Differential effects of classical and atypical antipsychotic drugs on A9 and A10 dopamine neurons

Prolonged treatment with classical antipsychotic drugs decreased the number of spontaneously active dopamine neurons in both the substantia nigra (A9) and the ventral tegmental area (A10) of the rat brain. In contrast, treatment with atypical antipsychotic drugs selectively decreased the number of A10 dopamine neurons. Related drugs lacking antipsychotic efficacy failed to decrease dopamine activity. These findings suggest that the inability of atypical antipsychotic drugs to decrease A9 dopamine neuronal activity may be related to their lower potential for causing tardive dyskinesia and that the inactivation of A10 neurons may be involved in the delayed onset of therapeutic effects during treatment.     

Narcolepsy: biogenic amine deficits in an animal model

Concentrations of biogenic amine metabolites in discrete brain areas differed significantly between dogs with genetically transmitted narcolepsy and age- and breed-matched controls. Dopamine and 3,4-dihydroxyphenylacetic acid were consistently elevated in the brains of narcoleptic animals, while homovanillic acid was not. Narcoleptic animals consistently exhibited lower utilization of dopamine and higher intraneuronal degradation of dopamine but no uniform decrease in serotonin utilization. Hence neuropathology appears to be associated with genetically transmitted canine narcolepsy. The data indicate a nonglobal depression of dopamine utilization or turnover or both.     

Plasma homovanillic acid concentration and the severity of schizophrenic illness

Concentrations of plasma homovanillic acid before treatment were highly correlated with global severity of illness in schizophrenic patients, both before and after treatment. In contrast, a fixed dose of haloperidol did not affect those concentrations. Thus, in patients with a diagnosis of schizophrenia, plasma homovanillic acid may reflect the severity of illness, but not be influenced by short-term pharmacological perturbations by neuroleptics.     

Schizophrenia: dopamine beta-hydroxylase activity and treatment response

Cerebrospinal fluid levels of dopamine beta-hydroxylase, found to be relatively constant over time in individual patients, were significantly lower in schizophrenic patients who became nonpsychotic during neuroleptic treatment than in those who remained psychotic. Dopamine beta-hydroxylase activity may delineate a subgroup of patients who have a dopamine-sensitive brain disorder.     

Perinatal dopamine-related drugs demasculinize rats

Administration of haloperidol, a common neuroleptic, to pregnant or lactating rats impaired the masculine sex behavior of their male offspring. Prenatal haloperidol did not affect testosterone concentrations in fetuses. Maternal administration of apomorphine, a dopamine agonist, and of alpha-methyl-p-tyrosine, an inhibitor of dopamine synthesis, also demasculinized male offspring. In both experiments other behaviors and developmental milestones were unaffected. Perinatal haloperidol, apomorphine, and alpha-methyl-p-tyrosine did not lower testosterone in adulthood. These drugs may act directly on neurons that control masculine behavior without lowering testosterone prenatally or in adulthood.     

Biogenic amine metabolites in cerebrospinal fluid of depressed and manic patients

A reduction in 5-hydroxyindoleacetic acid in cerebrospinal fluid was found in depressed and manic patients both while they were symptomatic and also after treatment. The concentration of homovanillic acid was initially reduced and then tended to increase after treatment.     

Spontaneous orofacial dyskinesia and dopaminergic function in rats after 6 months of neuroleptic treatment

A syndrome of spontaneous orofacial dyskinesia was identified in groups of rats treated for 6 months with a wide range of neuroleptic drugs. Phenothiazines, thioxanthenes, and substituted benzamides were particularly likely to induce the syndrome. It was observed in the presence of a functional blockade of dopamine receptors and endured for at least 2.5 months after drug withdrawal. There was no relation between the syndrome and changes in striatal dopamine receptors, as indexed by the binding of tritiated spiperone and tritiated cis(Z)-flupenthixol. The syndrome parallels several of the features of clinical tardive dyskinesia, whose pathophysiology thus may not involve changes in the characteristics of striatal dopamine receptors.     

Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation

Chronic blockade of dopamine D2 receptors, a common mechanism of action for antipsychotic drugs, down-regulates D1 receptors in the prefrontal cortex and, as shown here, produces severe impairments in working memory. These deficits were reversed in monkeys by short-term coadministration of a D1 agonist, ABT 431, and this improvement was sustained for more than a year after cessation of D1 treatment. These findings indicate that pharmacological modulation of the D1 signaling pathway can produce long-lasting changes in functional circuits underlying working memory. Resetting this pathway by brief exposure to the agonist may provide a valuable strategy for therapeutic intervention in schizophrenia and other dopamine dysfunctional states.     

