Subclinical effects of groundwater contaminants. II. Alteration of regional brain monoamine neurotransmitters by benzene in CD-1 mice

Benzene, a common groundwater contaminant, possesses neurotoxic and behavioral effects. Male, adult CD-1 mice were continuously fed drinking waterad libitum containing 0, 31, 166 and 790 mg/L benzene for four weeks. Endogenous levels of the catecholamines norepinephrine (NE) and dopamine (DA), the catecholamine metabolites 3-methoxy-4-hydroxymandelic acid (VMA), 3,4-di-hydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the indoleamine serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), were measured by high-performance liquid chromatography (HPLC) in six discrete brain regions. In the hypothalamus, the brain region richest in NE, concentrations of NE increased by 40, 58 and 61% when mice received doses at 31, 166 and 790 mg/L, respectively. Significant increases of NE were also observed in the medulla oblongata and cerebellum. Dopamine concentrations increased significantly in the hypothalamus and corpus striatum. Increases of catecholamine metabolites were seen in a number of brain regions: midbrain (DOPAC), corpus striatum (VMA, DOPAC, HVA), cerebral cortex (VMA) and cerebellum (VMA). Benzene ingestion significantly increased 5-HT concentrations in the hypothalamus, corpus striatum, midbrain, cerebral cortex and medulla oblongata. Concomitant with increases of 5-HT, 5-HIAA increased in corpus striatum, midbrain, cerebral cortex and medulla oblongata. The findings indicate that oral ingestion of benzene by CD-1 mice induced both synthesis and catabolism of the monoamine neurotransmitters investigated.     

Alteration of biogenic amines in mouse brain regions by alkylating agents. I. Effects of aflatoxin B1 on brain monoamines concentrations and activities of metabolizing enzymes

Young adult male CD-1 mice were treated orally twice weekly for three weeks with 0, 0.05, 0.15 or 0.65 mg/kg of aflatoxin B₁ (AFB₁) in corn oil. Two days after the last dose, the mice were killed by decapitation and the concentrations of the brain catecholamines, norepinephrine (NE), and dopamine (DA), and their metabolites, 3-methoxy-4-hydroxymandelic (VMA), homovanillic acid (HVA) and dihydroxyphenyl acetic acid (DOPAC) and the indoleamine serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were determined by high pressure liquid chromatography in six discrete brain regions. Major effects of AFB₁ were found in the concentrations of NE in most brain areas. Endogenous concentrations of DA were increased in the striatum and hypothalamus. The VMA level in the hypothalamus and striatum were decreased by the treatment. The activity of tyrosine hydroxylase, tryptophan hydroxylase, amino acid decarboxylase and monoamine oxidase (the enzymes important in synthetic and degradation pathways of biogenic amines) were investigated. Alterations in biogenic amine concentrations were often consistent with the changes observed in metabolizing enzymes. There was an increase noted in tryptophan hydroxylase activity. Activities of amino acid decarboxylase and monoamine oxidase were increased although the changes were not consistent in all regions or at all dose levels of AFB₁. These results suggest that dietary exposure to AFB₁ diets may cause alterations in various biogenic amine concentrations and related metabolizing enzymes.     

Effects of benzo[a]pyrene on steady-state levels of biogenic amines and metabolizing enzymes in mouse brain regions.

Benzo[a]pyrene (BaP) is a product of incomplete fossil fuel combustion, a well-known pollutant, and a carcinogenic agent. In the present study male CD-1 mice received ip injections of 0, 5, 25, and 100 mg/kg body weight BaP twice a week for 3 weeks. Endogenous levels of brain biogenic amines and their selected metabolites, norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), vanillylmandelic acid, dihydroxyphenylacetic acid (DOPAC), homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high performance liquid chromatography and electrochemical detection. The brain regions studied were cortex, striatum, hypothalamus, midbrain, medulla oblongata, and cerebellum. BaP treatment increased the steady-state levels of NE, DA, and 5-HT in the hypothalamus and striatum. Increased levels of DA and 5-HT and their major metabolites DOPAC and 5-HIAA were noticed in the same region, an indication of increased metabolism of these amines. The increase in the 5-HT level in the cortex was not dose-related. Levels of NE and DA were significantly higher in the medulla oblongata. There was a concurrent increase in activities of tyrosine hydroxylase and tryptophan hydroxylase in several brain regions. The effect of BaP on Dopa-decarboxylase was not consistent. Monoamine oxidase was occasionally inhibited. Results indicate that exposure to BaP altered the steady-state levels of biogenic amines in various brain regions and these changes were consistent with the activities of metabolizing enzymes.     

