Effects of nutritional status on contents of tryptophan, serotonin and 5-hydroxyindoleacetic acid in rat brain]

Effects of nutritional status on the levels of tryptophan (Trp), serotonin (5HT), and its metabolite, 5-hydroxyindoleacetic acid (5HIAA) in six brain regions of rats were investigated. 1) A low-protein high-carbohydrate diet decreased Trp, 5HT and 5HIAA levels in the cortex and hippocampus, and those of 5HT and 5HIAA in the hypothalamus. This diet did not affect the contents of Trp and 5HT in the midbrain, but decreased 5HIAA. No significant changes of Trp, 5HT and 5HIAA were observed in the pons and medulla and striatum. 2) A low-carbohydrate high-protein diet increased the levels of Trp, 5HT and 5HIAA in the striatum, and 5HT and 5HIAA in the cortex, but showed no effect on the contents of Trp, 5HT and 5HIAA in the hippocampus, midbrain, pons and medulla and hypothalamus. 3) An energy-restriction low-carbohydrate diet increased Trp, 5HT and 5HIAA contents in the striatum, and 5HT and 5HIAA in the cortex and pons and medulla. In the hypothalamus, only 5HIAA was increased by this diet. The diet did not influence Trp, 5HT and 5HIAA contents of the midbrain and hippocampus. These results suggest that i) lowered fat and carbohydrate intakes enhance 5HT synthesis and metabolism in the cortex and that lowered carbohydrate intake enhances them in the striatum, ii) energy restriction enhances the 5HT metabolism in the cortex, pons and medulla and hypothalamus, and 5HT synthesis in the cortex and pons and medulla, iii) lowered protein intake inhibits 5HT metabolism in the cortex, midbrain, hippocampus and hypothalamus, and 5HT synthesis in the cortex, hippocampus and hypothalamus.     

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.     

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.     

Evaluation of toluene exposure via drinking water on levels of regional brain biogenic monoamines and their metabolites in CD-1 mice

Toluene, a potentially neurotoxic substance, is found in trace amounts in groundwater. Adult male CD-1 mice were continuously fed drinking water ad libitum containing 0, 17, 80, and 405 mg/liter toluene. After a 28-day treatment, animals were tested for endogenous levels of the biogenic monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and their respective metabolites. 3-methoxy-4-hydroxymandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), in six discrete brain regions. The maximum toluene-induced increases of biogenic amines and their metabolites generally occurred at a toluene concentration of 80 mg/liter. In the hypothalamus, a major NE-containing compartment, the concentrations of NE significantly increased by 51, 63, and 34% in groups dosed with 17, 80, and 405 mg/liter, respectively. Significant increases of NE were also observed in the medulla oblongata and midbrain. Concomitantly, concentrations of VMA increased in various brain regions. Concentrations of DA were significantly higher in the corpus striatum and hypothalamus. Alterations in levels of DA metabolites, DOPAC and HVA, were marginal. Toluene significantly increased concentrations of 5-HT in all dissected brain regions, except cerebellum, and increased the 5-HIAA levels in the hypothalamus, corpus striatum, and cerebral cortex.     

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)     

Effects of perinatal exposure to bisphenol A on brain neurotransmitters in female rat offspring

Pregnant Sprague-Dawley (CD IGS) rats were orally administered doses of bisphenol A (BPA) at 4, 40, and 400 mg/kg, from gestation days 6 to postnatal day 20. Neurotransmitters such as dopamine (DA) and serotonin (5HT) were extracted from the brains of dams and female offspring, and measured using liquid chromatography. BPA at 400 mg/kg was toxic and dosed rats died. At 3 wk after birth, brain levels of 3,4-dihydroxyphenylacetic acid (DOPAC, a DA metabolite), homovanillic acid (HVA, a DA metabolite), 5HT, 5-hydroxyindoleacetic acid (5HIAA, a 5HT metabolite) in female offspring were increased and the HVA/DA ratio was high in some brain areas of BPA-treated groups as compared with controls. At the age of 6 wk, levels of choline (Ch) in BPA-treated groups at 4 and 40 mg/kg were higher than control in all of eight brain areas. No changes were observed in acetylcholine (ACh) contents. In 9-wk-old offspring, changes in monoamines and metabolites were scattered and not great. At 3 wk after delivery, levels of 5HIAA in some brain areas of dams treated with BPA were higher than in control dams. Dose dependent increases in HVA and the HVA/DA ratio of the occipital cortex, and in the HVA/DA ratio of the frontal cortex were observed. The turnover of DA and 5HT was accelerated in 3-wk-old offspring and dams. BPA possesses very weak estrogenic activity. Changes in cerebral neurotransmitters observed in offspring and dams in this study may have been related to the estrogenic activity of BPA. However, further investigation is needed to examine the contribution of hormonal activity to such neurotransmitter changes.     

