第十七届全国神经精神药理学学术会议论文摘要

2016年5月13-16日,安徽合肥专题1:精神分裂症与抑郁症T1-1急性及慢性应激诱导的小鼠中枢及外周神经递质谷氨酸、谷氨酰胺和γ-氨基丁酸的变化陈亚萍1,王闯2,程玉芳1,李亦文1,徐江平1(1.南方医科大学药学院神经药理与新药发现课题组,广东广州510515;2.宁波大学医学院,浙江宁波315211)摘要:目的通过测定急性应激造模和慢性应激造模小鼠的血浆和脑组织内谷氨酸、谷氨酰胺、γ-氨基丁酸3种神经递质的含量,比较抑郁症不同阶段脑组织和血浆中神经递质的变化。方法小鼠慢性应激造模8周,急性束缚应激3 h,用悬尾实验检查造模效果后取脑组织和血浆,以高丝氨     

淫羊藿苷对快速老化小鼠SAMP10脑组织单胺类及氨基酸类神经递质的影响

目的:探讨淫羊藿苷(ICA)对快速老化小鼠SAMP10脑组织单胺类及氨基酸类神经递质的影响。方法:本实验采取8月龄快速老化小鼠SAMP10为实验对象,随机分为模型SAMP10组、阳性药多奈哌齐组(1mg/kg)、ICA 3个剂量(50、100、200mg/kg)组,每组12只,以12只同月龄抗快速老化小鼠SAMR1为正常对照。灌胃给药30d,一天一次,高效液相-电化学法检测快速老化小鼠SAMP10大脑皮层的去甲肾上腺素(NE)、5-羟色胺(5-HT)、多巴胺(DA)及其代谢产物3,4-二羟苯乙酸(DOPAC)和高香草酸(HVA)的含量来探讨ICA对SAMP10脑组织单胺类神经递质的影响,通过检测谷氨酸(Glu)、谷氨酰胺(Gln)、天冬氨酸(Asp)、γ-氨基丁酸(GA-BA)、牛磺酸(Tau)、甘氨酸(Gly)的含量来探讨ICA对SAMP10脑组织氨基酸类神经递质的影响。结果:ICA可显著降低SAMP10大脑皮层内Glu、Gln、GABA含量(P<0.01),升高NE、DA、DOPAC、5-HT、HVA、Asp以及Tau的含量(P<0.01或P<0.05),但对SAMP10大脑皮层内Gly的含量并没有显著影响(P>0.05)。结论:ICA可能通过升高脑内单胺类神经递质的含量、调节兴奋性氨基酸类递质的代谢平衡以及调节抑制性氨基酸的代谢平衡达到改善SAMP10的学习记忆的作用。     

蒲公英总黄酮提取液对衰老模型小鼠脑组织单胺氧化酶及单胺类神经递质含量的影响

目的:探讨蒲公英总黄酮提取液对衰老模型小鼠脑组织单胺氧化酶(MAO)及单胺类神经递质含量的影响.方法:采用小鼠注射D-gal制成衰老模型,蒲公英总黄酮提取液灌胃30d,测定小鼠脑组织MAO活性及单胺类神经递质的含量.结果:蒲公英总黄酮提取液能降低衰老模型小鼠脑组织内MAO活性(P＜0.05),提高去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)含量(P＜0.05).结论:蒲公英总黄酮提取液可降低衰老模型小鼠脑组织MAO活性并能提高单胺类神经递质的含量,具有一定的抗衰老作用.     

依达拉奉注射液对急性一氧化碳中毒大鼠的脑保护作用

目的:观察急性一氧化碳中毒大鼠脑内的氨基酸神经递质的变化,以及依达拉奉对中毒大鼠的脑保护作用.方法:选择健康成年大鼠70只,体重300～350g.动物随机分为正常对照组,一氧化碳中毒组,依达拉奉注射液治疗组.一氧化碳中毒后1、5、7d及依达拉奉注射液治疗后1、5、7d、每时间点各10只,处死后测定天冬氨酸,γ氨基丁酸含量.结果:急性一氧化碳中毒大鼠随时间延长抑制性氨基酸神经递质逐渐增加,兴奋性氨基酸神经递质含量逐渐减少,依达拉奉可以减少抑制性氨基酸神经递质含量.结论:依达拉奉注射液对急性一氧化碳中毒大鼠具有脑保护作用.     