Effects of ethanol and low-carbohydrate diet on contents of noradrenaline, dopamine, serotonin and their metabolites in rat brain]

Effects of ethanol consumption and intake of low-carbohydrate (low-CHO) diet on noradrenaline (NA), dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), serotonin (5HT) and its metabolite, 5-hydroxyindoleacetic acid (5HIAA) contents in six brain regions of rats were investigated. 1) Change of DA neuron Ethanol-containing control diet (hypercaloric ethanol diet) did not affect DA content in any area of brain, but decreased HVA in cortex and hypothalamus and increased DOPAC and HVA in midbrain. Low-CHO diet increased DA content in striatum, DOPAC and HVA in midbrain, but decreased DOPAC in hippocampus and hypothalamus, and HVA in cortex, pons and medulla, hippocampus and hypothalamus. Ethanol-containing low-CHO diet (isocaloric ethanol diet) increased DA level in striatum, DOPAC and HVA in midbrain, but decreased HVA in cortex, hippocampus, striatum and hypothalamus. These results suggest that i) hypercaloric ethanol diet has an opposite effect to carbohydrate on DA metabolism: hypercaloric ethanol diet and lowered carbohydrate intake per se enhance DA metabolism in midbrain, whereas inhibit it in cortex and hypothalamus, ii) lowered carbohydrate intake also declines DA metabolism in pons and medulla and hippocampus, whereas enhances DA synthesis in striatum, iii) the combined effect of ethanol and carbohydrate intake on DA metabolism is inhibited each other in the rats of isocaloric ethanol diet feeding, and this diet decreased DA metabolism in striatum. 2) Change of 5HT neuron Hypercaloric ethanol diet did not affect the contents of 5HT and 5HIAA in any region of brain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increase in Dopamine Metabolites in Murine Striatum After Oral Exposure to Inorganic But Not Organic Form of Selenium

Selenium (Se) is an essential as well as a toxic trace element. Se intoxication has been reported in both livestock and humans. The central nervous system is sensitive to Se poisoning; exposure to Se causes blind staggers in cattle, poliomyelomalacia in pigs, and nervous system disorders in humans. Differences in neurotoxicity between inorganic and organic Se have been demonstrated. In this study, groups of five male BALB/c mice each were administered sodium selenite or selenomethionine in drinking water ad libitum at 0, 1, 3, and 9 ppm as Se for 14 days. At the end of Se exposure, their brains were removed and dissected into different regions. The concentration of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindolacetic acid (5-HIAA) were determined in each brain region. Food and water consumption and body weight gain were significantly decreased in the group treated with the highest concentration of sodium selenite. In mice administered sodium selenite at 3 and 9 ppm, DOPAC was significantly higher in the striatum than in the control group. The striatal HVA was also increased in the group treated with 3 ppm Se; the DA showed a similar pattern, but the increase was not statistically significant. No alterations of NE, 5-HT, or 5-HIAA levels were detected in any brain region of mice treated with sodium selenite. No significant differences in any parameter among the groups treated with selenomethionine were observed indicating that inorganic Se was more neurotoxic than organic Se via drinking water. The alterations of DA metabolites by inorganic Se in DA-rich striatum suggested a Se-specific increased neural activity of dopaminergic pathways. Results may be useful in further elucidation of neurotoxicity of Se and in establishing a safe level of intake for this element. Received: 10 September 1999/Accepted: 30 November 1999     

Effects of repeated intermittent exposures to nitrous oxide on central neurotransmitters and hepatic methionine synthetase activity in CD-1 mice.

