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Sample records for ampt-induced monoamine depletion

  1. Monoamine depletion attenuates the REM sleep deprivation-induced increase in clonidine response in the forced swimming test.

    PubMed

    Asakura, W; Matsumoto, K; Ohta, H; Watanabe, H

    1994-09-01

    Effect of monoamine depletion on the REM sleep (REMs) deprivation-induced increase in clonidine response in the forced swimming test was investigated. Mice were deprived of REMs by the small pedestal method. Clonidine HCl (10-1000 micrograms/kg, IP), an alpha 2-adrenoceptor agonist, dose dependently increased swimming activities in group-housed and socially isolated mice used as the control groups. The dose-response relationship shifted to the left following REMs deprivation (ED50 values in the group-housed, isolated, and REMs-deprived mice were 250, 200, and 27 micrograms/kg, respectively). Monoamine depletion, induced by reserpine (5 mg/kg, IP) plus alpha-methyl-p-tyrosine (250 mg/kg, IP), did not produce any changes in the effects of clonidine in the control groups. However, in REMs-deprived mice, monoamine depletion significantly decreased the effect of 100 micrograms/kg clonidine, but not that of 300 micrograms/kg clonidine on swimming activity. These results indicate that clonidine-induced increase in swimming activity in the forced swimming test is mainly mediated by postsynaptic alpha 2-adrenoceptor, and that endogenous noradrenaline in the brain plays an important role in the increase of clonidine response following REMs deprivation treatment. The neuronal mechanism of the increase in clonidine response is discussed.

  2. Depletion of rat cortical norepinephrine and the inhibition of (/sup 3/H)norepinephrine uptake by xylamine does not require monoamine oxidase activity

    SciTech Connect

    Dudley, M.W.

    1988-01-01

    Inhibition of monoamine oxidase A through pretreatment of rats with clorgyline or the pro-drug MDL 72,394 did not block the amine-depleting action of xylamine. Xylamine treatment resulted in a loss of approximately 60% of the control level of norepinephrine in the cerebral cortex. A 1-hr pretreatment, but not a 24-hr pretreatment, with the monoamine oxidase B inhibitor, L-deprenyl, prevented the depletion of norepinephrine by xylamine. In addition, pretreatment with MDL 72,974, a monoamine oxidase B inhibitor without amine-releasing or uptake - inhibiting effects, did not prevent cortical norepinephrine levels. Inhibition of monoamine oxidase by either MDL 72,974 or MDL 72,394 did not prevent the inhibition of (/sup 3/H)norepinephrine uptake into rat cortical synaptosomes by xylamine. These data indicate that monoamine oxidase does not mediate the amine-releasing or uptake inhibiting properties of xylamine. The protection afforded by L-deprenyl following a 1-hr pretreatment most probably was due to accumulation of its metabolite, L-amphetamine, which would inhibit the uptake carrier. A functional carrier is required for depletion since desipramine administered 1 hr prior to xylamine, was also able to prevent depletion of norepinephrine.

  3. Central administration of methamphetamine synergizes with metabolic inhibition to deplete striatal monoamines.

    PubMed

    Burrows, K B; Nixdorf, W L; Yamamoto, B K

    2000-03-01

    These studies examined, in vivo, the effect of local intrastriatal perfusion of methamphetamine (MA) on dopamine (DA) and glutamate release in relation to changes in striatal DA and serotonin (5-HT) content measured 1 week after treatment. Interactions between the inhibition of energy metabolism and the direct perfusion of MA on long-term decreases in DA and 5-HT content also were investigated. MA (100 microM), the succinate dehydrogenase inhibitor malonate, or the combination of MA and malonate was reverse-dialyzed into the striatum for 8 h. The continuous local perfusion of MA alone increased DA release by 30-fold, similar to that seen after systemic administration, but did not increase glutamate or body temperature, and did not deplete neurotransmitter content. Malonate perfusion increased both DA and glutamate overflow, and dose dependently decreased DA content. 5-HT content was not as affected by malonate perfusions (200 mM malonate depleted DA by 66% and 5-HT by 40%). When MA was coperfused with 200 mM malonate, DA content was reduced by 80% and to a greater extent compared with malonate alone. Coperfusion of MA and 200 mM malonate did not enhance 5-HT loss. Overall, the present findings provide evidence that energy metabolism plays an important role in MA toxicity and that striatal dopaminergic terminals are more vulnerable than 5-HT terminals to damage after metabolic stress.

  4. Chloride Requirement for Monoamine Transporters

    PubMed Central

    De Felice, Louis J

    2016-01-01

    This review focuses on the Cl− requirement for dopamine, serotonin, and norepinephrine (DA, 5-HT, and NE) transport and induced current via the transporters for these transmitters, DAT, SERT, and NET. Indirect evidence exists for the passage of Cl− ions through monoamine transporters; however, direct evidence is sparse. An unanswered question is why in some preparations, notably native neurons, it appears that Cl− ions carry the current through DAT, whereas in heterologous expression systems Na+ ions carry the current often referred to as the uncoupled current. It is suggested that different functional states in monoamine transporters represent conformational states that carry dominantly Cl− or Na+. Structures of monoamine transporters contribute enormously to structure-function relationships; however, thus far no structural features support the functionally relevant ionic currents that are known to exist in monoamine transporters. PMID:26794730

  5. Monoamine Oxidase Inhibitors: Clinical Review

    PubMed Central

    Remick, Ronald A.; Froese, Colleen

    1990-01-01

    Monoamine oxidase inhibitors (MAOIs) are effective antidepressant agents. They are increasingly and effectively used in a number of other psychiatric and non-psychiatric medical syndromes. Their potential for serious toxicity (i.e., hypertensive reaction) is far less than original reports suggest, and newer reversible substrate-specific MAOIs may offer even less toxicity. The author reviews the pharmacology, mechanism of action, clinical indications, and dosing strategies of MAOIs. The common MAOI side-effects (hypotension, weight gain, sexual dysfunction, insomnia, daytime sedation, myoclonus, and hypertensive episodes) are described and management techniques suggested. Recent clinical developments involving MAOIs are outlined. PMID:21233984

  6. Behavioral effects of bidirectional modulation of brain monoamines by reserpine and d-amphetamine in zebrafish

    PubMed Central

    Kyzar, Evan; Stewart, Adam Michael; Landsman, Samuel; Collins, Christopher; Gebhardt, Michael; Robinson, Kyle; Kalueff, Allan V.

    2013-01-01

    Brain monoamines play a key role in the regulation of behavior. Reserpine depletes monoamines, and causes depression and hypoactivity in humans and rodents. In contrast, d-amphetamine increases brain monoamines’ levels, and evokes hyperactivity and anxiety. However, the effects of these agents on behavior and in relation to monoamine levels remain poorly understood, necessitating further experimental studies to understand their psychotropic action. Zebrafish (Danio rerio) are rapidly emerging as a promising model organism for drug screening and translational neuroscience research. Here, we have examined the acute and long-term effects of reserpine and d-amphetamine on zebrafish behavior in the novel tank test. Overall, d-amphetamine (5 and 10 mg/L) evokes anxiogenic-like effects in zebrafish acutely, but not 7 days later. In contrast, reserpine (20 and 40 mg/L) did not evoke overt acute behavioral effects, but markedly reduced activity 7 days later, resembling motor retardation observed in depression and/or Parkinson’s disease. Three-dimensional ‘temporal’ (X, Y, Time) reconstructions of zebrafish locomotion further supports these findings, confirming the utility of 3D-based video-tracking analyses in zebrafish models of drug action. Our results show that zebrafish are highly sensitive to drugs bi-directionally modulating brain monoamines, generally paralleling rodent and clinical findings. Collectively, this emphasizes the potential of zebrafish tests to model complex brain disorders associated with monoamine dysregulation. PMID:23827499