不同外源物质对高温胁迫下平邑甜茶幼苗的缓解效应

为探究不同外源物质对高温胁迫下苹果植株的影响，以2年生平邑甜茶(Malus hupehensis)实生苗为试验材料，采用叶片喷施的方法，研究了水杨酸(SA)、褪黑素(MT)和多巴胺(DA)3种外源物质对植株叶片相关生理特性以及关键基因表达的影响。结果表明：高温胁迫下，3种外源物质预处理均显著提高了平邑甜茶幼苗叶片叶绿素、可溶性糖、淀粉和可溶性蛋白含量及光系统II的最大光量子产量(Fv/Fm)；降低了MDA、H2O2、相对电导率以及超氧阴离子产生速率；提高了SOD、POD和APX等抗氧化酶活性；同时还上调表达了MhSOD、MhPOD、MhcAPX等抗氧化酶相关基因，MhHSP17.3、MhHSP90-5、MhHSP70等热休克蛋白基因以及MhATG3a、MhATG5-1、MhATG18α等自噬相关基因。综上所述，施加SA、MT和DA能够通过延缓叶绿素降解、清除活性氧、提高抗氧化酶活性、上调热休克蛋白和自噬相关基因表达等途径缓解高温对平邑甜茶幼苗的伤害，其中以喷施100μmol/L的外源SA效果最佳。     

Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics

In postmortem studies of patients with schizophrenia, D2 dopamine receptors in the basal ganglia have been observed to be more numerous than in patients with no history of neurological or psychiatric disease. Because most patients with schizophrenia are treated with neuroleptic drugs that block D2 dopamine receptors in the caudate nucleus, it has been suggested that this increase in the number of receptors is a result of adaptation to these drugs rather than a biochemical abnormality intrinsic to schizophrenia. With positron emission tomography (PET), the D2 dopamine receptor density in the caudate nucleus of living human beings was measured in normal volunteers and in two groups of patients with schizophrenia--one group that had never been treated with neuroleptics and another group that had been treated with these drugs. D2 dopamine receptor densities in the caudate nucleus were higher in both groups of patients than in the normal volunteers. Thus, schizophrenia itself is associated with an increase in brain D2 dopamine receptor density.     

Histochemical fluorescence after application of neurochemicals to caudate nucleus and septal area in vivo

The movement of carbachol, norepinephrine, and dopamine from cannula sites in caudate nucleus and septal area of freely moving rats was traced by means of biogenic amine fluorescence. Fluorescent patterns seen after application of carbachol and norepinephrine to brain tissue did not appear to differ from controls. Three types of movement from the cannula site after administration of dopamine were observed. There was a spherical distribution approximately 2 millimeters in diameter. Fluorescence also followed axonal pathways in the orthodromic direction, suggesting that dopamine may have been transported by " axonal streaming " or by some other unknown mechanism in periaxonal spaces. Because fluorescence was present in both the ependymal lining and the choroid plexus, it was inferred that the cerebral ventricles were also involved in the movement of chemical. Any attempt to ascribe anatomical localization to behavioral effects resulting from chemical stimulation of the brain should take into account the widespread movement of chemicals after their local application to brain tissue.     

Delta 9 -tetrahydrocannabinol and ethanol: differential effects on sympathetic activity in differing environmental setting

Serum dopamine beta-hydroxylase activity, a useful biochemical index of peripheral sympathetic nervous activity, was measured in rats treated with Delta(9)-tetrahydrocannabinol or ethanol or both substances. After 7 days of treatment with either substance, serum dopamine beta-hydroxylase activity decreased significantly. Combined treatment with both agents enhanced the effects of each given alone. In rats subjected to immobilization stress, treatment with Delta(9)- tetrahydrocannabinol appeared to potentiate the stress-induced increase in serum enzyme activity. Treatment with ethanol, with or without Delta(9)-tetrahydrocannabinol, effectively blocked this increase in enzyme activity. These results show that both substances have significant effects on the sympathetic nervous system which are critically influenced by environmental setting.     