The central neurotransmitters and hepatic methionine synthetase (MS) appear to play an important role in mediating the side effects associated with N2O exposure. Male CD-1 mice were exposed to 0, 50, 500, and 5,000 ppm of N2O 6 hr per day, 5 days a week for 2 or 13 weeks. One day after the last day of exposure, the animals were decapitated and steady state concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3-methoxy-4-hydroxy-mandelic acid (VMA), 3-methoxy-4-hydroxyphenyl glycol (MOPEG), dihydroxphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in six discreet brain regions using electrochemical high-performance liquid chromatography. Hepatic MS activity was measured using a newly developed non-isotopic method. After a 2-week exposure to 5,000 ppm N2O, levels of NE and DA in some brain regions were significantly increased and were accompanied by significant decreases in the levels of their major metabolites. Serotonin levels were significantly decreased in certain brain regions. After the 13-week exposure to 5,000 ppm N2O, levels of NE, DA, and 5-HT significantly increased in the hypothalamus. Hepatic MS activity was not affected at any dose level of N2O used. The alterations in neurotransmitter levels may be related to the reported clinical and behavioral effects associated with N2O misuse or occupational exposures.     

一次力竭运动小鼠中枢单胺类神经递质的代谢特点

目的：探讨力竭运动中枢单胺类神经递质的代谢变化特点,以期为运动疲劳的中枢机制提供一定实验室依据。方法：4月龄C57/BL小鼠,随机分为安静对照组（SC组）和一次性游泳力竭组（SE组）。力竭游泳即刻取材（皮层、下丘脑、纹状体、海马、脑干和小脑）六个脑区,高功率微波灭活脑组织相关酶类;HPLC测定去甲肾上腺素（NE）、多巴胺（DA）及其代谢产物多巴克（DOPAC）、5羟色胺（5-HT）、5-羟吲哚乙酸（5-HIAA）含量。结果：力竭时皮层、海马和脑干NE含量较安静时明显增加（P〈0.05）,而下丘脑、纹状体和小脑NE含量有降低趋势。海马、脑干组织DA含量力竭时极显著增加（P〈0.01）,皮层、纹状体区仅有增加趋势,而下丘脑DA含量较安静时有降低趋势;DA的代谢产物DOPAC仅在脑干有明显增加。各脑区力竭时5-HT均较安静时明显增加（P〈0.05）,其代谢产物5-HIAA在皮层、下丘脑及小脑也增加显著（P〈0.05）。结论：运动至力竭过程中各脑区单胺类神经元激活程度不相同,其中5-HT和NE可以作为中枢皮层疲劳的一个标志。     

The alterations in neurotransmitters and their metabolites in discrete brain regions in the rats after inhalation of disinfectant, glutaraldehyde or ortho-phthalaldehyde for 4 weeks

Glutaraldehyde (GA) and ortho-phtalaldehyde (OPA) have been widely used as major components of disinfectants in hospitals. We evaluated the alterations in GA or OPA in rats after subacute inhalation exposure by determining levels of neurotransmitters (norepinephrine [NE], dopamine [DA], DA metabolites, dihydroxyphenylacetic acid [DOPAC] and homovanillic acid [HVA], indoleamine serotonin [5-HT] and 5-HT metabolite, 5-hydroxyindoleacetic acid [5-HIAA]) in discrete brain regions using high performance liquid chromatography (HPLC) equipped with an electrochemical detector. Female Wistar rats were exposed to 0, 50, 100, or 200 ppb gaseous GA or OPA by inhalation for 1 h per day, 5 d per week for 4 wk. Following the exposure, the brain of each rat was removed and dissected into cerebrum, cerebellum, medulla oblongata, midbrain, corpus striatum and hypothalamus. The neurotransmitters and their metabolites were extracted from each brain region, and determined by HPLC. Regarding GA, the daily water intake of the 50 or the 200 ppb exposed groups was significantly lower than that of the control. DA and 5-HIAA levels in the medulla oblongata among the GA exposed groups were significantly lower than those of the control. For OPA, the mean final body weight and daily food intake of the 100 or 200 ppb exposed groups were significantly lower than those of the control. The mean DA concentrations in the cerebrum in the groups exposed to OPA were significantly lower than those of the control. OPA may modulate DA metabolism in the cerebrum of female rats. The levels GA or OPA that induced alienations in neurotransmitters were comparable to those levels usually found in hospitals, further studies are warranted to evaluate the of safety of disinfectants containing GA or OPA.     