  7. Dietary inhibitors of monoamine oxidase A.

    PubMed

    Dixon Clarke, Sarah E; Ramsay, Rona R

    2011-07-01

    Inhibition of monoamine oxidase is one way to treat depression and anxiety. The information now available on the pharmacokinetics of flavonoids and of the components of tobacco prompted an exploration of whether a healthy diet (with or without smoking) provides active compounds in amounts sufficient to partially inhibit monoamine oxidase. A literature search was used to identify dietary monoamine oxidase inhibitors, the levels of these compounds in foods, the pharmacokinetics of the absorption and distribution, and tissue levels observed. An estimated daily intake and the expected tissue concentrations were compared with the measured efficacies of the compounds as inhibitors of monoamine oxidases. Norharman, harman and quercetin dietary presence, pharmacokinetics, and tissue levels were consistent with significant levels reaching neuronal monoamine oxidase from the diet or smoking; 1,2,3,4-tetrahydroisoquinoline, eugenol, 1-piperoylpiperidine, and coumarin were not. Quercetin was equipotent with norharman as a monoamine oxidase A inhibitor and its metabolite, isorhamnetin, also inhibits. Total quercetin was the highest of the compounds in the sample diet. Although bioavailability was variable depending on the source, a healthy diet contains amounts of quercetin that might give sufficient amounts in brain to induce, by monoamine oxidase A inhibition, a small decrease in neurotransmitter breakdown.

  8. Monoamine metabolism in human brain.

    PubMed

    Robinson, D S; Sourkes, T L; Nies, A; Harris, L S; Spector, S; Bartlett, D L; Kaye, I S

    1977-01-01

    Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent pattern of correlation was found for COMT and TH. Mean MAO activity was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system.

  9. Effects of 071031B, a novel serotonin and norepinephrine reuptake inhibitor, on monoamine system in mice and rats.

    PubMed

    Xue, Rui; He, Xin-Hua; Yuan, Li; Chen, Hong-Xia; Zhang, Li-Ming; Yong, Zheng; Yu, Gang; Fan, Shi-Yong; Li, Yun-Feng; Zhong, Bo-Hua; Zhang, You-Zhi

    2016-01-01

    Our previous study indicated that 071031B, a novel potential serotonin and norepinephrine reuptake inhibitor, showed robust antidepressant activity in multiple depression models, and could simultaneously inhibit 5-HT and NE reuptake in vitro. The present study was to evaluate the effects of 071031B on monoamine system in vivo, by using pharmacological models, including 5-HTP induced head-twitch test, yohimbine toxicity potentiation test, and reserpine induced hypothermia test, and determining monoamine transmitter levels in reserpine induced monoamine depletion model or chronic unpredictable stress (CUS) model. Results in pharmacological models indicated that acute administration of 071031B at 5-20 mg/kg significantly enhanced 5-HTP induced head-twitch behavior, potentiated yohimbine induced lethal rate, and reversed reserpine induced hypothermia. Further monoamine assays demonstrated that acute or chronic administration of 071031B at 10 or 20 mg/kg increased 5-HT and/or NE levels in various brain regions in reserpine or CUS induced monoamine depletion models, respectively, without effect on DA and its metabolites. Our results revealed that 071031B produces potent inhibition of 5-HT and NE reuptake in vivo.

  10. [Monoamines stimulations in experimental carcinogenesis].

    PubMed

    Popov, I; Spuzić, I; Rakić, Lj

    1994-01-01

    Facts about the role of CNS monoamines in cancerogenesis have been accumulated for many years. The aim of the present study was to investigate the effect of interaction of psychoactive drug (Piracetam) and other treatments on survival time of tumour-bearing rats. 138 Wistar rats were used in the experiment. The animals were injected 1% 3--Methilcholantren suspension in 10% Tylose, s.c. under the dorsal skin of the neck in a dose of 3 mg/animal. Within 4-9 months after a single injection, the rats developed tumours at the site of injection. The surgical removal was performed when tumours reached the size of 1-3 cm. After surgical extirpation of tumours different groups of animals were treated by cyclophosphamide (s.c. one-time dose of 50 mg/kg for female and 100 mg/kg for male) or by psychoactive drug (Piracetam) administrated by GE tube 5 time/week, 100 mg/kg. Autopsy and histological examinations were carried out in all animals. Survival time (> 120 days) was the greatest in group B (Piracetam, after surgical removal of tumours) 81.2%, and group C (Cyclophosphamid, after surgical removal of tumours) 68.8% and in group A (only surgical removal of tumours) 50%. In group B the incidence of metastases was the smallest (87.1% of animals were without metastases), compared with group C (45.4% of animals were without metastases) and group A (27.3% of animals were without metastases). The diference is statistically significant. The mechanism of antineoplastic effect of Piracetam consisted of the interaction of influences both on metabolism of the Central nervous system and the tumour. Probably, it is the neurotransmitter modulation that had its effect on carcinogenesis not only by regulation/disregulation of brain homeostasis, but also via direct effect on intracellular processes during cell development and differentation.

  11. Monoamine theories of depression: historical impact on biomedical research.

    PubMed

    Mulinari, Shai

    2012-01-01

    Monoamine theories associate depression with reduced brain monoamine levels. These theories achieved broad popularity in the mid-1960s. The present article reviews the historical development of monoamine theories and their subsequent impact on biomedical research. Alleged divisions between West European and US researchers over competing versions of the theories are investigated using bibliometrics. Subsequently, the application of monoamine theories in the NIMH Collaborative Program on the Psychobiology of Depression is covered. The article argues that the impact of monoamine theories is best explained by the ability of researchers, governmental agencies, and pharmaceutical companies to invoke theories that advance various projects and agendas.

  12. Dopamine depletion attenuates some behavioral abnormalities in a hyperdopaminergic mouse model of bipolar disorder

    PubMed Central

    van Enkhuizen, Jordy; Geyer, Mark A.; Halberstadt, Adam L.; Zhuang, Xiaoxi; Young, Jared W.

    2014-01-01

    Background Patients with BD suffer from multifaceted symptoms, including hyperactive and psychomotor agitated behaviors. Previously, we quantified hyperactivity, increased exploration, and straighter movements of patients with BD mania in the human Behavioral Pattern Monitor (BPM). A similar BPM profile is observed in mice that are hyperdopaminergic due to reduced dopamine transporter (DAT) functioning. We hypothesized that dopamine depletion through alpha-methyl-p-tyrosine (AMPT) administration would attenuate this mania-like profile. Methods Male and female DAT wild-type (WT; n=26) and knockdown (KD; n=28) mice on a C57BL/6 background were repeatedly tested in the BPM to assess profile robustness and stability. The optimal AMPT dose was identified by treating male C57BL/6 mice (n=39) with vehicle or AMPT (10, 30, or 100 mg/kg) at 24, 20, and 4 h prior to testing in the BPM. Then, male and female DAT WT (n=40) and KD (n=37) mice were tested in the BPM after vehicle or AMPT (30 mg/kg) treatment. Results Compared to WT littermates, KD mice exhibited increased activity, exploration, straighter movement, and disorganized behavior. AMPT-treatment reduced hyperactivity and increased path organization, but potentiated specific exploration in KD mice without affecting WT mice. Limitations AMPT is not specific to dopamine and also depletes norepinephrine. Conclusions KD mice exhibit abnormal exploration in the BPM similar to patients with BD mania. AMPT-induced dopamine depletion attenuated some, but potentiated other, aspects of this mania-like profile in mice. Future studies should extend these findings into other aspects of mania to determine the suitability of AMPT as a treatment for BD mania. PMID:24287168

  13. Neural response to catecholamine depletion in remitted bulimia nervosa: Relation to depression and relapse.

    PubMed

    Mueller, Stefanie Verena; Mihov, Yoan; Federspiel, Andrea; Wiest, Roland; Hasler, Gregor