健忆口服液对老年小鼠全脑组织重量、单胺类神经递质和β淀粉样蛋白作用的实验研究

目的观察健忆口服液对老年小鼠脑组织重量、单胺类神经递质和β淀粉样蛋白(Aβ)的作用.方法设昆明种老年小鼠(18～20月龄)中药治疗组(健忆口服液20 g·kg-1·d-1)及对照组;另设8～10月龄小鼠为青年对照.灌胃给药,疗程为4周.观察指标:1、小鼠脑重量;2、全脑组织去甲肾上腺素(NA)、多巴胺(DA)、5-羟色胺(5-HT)含量;3、全脑组织Aβ含量.结果老年鼠的脑重量及脑组织NA、DA、5-HT和Aβ含量变化均较青年小鼠有非常显著差异(P＜0.01);服药四周后治疗组上述指标变化,与对照组比较均有显著差异(P＜0.05),但与青年鼠比较仍有显著差异(P＜0.05).结论健忆口服液对老年小鼠脑组织Aβ具有明显降低治疗作用,提示可能对阿尔茨海默病相关指标具有相似治疗作用;其对老年小鼠脑萎缩和单胺类神经递质下降也有明显改善治疗作用,提示可能具有多水平、多靶点的治疗作用.     

灯银脑通胶囊对衰老小鼠脑组织内单胺类神经递质含量的影响

目的研究灯银脑通胶囊对衰老小鼠脑组织内单胺类神经递质含量的影响。方法给ICR小鼠眼球后注射D-半乳糖造成衰老动物模型,分组灌胃给予不同剂量的灯银脑通胶囊（0．5、1、2g／kg）,每日一次,连续两周,然后测试衰老小鼠脑组织内单胺类神经递质含量。结果衰老小鼠脑内NA、DA、5-HT等单胺类神经递质含量增加。结论灯银脑通胶囊能增加衰老小鼠脑内NA、DA、5-HT等单胺类神经递质。     

急性色氨酸、苯丙氨酸和酪氨酸剥夺对酒依赖者线索暴露诱导的饮酒迫促性的作用

目的:评价急性色氨酸、苯丙氨酸和酪氨酸剥夺(CMD)对酒依赖者线索暴露诱导的饮酒迫促性的作用。方法:采用随机双盲交叉对照的方法,选择符合ICD-10和DSM-Ⅳ诊断标准的男性酒依赖患者12名,并排除任一符合DSM-Ⅳ轴Ⅰ诊断的其他精神障碍。在签署知情同意书的情况下,每位受试者间隔至少7d分别在实验当天禁食的情况下给予含人体必需的16种氨基酸的氨基酸饮料(BLANCE)或缺失色氨酸、苯丙氨酸和酪氨酸的氨基酸饮料(CMD),实验的前一天低蛋白饮食,实验当天结束后给予高蛋白饮食。实验当天,在给予氨基酸饮料前后进行Tiffany饮酒迫促性量表、焦虑可视模拟标尺、抑郁可视模拟标尺、副反应量表测查以及血压、心率检测。给予氨基酸饮料6h后进行非酒精(纯净水)相关线索和酒精(白酒)相关线索暴露,并评价暴露前后饮酒迫促性、焦虑可视模拟标尺分、抑郁可视模拟标尺分和血压、心率的变化。结果:CMD组在非酒精相关线索和酒精相关线索暴露后饮酒意愿(Intention/desire to drinking)和舒张压均增加,差异具有显著性(P=0.0217,0.038),而BLANCE组在非酒精相关线索和酒精相关线索暴露后饮酒意愿、舒张压差异均无显著性。焦虑可视模拟标尺分、抑郁可视模拟标尺分、收缩压、心率在两组中的非酒精相关线索和酒精相关线索暴露前后的差异无显著性。在安全性方面,所有受试者中有1名出现腹泻,但是病人尚能耐受。其余少见的副反应主要有恶心、头晕、困倦等,皆为轻度或中度。结论:急性色氨酸、苯丙氨酸和酪氨酸剥夺(CMD)后酒依赖患者在非酒精和酒精相关线索暴露后的饮酒意愿增加,舒张压增高,但是对焦虑和抑郁情绪没有影响。口服氨基酸饮料的副反应少且轻微。     