Benzodiazepine receptor-mediated experimental "anxiety" in primates

The ethyl ester of beta-carboline-3-carboxylic acid has a high affinity for benzodiazepine receptors in the brain. In the rhesus monkey this substance produces an acute behavioral syndrome characterized by dramatic elevations in heart rate, blood pressure, plasma cortisol, and catecholamines. The effects are blocked by benzodiazepines and the specific benzodiazepine receptor antagonist Ro 15-1788. The benzodiazepine receptor may consist of several subsites or functional domains that independently recognize agonist, antagonists, or "active" antagonists such as beta-carboline-3-carboxylic acid ethyl ester. These results suggest that the benzodiazepine receptor is involved in both the affective and physiological manifestations of anxiety, and that the administration of beta-carboxylic acid ethyl ester to monkeys may provide a reliable and reproducible animal model of human anxiety.     

不同营养水平对湖羊黄体期血液理化指标及卵泡发育的影响

【目的】研究不同营养水平对湖羊黄体期血液理化指标及卵泡发育的影响。【方法】选择28只经产母羊,于发情周期第6天分别按0.5倍体重维持需要量（R组）,1倍体重维持需要量（C组）和1.5倍体重维持需要量（S组）饲喂6 d,第12天每组屠宰6头;剩下的湖羊用于观察发情;分别于发情周期第7、8、10和12天采血。【结果】随着营养水平的提高,≥3.5 mm的卵泡数量显著增加（P＜0.05）、2.5-3.5 mm的卵泡数量显著降低（P＜0.05）,平均发情周期缩短（P＜0.05）,血液尿素、胆固醇和游离脂肪酸含量显著下降（P＜0.05）,甘油三酯含量显著提高（P＜0.05）;S组乳酸脱氢酶活性显著高于C组（P＜0.05）;血液尿酸、血氨、高密度脂蛋白、低密度脂蛋白浓度和谷草转氨酶和谷丙转氨酶活性差异不显著（P＞0.05）,但尿酸、血氨、低密度脂蛋白含量和谷草转氨酶活性具有时间效应（P＜0.05）。【结论】绵羊黄体期不同生理阶段具有不同的营养需求和代谢特点,黄体期限饲抑制卵泡发育与蛋白质和脂类合成降低、分解增强有关。     

血液内溶血磷脂酸浓度与奥扎格雷钠治疗TIA疗效关系的研究

目的研究血液内溶血磷脂酸浓度与奥扎格雷钠治疗短暂脑缺血发作（TIA）的疗效关系.方法选择TIA患者60例,分别检测其血液内LPA浓度,根据其血液内LPA浓度将其分为LPA浓度升高组（39例）和LPA浓度正常组（21例）.2组患者应用奥扎格雷钠80 mg/d进行治疗,随访1个月,观察TIA患者的发作频率以及发展成为脑梗死的发病率.结果经过1个月的奥扎格雷钠治疗,LPA浓度升高组的39例TIA患者中,平均发作次数为（1.60±0.39）次,共有5例发展成为脑梗死,发病率为12.82%;而LPA浓度正常的21例TIA患者中,平均发作次数为（2.45±0.56）次,有7例发展成为脑梗死,发病率为33.33%.结论奥扎格雷钠治疗高血浓度LPA的TIA患者疗效明显优于低血浓度LPA患者.     

不同粒径腐殖酸颗粒对土壤有效态镉的影响

为探究腐殖酸对土壤有效态镉的影响及其作用机制,利用不同研磨条件下获得的腐殖酸的可溶成分与残渣成分,以吸附试验、电镜扫描、红外光谱分析等手段开展其对土壤Cd吸附,以及土壤pH、有机质含量的影响。结果表明,腐殖酸和滤渣对Cd的吸附曲线可用朗缪尔(Langmuir)吸附模型拟合。相对于腐殖酸,腐殖酸滤渣显著(P<0.05)降低了土壤pH和有效态Cd含量,而相应的腐殖酸溶液活化了土壤Cd。研磨处理后,腐殖酸残渣的比表面积和羧基基团含量增加,而腐殖酸溶液中酚羟基基团含量增加。经研磨处理,减小腐殖酸粒径,可提高腐殖酸溶解率,从而可分别强化腐殖酸可溶性组分和残渣组分对土壤Cd的活化和钝化作用。     