    2017-07-01

    Bulimia nervosa has been associated with a dysregulated catecholamine system. Nevertheless, the influence of this dysregulation on bulimic symptoms, on neural activity, and on the course of the illness is not clear yet. An instructive paradigm for directly investigating the relationship between catecholaminergic functioning and bulimia nervosa has involved the behavioral and neural responses to experimental catecholamine depletion. The purpose of this study was to examine the neural substrate of catecholaminergic dysfunction in bulimia nervosa and its relationship to relapse. In a randomized, double-blind and crossover study design, catecholamine depletion was achieved by using the oral administration of alpha-methyl-paratyrosine (AMPT) over 24 h in 18 remitted bulimic (rBN) and 22 healthy (HC) female participants. Cerebral blood flow (CBF) was measured using a pseudo continuous arterial spin labeling (pCASL) sequence. In a follow-up telephone interview, bulimic relapse was assessed. Following AMPT, rBN participants revealed an increased vigor reduction and CBF decreases in the pallidum and posterior midcingulate cortex (pMCC) relative to HC participants showing no CBF changes in these regions. These results indicated that the pallidum and the pMCC are the functional neural correlates of the dysregulated catecholamine system in bulimia nervosa. Bulimic relapse was associated with increased depressive symptoms and CBF reduction in the hippocampus/parahippocampal gyrus following catecholamine depletion. AMPT-induced increased CBF in this region predicted staying in remission. These findings demonstrated the importance of depressive symptoms and the stress system in the course of bulimia nervosa. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Towards rational therapy with monoamine oxidase inhibitors.

    PubMed

    Tyrer, P

    1976-04-01

    A rational approach to the use of monoamine oxidase inhibitors (MAOIs) is outlined. Patients suitable for treatment cannot be classified adequately using conventional diagnostic labels. They include those with primary symptoms of hypochondriasis, agoraphobia and social phobias, irritability, somatic anxiety and anergia; those with primary depressed mood, guilt, ideas of reference and personality disorders seldom respond. There is great variation in the interval between the first administration of these drugs and clinical response, and this may account for the inconsistencies in published trials. The type of drug and its dose may affect rate of response, as may biochemical factors, including acetylator and monoamine oxidase status. To obtain maximum benefit, a course of therapy with MAOIs should last for several months.

  15. Platelet monoamine oxidase in early childhood autism.

    PubMed

    Cohen, D J; Young, J G; Roth, J A

    1977-05-01

    Platelet monoamine oxidase (MAO) activity was studied in 31 individuals suffering from early childhood autism and was not significantly different from that found in normal children or adults. In the autistic children, MAO activity decreased with age, and there was a trend toward greater platelet MAO activity in prepubertal and pubertal male autistic children relative to normal male children. Total platelet counts were not elevated in autistic children.

  16. Imaging Monoamine Oxidase in the Human Brain

    SciTech Connect

    Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Logan, Jean

    1999-11-10

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets.

  17. Monoamine Reuptake Inhibitors in Parkinson's Disease

    PubMed Central

    Huot, Philippe; Fox, Susan H.; Brotchie, Jonathan M.

    2015-01-01

    The motor manifestations of Parkinson's disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia. PMID:25810948

  18. Treatment of hyperactive children with monoamine oxidase inhibitors. II. Plasma and urinary monoamine findings after treatment.

    PubMed

    Zametkin, A; Rapoport, J L; Murphy, D L; Linnoila, M; Karoum, F; Potter, W Z; Ismond, D

    1985-10-01

    Urinary monoamines and metabolites as well as plasma norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol were measured in 14 boys (mean age, 9.2 years) with Attention Deficit Disorder With Hyperactivity during an initial placebo period, after four weeks of treatment with either dextroamphetamine sulfate (N=5) or a monoamine oxidase inhibitor (N=9) and at the end of a subsequent two-week placebo "washout" period. Both dextroamphetamine and monoamine oxidase inhibitors produced persistent changes in monoamines and metabolites, which were most marked and consistent for NE and its metabolite 3-methoxy-4-hydroxyphenylglycol. These changes did not correlate in a consistent fashion with clinical response during drug treatment. Moreover, there was rapid clinical relapse following cessation of either treatment while the alterations in NE metabolism remained during the two weeks following drug, further demonstrating the independence of these changes from clinical state. Future studies with dextroamphetamine need drug-free periods that are greater than 14 days to obtain true "baseline" conditions.

  19. Simultaneous depletion of serotonin and catecholamines impairs sustained attention in healthy female subjects without affecting learning and memory.

    PubMed

    Matrenza, Cathy; Hughes, Jay-Maree; Kemp, Andrew H; Wesnes, Keith A; Harrison, Ben J; Nathan, Pradeep J

    2004-03-01

    Monoamine neurotransmitters, serotonin, noradrenaline and dopamine modulate many important cognitive processes such as attention, learning and memory. While the selective effects of serotonin and catecholamine depletion on such processes have been investigated, the effects of simultaneous depletion of these monoamines on cognition remain unclear. This is of particular interest given that multiple neurotransmitter abnormalities have been implicated in many psychiatric disorders. The aim of the current study was to examine the effects of lowered brain monoamine function on cognitive performance, using the technique of amino acid precursor depletion. The study was a double-blind, placebo-controlled design in which 20 healthy female subjects were tested under a combined monoamine depletion condition (CMD) and a balanced control condition (B). Cognitive testing was conducted at baseline and 5 h post-depletion. The CMD condition relative to the B condition resulted in deficits in digit vigilance (accuracy and reaction time), a measure of sustained attention. There were no effects on measures of learning and memory or psychomotor function. These findings suggest that simultaneously depleting the availability of brain serotonin and catecholamines in healthy female subjects selectively impairs sustained attention, without affecting other cognitive domains.

  20. Effect of contraceptive steroids on monoamine oxidase activity

    PubMed Central

    Southgate, Jennifer; Collins, G. G. S.; Pryse-Davies, J.; Sandler, M.

    1969-01-01

    Cyclical variations in monoamine oxidase activity during the human menstrual cycle, specific to the endometrium and modified in women undergoing contraceptive steroid treatment, may reflect changes in hormonal environment. Treatment of rats with individual constituents of the contraceptive pill causes analogous changes: oestrogens inhibit and progestogens potentiate uterine monoamine oxidase activity. ImagesFig. 2Fig. 3

  1. Platelet monoamine oxidase activity in megaloblastic anaemia.

    PubMed Central

    Glover, V; Sandler, M; Hughes, A; Hoffbrand, A V

    1980-01-01

    Platelet monoamine oxidase activity has been measured in 17 patients with megaloblastic anaemia due to either vitamin B12 or folate deficiency, and in 20 healthy subjects. There was a highly significant increase in patients compared with controls. In two patients, platelet activity decreased following successful treatment. A significant correlation between platelet activity and the severity of bone marrow megaloblastic change, assessed by the deoxyuridine suppression test and bone marrow morphology, was also observed. If the change in activity also occurs in the nervous system, this may contribute to the mental disturbance associated with vitamin B12 or folate deficiency. PMID:7430361

  2. Combining tricyclic and monoamine oxidase inhibitor antidepressants.

    PubMed

    Spiker, D G; Pugh, D D

    1976-07-01

    The charts of 150 inpatients and 51 outpatients treated with a monoamine oxidase inhibitor (MAOI)-tricyclic antidepressant combination were reviewed. The incidence and severity of side effects among the patients on the combined regimen were essentially the same as those seen in the control groups. There were no deaths or strokes resulting from use of this regimen. The most frequent troublesome side effect was orthostatic hypotension. We conclude that the use of a MAOI-tricyclic combination in oral therapeutic doses is safe. However, the efficacy of this combination has not yet been proved, and it may be particularly toxic if taken in an overdose.

