Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The localization of serotonin-immunoreactivity (5-HT-IR) in the locus ceruleus (LC) of rats was studied by the peroxidase-anti-peroxidase method using a purified antibody obtained from a rabbit. Antibody production was performed according to the method of Grota and Brown (1974). The antibody was applied to serial cryostat sections with alternate counterstaining by cresyl violet, after intraventricular injections of 5,6-dihydroxytryptamine or 5,7-dihydroxytryptamine prior to treatment with pargyline and a precursor of 5-HT. The majority of LC neurons were immunopositive, and more than half of all LC neurons clearly showed 5-HT-IR. Although core cells were the most predominant, all types of neurons were immunopositive, and randomly scattered throughout the LC. The uptake inhibitor, Lilly 110140, administered in sufficient amounts prior to an injection of pargyline, did not reduce 5-HT-IR within the LC. The results suggest that LC neurons receive 5-hydroxytryptophan (5-HTP) through an afferent vascular-neuronal channel and/or by diffusion from blood capillaries much more than 5-HT itself. We consider from these results that all types of LC neurons throughout the nucleus are masked 5-HT cells, and that the majority of LC neurons utilize blood-borne 5-HTP as an immediate precursor for intraneuronal 5-HT synthesis.
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PMID:The distribution of serotonin immunoreactivity in the rat locus ceruleus after intraventricular injections of either 5,6- or 5,7-dihydroxytryptamine with special reference to serotonin synthesis. 209 64

Concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), free 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in brain regions of 5-, 20-, and 32-month-old male Brown-Norway rats using high pressure liquid chromatography. In view of the activating effects of sex steroids on peptide and monoamine transmitter systems and the declining plasma testosterone levels with aging, the effects of testosterone supplementation on age-related changes in central monoamine metabolism were also studied. Age-related decreases in monoamine metabolism were observed in nigrostriatal, mesocortical and coeruleohippocampal systems. Marked reductions in DOPAC (35%) and HVA (50%) occurred in the ventral tegmental area between 20 and 32 months of age. 5-HT and 5-HIAA levels showed reductions and increases depending on the brain region. Testosterone administration resulted in elevations of HVA in the substantia nigra and MHPG in the locus coeruleus and hippocampus, which were most pronounced in young animals. It is concluded that there are marked differences in age-related changes between nigrostriatal, mesocortical and coeruleohippocampal systems and that testosterone exerts a stimulatory influence on some aspects of monoamine metabolism in young but not in aged animals.
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PMID:Central monoamine metabolism in the male Brown-Norway rat in relation to aging and testosterone. 228 64

We have recently demonstrated that tissue resistance increases during the early response (ER) to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate the in vitro airway and tissue responses to antigen and the involvement of the potential mediators serotonin (5-HT) and leukotriene D4 (LTD4). We sensitized Brown-Norway rats with ovalbumin (OA) and subsequently challenged bronchial rings and subpleural parenchymal strips with OA in the organ bath. In selected experiments tissues were incubated with methysergide (a 5-HT receptor antagonist), ketanserin (a 5-HT2 receptor antagonist), MK-571 (a LTD4 receptor antagonist), or MK-886 (5-lipoxygenase inhibitor) prior to challenge. Both bronchial rings and parenchymal strips constricted in response to OA. Methysergide and ketanserin completely inhibited OA-induced constriction of bronchial rings. The effect of MK-571 was not significant, whereas MK-886 partially blocked OA-induced bronchial constriction, suggesting a potential role for LTC4 in antigen-induced airway constriction. In parenchymal strips, methysergide, ketanserin, MK-571, and MK-886 all partially inhibited the OA response, whereas the combinations of methysergide and MK-571 or ketanserin and MK-886 completely ablated the response. These data suggest that both bronchial rings and parenchymal strips constrict after OA challenge but that the relative contributions of 5-HT and LTD4 to the allergic response in central airways and parenchymal tissues differ.
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PMID:In vitro airway and tissue response to antigen in sensitized rats. Role of serotonin and leukotriene D4. 759 67