Biochemical evidence for activation of specific monoamine pathways by ethanol

The effects of an acute intraperitoneal (IP) low (0.5 g/kg) or high (2.5 g/kg) dose of ethanol on the contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in 7 selected CNS regions of the rat were examined after 15, 30 and 60 minutes. The IP administration of 0.5 g/kg ethanol produced blood alcohol concentrations (BACs) of 41 +/- 4, 40 +/- 4 and 15 +/- 1 mg% (N = 8 each) after 15, 30 and 60 minutes, respectively. This low dose of ethanol did not alter the levels of DA, DOPAC, HVA, 5-HT and 5-HIAA in any of the 7 CNS regions at any of the time points examined. The dose of 2.5 g/kg ethanol produced BACs of 254 +/- 26, 268 +/- 20 and 282 +/- 10 mg% (N = 8 each) after 15, 30 and 60 minutes, respectively. This high dose of ethanol did not alter the contents of DA and 5-HT in any of the regions examined at any of the times, except for a 30% increase in the content of DA in the posterior striatum after 60 minutes. The administration of 2.5 g ethanol/kg elevated the levels of DOPAC and/or HVA 25 to 70% over saline control values in the (a) nucleus accumbens (ACC) and hypothalamus (HYPO) after 15, 30 and 60 minutes, and (b) posterior striatum (PSTR), lateral septal nucleus (LSN) and frontal cortex (FCTX) after 60 minutes. The contents of DOPAC and/or HVA were not altered by the high dose of ethanol in either the thalamus or olfactory bulbs.(ABSTRACT TRUNCATED AT 250 WORDS)     

不同暴露时间TiO2纳米粒子对雌性小鼠脑单胺类神经递质的影响

目的探讨小鼠鼻腔滴注二氧化钛（TiO2）纳米粒子对脑中单胺类神经递质的影响。方法以50mg／kg的剂量给CD雌性小鼠隔天鼻腔滴注不同粒径大小的TiO：（25、80和155nm）水悬浮液（浓度为10^5mg／L）,同时设定对照组。分别在暴露2、10、20和30d后用电感耦合等离子体质谱仪分析小鼠脑组织中钛元素的含量,采用反相高效液相色谱-电化学检测法测定暴露20和30d后小鼠脑中单胺类神经递质的含量。结果在暴露10d时,小鼠脑中钛的含量上升较快,25nm组小鼠脑中钛的含量即达到（1059．3±293.5）ng／g;在暴露20d之后,脑中钛的含量有一定降低,仍维持在较高水平,25nm组中钛的含量下降为（654.7±269．2）ng／g。暴露30d时钛含量没有明显改变。由于吸入的TiO2粒子在小鼠脑中的蓄积,导致80nm和155nm组中小鼠脑中去甲肾上腺素（NE）和5-羟色胺（5-HT）含量在暴露20d时明显升高,而多巴胺（DA）、3、4-双羟苯乙酸（DOPAC）、高香草酸（HVA）和5-羟吲哚乙酸（5-HIAA）的含量有一定下降。结论吸入的TiO2颗粒可以经鼻黏膜吸收入脑并能蓄积于小鼠的脑组织中,影响脑中单胺类神经递质的代谢。     

Prefrontal levels of 5-HIAA,but not dopamine,predict alcohol consumption in male wistar rats following 6-OHDA lesions

To examine the effects of dopamine (DA) on alcohol consumption, male Wistar rats were subjected iether to 6-OHDA lesions of the frontal cortex (MPFC) or to a sham lesion/no lesion. Following surgery, rats were trained to drink alcohol on a sucrose-fading paradigm over the course of 6 weeks, at the completion of which they consumed a solution of 3% sucrose/10% alcohol. Daily consumption of alcohol was computed for each rat. Animals were sacrificed and the MPFC, nucleus accumbens (NA), and ventral tegmentum (VTA) were removed. Levels of DA and its metabolites (i.e., HVA and DOPAC), norepinephrine (NE), and serotonin (5-HT) and its metabolite (i.e., 5-HIAA) were measured for each brain region using HPLC with electrochemical detection. Post hoc analyses were run examining the relationship of DA and its metabolites, 5-HT and its metabolite (5-HIAA), and norepinephrine (NE) in the MPFC, NA, and VTA with alcohol consumption. The 6-OHDA lesions depleted DA to 74.5% of control levels in the MPFC, but did not significantly affect alcohol consumption. Post hoc analyses found that the “high” alcohol consumption group had significantly reduced levels of MPFC 5-HIAA in comparison to the “low” consumption group, but that there was no relationship of 5-HIAA levels in the VTA or NA to alcohol consumption. These findings suggest that MPFC DA is not critically involved in the regulation of alcohol consumption. They further suggest that MPFC serotonergic systems may play an important role in the regulation of alcohol consumption, although future experimentation directly manipulating 5-HT systems in the MPFC will be required to fully assess these findings.     