beta-Naphthoflavone and benzo(a)pyrene alter dopaminergic, noradrenergic, and serotonergic systems in brain and pituitary of rainbow trout (Oncorhynchus mykiss)

In the present study we evaluate for the first time the potential of the flavonoid compound beta-naphthoflavone (BNF) and the high molecular weight- Polycyclic aromatic hydrocarbon (PAH) benzo(a)pyrene (BaP) to alter brain neurotransmitter metabolism in fish. Fish of three different groups were intraperitoneally (i.p.) injected (2 microl g(-1)) with vegetable oil alone (control) or containing BNF or BaP (10 mg kg(-1)) and sacrificed 3, 24, and 72 h after treatment. Contents of dopamine (DA), noradrenaline (NA) and serotonin (5HT), as well as the amine oxidative metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole-3-acetic acid (5HIAA) were assayed in telencephalon, hypothalamus, preoptic region, optic tectum, and brain stem, as well as the pituitary. Fish treated with PAHs showed after 3h decreases in 5HT content in telencephalon, hypothalamus, preoptic region (with both BNF and BaP), and pituitary (with BaP), resulting in increased 5HIAA/5HT ratio. An increased ratio was also observed in hypothalamus 24h after BaP, and in preoptic region 72 h after BNF, in both cases due to an increased 5HIAA content. In other brain regions PAHs effects on 5-HT metabolism were less consistent. With respect to the dopaminergic system, changes induced by PAHs mainly occurred after 24 and 72 h of treatment, with increased DOPAC/DA ratio in preoptic region and brain stem. In hypothalamus, tectum, and pituitary, changes in DA metabolism showed strong variability. Finally, a decreased content of NA was evident in preoptic region (3h) and in telencephalon (24h) after both BNF and BaP treatments. Therefore, both BNF and BaP seem to act in rainbow trout brain by impairing 5HT availability at short term (3h) and increasing neuronal metabolic utilization of both 5HT and DA after 24 and 72 h. Data collected in the present study suggest that brain monoamine neurotransmitters are potential targets of BNF and BaP, and their alteration could have a role in known effects of PAHs on several neuroendocrine processes that are centrally regulated or modulated by brain monoamines.     

Effect of deoxynivalenol on neurotransmitters in discrete regions of swine brain

The effect of deoxynivalenol (DON, vomitoxin) on brain amine levels was investigated in swine. DON, a trichothecene mycotoxin, causes suppression of feed intake (anorexia) in susceptible species. Following acute administration of DON to pigs (0.25 mg/kg, IV), concentrations of endogenous catecholamines norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenyl-acetic acid (DOPAC), and homovanillic acid (HVA), and the indoleamines, 5-hydroxytryptamine (5HT, serotonin) and 5-hydroxyindoleacetic acid (5HIAA) were determined in five brain regions, periodically during the 24 h post-dosing. Analysis was carried out by high performance liquid chromatography, using electrochemical detection.Effects of DON in the swine brain were transmitter, time and region-specific. It was observed that levels of the major transmitters (NE, DA and 5HT) were statistically different from controls in the hypothalamus (Hypo), frontal cortex (FCX) and cerebellum (Cb) up to 8 h post-dosing. Overall, DON administration elevated NE and depressed DA concentrations in these regions, and levels of 5HT which increased initially in Hypo (1 h), had dropped significantly below controls in both Hypo and FCX at 8 h. These alterations, however, were not indicative of known neurochemical changes associated with chemical-induced anorexia. Instead, this data suggested that the neurochemical effects of acute DON exposure might be due to peripheral toxicological events (i.e., vomiting), which overwhelmed its more subtle feed refusal activity.Animal Research Centre; Contribution No. 1743.Research Program Service; Contribution No. R082.     

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.     

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.     

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.     

Brain microdialysis study of the effects of hazardous chemicals on the central nervous system. 1. Changes in monoamine metabolites induced by cerebral methyl bromide administration measured by two-probe microdialysis (TPMD) method.