The adaptive response of the neuroendocrine system to stress is known to be impaired during ageing, and this impairment may be genetically determined. To elucidate further the effect of genotype, inbred male rats of the Wistar-Kyoto (WKY) strain, characterized by their hyper-reactivity to stressors and shorter life span, were compared with Brown-Norway (BN) rats. In young BN rats, resting prolactin concentrations were lower than in WKY animals and were reduced with age, while in WKY rats they remained unchanged with age. In young rats of both strains prolactin concentrations were highest after subjecting them to stressful stimuli for 15 min. After 2 h of restraint stress (during which the animals were confined to a narrow space that restricted movement) prolactin concentrations in young rats returned to pre-stress values, while remaining high in aged rats of both strains. Concentrations of corticotrophin (or adrenocorticotrophic hormone, ACTH) were lower in BN than in WKY rats and did not change with age in either strain. After 2 h of stress, ACTH concentrations were still slightly higher than normal in both young and aged BN rats, but not in WKY rats. Corticosterone concentrations were similar in young WKY and BN rats and were reduced in aged rats of both strains. After 2 h of stress, corticosterone concentrations were still high in aged, but not in young rats of both strains. However, this stress-induced increase was larger (3.7 times as much) in the BN strain than in the WKY strain (in which the increase was 1.7 times as much). The concentrations of hypothalamic monoamines were similar in young rats of both strains, although stress resulted in reduced noradrenaline concentrations, as previously documented, and in minor increases in 3,4-dihydroxyphenylacetic acid in both strains. During ageing, basal noradrenaline concentrations were reduced only in WKY rats, while the amount of 5-HT increased selectively in BN rats. Concentrations of 5-hydroxyindoleacetic acid were increased after stress in aged WKY rats only. The results demonstrate that resting plasma concentrations of the stress hormones ACTH and corticosterone and of prolactin are lower in BN than in WKY rats. In ageing, however, the stress-induced increases in the concentrations of these hormones are relatively higher in the BN strain, which is characterized by a longer life span.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of genotype on age-related alterations in the concentrations of stress hormones in plasma and hypothalamic monoamines in rats. 768 29

Given that an important proportion of patients with obsessive-compulsive disorder (OCD) fail to respond adequately to serotonin (5-HT) reuptake inhibitors (SRI), augmentation strategies aimed at enhancing further 5-HT transmission by different mechanisms were attempted sequentially in 13 SRI-resistant patients. Addition of the 5-HT1A l beta-adrenergic antagonist pindolol did not alter OCD symptomatology but produced a rapid improvement of depressive symptoms. The 5-HT1A agonist buspirone as well as 5-hydroxytryptophan, the immediate precursor of 5-HT, added to the SRI-pindolol regimen, were not effective in attenuating the intensity of OCD. Tryptophan, added to the SRI-pindolol regimen, produced a significant improvement after 4 weeks, with further amelioration after 6 weeks (36% decrease of the Yale-Brown Obsessive Compulsive Score), which was maintained with treatment prolongation.
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PMID:Sequential administration of augmentation strategies in treatment-resistant obsessive-compulsive disorder: preliminary findings. 873 12

Prolactin (PRL) responses to acute challenge with the serotonin (5-HT) releaser/uptake inhibitor, d-fenfluramine (PRL[d-FEN]), were correlated with three different measures of aggression in 14 male personality-disordered subjects. Consistent with previous work, PRL[d-FEN] responses were inversely correlated with scores on the Buss-Durkee Hostility Inventory-Assault scale (BDHI-Assault) and with the Brown-Goodwin Aggression-Revised (BGA-R) Aggression scale. In addition, PRL[d-FEN] responses were inversely correlated with a direct laboratory measure of aggressive behavior (Point-Subtraction Aggression Paradigm: PSAP). Although all measures of aggression correlated with PRL[d-FEN] response, differences among the intercorrelations of these measures were found. Specifically, BGA-R Aggression scores correlated with both BDHI-Assault and PSAP scores, but no relation was found between BDHI-Assault and PSAP scores. The results suggest that central 5-HT function may be associated with both self-report and behavioral measures of aggressive behavior, which may represent somewhat separate aspects of aggressive behavior.
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PMID:Relationship of prolactin response to d-fenfluramine to behavioral and questionnaire assessments of aggression in personality-disordered men. 914 28

The similarities between the serotonin (5-HT) transporter in both human platelets and human brain permit us to investigate this structure in patients with different psychiatric disorders. Several reports have shown abnormalities of the 5-HT transporter, by means of the measurement of the 5-HT uptake or of the 3H-imipramine binding, in platelets of patients with obsessive-compulsive disorder (OCD). The availability of the ligand 3H-paroxetine, a selective 5-HT reuptake inhibitor, to label the 5-HT transporter, promoted us to evaluate the binding of 3H-paroxetine in platelets of 18 drug-free patients with OCD. The results, showing that the patients had a lower number of 3H-paroxetine sites, which is inversely correlated with the Yale Brown Obsessive-Compulsive Scale total score, than a similar group of controls, add supporting evidence to the involvement of 5-HT in OCD. In addition, the decreased functionality of the 5-HT transporter seems to be linked to the severity of OC symptoms.
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PMID:Decreased platelet 3H-paroxetine binding in obsessive-compulsive patients. 912 18

