甲状腺素和甲巯咪唑对大鼠视前区-下丘脑前部中及血清中单胺类递质的影响

反复皮下注射甲状腺素(T_4,1mg/100g·d,连续10d)和胃饲甲巯咪唑(10mg/100g·d,连续15d)后,用高效液相色谱加电化学检测器(HPLC-EGD)分析了大鼠视前区-下丘脑前部(PO/AH)中单胺神经递质的含量。发现经甲状腺素处理后,PO/AH区中多巴胺(DA)和高香草酸(HVA)含量显著增加,具有统计学意义(P<0.01),5-羟色胺(5-HT)和5-羟吲哚乙酸(5-HIAA)轻度上升,但无统计学意义(P>0.05),去甲肾上腺素(NE)无明显变化;经甲巯咪唑处理后的动物则出现NE含量显著下降(P<0.05),但DA、HVA、5-HT和5-HIAA各项变化不显著。本文还同步观察了外周血清中单胺介质含量的变化,结果表明其与中枢单胺介质含量变化基本上不同步。本文还讨论了甲状腺素和甲巯咪唑影响单胺介质含量和影响体温变化之间的关系。     

Changes of body temperature and extracellular serotonin level in the preoptic area and anterior hypothalamus after thermal or serotonergic pharmacological stimulation of freely moving rats

Although many studies has been shown that serotonin (5-HT) in the preoptic area and anterior hypothalamus (PO/AH) is important for regulating body temperature (Tb), the exact role is not established yet due to conflicting results probably related to experimental techniques or conditions such as the use of anesthesia. The purpose of present study was to clarify the role of 5-HT in the PO/AH using the combined methods of telemetry, microdialysis and high performance liquid chromatography (HPLC), with a special emphasis on the regulation of Tb in freely moving rats. Firstly, we measured changes in Tb and levels of extracellular 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the PO/AH during cold (5 degrees C) and heat (35 degrees C) exposure. We also perfused fluoxetine (5-HT re-uptake inhibitor) and 8-hydroxy-2-(Di-n-propylamino)tetralin (8-OH-DPAT: 5-HT1A agonist) into the PO/AH. During both exposures, although Tb changed significantly, no significant changes were noted in extracellular levels of 5-HT and 5-HIAA in the PO/AH. In addition, although perfusion of fluoxetine or 8-OH-DPAT into the PO/AH increased or decreased extracellular 5-HT and 5-HIAA levels in the PO/AH respectively, but Tb did not change at all. Our results suggest that 5-HT in the PO/AH may not mediate acute changes in thermoregulation.     

Monoamines and Their Precursors and Metabolites in the Chicken Brain, Pineal, and Retina: Regional Distribution and Day/Night Variations

Levels of norepinephrine, epinephrine, dopamine, and serotonin (5-HT) and their precursors [tyrosine, L-3,4-dihydroxyphenylalanine, tryptophan, and 5-hydroxytryptophan (5-HTP)] and metabolites [3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, and 5-hydroxyindoleacetic acid (5-HIAA)] were determined concurrently in samples of chick retina, pineal gland, and nine selected areas of the brain (optic lobes, thalamus, hypothalamus, optic chiasm, pons/medulla, cerebellum, neostriatum/ectostriatum, hyperstriatum, and basal forebrain) using HPLC coupled with a coulometric electrode array detection system. The norepinephrine level was highest in the pineal gland, but it was also widely distributed throughout the chick brain, with the thalamus and hypothalamus showing substantial levels. The dopamine level was highest in the basal forebrain. The epinephrine level was highest in the hypothalamus. The thalamus and hypothalamus showed the highest levels of 5-HT. Daytime levels (1100 h) of these compounds were compared with levels in chicks killed in the middle of the dark phase (2300 h). In the brain areas examined, no day/night variations in levels of norepinephrine, epinephrine, dopamine, or 5-HT were seen, although significant nocturnal changes in levels of their metabolites were observed in some areas. Pineal levels of 5-HIAA decreased significantly at night. The retina showed significant nocturnal increases in 5-HTP, 5-HT, and 5-HIAA levels. Retinal levels of 3-MT and DOPAC were significantly decreased at night.     