通窍活血汤对脑缺血再灌注小鼠血脑屏障通透性及脑内单胺类神经递质含量的影响

目的：观察通窍活血汤（TQHXD）对脑缺血再灌注损伤小鼠血脑屏障（BBB）通透性及脑组织中单胺类神经递质的影响。方法将昆明种小鼠随机分为假手术组,模型组,尼莫地平组,脑脉泰组,通窍活血汤低、中、高剂量组（分别为3．85,7．7,15．4 g·kg－1）。于给药第7天采用双侧颈总动脉结扎法制造急性脑缺血再灌注模型,通过测定渗出脑血管外的伊文思蓝含量分析药物对BBB通透性的影响,及采用酶联免疫法（ELISE）测定脑组织中单胺类神经递质去甲肾上腺素（NE）、多巴胺（DA）和5－羟色胺（5-HT）的含量。结果 TQHXD各剂量组均能降低小鼠脑中伊文思蓝的含量,且均能阻止脑损伤后单胺类神经递质的降低。结论 TQHXD对脑缺血再灌注模型小鼠有一定的保护作用。     

纳米氧化铝暴露对小鼠神经行为学的持续影响及其机制探讨

目的探讨纳米氧化铝吸入暴露染毒对小鼠神经行为学的持续影响及其可能存在的机制。方法将40只健康ICR小鼠随机分成4组,每组10只,1组为对照组,3组为纳米氧化铝暴露染毒。应用动式吸入染毒柜,同时给予各暴露染毒组小鼠纳米氧化铝动态吸入染毒,染毒浓度1 mg/m3,每天暴露8 h,连续染毒14 d,于染毒开始前1 d(对照组),染毒结束后1 d(暴露后1 d组)、60 d(暴露后60 d组)、90 d(暴露后90 d组),采用旷场试验和Morris水迷宫试验检测小鼠的空间学习和记忆能力,取大脑皮层组织作苏木素-伊红(HE)染色和淀粉样蛋白前体(amyloid precursor protein,APP)免疫组化染色,qRT-PCR检测APP mRNA的表达水平,并用试剂盒法检测脑组织中腺嘌呤核苷三磷酸(ATP)、丙二醛(MDA)、活性氧(ROS)含量。结果旷场试验中,与对照组相比,除暴露后1 d组小鼠在进入中心区频率差异无统计学意义,其余各组小鼠各项指标均降低且差异有统计学意义(P0.05);水迷宫试验中,各暴露染毒组小鼠平台象限停留时间均降低,差异均有统计学意义(P0.05);穿越平台区频率均降低,仅暴露后90 d组小鼠差异有统计学意义(P0.05)。大脑皮层的HE染色均未见明显的病理改变,APP免疫组化染色显示暴露后90 d组APP阳性细胞明显增加;qRT-PCR检测显示,APP mRNA的表达水平随暴露后天数增加而升高,且差异均有统计学意义(P0.05);脑组织中ATP水平与对照组相比均降低,暴露后60和90 d组小鼠ATP水平差异有统计学意义(P0.05),MDA含量和ROS含量均升高且差异均有统计学意义(P0.05)。结论经纳米氧化铝暴露染毒,脱离暴露环境后,仍然会提高小鼠脑组织氧化应激水平并改变其神经行为学。APP的过度表达以及脑组织氧化应激反应可能是纳米氧化铝导致小鼠神经行为学改变的重要机制之一。     