SEROTONIN IS REDUCED IN THE FRONTAL CORTEX OF SARDINIAN ETHANOL-PREFERRING RATS

Ethanol-naive Sardinian alcohol-preferring (sP) and Sardinianalcohol-non-preferring (sNP) rats were tested to evaluate thelevels of serotonin (5-HT) and 5-hydroxyindol-3-yl-acetic acid(5-HIAA) in the frontal cortex, hypothalamus, and nucleus accumbens,and the levels of dopamine (DA) and 3,4-dihydroxyphenylaceticacid (DOPAC) in the hypothalamus and nucleus accumbens. Comparedwith the sNP line, the sP rats had lower 5-HT and 5-HIAA concentrationsin the frontal cortex, whereas no differences were found inthe other brain areas tested, neither for neurotransmittersnor their metabolites. As the decreased 5-HT function is a featureshared by different alcohol-preferring strains, it could belinked to the genetic predisposition to voluntary ethanol consumption.     

Subacute administration of tributyltin chloride modulates neurotransmitters and their metabolites in discrete brain regions of maternal mice and their F1 offspring

Tributyltin (TBT) compounds have been used as anti-fouling agents and the central nervous system is one of its target organs. TBT-induced modulations of neurotransmitters in the brains of adult mice have been reported. However, little is known about the developmental neurotoxicity of TBT. In this study, we evaluated the effects of TBT on neurotransmitters and their metabolites in discrete brain regions of female ICR mice and their offspring. Pregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15 or 50 ppm in water or 125 ppm in food. Male offspring were sacrificed at one, two and three weeks after birth. The concentrations of norepinephrine, dopamine (DA), dihydoxyphenylacetic acid, homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in different brain regions by HPLC. All offspring from the 125 ppm group died immediately after birth. A significant decrease in the body weight of the TBT-treated F1 groups compared to the control group was observed in the first week. Significant increases compared to the controls were observed for the DA concentration in the striatum of the 50 ppm F1 group, and for the HVA concentration in the cerebrum and the 5-HT concentration in the medulla oblongata of the 15 and 50 ppm F1 groups in the third week. At three weeks of age, the neurotransmitters and their metabolites may be useful indexes for developmental neurotoxicity. For the dams, a significant decrease in the 5-HT concentration was observed in the cerebellum, medulla, midbrain and striatum of the 125 ppm group compared to the control group. A significant decrease in the 5-HIAA concentration was also observed in the cerebellum, midbrain and striatum of the dams in the 125 ppm group compared to the control. TBT may induce a decrease in the synthesis of 5-HT in the dams. The discrepancy between dams and offspring may be due to several factors such as age, dose, route, sex and pregnancy.     

OCCURRENCE IN VIVO OF 5-HYDROXYTRYPTOPHOL IN THE BRAIN OF RATS TREATED WITH ETHANOL

The effect of ethanol (EtOH) on the release of dopamine (DA)and 5-hydroxytryptamine (5-HT) and the efflux of their metabolites,3, 4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindol-3-ylaceticacid (5-HIAA) and 5-hydroxytryptophol (5-HTOL) from the striatumof the freely moving rat were studied in vivo using brain microdialysis.Striatal DA and 5-HT release was maximally enhanced at firstfraction after the administration of EtOH (2 g/ kg, i.p.). Thelevel of the DA-oxidized metabolite, DOPAC, decreased significantly.In the 5-HT metabolic pathway, the oxidized metabolite, 5-HIAA,did not show significant changes, whereas levels of the biogenicalcohol 5-HTOL were increased to 180% at 90 min following EtOHadministration. It is suggested that EtOH, most probably viaacetaldehyde, could shift 5-HT metabolism from the oxidativeto the reductive pathway in the rat brain.     