人参皂甙Re对神经内分泌系统功能的影响

研究人参皂甙Re对神经内分泌系统的保护作用。采用高效液相色谱检测法测定水浸．束缚应激大鼠脑内单胺类递质和血清皮质酮的含量。水浸-束缚应激模型能使大鼠额叶、纹状体、下丘脑三个脑区的单胺类递质及其代谢产物（去甲肾上腺素、多巴胺、高香草酸、5-羟色胺、5．羟吲哚乙酸）和血清皮质酮的含量明显增高。预先给予人参皂甙Re（4．5和9mg／kg,ig）后均有不同程度的降低,并呈一定的量效关系。结果表明人参皂甙Re具有一定的神经保护作用。     

Effect of Transient Cerebral Ischaemia and Cardiac Arrest on Brain Extracellular Dopamine and Serotonin as Determined by In Vivo Dialysis in the Rat

The effects of 20-min transient, global, forebrain ischaemia and cardiac arrest on extracellular concentrations of dopamine (DA), serotonin (5-HT), and their respective metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), were measured in vivo by dialysis of rat striatum and hippocampus. During the ischaemic period, striatal DA content increased (250-fold basal concentrations) with parallel but much less marked increases of both striatal and hippocampal 5-HT content (eight- to 10-fold). Baseline values were restored during reperfusion. Subsequent increases of DA and 5-HT levels on cardiac arrest were comparable after both sham operation and ischaemia. Significant decreases of HVA and 5-HIAA levels were observed following ischaemia or cardiac arrest. The differential effects of ischaemia on DA and 5-HT suggest selective alterations in disposition or metabolism of the two transmitters and that dopaminergic neurones may be more vulnerable to ischaemic insults.     

Polyunsaturated fatty acids (PUFA) regulate neurotransmitter contents in rat brain

The effects of feeding of 6-propylthiouracil (6-PTU) and polyunsaturated fatty acids (PUFA) independently and in combination and administration (ip) of a single dose of triiodothyronine (T3) (2.5 microg/100 g body wt) along with feeding of 6-PTU and PUFA were studied in rat brain. Dopamine (DA), 5-hydroxytryptophan (5-HTP), serotonin (5-HT), 5-hydroxy indole acetic acid (5-HIAA), norepinephrine (NE) and epinephrine (EPI) contents were assayed in the hypothalamus and cerebral cortex regions. It was found that 6-PTU feeding resulted in decrease in dopamine, 5-HT, 5-HTP and 5-HIAA in both regions. In animals fed with PUFA followed by administration of T3, the DA level was found normal.     

Effect of aging on monoamines and their metabolites in the rat brain

Concentrations of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their acid merabolites were assayed in specific brain areas of Wistar rats of various ages. DA and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were significantly lower in striatum and mesolimbic areas of old (24 mos) rats than young adult (3 mos), but not mature (12 mos) rats. The decrease of homovanillic acid (HVA) was significant in mesolimbic areas but not in striatum. Neither cortical NE nor its metabolite methoxydroxyphenylglycol sulphate (MHPG-SO₄) were significantly changed by aging. 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the brainstem showed a tendency to a decrease and increase respectively in aged animals compared with young adults, but the differences were not statistically significant. However, the ratio of 5-HIAA to 5-HT concentrations was significantly higher in aged animals. The conclusion can be drawn that, in these brain areas, DA is more vulnerable to aging than NE and 5-HT, the metabolism of the latter being even enhanced.     

Social rank and brain levels of monoamines and monoamine metabolites in Arctic charr,Salvelinus alpinus (L.)