  3. Exercise Benefits Brain Function: The Monoamine Connection

    PubMed Central

    Lin, Tzu-Wei; Kuo, Yu-Min

    2013-01-01

    The beneficial effects of exercise on brain function have been demonstrated in animal models and in a growing number of clinical studies on humans. There are multiple mechanisms that account for the brain-enhancing effects of exercise, including neuroinflammation, vascularization, antioxidation, energy adaptation, and regulations on neurotrophic factors and neurotransmitters. Dopamine (DA), noradrenaline (NE), and serotonin (5-HT) are the three major monoamine neurotransmitters that are known to be modulated by exercise. This review focuses on how these three neurotransmitters contribute to exercise affecting brain function and how it can work against neurological disorders. PMID:24961306

  4. Relative nutritional deficiencies associated with centrally acting monoamines

    PubMed Central

    Hinz, Marty; Stein, Alvin; Uncini, Thomas

    2012-01-01

    Background Two primary categories of nutritional deficiency exist. An absolute nutritional deficiency occurs when nutrient intake is not sufficient to meet the normal needs of the system, and a relative nutritional deficiency exists when nutrient intake and systemic levels of nutrients are normal, while a change occurs in the system that induces a nutrient intake requirement that cannot be supplied from diet alone. The purpose of this paper is to demonstrate that the primary component of chronic centrally acting monoamine (serotonin, dopamine, norepinephrine, and epinephrine) disease is a relative nutritional deficiency induced by postsynaptic neuron damage. Materials and methods Monoamine transporter optimization results were investigated, reevaluated, and correlated with previous publications by the authors under the relative nutritional deficiency hypothesis. Most of those previous publications did not discuss the concept of a relative nutritional deficiency. It is the purpose of this paper to redefine the etiology expressed in these previous writings into the realm of relative nutritional deficiency, as demonstrated by monoamine transporter optimization. The novel and broad range of amino acid precursor dosing values required to address centrally acting monoamine relative nutritional deficiency properly is also discussed. Results Four primary etiologies are described for postsynaptic neuron damage leading to a centrally acting monoamine relative nutritional deficiency, all of which require monoamine transporter optimization to define the proper amino acid dosing values of serotonin and dopamine precursors. Conclusion Humans suffering from chronic centrally acting monoamine-related disease are not suffering from a drug deficiency; they are suffering from a relative nutritional deficiency involving serotonin and dopamine amino acid precursors. Whenever low or inadequate levels of monoamine neurotransmitters exist, a relative nutritional deficiency is present

  5. Monoamine oxidase inactivation: from pathophysiology to therapeutics

    PubMed Central

    Bortolato, Marco; Chen, Kevin; Shih, Jean C

    2008-01-01

    Monoamine oxidases (MAOs) A and B are mitochondrial bound isoenzymes which catalyze the oxidative deamination of dietary amines and monoamine neurotransmitters, such as serotonin, norepinephrine, dopamine, β-phenylethylamine and other trace amines. The rapid degradation of these molecules ensures the proper functioning of synaptic neurotransmission and is critically important for the regulation of emotional behaviors and other brain functions. The byproducts of MAO-mediated reactions include several chemical species with neurotoxic potential, such as hydrogen peroxide, ammonia and aldehydes. As a consequence, it is widely speculated that prolonged excessive activity of these enzymes may be conducive to mitochondrial damages and neurodegenerative disturbances. In keeping with these premises, the development of MAO inhibitors has led to important breakthroughs in the therapy of several neuropsychiatric disorders, ranging from mood disorders to Parkinson’s disease. Furthermore, the characterization of MAO knockout (KO) mice has revealed that the inactivation of this enzyme produces a number of functional and behavioral alterations, some of which may be harnessed for therapeutic aims. In this article, we discuss the intriguing hypothesis that the attenuation of the oxidative stress induced by the inactivation of either MAO isoform may contribute to both antidepressant and antiparkinsonian actions of MAO inhibitors. This possibility further highlights MAO inactivation as a rich source of novel avenues in the treatment of mental disorders. PMID:18652859

  6. Monoamine pharmacology of the lobster cardiac ganglion.

    PubMed

    Berlind, A

    2001-03-01

    Monoamine agonists and antagonists were applied to the lobster cardiac ganglion in an attempt to clarify the different actions of 5-hydroxytryptamine (5HT) and dopamine (DA) on this rhythmic pattern generator. Experiments were designed to determine whether the similar responses to 5HT and DA applied to the anterior region of the ganglion could be separated by pharmacological approaches, and whether the different responses to 5HT applied to the anterior and posterior regions of the ganglion could be attributed to mediation by different receptors. A small number of the 5HT agonists which were tested mimic the effects of 5HT, in that they increase the frequency of bursting and decrease burst duration when applied to the whole ganglion, but decrease burst frequency and increase burst duration when applied only to the posterior half. Other 5HT agonists decrease frequency and prolong bursts when applied to the whole ganglion. Of the DA agonists tested, none acts as DA itself does. Rather, they mimic the effects of 5HT applied to the posterior ganglion, by slowing bursting and prolonging bursts. The actions of agonists do not correspond in any clear way to the receptor specificities as defined in vertebrates. Most antagonists tested do not show similar specificities to their effects in vertebrates. In particular, most of the DA antagonists tested are more effective in blocking exogenous 5HT than DA. One monoamine agonist directly alters the properties of endogenous burst-organizing potentials (driver potentials) in the motorneurons of the ganglion.

  7. Vesicular monoamine transporter 2 and the acute and long-term response to 3,4-(±)-methylenedioxymethamphetamine.

    PubMed

    Lizarraga, Lucina E; Cholanians, Aram B; Phan, Andy V; Herndon, Joseph M; Lau, Serrine S; Monks, Terrence J

    2015-01-01

    3,4-(±)-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a ring-substituted amphetamine derivative with potent psychostimulant properties. The neuropharmacological effects of MDMA are biphasic in nature, initially causing synaptic monoamine release, primarily of serotonin (5-HT). Conversely, the long-term effects of MDMA manifest as prolonged depletions in 5-HT, and reductions in 5-HT reuptake transporter (SERT), indicative of serotonergic neurotoxicity. MDMA-induced 5-HT efflux relies upon disruption of vesicular monoamine storage, which increases cytosolic 5-HT concentrations available for release via a carrier-mediated mechanism. The vesicular monoamine transporter 2 (VMAT2) is responsible for packaging monoamine neurotransmitters into cytosolic vesicles. Thus, VMAT2 is a molecular target for a number of psychostimulant drugs, including methamphetamine and MDMA. We investigated the effects of depressed VMAT2 activity on the adverse responses to MDMA, via reversible inhibition of the VMAT2 protein with Ro4-1284. A single dose of MDMA (20 mg/kg, subcutaneous) induced significant hyperthermia in rats. Ro4-1284 (10 mg/kg, intraperitoneal) pretreatment prevented the thermogenic effects of MDMA, instead causing a transient decrease in body temperature. MDMA-treated rats exhibited marked increases in horizontal velocity and rearing behavior. In the presence of Ro4-1284, MDMA-mediated horizontal hyperlocomotion was delayed and attenuated, whereas rearing activity was abolished. Finally, Ro4-1284 prevented deficits in 5-HT content in rat cortex and striatum, and reduced depletions in striatal SERT staining, 7 days after MDMA administration. In summary, acute inhibition of VMAT2 by Ro4-1284 protected against MDMA-mediated hyperthermia, hyperactivity, and serotonergic neurotoxicity. The data suggest the involvement of VMAT2 in the thermoregulatory, behavioral, and neurotoxic effects of MDMA.

  8. Vesicular Monoamine Transporter 2 and the Acute and Long-Term Response to 3,4-(±)-Methylenedioxymethamphetamine

    PubMed Central

    Lizarraga, Lucina E.; Cholanians, Aram B.; Phan, Andy V.; Herndon, Joseph M.; Lau, Serrine S.; Monks, Terrence J.