超声波辅助食盐腌制对不同部位秦川牛肉脂肪酸组成的影响

【目的】探索超声波辅助食盐腌制对牛肉脂肪酸组成的影响。【方法】以秦川牛肉为研究对象,研究测定超声波结合3%和6%食盐腌制后不同部位牛肉脂肪含量及脂肪酸含量。【结果】高档牛肉部位的脂肪含量较高,处理后高档牛肉的脂肪含量显著降低（P＜0.05）。经处理,不同部位不同脂肪酸含量的排序发生了明显变化,部分脂肪酸含量也随之发生了显著变化（P＜0.05）。其中,饱和脂肪酸含量变化不显著（P＞0.05）,但显著降低了月桂酸、肉豆蔻酸、15:0、17:0的含量（P＜0.05）,以月桂酸和17:0的差异最为明显;单不饱和脂肪酸含量变化也不显著（P＞0.05）,但显著降低了肉豆蔻油酸、反式棕榈油酸、棕榈油酸、17:1trans-9、17:1cis-9、反式油酸的含量（P＜0.05）,以17:1trans-9和17:1cis-9的差异最明显;多不饱和脂肪酸含量及其脂肪酸组成均显著增加（P＜0.05）,而且超声波辅助6%食盐处理效果更佳。【结论】超声波辅助低盐腌制对于降低秦川牛各部位牛肉脂肪的含量、提高牛肉多不饱和脂肪酸含量有明显的影响,为各部位牛肉加工提供了有利的理论依据。     

Luteinizing hormone-releasing activity in hypophysial stalk blood and elevation by dopamine

Pituitary halves incubated in pituitary stalk plasma release more luteinizing hormone than their opposite halves incubated in plasma from peripheral blood. Glands incubated in stalk plasma from dopamine-treated rats release more luteinizing hormone than glands incubated in stalk plasma from untreated controls. Luteinizing hormone-releasing activity in stalk plasma may be due to the luteinizing hormone-releasing factor, and the secretion of luteinizing hormone-releasing factor may be controlled by a dopaminergic mechanism.     

苹果酸和柠檬酸对盐胁迫下荞麦幼苗生理特性的影响

以盐敏感荞麦品种为试验材料,探讨盐胁迫下不同浓度苹果酸和柠檬酸对荞麦幼苗生理特性的影响.结果表明,适宜浓度的苹果酸和柠檬酸可以显著增加盐胁迫下荞麦幼苗根系活力和叶片叶绿素含量,显著降低盐胁迫下荞麦叶片质膜透性和MDA含量,适宜浓度的苹果酸和柠檬酸可以明显改善盐胁迫下荞麦幼苗生理特性,苹果酸和柠檬酸处理的最适浓度分别为0.6和0.8 mmol/L,柠檬酸的处理效果优于苹果酸.     

高效液相色谱—电化学法检测蜜蜂脑部单胺类神经递质及其酸性代谢产物含量

建立同时测定蜜蜂脑部神经物质左旋多巴(l-DOPA)、去甲肾上腺素(NE)、3,4-二羟基苯乙酸(DOPAC)、多巴胺(DA)、5-羟吲哚乙酸(5-HIAA)、高香草酸(HVA)和5-羟色胺(5-HT)的高效液相色谱—电化学检测(HPLC-ECD)法.采用Acclaim C18色谱柱,以磷酸二氢钠、辛烷磺酸钠、柠檬酸、乙二胺四乙酸及乙腈的混合液为流动相,流速0.2 m L·min-1,进样量10μL,柱温38℃,检测电压300 m V.蜜蜂脑组织样品经高氯酸、焦亚硫酸钠和乙二胺四乙酸混合溶液去除蛋白,再由0.22μm滤膜过滤后上样检测.结果表明:脑组织中各待测神经物质线性回归方程相关系数均大于0.997,加样回收率平均值大于90%,日内、日间精密度指数RSD平均小于5.7%.经初步研究,意大利蜜蜂脑部l-DOPA、NE、DOPAC、DA和5-HIAA的含量分别为(0.232±0.107)、(1.288±0.630)、(2.555±1.201)、(0.574±0.233)、(0.393±0.123)ng·脑-1,中华蜜蜂脑部的对应物质含量分别为(0.331±0.162)、(0.894±0.395)、(2.819±0.974)、(0.636±0.255)、(0.353±0.163)ng·脑-1.