Summary Dominance hierarchy was determined in 5 groups of juvenile Arctic charr (Salvelinus alpinus), each group consisting of 4 fish. Telencephalon and brain stem (remaining parts of the brain) were analyzed with regard to their content of monoamines and monoamine metabolites. No significant differences were observed in the concentrations of norepinephrine (NE), dopamine (DA), or serotonin (5-hydroxytryptamine, 5-HT) between fish with different social rank. However, the concentration of 5-hydroxyindoleacetic acid (5-HIAA), the principle metabolite of 5-HT, was significantly higher in subordinate fish, and a significant inverse linear correlation was found between 5-HIAA concentration and social rank (as measured by dominance index) in the brain stem. In the telencephalon the dominant fish had a significantly higher level of homovanillic acid (HVA), a major DA metabolite. These findings indicate a greater serotonergic activity, possibly associated with increased stress, as well as a lower dopaminergic activity, possibly associated with reduced aggression, in subordinate charr. The differences between dominant and subordinate fish could either be caused by social interactions or reflect innate individual differences in monoamine utilization, predisposing individuals for dominant or subordinate positions in the dominance hierarchy.Abbreviations DA dopamine - DI dominance index - NE norepinephrine - 5-HT serotonin (5-hydroxytryptamine) - 5-HIAA 5-hydroxyindoleacetic acid - 5-HTOH 5-hydroxytryptophol - HVA homovanillic acid     

Effect of barbitone sodium and thiopental sodium on brain dopamine, noradrenaline, serotonin and 5-hydroxyindoleacetic acid content in Arvicanthis niloticus

The quantitative estimation of total dopamine (DA), noradrenaline (NE), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content in the whole brain tissue of normal Nile grass rat, Arvicanthis niloticus, gives and average of 631 +/- 12 ng DA/g, 366 +/- 12 ng NE/g, 617 +/- 15 ng 5-HT/g and 431 +/- 10 ng 5-HIAA/g fresh brain tissue. The effect of barbitone sodium and thiopental sodium on the total DA, NE, 5-HT and 5-HIAA content in the brain tissue of the Nile grass rat, Arvicanthis niloticus, was studied. The total DA, NE, 5-HT and 5-HIAA contents were determined 5 hr after i.p. injection of different doses of barbitone sodium (20, 40 and 80 mg/ml/100 g body wt) and thiopental sodium (5, 10 and 20 mg/ml/100 g body wt). The effect of different time intervals (1, 10, 30 min, 1, 2.5, 5, 8, 16, 24 and 48 hr) on the total brain DA, NE, 5-HT and 5-HIAA content was investigated after i.p. injection of 40 mg of barbitone sodium and 10 mg of thiopental sodium/ml/100 g body wt. Both barbitone sodium and thiopental sodium caused an increase in DA, NE and 5-HT content and a decrease in 5-HIAA content in the brain tissue of Arvicanthis niloticus. The increase in the whole brain contents of DA, NE and 5-HT after the administration of barbitone sodium and thiopental sodium may be due either to inhibition of transmitter release by an action at the monoamine nerve terminal or to effects causing a decrease in nerve impulse flow. On the other hand, the decrease in 5-HIAA may be due to the decrease in the turnover of 5-HT.     

Altered dopamine turnover in murine hypothalamus after low-dose continuous oral administration of aluminum.

Aluminum, a known neurotoxic substance, has been suggested as a possible contributing factor in the pathogenesis of Alzheimer's disease. Ground-water pollution by aluminum has been recently reported. In the current study groups of 5 male BALB/c mice were administered aluminum ammonium sulfate in drinking water ad libitum at 0, 5, 25, and 125 mg/L aluminum for 4 weeks. At the termination of aluminum exposure, their brains were removed and dissected into cerebrum, cerebellum, medulla oblongata, midbrain, corpus striatum, and hypothalamus. The concentration of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA), were determined in each brain area. DA, DOPAC, and HVA levels were lower in the hypothalamus of aluminum-treated mice, most notably in the low-dose group, as compared with control. No marked alterations in NE, 5-HT, and 5-HIAA levels were detected in any brain region. Changes in the concentration of DA and its metabolites measured in the hypothalamus suggest an inhibition of DA synthesis by aluminum.