    2015-01-01

    3,4-(±)-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a ring-substituted amphetamine derivative with potent psychostimulant properties. The neuropharmacological effects of MDMA are biphasic in nature, initially causing synaptic monoamine release, primarily of serotonin (5-HT). Conversely, the long-term effects of MDMA manifest as prolonged depletions in 5-HT, and reductions in 5-HT reuptake transporter (SERT), indicative of serotonergic neurotoxicity. MDMA-induced 5-HT efflux relies upon disruption of vesicular monoamine storage, which increases cytosolic 5-HT concentrations available for release via a carrier-mediated mechanism. The vesicular monoamine transporter 2 (VMAT2) is responsible for packaging monoamine neurotransmitters into cytosolic vesicles. Thus, VMAT2 is a molecular target for a number of psychostimulant drugs, including methamphetamine and MDMA. We investigated the effects of depressed VMAT2 activity on the adverse responses to MDMA, via reversible inhibition of the VMAT2 protein with Ro4-1284. A single dose of MDMA (20 mg/kg, subcutaneous) induced significant hyperthermia in rats. Ro4-1284 (10 mg/kg, intraperitoneal) pretreatment prevented the thermogenic effects of MDMA, instead causing a transient decrease in body temperature. MDMA-treated rats exhibited marked increases in horizontal velocity and rearing behavior. In the presence of Ro4-1284, MDMA-mediated horizontal hyperlocomotion was delayed and attenuated, whereas rearing activity was abolished. Finally, Ro4-1284 prevented deficits in 5-HT content in rat cortex and striatum, and reduced depletions in striatal SERT staining, 7 days after MDMA administration. In summary, acute inhibition of VMAT2 by Ro4-1284 protected against MDMA-mediated hyperthermia, hyperactivity, and serotonergic neurotoxicity. The data suggest the involvement of VMAT2 in the thermoregulatory, behavioral, and neurotoxic effects of MDMA. PMID:25370842

  9. [An endogenous inhibitor of monoamine oxidase A (tribulin A) from brain: purification and structure identification].

    PubMed

    Medvedev, A E; Kamyshanskaia, N S; Halket, J; Glover, V; Sandler, A

    1995-05-01

    The endogenous monoamine oxidase inhibitor, tribulin, contains several components which selectively (or nonselectively) inhibit monoamine oxidases A and B. The pig brain tribulin component selectively inhibiting monoamine oxidase A was purified and identified as 4-hydroxyphenylethanol using gas chromatography-mass spectrometry. This compound was also found in the rabbit brain tribulin fraction which selectively inhibits monoamine oxidase A but has no influence on monoamine oxidase B. 4-Hydroxyphenylethanol inhibits monoamine oxidase A in an incompetitive manner with respect to the substrate, serotonin (Ki = 1.4 mM). Possible pathways of 4-hydroxyphenylethanol synthesis and its biological importance as the monoamine oxidase A inhibiting component of tribulin are discussed.

  10. Selective transport of monoamine neurotransmitters by human plasma membrane monoamine transporter and organic cation transporter 3.

    PubMed

    Duan, Haichuan; Wang, Joanne

    2010-12-01

    The plasma membrane monoamine transporter (PMAT) and organic cation transporter 3 (OCT3) are the two most prominent low-affinity, high-capacity (i.e., uptake(2)) transporters for endogenous biogenic amines. Using the Flp-in system, we expressed human PMAT (hPMAT) and human OCT3 (hOCT3) at similar levels in human embryonic kidney 293 cells. Parallel and detailed kinetics analysis revealed distinct and seemingly complementary patterns for the two transporters in transporting monoamine neurotransmitters. hPMAT is highly selective toward serotonin (5-HT) and dopamine, with the rank order of transport efficiency (V(max)/K(m)) being: dopamine, 5-HT ≫ histamine, norepinephrine, epinephrine. The substrate preference of hPMAT toward these amines is substantially driven by large (up to 15-fold) distinctions in its apparent binding affinities (K(m)). In contrast, hOCT3 is less selective than hPMAT toward the monoamines, and the V(max)/K(m) rank order for hOCT3 is: histamine > norepinephrine, epinephrine > dopamine >5-HT. It is noteworthy that hOCT3 demonstrated comparable (≤2-fold difference) K(m) toward all amines, and distinctions in V(max) played an important role in determining its differential transport efficiency toward the monoamines. Real-time reverse transcription-polymerase chain reaction revealed that hPMAT is expressed at much higher levels than hOCT3 in most human brain areas, whereas hOCT3 is selectively and highly expressed in adrenal gland and skeletal muscle. Our results suggest that hOCT3 represents a major uptake(2) transporter for histamine, epinephrine, and norepinephrine. hPMAT, on the other hand, is a major uptake(2) transporter for 5-HT and dopamine and may play a more important role in transporting these two neurotransmitters in the central nervous system.

  11. Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression.

    PubMed

    Meyer, Jeffrey H; Ginovart, Nathalie; Boovariwala, Anahita; Sagrati, Sandra; Hussey, Doug; Garcia, Armando; Young, Trevor; Praschak-Rieder, Nicole; Wilson, Alan A; Houle, Sylvain

    2006-11-01

    The monoamine theory of depression proposes that monoamine levels are lowered, but there is no explanation for how monoamine loss occurs. Monoamine oxidase A (MAO-A) is an enzyme that metabolizes monoamines, such as serotonin, norepinephrine, and dopamine. To determine whether MAO-A levels in the brain are elevated during untreated depression. Tertiary care psychiatric hospital. Seventeen healthy and 17 depressed individuals with major depressive disorder that met entry criteria were recruited from the care of general practitioners and psychiatrists. All study participants were otherwise healthy and nonsmoking. Depressed individuals had been medication free for at least 5 months. Harmine labeled with carbon 11, a radioligand selective for MAO-A and positron emission tomography, was used to measure MAO-A DVS (specific distribution volume), an index of MAO-A density, in different brain regions (prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, caudate, putamen, thalamus, anterior temporal cortex, midbrain, hippocampus, and parahippocampus). The MAO-A DVS was highly significantly elevated in every brain region assessed (t test; P=.001 to 3x10(-7)). The MAO-A DVS was elevated on average by 34% (2 SDs) throughout the brain during major depression. The sizable magnitude of this finding and the absence of other compelling explanations for monoamine loss during major depressive episodes led to the conclusion that elevated MAO-A density is the primary monoamine-lowering process during major depression.

  12. Platelet monoamine oxidase in affective disorders.

    PubMed

    Edwards, D J; Spiker, D G; Kupfer, D J; Foster, G; Neil, J F; Abrams, L

    1978-12-01

    Platelet monoamine oxidase (MAO) activity was determined with tryptamine as substrate for 61 drug-free patients who had a primary major depressive disorder and for 32 normal controls. Although there were no significant differences between the mean platelet MAO activity of 19 bipolar patients (4.94 nmoles/hr/mg of protein), 42 unipolar patients (4.97 nmoles), and the controls (4.78 nmoles), an analysis of variance indicated that the variance of the bipolar group was significantly greater than that of the other groups. This suggests that there may be subgroups of bipolar patients that differ in their platelet MAO activity but that appear to be distinct from the bipolar I vs bipolar II classification.

  13. Blood monoamine metabolism in Huntington's disease.

    PubMed

    Belendiuk, K; Belendiuk, G W; Freedman, D X

    1980-03-01

    In 25 patients with Huntington's disease (HD), the mean blood concentration of serotonin (5-HT) and percentage of plasma free tryptophan were significantly increased while plasma concentrations of total and protein-bound tryptophan were significantly decreased. The pattern of changes in tryptophan concentrations was related to clinical severity but not to 5-HT levels. Platelet monoamine oxidase (MAO) activity was significantly increased in patients with HD; kinetic and marker enzyme studies suggested an increased enzyme concentration. Offspring at risk for HD also had elevated platelet MAO activity but normal concentrations of blood 5-HT and plasma tryptophan. In ten patients, plasma epinephrine concentrations were significantly increased; plasma dopamine and norepinephrine concentrations were positively related to MAO activity. The finding of peripheral neurotransmitter abnormalities in HD raises the question of an interaction between CNS and peripheral processes or a systemic disorder of neurotransmitter metabolism.