The Brown Norway/Fischer 344 F1 hybrid rats (F344BNF1) is a newer rat model and is emerging as an important rodent model of aging. In the present study we used motoric performance tests, intracerebral microdialysis, and neurochemical measures of postmortem brain tissue to investigate the effects of aging in young (4-5 months), middle-aged (18-19), and old (24-25 months) F344BNF1 hybrid rats. We observed that old F344BNF1 rats exhibited decreased motoric performance, and lower levels of spontaneous and d-amphetamine-induced locomotor activity than those observed in young F344BNF1 rats. Microdialysis measures of extracellular basal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid (HVA) were significantly diminished in the striata of the middle-aged and old rats as compared to levels in young animals. In addition, d-amphetamine-evoked overflow of DA was significantly decreased in the middle-aged and aged rat striatum as compared to DA overflow in young F344BNF1 rats. Studies of postmortem brain tissue showed that the changes in overflow of DA correlated with significantly lower DA tissue content in ventral striatum and midbrain. Moreover, both dopamine turnover ratios (DOPAC/DA, HVA/DA) and the serotonin turnover ratio (5-HIAA/5-HT) were significantly elevated in the ventral striatum and nucleus accumbens. The results of this study demonstrate a correlation between reductions in striatal DA neurochemistry and diminished motor function in aged F344BNF1 rats.
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PMID:Age-related decline in striatal dopamine release and motoric function in brown Norway/Fischer 344 hybrid rats. 959 19

The potential contribution of microvascular leakage to airway narrowing during the early (ER) and late (LR) responses following allergen challenge was determined in Brown Norway (BN) rats actively sensitized with ovalbumin (OA). To study leak into the airway wall, rats (n = 46) were challenged 2 weeks later with aerosolized OA, saline, or serotonin (5-HT) to study either ER (n = 25), LR (n = 15), or 5-HT (n = 6) responses. Pulmonary resistance (RL) was used to measure airway narrowing. Microvascular leak was determined by the Evans blue (EB) technique in the airway tissues, and in another group of BN, by EB in bronchoalveolar lavage (BAL) in the airway lumen (n = 43). EB increased in the airways of 5-HT challenged rats (P < 0.05), but not during ER or LR. EB in BAL increased significantly during the ER (101 +/- 31.35 ng/ml BAL), vs saline challenge (10.82 +/- 1.66; P < 0.05) and during the LR at 3, 4, 5, and 7 h following OA challenge compared with controls (P < 0.05). These results suggest that fluid transits rapidly from the airway microvascular circulation and into the airway lumen following allergen challenge. The measurement of EB in BAL can detect microvascular leak into the airway lumen during the ER and LR. Plasma leak into the airway lumen may contribute to the increase in pulmonary resistance observed during ER and LR in BN rats.
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PMID:Microvascular leakage in the airway wall and lumen during allergen induced early and late responses in rats. 969 46

Ozone is known to induce airway hyperresponsiveness (AHR) in humans and animals. Previous studies in animals used high exposure levels and reported inconsistent results. The aim of this study was to investigate the effect of a single low-level ozone exposure on different inbred rat strains. Nine rat strains were exposed to 0.05 parts per million (ppm) for 4 h and airway responsiveness to intravenous 5-hydroxytryptamine (HT) examined. Bronchoalveolar lavage fluid (BALF) was examined for the presence of inflammatory cells and markers. Lewis, BDII and Long-Evans rats developed AHR 90 min after ozone exposure, whereas Wistar, Sprague-Dawley, Fisher 344, Brown-Norway, BDE and DA rats did not. Baseline airway responsiveness to 5-HT differed significantly between rat strains, but did not correlate with the presence or absence of ozone-induced AHR. No inflammatory cell influx was found in BALF of any rat strain. In Long-Evans rats, AHR lasted up to 12 h after ozone exposure despite the absence of an inflammatory cell influx or increase in lactate dehydrogenase, alkaline phosphatase or total protein in BALF. In conclusion, exposure to an ambient concentration of ozone induced airway hyperresponsiveness without airway inflammation in some highly inbred rat strains. Genetic factors are likely to account for the observed variability in sensitivity of the airways to ozone.
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PMID:Ambient ozone concentrations induce airway hyperresponsiveness in some rat strains. 1048 39


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