纳米氧化铝暴露对小鼠神经行为学的持续影响及其机制探讨北大核心CSCD

目的探讨纳米氧化铝吸入暴露染毒对小鼠神经行为学的持续影响及其可能存在的机制。方法将40只健康ICR小鼠随机分成4组,每组10只,1组为对照组,3组为纳米氧化铝暴露染毒。应用动式吸入染毒柜,同时给予各暴露染毒组小鼠纳米氧化铝动态吸入染毒,染毒浓度1 mg/m3,每天暴露8 h,连续染毒14 d,于染毒开始前1 d(对照组),染毒结束后1 d(暴露后1 d组)、60 d(暴露后60 d组)、90 d(暴露后90 d组),采用旷场试验和Morris水迷宫试验检测小鼠的空间学习和记忆能力,取大脑皮层组织作苏木素-伊红(HE)染色和淀粉样蛋白前体(amyloid precursor protein,APP)免疫组化染色,qRT-PCR检测APP mRNA的表达水平,并用试剂盒法检测脑组织中腺嘌呤核苷三磷酸(ATP)、丙二醛(MDA)、活性氧(ROS)含量。结果旷场试验中,与对照组相比,除暴露后1 d组小鼠在进入中心区频率差异无统计学意义,其余各组小鼠各项指标均降低且差异有统计学意义(P<0.05);水迷宫试验中,各暴露染毒组小鼠平台象限停留时间均降低,差异均有统计学意义(P<0.05);穿越平台区频率均降低,仅暴露后90 d组小鼠差异有统计学意义(P<0.05)。大脑皮层的HE染色均未见明显的病理改变,APP免疫组化染色显示暴露后90 d组APP阳性细胞明显增加;qRT-PCR检测显示,APP mRNA的表达水平随暴露后天数增加而升高,且差异均有统计学意义(P<0.05);脑组织中ATP水平与对照组相比均降低,暴露后60和90 d组小鼠ATP水平差异有统计学意义(P<0.05),MDA含量和ROS含量均升高且差异均有统计学意义(P<0.05)。结论经纳米氧化铝暴露染毒,脱离暴露环境后,仍然会提高小鼠脑组织氧化应激水平并改变其神经行为学。APP的过度表达以及脑组织氧化应激反应可能是纳米氧化铝导致小鼠神经行为学改变的重要机制之一。     

Effect of kindled seizures on rat behavior in water Morris maze test and amino acid concentrations in brain structures

The effects of kindled seizures elicited by repeated pentetetrazole (PTZ) injections, on learning and memory in the Morris water maze test and on concentration of brain amino acids, were examined in rats. It was found that kindled seizures (a model of temporal lobe epilepsy) produced a profound decrease in learning and memory accompanied by a selective and long-lasting decrease in hippocampal and striatal concentration of glutamate, glycine and alanine in the striatum (ex vivo measurement). The concentrations of histamine, serine and gamma-aminobutyric acid (GABA) were not selectively affected by kindling. Alower concentration of glutamate and N-methyl-D-aspartate (NMDA) receptor co-agonists in the striatum (glycine and alanine) indicates the general malfunction of the brain glutamatergic system. It is suggested that a selective decrease in hippocampal glutamate concentration may account for deterioration in learning and memory processes in kindled rats, considering the important role of this neurotransmitter in the cognitive processes (e.g. in the long-term potentiation), and the key contribution of the hippocampus to the spatial memory. The intrinsic mechanisms of the reported behavioral effects may involve neuronal damage in the brain limbic structures, secondary to seizure-induced ischemia and hypoxia.     

A microdialysis study of glycinamide, glycine and other amino acid neurotransmitters in rat frontal cortex and hippocampus after the administration of milacemide, a glycine pro-drug

Milacemide is a glycinamide derivative which readily enters the brain and is metabolised to glycine. As its mechanism of action as an anticonvulsant drug is unknown we used the technique of microdialysis to study the temporal inter-relationship of glycinamide, glycine and other amino acid neurotransmitters in the extracellular fluid of rat hippocampus and frontal cortex. After milacemide administration (400 or 800 mg/kg i.p.), glycinamide concentrations rose linearly and dose-dependently in both hippocampus and frontal cortex. In contrast, whilst glycine concentrations rose in the hippocampus, glycine was unaffected in the frontal cortex. Concomitant increases in taurine hippocampal concentrations were observed. An increase in serine and a decrease in alanine concentrations was only observed at the highest milacemide dose (800 mg/kg). Other amino acids were unaffected. Thus, while glycinamide appears to be universally distributed throughout the brain, its metabolism to glycine and its effects on brain amino acids appear to be region specific.     

Neurochemical correlates of behavior: levels of amino acids in four areas of the brain of the rat during drug-induced behavioral excitation.