The two-probe microdialysis (TPMD) method, in which two probes were applied simultaneously to the rat head, was developed to directly investigate the effects of chemicals on the brain. The first and the second probes were implanted into the right striatum and the left ventricle, respectively. Chemicals were dissolved in the perfusion fluid and given into the brain by diffusion through the ventricle probe. Monoamine metabolites were recovered through the striatum probe to investigate changes in neurotransmitter substances. Both intraperitoneal and intraventricular administration of haloperidol (a dopamine receptor blocker) increased 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA, dopamine metabolites) concentrations in the striatum. On the other hand, apomorphine (a dopamine receptor stimulant), which was given both intraperitoneally and intraventricularly, decreased striatal DOPAC and HVA concentrations. 5-Hydroxyindoleacetic acid (5HIAA, a serotonin metabolite) concentration was not affected by these drugs. Regarding changes in monoamine neurotransmitters, systemic and intraventricular administration produced similar effects. These findings indicate that the drugs were effectively incorporated into the brain by the TPMD method and the drug effect was observed in the opposite brain hemisphere. In the same procedure as used in the administration of haloperidol and apomorphine, methyl bromide was given into the rat brain. DOPAC and HVA in the striatum were increased by methyl bromide given by the TPMD method. These changes were the same as observed in the homogenate of rat brain exposed to methyl bromide. 5HIAA was reduced by intraventricular administration by the TPMD method, and this change in 5HIAA was not observed in the exposure experiments. We could detect the direct effects of methyl bromide on the brain by the TPMD method.     

Distribution, depletion and recovery of docosahexaenoic acid are region-specific in rat brain

The present study examined: (i) age-induced regional changes in fatty acid composition of brain phospholipids; (ii) alpha-linolenic acid deficiency-induced regional depletion and recovery of DHA in the brain. DHA and arachidonic acid (AA) did not distribute evenly in the brain. In weaning and adult rats, the region with the highest DHA percentage was the cortex whereas the medulla had the lowest DHA percentage. In the aged rats, both the cortex and cerebellum were the regions with the highest DHA percentage whereas in the neonatal rats, the striatum had the greatest percentage of DHA, and the hypothalamus and hippocampus had the least percentage of DHA. Regarding AA, the hippocampus was the region that had the highest percentage whereas the medulla was the region with the lowest percentage except for the neonatal rats, whose cerebellum, hypothalamus, striatum and midbrain had AA percentage lower than hippocampus and cortex. DHA was not proportionally depleted in various regions of brain when the rats were maintained on an n-3-deficient diet for two generations. The results demonstrated that the cortex, hippocampus, striatum, cerebellum and hypothalamus had DHA depleted by >71 %, whereas the midbrain and medulla had only 64 and 57 % DHA depleted, respectively. The most important observation was that the diet reversal for 12 weeks resulted in complete DHA recovery in all regions except for the medulla where the recovery was only 62 %. It was concluded that the location of DHA, n-3 deficiency-induced DHA depletion and reversibility of DHA deficiency across the brain were region-specific.     

Dietary variation of protein-carbohydrate: effect on hypothalamic and hippocampal GABA-glutamate in relation to aging

Dietary protein variation has been found to alter brain regional neurochemistry with aging. In the present investigation, we studied the effect of short-term treatment of protein-carbohydrate variable diet to rat on hypothalamic and hippocampal gamma-amino butyric acid (GABA)-glutamate metabolism with increase of age. Exposure of male albino rats with diet containing normal protein (20%)-normal carbohydrate (68%) increased GABA metabolism and decreased glutamate metabolism in both hypothalamus and hippocampus with the increase of age. GABA-glutamate metabolism of rats having low protein (8%)-high carbohydrate (80%) diet for short-term period (STP), was activated in young age (3 months) and decreased in old age (18 months) in both the brain regions. On the contrary, intake of high protein (50%)-low carbohydrate (38%) diet under similar condition decreased GABA-glutamate metabolism in both hypothalamus and hippocampus of young brain and increased only in hypothalamus of aged brain. In hippocampus of aged brain the same diet decreased glutamate metabolism without changing its GABA metabolism. These results suggest that an age-associated change in GABA-glutamate metabolism depends on the amount of dietary protein and carbohydrate and also on the brain region.     