  14. Visualization of monoamine oxidase in human brain

    SciTech Connect

    Fowler, J.S.; Volkow, N.D.; Wang, G.J.; Pappas, N.; Shea, C.; MacGregor, R.R.; Logan, J.

    1996-12-31

    Monoamine oxidase is a flavin enzyme which exists in two subtypes, MAO A and MAO B. In human brain MAO B predominates and is largely compartmentalized in cell bodies of serotonergic neurons and glia. Regional distribution of MAO B was determined by positron computed tomography with volunteers after the administration of deuterium substituted [11C]L-deprenyl. The basal ganglia and thalamus exhibited the greatest concentrations of MAO B with intermediate levels in the frontal cortex and cingulate gyrus while lowest levels were observed in the parietal and temporal cortices and cerebellum. We observed that brain MAO B increases with are in health normal subjects, however the increases were generally smaller than those revealed with post-mortem studies.

  15. Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: correlations between behavior and neurochemistry.

    PubMed

    Murnane, Kevin Sean; Perrine, Shane Alan; Finton, Brendan James; Galloway, Matthew Peter; Howell, Leonard Lee; Fantegrossi, William Edward

    2012-04-01

    Considerable evidence indicates that amphetamine derivatives can deplete brain monoaminergic neurotransmitters. However, the behavioral and cognitive consequences of neurochemical depletions induced by amphetamines are not well established. In this study, mice were exposed to dosing regimens of 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH), or parachloroamphetamine (PCA) known to deplete the monoamine neurotransmitters dopamine and serotonin, and the effects of these dosing regimens on learning and memory were assessed. In the same animals, we determined deficits in learning and memory via passive avoidance (PA) behavior and changes in tissue content of monoamine neurotransmitters and their primary metabolites in the striatum, frontal cortex, cingulate, hippocampus, and amygdala via ex vivo high-pressure liquid chromatography. Exposure to METH and PCA impaired PA performance and resulted in significant depletions of dopamine, serotonin, and their metabolites in several brain regions. Multiple linear regression analysis revealed that the tissue concentration of dopamine in the anterior striatum was the strongest predictor of PA performance, with an additional significant contribution by the tissue concentration of the serotonin metabolite 5-hydroxyindoleacetic acid in the cingulate. In contrast to the effects of METH and PCA, exposure to MDMA did not deplete anterior striatal dopamine levels or cingulate levels of 5-hydroxyindoleacetic acid, and it did not impair PA performance. These studies demonstrate that certain amphetamines impair PA performance in mice and that these impairments may be attributable to specific neurochemical depletions.

  16. Sex-specific development of cortical monoamine levels in mouse.

    PubMed

    Connell, Shelley; Karikari, Collins; Hohmann, Christine F

    2004-07-19

    Several mental health disorders exhibit sex differences in monoamine levels associated with dimorphic cortical ontogeny. Studies in rodents support the notion that monoamines can profoundly modulate morphogenesis. Here, we show significant sex and hemisphere differences in BALB/cByJ mice on postnatal day 3 for dopamine (DA) and serotonin (5-TH), supporting the notion that sex differences in early monoaminergic ontogeny may result in dimorphic cortical development. Such sex differences may also influence differential behavioral and/or clinical outcomes.

  17. Alterations in Brain Monoamine Neurotransmitter Release at High Pressure

    DTIC Science & Technology

    1989-01-01

    exposure results from a general imbalance of encephalopathies. Parkinson’s Syndrome, MPTP the three monoamine neurotransmitter systems toxicity . or...the [3 H]monoamines by Dopamine release, on the other hand, was reduced synaptosomes isolated from the CNS. 5-A n 4 A Pn5 p<.05 0.05 LI * 4- U) 4...Lffect of’ pressure of 3.4-miethylenledioxy-miethamiiphetamnine ( MDMA ) and re- on the release of radioaetive glycine and (IABA from spinal lated

  18. Gastroduodenal mucosal protection induced by dehydroleucodine: mucus secretion and role of monoamines.

    PubMed

    Penissi, A B; Fogal, T H; Guzmán, J A; Piezzi, R S

    1998-04-01

    In previous work we have demonstrated that dehydroleucodine (DhL) prevents gastric damage induced by necrosis-inducing agents such as absolute ethanol (EtOH). In this study we examine the effects of DhL on gastroduodenal morphology and monoamine levels by histological and biochemical methods, respectively, as an approach to elucidating the cytoprotective mechanism of the drug. Histological evidence shows that DhL prevents formation of gastroduodenal mucosal lesions induced by EtOH and that this protective effect is related to the ability of the drug to stimulate mucus production. DhL itself does not affect the tissue concentration of NE, DA and 5-HT. However, it prevents the depletion of DA and 5-HT provoked by EtOH. We propose that the abundant mucoid blanket secreted after treatment with DhL acts as a diffusion barrier against EtOH. It is also possible that DhL could act as a "cell stabilizer," by inhibiting the degranulation of cells containing monoamines.

  19. Changes in brain monoamine levels and monoamine oxidase activity in the catfish, Clarias batrachus, during chronic treatments with mercurials

    SciTech Connect

    Kirubagaran, R.; Joy, K.P. )

    1990-07-01

    In mammals, the central nervous system is the primary target for CH{sub 3}Hg poisoning which is clinically known as Minamata disease. Hg is a widely recognized neurotoxin and has been reported to impair brain monoamine neurotransmitter metabolism. Reports on effects of Hg on brain monoamine activity in fishes are scarce. In the present study, therefore, changes in the brain monoamine levels and the degradation enzyme, monoamine oxidase (MAO), are described in the catfish, Clarias batrachus, exposed to sublethal concentrations of mercuric chloride (HgCl{sub 2}-inorganic Hg), methylmercuric chloride (CH{sub 3}HgCl-organic Hg), and a commercial mercurial fungicide formulation, emisan 6 (methoxyethyl Hg-organic Hg) for 45, 90 and 180 d during gonadal recrudescence. These intervals correspond to late preparatory, prespawning and spawning phases, respectively, of the annual reproductive cycle of the catfish.

  20. Involvement of monoamines and proinflammatory cytokines in mediating the anti-stress effects of Panax quinquefolium.

    PubMed

    Rasheed, Naila; Tyagi, Ethika; Ahmad, Ausaf; Siripurapu, Kiran Babu; Lahiri, Shawon; Shukla, Rakesh; Palit, Gautam

    2008-05-08

    Panax quinquefolium (PQ) is well acclaimed in literature for its effects on central and peripheral nervous system. The present study explores the effects of PQ on stress induced changes of corticosterone level in plasma, monoamines (NA, DA and 5-HT) and interleukin (IL-2 and IL-6) levels in cortex and hippocampus regions of brain and also indicate their possible roles in modulating stress. Mice subjected to chronic unpredictable stress (CUS, for 7 days) showed significant increase in plasma corticosterone level and depletion of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in cortex and hippocampal regions along with an increased level of IL-2 and IL-6 in the same areas. Aqueous suspension of PQ was administered daily at a dose of 100 and 200mg/kg p.o. prior to the stress regimen and its effects on selected stress markers in plasma and brain was evaluated. PQ at a dose of 200mg/kg p.o. was found to be effective in normalizing the CUS induced elevation of plasma corticosterone and IL-2, IL-6 levels in brain. Moreover, it was significantly effective in reinstating the CUS induced depletion of NA, DA and 5-HT in hippocampus, while NA and 5-HT in cortex of brain. However, PQ at a dose of 100mg/kg p.o. was found ineffective in regulating any of these CUS induced changes. Present study provides an insight into the possible role of PQ on hyperactive HPA axis in the regulation of immediate stress effectors like corticosterone, cytokines and brain monoamines. In this study, PQ has emerged as a potential therapeutic in the cure of stress related disorders and needs to be evaluated in clinical studies to ascertain its efficacy.