The levels of GABA, aspartate, glutamate, glycine and alanine were determined in 4 specific brain areas (telencephalon, diencephalon-mesencephalon cerebellum and pons-medulla oblongata) of rats killed during a period of drug-induced behavioral excitation. Behavioral excitation was obtained in adult, male Wistar rats working on a Sidman shock-avoidance schedule following administration of 2 mg/kg tetrabenazine (TBZ) 18 hr after iproniazid (50 mg/kg) pretreatment. When compared to trained animals (working on the avoidance schedule but receiving no drugs), the excited rats had increased levels of GABA in the telencephalon and diencephalon-mesencephalon, decreased levels of aspartate in all 4 brain areas, and a lower content of glycine in the pons-medulla region. The changes in the levels of aspartate in all areas of the brain, GABA in the diencephalon-mesencephalon, and glycine in the pons-medulla were significantly correlated (p less than 0.01) with the degree of excitation. It was observed that avoidance training alone produced increases in the levels of four amino acids: aspartate in telencephalon and cerebellum, GABA in cerebellum, and glycine and glutamate in the pons-medulla. The injection of iproniazid alone or iproniazid followed by TBZ into naive animals had little effect on the levels of the five amino acids. The data are discussed in terms of aspartate and GABA interacting as neurotransmitters with cholinergic and catecholaminergic and/or serotonergic neurons to produced the behavioral excitation.     

Ontogeny of amino acids related to excitatory amino acidergic transmission in the rat forebrain

Developmental changes in the concentration of putative amino acid neurotransmitters were investigated in the forebrain of prenatal and postnatal rats. Glutamate and aspartate, which interact with three-typed agonist sites of excitatory amino acid receptors, decreased until birth and then increased with maturation. Agonists for strychnine-insensitive glycine sites, i.e., glycine, serine and alanine, showed progressive decreases in the postnatal period. Although alanine rapidly decreased in preterm, there was no change in glycine and serine contents in this period. These developmental patterns of the compounds related to EAA transmission differed from those of inhibitory amino acid transmitters. GABA showed a steady increase during ontogeny. Taurine increased until birth and then decreased to the adult level. These results suggested that the ontogenic profile for EAA is different from that for the glycine receptor agonists and that other inhibitory amino acid transmitters develop with patterns different from those of amino acids related to EAAergic transmission.     

Toluene induces rapid and reversible rise of hippocampal glutamate and taurine neurotransmitter levels in mice

Toluene, a widely used aromatic organic solvent, has been well characterized as a neurotoxic chemical. Although the neurobehavioral effects of toluene have been studied substantially, the mechanisms involved are not clearly understood. Hippocampus, which is one of the limbic areas of brain associated with neuronal plasticity, and learning and memory functions, may be a principal target of toluene. In the present study, to establish a mouse model for investigating the effects of acute toluene exposure on the amino acid neurotransmitter levels in the hippocampus, in vivo microdialysis study was performed in freely moving mice after a single intraperitoneal administration of toluene (150 and 300 mg/kg). Amino acid neurotransmitters in microdialysates were measured by a high performance liquid chromatography system. The extracellular levels of glutamate and taurine were rapidly and reversibly increased within 30 min after the toluene administration in a dose-dependent manner and returned to the basal level by 1h. Conversely, the extracellular level of glycine and GABA were stable, and no significant change was observed after the toluene administration. To further investigate the brain toluene level in the hippocampus of toluene-administered mice, we used a solid-phase microextraction (SPME) method and examined the time course changes of toluene in the hippocampus of living mice. The brain toluene level reached the peak at 30 min after injection and returned to the basal level after 2h. In the present study, we observed the relationship between brain toluene levels and amino acid neurotransmitter glutamate and taurine levels in the hippocampus. Therefore, we suggest that toluene may mediate its action through the glutamatergic and taurinergic neurotransmission in the hippocampus of freely moving mice.     

Dog bites man or man bites dog? The enigma of the amino acid conjugations

The proposition posed is that the value of amino acid conjugation to the organism is not, as in the traditional view, to use amino acids for the detoxication of aromatic acids. Rather, the converse is more likely, to use aromatic acids that originate from the diet and gut microbiota to assist in the regulation of body stores of amino acids, such as glycine, glutamate, and, in certain invertebrates, arginine, that are key neurotransmitters in the central nervous system (CNS). As such, the amino acid conjugations are not so much detoxication reactions, rather they are homeostatic and neuroregulatory processes. Experimental data have been culled in support of this hypothesis from a broad range of scientific and clinical literature. Such data include the low detoxication value of amino acid conjugations and the Janus nature of certain amino acids that are both neurotransmitters and apparent conjugating agents. Amino acid scavenging mechanisms in blood deplete brain amino acids. Amino acids glutamate and glycine when trafficked from brain are metabolized to conjugates of aromatic acids in hepatic mitochondria and then irreversibly excreted into urine. This process is used clinically to deplete excess nitrogen in cases of urea cycle enzymopathies through excretion of glycine or glutamine as their aromatic acid conjugates. Untoward effects of high-dose phenylacetic acid surround CNS toxicity. There appears to be a relationship between extent of glycine scavenging by benzoic acid and psychomotor function. Glycine and glutamine scavenging by conjugation with aromatic acids may have important psychosomatic consequences that link diet to health, wellbeing, and disease.     