Striatal and hypothalamic neurotransmitter changes during ethanol withdrawal in mice

The alterations in striatal and hypothalamic GABA, DA and its metabolites DOPAC and HVA, and in hypothalamic NE were investigated immediately after ethanol removal and during the withdrawal phase following 10 or 30 days of chronic ethanol administration. After 10 days of ethanol, GABA levels were increased immediately after ethanol removal in both the corpus striatum and the hypothalamus. The concentration of striatal DA was increased at days 2 and 3 of withdrawal and was unchanged at any other time. There was no change in the concentration of DOPAC and HVA in the hypothalamus at any time during withdrawal. Striatal DOPAC and HVA levels were increased only at day 7 of withdrawal after 10 and 30 days of ethanol feeding which was associated with a return of striatal DA to control levels. The concentration of NE in the hypothalamus was increased at days 1, 2 and 7 of withdrawal. After 30 days of ethanol, striatal GABA was increased only at day 7 of withdrawal whereas striatal DA levels were only increased at days 2 and 3 of withdrawal. Hypothalamic NE was markedly increased at days 2, 3 and 7 of withdrawal. The increase in DA concentration associated with no change in DOPA accumulation following inhibition of DOPA decarboxylase and a decrease in the striatal disappearance of DA after alphamethylparatyrosine (alpha-MT) suggests the presence of a hypodopaminergic state. On the other hand an increase in the disappearance of NE in the hypothalamus after alpha-MT suggests an increased NE turnover and a hyperadrenergic state during withdrawal. The increase in striatal GABA at day 7 of withdrawal after 30 days of ethanol may be a rebound phenomenon and may reflect the presence of a hypogabaergic state which has been shown to occur during ethanol withdrawal.     

Alterations in dopamine metabolism by intraperitoneal ethanol in rats selected for high and low ethanol preference: A 3-methoxytyramine study

Effects of an ethanol dose (1 g/kg, IP) on the metabolism of dopamine (DA) in the nucleus accumbens, striatum and hypothalamus of ethanol-naive alcohol-preferring (AA) and alcohol-avoiding (ANA) rats were studied. Rats were sacrificed by focused-beam microwave irradiation of the brain 20 minutes after ethanol administration, and the concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), assumed to reflect DA metabolism, and of 3-methoxytyramine (3-MT), assumed to reflect DA release, were measured using gas chromatography-mass spectrometry. Basal striatal DOPAC and HVA concentrations were higher in the AA rats in comparison with ANA rats. Ethanol increased HVA, but not DOPAC, concentration in the nucleus accumbens and striatum, but not in the hypothalamus. There was a significant rat line × ethanol treatment interaction with respect to HVA concentration in the nucleus accumbens. The increase in HVA was higher in the AA than ANA rats. Basal 3-MT concentration was not changed by ethanol, except in the nucleus accumbens, where a significant rat line × ethanol treatment interaction was found. A decrease in 3-MT concentration was only detected in the ANA rats. After inhibition of monoamine oxidase with pargyline hydrochloride (75 mg/kg, IP, 10 min before sacrifice), 3-MT accumulation was decreased by ethanol, especially in the nucleus accumbens of both AA and ANA rat lines as well as in that of nonselected Wistar rats. The results suggest that 1) DA metabolism to DOPAC and HVA is dissociable from DA release as reflected by 3-MT production, 2) ethanol, if anything, reduces DA release, and that 3) the AA and ANA rats differ in their basal DA metabolism and in the ethanol effects thereupon, but not in ethanol-induced changes in DA release.     

Tyrosine-stimulated dopamine synthesis fails to affect urinary aldosterone and sodium relationship in normal weight and obese women

The effect of L-tyrosine-induced increases in dopamine (DA) and norepinephrine (NE) turnover on the relationship between sodium and aldosterone excretion was assessed in normal weight and obese women adapting to a low sodium diet. During four continuous days, all study subjects consumed a liquid diet, Ensure^®, as the main nutrient source, which provided an average daily intake of 51 mmol sodium. In six normal weight controls, urinary DA and NE metabolites were unchanged while urine sodium decreased until balance was achieved and aldosterone increased. The inverse relationship between urinary sodium and aldosterone was also present in six normal weight subjects even after tyrosine-induced increases in the urinary DA metabolite, homovanillic acid (HVA), and in the NE metabolites, vanillylmandelic acid (VMA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG). Similarly, while tyrosine supplements increased urinary HVA and VMA in nine obese subjects, sodium and aldosterone remained inversely related. We conclude that tyrosine-induced variations in DA and NE synthesis and catabolism, as measured by urinary HVA, VMA and MHPG, have no effect on the expected relationship between urinary sodium and aldosterone or on the excretion of either one by obese and normal weight women, at least in the short term.     

