cerebral ischaemia

The central neurochemical and neuroendocrine effects of a psychogenic (ferret exposure) and a neurogenic (restraint) stressor were assessed in rats that had been selectively bred for differences in amygdala excitability manifested by either Fast or Slow amygdala kindling epileptogenesis. While these rat lines differ in their emotionality, their behavioral styles were dependent on the nature of the stressor to which they were exposed. During restraint, the Slow rats were mostly immobile, while Fast rats persistently struggled. In contrast, Fast rats were more immobile in response to the ferret. Yet, the more emotional Slow rats exhibited a greater corticosterone response to the ferret, while comparable corticosterone responses between lines were evident following restraint. Although both stressors influenced norepinephrine (NE), dopamine (DA) and/or serotonin (5-HT) activity in brain regions typically associated with stressors (e.g., locus coeruleus, paraventricular nucleus of the hypothalamus, nucleus accumbens, prefrontal cortex), considerable amine alterations were evident in the medial and basolateral amygdala nuclei, but not in the central nucleus. Moreover, greater NE changes were apparent in the medial amygdala of the left hemisphere. Similarly, DA alterations also were greater in the left medial amygdala in response to stressors. Despite very different behavioral styles, however, the two lines often exhibited similar amine alterations in response to both stressors.     

Selective changes in the contents of noradrenaline, dopamine and serotonin in rat brain areas during aging

This study examines the age-associated changes in noradrenaline (NA), dopamine (DA), 3,4-dihydroxyphenyl-acetic acid (DOPAC), serotonin (5-HT) and 5-hydroxy-3-indoleacetic acid (5-HIAA) in different brain areas of rats. DA and DOPAC concentrations in striatum increased at third month of age, remaining without significant variations until 12th month of age, and decreasing in 24-month-old rats. DA concentration dropped in hippocampus, amygdala and brainstem of 24-month-old-rats, whereas DOPAC levels decreased only in hippocampus. These changes suggest an age-dependent deficit of the dopaminergic system, presumably related to a reduced number/activity of DA nigrostriatal and mesolimbic neurons. An age-induced decline in NA content was found in the pons-medulla, the area containing NA neuronal bodies. Concentrations of 5-HT were reduced with aging in frontal cortex, showing a tendency to decrease in all brain areas examined. The increased 5-HIAA/5-HT ratio found in frontal cortex, amygdala and striatum suggests an age-related decreased synthesis and an accelerated 5-HT metabolism. The 5-HIAA content decreased in brainstem of the oldest rats. These findings point to a selective impairment of nigrostriatal and mesolimbic DA in aging rats, whereas reductions in NA were restricted to cell bodies region and 5-HT showed changes of different extent in areas of terminals and neuronal cell bodies.     

Attenuating effects of the isolated rearing condition on increased brain serotonin and dopamine turnover elicited by novelty stress

Isolation and acute environmental change are risk factors in human depression. In the present study, we investigated the differences in the brain monoamine activity of rats between two rearing conditions, isolated and group. Moreover, we examined the responses to novelty stress. Male F344 rats aged 11 weeks were divided into the above two groups. Four weeks later they were further divided into non-stress and stress groups. The latter received 20 min exposure to novelty stress. Isolation significantly changed brain monoamine levels, with the levels of dopamine (DA) in the nucleus accumbens and midbrain, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the midbrain, and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus increasing. Serotonin (5-HT) levels also increased in all brain areas except the raphe nuclei. HVA levels in the raphe nuclei decreased. Novelty stress significantly altered brain monoamine levels. DA, DOPAC, and HVA levels in the prefrontal cortex decreased, as did those of 5-HT in the prefrontal cortex and hippocampus. DA levels in the nucleus accumbens increased. Isolation attenuated the enhanced brain monoamine turnover elicited by novelty stress. The enhanced DA turnover ratio in the prefrontal cortex of the group-reared group was attenuated in the isolated-reared group, and the unchanged DA turnover ratio in the nucleus accumbens of the group-reared group declined in the isolated-reared group. The enhanced 5-HT turnover ratio in the prefrontal cortex, nucleus accumbens, and hippocampus of the group-reared group was attenuated in the isolated-reared group. Isolation may exacerbate adaptation to stress, and be related to the etiology of human depression.     

Influence of aging and social isolation on changes in brain monoamine turnover and biosynthesis of rats elicited by novelty stress

Aging is a risk factor of human depression. Middle-aged or older men are vulnerable to adverse life events and an absence of social contact and easily become depressed. In the present study, we investigated the influence of aging on responses to life events in socially isolated conditions. We applied isolation-rearing (4 W) to two age groups, older (18 M) and younger (11 W), of male F344 rats that had been reared in a group and then examined responses to novelty stress (20 min). Changes in brain monoamines and their metabolites such as dopamine (DA), serotonin (5-HT), dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in six regions: the prefrontal cortex, nucleus accumbens, hippocampus, amygdala, midbrain, and raphe nuclei. MANOVA was carried out for rearing condition, age, and novelty stress. Isolation significantly changed monoamines and their metabolites, except in amygdala and raphe nuclei. Aging significantly altered them in all regions, although novelty stress did not. In the amygdala and midbrain, isolation significantly changed monoamine biosynthesis, with monoamine turnover remaining unchanged. In the prefrontal cortex and nucleus accumbens, aging significantly altered turnover, while biosynthesis remained unchanged. Novelty stress significantly varied only the turnover in the prefrontal cortex. The interaction between isolation and aging indicated that aging influences changes in turnover and biosynthesis elicited by isolation primarily at the center of the mesolymbic DA system, the midbrain, and in raphe nuclei of the 5-HT system. In peripheral regions of the mesolymbic system, aging primarily affects changes in turnover induced by isolation.     

Regional changes in monoamine content and uptake of the rat brain during postnatal development.

Regional norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) contents in the developing rat brain were estimated. The rate of increase in NE content was the highest in diencephalon, followed by the lower brain stem, limbic-striatum, neocortex and cerebellum. With postnatal aging, DA concentration increased markedly in limbic-striatum, slightly in the neocortex and negligibly in other regions. In each region except cerebellum, 5-HT content increased gradually but the rate of increase in diencephalon was relatively high. Comparison of the kinetics of high affinity uptake of L-[3H]NE and [3H]5-HT between the neonatal and the adult brain indicated that Km values of L-[3H]NE and [3H]5-HT uptake were 2.9 X 10(-7) M and 1.7 X 10(-7) M respectively in neocortex, diencephalon and lower brain stem and 4.3 X 10(-7) M and 2.3 X 10(-7) M in limbic-striatum in the neonate as well as in the adult. Vmax values of both amines uptake differed regionally and the values in the neonate were lower than those in the adult in all regions. Limbic-striatum showed a higher Vmax value than other regions in uptake of both amines. These results suggested that innervation of monoaminergic neurons in the brain progressed with increasing age, that projections of both NE and 5-HT neurons were relatively high into hypothalamus and limbic-striatum and that DA neuron projections concentrated at striatum. Although the brain, except for limbic-striatum, showed neither regional nor developmental differences in affinity of L-[3H]NE and [3H]5-HT to synaptosomes, the density of nerve terminal of both monoaminergic neurons increased in all regions of the brain during postnatal development. In limbic-striatum, higher Km and Vmax values of both amines, uptake suggest the existence of both amines' uptake into DA terminal to some extent.