Bipolar mania and plasma amino acids: increased levels of glycine.

Previous studies have suggested that the N-methyl-d-aspartate (NMDA) glutamate receptor complex is implicated in the pathophysiology of several neuropsychiatric disorders. Especially the glycine coagonist site of this receptor has been proposed as a therapeutic target. It has been hypothesized that the NMDA receptor and the serotonergic system, which function is compromised in affective disorders, are functionally coupled. Furthermore, several studies suggest that peripheral levels of amino acids are associated with psychotic symptomatology. We therefore measured plasma levels of glutamate, glycine, tryptophan and the tryptophan ratio in 20 bipolar-I patients during the manic phase and at remission of symptomatology. Data were compared to a matched group of healthy controls and a group of euthymic bipolar-I patients. During the manic phase, a significant increase of both glutamate and glycine was found, that persisted at remission. Tryptophan and the tryptophan ratio were decreased in manic patients. Subsequent analysis showed that changes in glutamate, tryptophan and tryptophan ratio could be attributed to the use of anticonvulsants. The increased glycine, however, was not related to the use of mood stabilizers. Although the exact relationship between peripheral measures of amino acids, e.g., glycine is not fully clear, the results of this study suggest an involvement of glycine and/or its coagonist site of the NMDA receptor in a manic relapse of patients with a bipolar-I disorder.     

In vivo microdialysis study of the relationship between lead-induced impairment of learning and neurotransmitter changes in the hippocampus

Chronic exposure to lead during development is associated with cognitive dysfunction in children and animals and impairment of release of neurotransmitters in the brain. Some amino acid neurotransmitters in the CNS are critical for the induction of LTP, which is considered a potential mechanism of learning and memory. In this study, the extracellular levels of amino acids in the dentate gyrus (DG) of the hippocampus of early postnatal rats exposed to lead were measured by in vivo microdialysis, before and after 50 days of training. Samples of cerebrospinal fluid were analyzed by high-pressure liquid chromatography (HPLC) and fluorescence detection. Compared to pre-training, the concentration of glutamate in the post-training samples increased by 164.2 and 222.6% in the control and lead-exposure rats, respectively. After training, the extracellular concentration of GABA and glycine decreased by 49.4 and 44.3% in lead-exposed rats, respectively, whereas in the after-training samples of control rats, the concentration of GABA was unchanged and glycine decreased by 21.8%. The results of this study may suggest that concentrations of the neurotransmitters were changed during the learning process and lead impaired the neurotransmitter systems, especially glutamate and GABA systems.     

Effect of the convulsive agent 3-mercaptopropionic acid on the levels of GABA, other amino acids and glutamate decarboxylase in different regions of the rat brain

Intraperitoneal injection of 3-mercaptopropionic acid into rats caused severe convulsions which started after about 7 min. Of the amino acids examined only the level of GABA changed after 4 min and immediately before (6.5–7 min) the convulsions started. The decrease in GABA concentration detected immediately before the onset of convulsions was about 35 per cent in the cerebral cortex, corpus striatum and cerebellum, 30 per cent in pons-medulla and 20% in hippocampus. Concomitant with the fall in GABA there was a large, reversible inhibition of glutamate decarboxylase activity in the brain. The uptake of GABA into synaptosomes isolated after injection of the convulsive agent was not reduced, and the uptake of GABA into synaptosomes was not inhibited by high concentrations of 3-mercaptopropionic acid added in vitro. During convulsions levels of aspartate and taurine decreased significantly in all the brain regions investigated. A small increase in glutamine was detected in pons-medulla and in cerebellum. Major changes in the concentrations of other amino acids such as glutamate, alanine, serine and glycine were found only in corpus striatum.