Regional brain contents of serotonin, dopamine and their metabolites in the selectively bred high- and low-alcohol drinking lines of rats

The contents of dopamine (DA), serotonin (5-HT) and their primary acid metabolites were assayed in ten brain regions of the selectively bred high-alcohol drinking (HAD) and low-alcohol drinking (LAD) lines of rats. Compared with the LAD line, the contents of 5-HT and/or 5-hydroxyindoleacetic acid were approximately 10-20% (p less than 0.05) lower in several brain regions of the HAD line (cerebral cortex, striatum, nucleus accumbens, septal nuclei, hippocampus and hypothalamus). The levels of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid were also 10-20% lower in the nucleus accumbens and anterior striatum (p less than 0.05) of the HAD animals. These data are in agreement with previous findings that comparatively lower levels in 5-HT and DA systems are associated with high-alcohol drinking in rodents and support the involvement of certain 5-HT and DA pathways in the mediation of alcohol drinking behavior.     

Changes in neurotransmitter levels associated with the deficiency of some essential amino acids in the diet.

The contents of dopamine (DA) and serotonin (5-HT) and their metabolites were measured in rat substantia nigra and corpus striatum following dietary changes, including restriction of protein content (low-protein diet; LPD) and the contents of several large neutral amino acids (isoleucine, leucine, methionine, phenylalanine, tryptophan and valine) for 25 d. The LPD produced an increase in the concentration of tyrosine (TYR) in the two regions of the brain studied. This effect was also observed with all amino acid deficiencies studied except for valine in the substantia nigra, tryptophan in the striatum and phenylalanine in both regions. Likewise, the concentration of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, increased in the substantia nigra but not in the striatum after LPD, as well as with all the amino acid deficiencies studied, with the exception of tryptophan deficiency. In this case there was a dramatic effect on all components of the serotoninergic system, with decreases in the concentration of tryptophan (TRP; precursor), 5-HT and 5-HIAA. This behaviour clearly shows an interrelationship between precursor (TRP) availability and 5-HT synthesis and metabolism. With valine deficiency, dopaminergic and serotoninergic systems demonstrated opposite effects in the substantia nigra and the corpus striatum, and the behaviour of the two monoamines was also opposite within each structure. The significance of these changes is discussed.     

Effects of whole body vibration on biogenic amines in rat brain

The effects of whole body vibration on the concentrations of noradrenaline (NA), dopamine (DA), and serotonin (5-HT) in the whole brain and brain regions of rats were investigated. Compared with control rats, vibration with 20 Hz frequency decreased the brain concentration of NA only when the acceleration (intensity) was increased to 5.0 G (p less than 0.05). The concentration of DA in the whole brain was not affected by acceleration. When acceleration was kept at a constant 0.4 G level and rats were exposed for the same 240 minute period to 5, 20, or 30 Hz vibration, neither NA nor DA concentrations changed in the whole brain. Regional changes in the concentration of biogenic amines in the brain of rats exposed to vibration of 20 Hz and 5.0 G showed few significant differences. Thus NA significantly decreased only in the hypothalamus (p less than 0.01), although in the hippocampus the decrease was nearly significant (p less than 0.10). The concentration of 5-HT significantly increased in the hypothalamus and cerebellum (p less than 0.05). DA tended to increase in the cortex and decrease in the striatum (p less than 0.10). These experiments seem to indicate that NA in the whole brain and especially in the hypothalamus is a better indicator of vibration exposure than 5-HT, and that NA is affected by the intensity but not by the frequency of vibration. NA and 5-HT in the hypothalamus change in the opposite direction. DA concentrations in the brain are basically unaffected by vibration.