Dietary variation of protein–carbohydrate: Effect on hypothalamic and hippocampal GABA–glutamate in relation to aging

Abstract

Dietary protein variation has been found to alter brain regional neurochemistry with aging. In the present investigation, we studied the effect of short-term treatment of protein–carbohydrate variable diet to rat on hypothalamic and hippocampal γ-amino butyric acid (GABA)–glutamate metabolism with increase of age. Exposure of male albino rats with diet containing normal protein (20%)–normal carbohydrate (68%) increased GABA metabolism and decreased glutamate metabolism in both hypothalamus and hippocampus with the increase of age. GABA–glutamate metabolism of rats having low protein (8%)–high carbohydrate (80%) diet for short-term period (STP), was activated in young age (3 months) and decreased in old age (18 months) in both the brain regions. On the contrary, intake of high protein (50%)–low carbohydrate (38%) diet under similar condition decreased GABA–glutamate metabolism in both hypothalamus and hippocampus of young brain and increased only in hypothalamus of aged brain. In hippocampus of aged brain the same diet decreased glutamate metabolism without changing its GABA metabolism. These results suggest that an age-associated change in GABA–glutamate metabolism depends on the amount of dietary protein and carbohydrate and also on the brain region.     

Effect of the edible mushroom Mycoleptodonoides aitchisonii on transient global ischemia-induced monoamine metabolism changes in rat cerebral cortex

We performed a transient bilateral common carotid artery occlusion on rats and investigated whether feeding an aqueous extract of Mycoleptodonoides aitchisonii, an edible mushroom, affected metabolism of monoamines in the cerebral cortex, possibly protecting against ischemic damage. Seventeen days after the surgery, concentrations of the dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and of homovanillic acid (HVA) in the cerebral cortex of the M. aitchisonii-fed group (MV) were higher than in the control ischemia (CV) group. The turnover rate of DA, which was indicated by (DOPAC+HVA)/DA, for the CV group was significantly lower than for the MV group, and the MV group value was the same rate as the sham-operated group. These data indicate that M. aitchisonii affects the dopaminergic neuronal system following brain ischemia damage in the cerebral cortex.     

拟除虫菊酯对大鼠脑黑质纹状体系统多巴胺及其代谢产物的影响

目的 初步探讨拟除虫菊酯类农药对雄性SD大鼠脑黑质纹状体多巴胺(DA)系统的毒性作用及其可能机制。方法 采用不同剂量的溴氰菊酯(DM,6.25、12.50 mg/kg)、氯菊酯(PM,200、400mg/kg)给雄性SD大鼠连续10 d经口灌胃给药后,HPLC荧光检测法分别检测其脑黑质、纹状体内DA及其代谢产物3,4-二羟基苯乙酸(DOPAC)、3-甲氧基-4-羟基苯乙酸(HVA)的含量。结果 给药各组大鼠纹状体内DA含量都有不同程度的下降,且12.50 mg/kg DM组(6.14±0.57μg/g湿重)与对照组(9.46±1.95 μg/g湿重)的差异有统计学意义(P<0.05);200、400 mg/kg PM组和6.25、12.50 mg/kgDM 4个组的DA更新率[(DOPAC HVA)/DA]与对照组相比,分别增加了133.33％、166.67％、166.67％和266.67％,差异均有统计学意义(P<0.05或P<0.01);而黑质内DA及其代谢产物水平均无明显变化。结论 DM可能抑制酪氨酸羟化酶合成DA,使其在纹状体内的含量下降,PM和DM都可以加强DA的代谢。     

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.     

乙醇对大鼠脑纹状体和海马神经递质的影响

[目的]研究乙醇对大鼠脑组织神经递质的影响。[方法]雄性SD大鼠25只，随机分为低剂量组、高剂量组和对照组(分别为8、8、9只)。用相应25．6%(V／V)、51．3％(V／V)乙醇浓度和对照组用蒸馏水，一次灌胃(灌胃体积为1．0ml/100g体重)染毒。1h后处死大鼠，取血、脑纹状体和海马，分别测定血中乙醇浓度、脑纹状体单胺类递质含量及海马中强啡肽A水平。[结果]纹状体多巴胺(DA)含量随乙醇染毒剂量增加而升高，呈剂量一效应关系。低剂量组3，4-双羟苯乙酸(DOPAC)、强啡肽A(dynorphin A，DynA)含量显著升高；高剂量组5-羟色胺(5-HT)含量显著高于低剂量组和对照组。5-HT、5-羟吲哚乙酸(5-HIAA)含量与血中乙醇浓度(BAC)显著相关。[结论]脑组织神经递质的变化，可能是乙醇神经毒性的机制之一。