  1. Leflunomide, a Reversible Monoamine Oxidase Inhibitor.

    PubMed

    Petzer, Jacobus P; Petzer, Anél

    2016-01-01

    A screening study aimed at identifying inhibitors of the enzyme, monoamine oxidase (MAO), among clinically used drugs have indicated that the antirheumatic drug, leflunomide, is an inhibitor of both MAO isoforms. Leflunomide inhibits human MAO-A and MAO-B and exhibits IC50 values of 19.1 μM and 13.7 μM, respectively. The corresponding Ki values are 17.7 μM (MAO-A) and 10.1 μM (MAO-B). Dialyses of mixtures of the MAO enzymes and leflunomide show that inhibition of the MAOs by leflunomide is reversible. The principal metabolite of leflunomide, teriflunomide (A77 1726), in contrast is not an MAO inhibitor. This study concludes that, although leflunomide is only moderately potent as an MAO inhibitor, isoxazole derivatives may represent a general class of MAO inhibitors and this heterocycle may find application in MAO inhibitor design. In this respect, MAO inhibitors are used in the clinic for the treatment of depressive illness and Parkinson's disease, and are under investigation as therapy for certain types of cancer, Alzheimer's disease and age-related impairment of cardiac function.

  2. Monoamine neurons in aging and Alzheimer's disease.

    PubMed

    Palmer, A M; DeKosky, S T

    1993-01-01

    The integrity of dopaminergic, noradrenergic and serotonergic neurons in normal aging and Alzheimer's disease is reviewed. Loss of dopaminergic innervation of the neostriatum is a prominent age-related change, which corresponds with the age-related loss of dopaminergic cell bodies from the substantia nigra. This change is regionally specific, since dopaminergic innervation of the neocortex and the neostriatum are not affected. Although there is an age-related loss of noradrenergic cell bodies from the locus coeruleus, most studies indicate normal concentrations of noradrenaline in target areas. There is also evidence for reduced serotonergic innervation of the neocortex and, less convincingly, the neostriatum. Alzheimer's disease is associated with more pronounced noradrenergic and serotonergic denervation but, unlike normal aging, dopaminergic innervation of neostriatum is intact; although dopamine neurons are probably dysfunctional in this region. Studies relating neuronal markers to the symptomatology of Alzheimer's disease indicate that dysfunction of monoamine neurons is more closely linked to non-cognitive than to cognitive changes in behavior. In addition, monoaminergic therapies have been successful in ameliorating affective and psychotic behaviors along with sleep disturbances in both Alzheimer's disease and senescence. It seems likely that monoaminergic therapies (developed as we learn more about alterations in dopamine, noradrenaline and serotonin) will continue to be necessary to treat such behavioral disturbances.

  3. MONOAMINE OXIDASE: RADIOTRACER DEVELOPMENT AND HUMAN STUDIES.

    SciTech Connect

    FOWLER,J.S.; LOGAN,J.; VOLKOW,N.D.; WANG,G.J.; MACGREGOR,R.R.; DING,Y.S.

    2000-09-28

    PET is uniquely capable of providing information on biochemical transformations in the living human body. Although most of the studies of monoamine oxidase (MAO) have focused on measurements in the brain, the role of peripheral MAO as a phase 1 enzyme for the metabolism of drugs and xenobiotics is gaining attention (Strolin Benedetti and Tipton, 1998; Castagnoli et al., 1997.). MAO is well suited for this role because its concentration in organs such as kidneys, liver and digestive organs is high sometimes exceeding that in the brain. Knowledge of the distribution of the MAO subtypes within different organs and different cells is important in determining which substrates (and which drugs and xenobiotics) have access to which MAO subtypes. The highly variable subtype distribution with different species makes human studies even more important. In addition, the deleterious side effects of combining MAO inhibitors with other drugs and with foodstuffs makes it important to know the MAO inhibitory potency of different drugs both in the brain and in peripheral organs (Ulus et al., 2000). Clearly PET can play a role in answering these questions, in drug research and development and in discovering some of the factors which contribute to the highly variable MAO levels in different individuals.

  4. Monoamine oxidase: Radiotracer chemistry and human studies

    SciTech Connect

    Fowler, Joanna S.; Logan, Jean; Shumay, Elena; Alia-Klein, Nelly; Wang, Gene-Jack; Volkow, Nora D.

    2015-03-01

    Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson’s disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variables which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.

  5. Monoamine transporters: insights from molecular dynamics simulations

    PubMed Central

    Grouleff, Julie; Ladefoged, Lucy Kate; Koldsø, Heidi; Schiøtt, Birgit

    2015-01-01

    The human monoamine transporters (MATs) facilitate the reuptake of the neurotransmitters serotonin, dopamine, and norepinephrine from the synaptic cleft. Imbalance in monoaminergic neurotransmission is linked to various diseases including major depression, attention deficit hyperactivity disorder, schizophrenia, and Parkinson’s disease. Inhibition of the MATs is thus an important strategy for treatment of such diseases. The MATs are sodium-coupled transport proteins belonging to the neurotransmitter/Na+ symporter (NSS) family, and the publication of the first high-resolution structure of a NSS family member, the bacterial leucine transporter LeuT, in 2005, proved to be a major stepping stone for understanding this family of transporters. Structural data allows for the use of computational methods to study the MATs, which in turn has led to a number of important discoveries. The process of substrate translocation across the membrane is an intrinsically dynamic process. Molecular dynamics simulations, which can provide atomistic details of molecular motion on ns to ms timescales, are therefore well-suited for studying transport processes. In this review, we outline how molecular dynamics simulations have provided insight into the large scale motions associated with transport of the neurotransmitters, as well as the presence of external and internal gates, the coupling between ion and substrate transport, and differences in the conformational changes induced by substrates and inhibitors. PMID:26528185

  6. Monoamine oxidase: Radiotracer chemistry and human studies

    DOE PAGES

    Fowler, Joanna S.; Logan, Jean; Shumay, Elena; ...

    2015-03-01

    Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson’s disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variablesmore » which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.« less

  7. Age-related changes in brain biogenic monoamines and monoamine oxidase.

    PubMed

    Petkov, V D; Stancheva, S L; Petkov, V V; Alova, L G

    1987-01-01

    In experiments on 2-, 10- and 22-month old rats, it was found that essential age-related changes occurred in the brain level of biogenic monoamines (BMA) and in the monoamine oxidase (MAO) activity. In 22-month old rats the levels of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) markedly declined in most of the brain structures studied. 5-HT significantly decreased in the frontal cortex, striatum and hypothalamus. DA decreased in the cerebral cortex and striatum and NA in the cerebral cortex. However, the NA level in the striatum of 22-month old rats was increased as compared to that in 2-month old rats. In most cases we observed significant differences (a decrease mainly) also in the level of BMA in 22-month old rats as compared to 10-month old rats. The differences, if any, in the BMA levels between 10- and 2-month old rats were less pronounced. The level of 5-hydroxyindole acetic acid (5-HIAA) in the cerebral cortex and striatum of 22-month old rats was significantly higher as compared to that in 2-month old rats. The MAO-T and MAO-A activities in the brain structures studied were significantly higher in 22-month old rats as compared to those in 2-month old rats. The possibility that the age-related changes in brain neurotransmission might be an important element in the neurochemical basis of some behavioral changes in advanced age is considered.

  8. Monoamine transporter inhibitors and substrates as treatments for stimulant abuse.

    PubMed

    Howell, Leonard L; Negus, S Stevens

    2014-01-01

    The acute and chronic effects of abused psychostimulants on monoamine transporters and associated neurobiology have encouraged development of candidate medications that target these transporters. Monoamine transporters, in general, and dopamine transporters, in particular, are critical molecular targets that mediate abuse-related effects of psychostimulants such as cocaine and amphetamine. Moreover, chronic administration of psychostimulants can cause enduring changes in neurobiology reflected in dysregulation of monoamine neurochemistry and behavior. The current review will evaluate evidence for the efficacy of monoamine transporter inhibitors and substrates to reduce abuse-related effects of stimulants in preclinical assays of stimulant self-administration, drug discrimination, and reinstatement. In considering deployment of monoamine transport inhibitors and substrates as agonist-type medications to treat stimulant abuse, the safety and abuse liability of the medications are an obvious concern, and this will also be addressed. Future directions in drug discovery should identify novel medications that retain efficacy to decrease stimulant use but possess lower abuse liability and evaluate the degree to which efficacious medications can attenuate or reverse neurobiological effects of chronic stimulant use.

  9. Monoamine Transporter Inhibitors and Substrates as Treatments for Stimulant Abuse

    PubMed Central

    Howell, Leonard L.; Negus, S. Stevens

    2015-01-01

    The acute and chronic effects of abused psychostimulants on monoamine transporters and associated neurobiology have encouraged development of candidate medications that target these transporters. Monoamine transporters in general, and dopamine transporters in particular, are critical molecular targets that mediate abuse-related effects of psychostimulants such as cocaine and amphetamine. Moreover, chronic administration of psychostimulants can cause enduring changes in neurobiology reflected in dysregulation of monoamine neurochemistry and behavior. The current review will evaluate evidence for the efficacy of monoamine transporter inhibitors and substrates to reduce abuse-related effects of stimulants in preclinical assays of stimulant self-administration, drug discrimination and reinstatement. In considering deployment of monoamine transport inhibitors and substrates as agonist-type medications to treat stimulant abuse, the safety and abuse liability of the medications are an obvious concern, and this will also be addressed. Future directions in drug discovery should identify novel medications that retain efficacy to decrease stimulant use but possess lower abuse liability, and evaluate the degree to which efficacious medications can attenuate or reverse neurobiological effects of chronic stimulant use. PMID:24484977

  10. Monoamine oxidase inhibitory components from Cayratia japonica.

    PubMed

    Han, Xiang Hua; Hong, Seong Su; Hwang, Ji Sang; Lee, Myung Koo; Hwang, Bang Yeon; Ro, Jai Seup

    2007-01-01

    Seven flavonoids were isolated from the whole plants and fruits of Cayratia japonica through the activity-guided isolation of a methanol extract using a monoamine oxidase (MAO) inhibition assay as a monitor. The chemical structures of the isolates were assigned as apigenin-7-O-beta-D-glucuronopyranoside (1), apigenin (2), luteolin (3), luteolin-7-O-beta-D-glucopyranoside (4), (+)-dihydroquercetin (taxifolin) (5), (+)-dihydrokaempferol (aromadendrin) (6) and quercetin (7). Among the isolated compounds, flavones such as apigenin (2) and luteolin (3), as well as the flavonol, quercetin (7) showed potent inhibitory effects against the MAO activity with IC50 values of 6.5, 22.6, and 31.6 microM, respectively. However, the flavone glycosides, apigenin-7-O-beta-D-glucuronopyranoside (1) and luteolin-7-O-beta-D-glucopyranoside (4), showed mild MAO inhibition (IC50 values: 81.7 and 118.6 microM, respectively). The flavanonol derivatives, taxifolin (5) and aromadendrin (6), also showed weak inhibition (IC50 values: 154.7 and 153.1 microM, respectively). Furthermore, quercetin (7) had a more potent inhibitory effect on MAO-A (IC50 value: 2.8 microM) than MAO-B (IC50 value: 90.0 microM). Apigenin (2) and luteolin (3) also preferentially inhibited MAO-A (IC50 values: 1.7 and 4.9 microM, respectively) compared with MAO-B (IC50 values: 12.8 and 59.7 microM, respectively).

  11. Predominant role of plasma membrane monoamine transporters in monoamine transport in 1321N1, a human astrocytoma-derived cell line.

    PubMed

    Naganuma, Fumito; Yoshikawa, Takeo; Nakamura, Tadaho; Iida, Tomomitsu; Harada, Ryuichi; Mohsen, Attayeb S; Miura, Yamato; Yanai, Kazuhiko

    2014-05-01

    Monoamine neurotransmitters should be immediately removed from the synaptic cleft to avoid excessive neuronal activity. Recent studies have shown that astrocytes and neurons are involved in monoamine removal. However, the mechanism of monoamine transport by astrocytes is not entirely clear. We aimed to elucidate the transporters responsible for monoamine transport in 1321N1, a human astrocytoma-derived cell line. First, we confirmed that 1321N1 cells transported dopamine, serotonin, norepinephrine, and histamine in a time- and dose-dependent manner. Kinetics analysis suggested the involvement of low-affinity monoamine transporters, such as organic cation transporter (OCT) 2 and 3 and plasma membrane monoamine transporter (PMAT). Monoamine transport in 1321N1 cells was not Na(+) /Cl(-) dependent but was inhibited by decynium-22, an inhibitor of low-affinity monoamine transporters, which supported the importance of low-affinity transporters. RT-PCR assays revealed that 1321N1 cells expressed OCT3 and PMAT but no other neurotransmitter transporters. Another human astrocytoma-derived cell line, U251MG, and primary human astrocytes also exhibited the same gene expression pattern. Gene-knockdown assays revealed that 1321N1 and primary human astrocytes could transport monoamines predominantly through PMAT and partly through OCT3. These results might indicate that PMAT and OCT3 in human astrocytes are involved in monoamine clearance.

  12. Monoamine oxidase inhibitory properties of milacemide in rats.

    PubMed

    Truong, D D; Diamond, B; Pezzoli, G; Mena, M A; Fahn, S

    1989-01-01

    Milacemide is a glycine prodrug with reported antiepileptic antimyoclonic properties. In this study, milacemide increased "wet dog shakes" in rats pretreated with 5-Hydroxytryptophan (5-HTP) and carbidopa. Moreover, it worsened the serotonin behavior syndrome precipitated by 5-HTP and the monoamine oxidase inhibitor tranylcypromine. The serotonin syndrome was also elicited by the combination of milacemide and 5-HTP without tranylcypromine. In vitro, milacemide inhibited both monoamine oxidase A and B from the frontal cortex of rats, to a greater extent for MAO B. This drug is currently under investigation in humans as an antiepileptic agent and precautions for the consequences of monoamine oxidase inhibition should be considered when the drug is used in high doses.

  13. Metabolism of biogenic monoamines in the ciliated protozoan, Tetrahymena pyriformis.

    PubMed

    Takeda, N; Sugiyama, K

    1993-09-01

    1. The three-dimensional HPLC system was used to detect the presence and determine the levels of biogenic monoamines, including precursor amino acids and metabolites, simultaneously in an extract of the ciliated protozoan, Tetrahymena pyriformis. 2. Representative biogenic monoamines, such as dopamine (DA), 5-hydroxytryptamine (5-HT), epinephrine (E) and kynurenine (KYN) were found to be synthesized in Tetrahymena and released into the growth medium. 3. The following metabolic pathways were suggested to be operative: (L-DOPA)-DA-(Epinine)-E-dihydroxyphenylethyleneglycol (DOPEG)-vanillylmandelic acid (VMA) and tyrosine-4 (TYR-4)-tyramine (TYRA)-hydroxyphenylacetic acid-4 (HPAC-4) in the case of catecholamines, and tryptophan (TRP)-5-HT and TRP-KYN-xanthurenic acid (XA) in the case of indolalkylamines. 4. As judged from the released metabolites, systems for generation of biogenic monoamines in Tetrahymena seem to be active during the logarithmic phase of its growth.

  14. Ruthenium-catalyzed selective monoamination of vicinal diols.

    PubMed

    Bähn, Sebastian; Tillack, Annegret; Imm, Sebastian; Mevius, Kathleen; Michalik, Dirk; Hollmann, Dirk; Neubert, Lorenz; Beller, Matthias

    2009-01-01

    The monoamination of vicinal diols in the presence of in situ generated ruthenium catalysts has been investigated. Among the various phosphines tested in combination with [Ru(3)(CO)(12)], N-phenyl-2-(dicyclohexyl-phosphanyl)pyrrole showed the best performance. After optimization of the reaction conditions this system was applied to different secondary amines and anilines as well as a number of vicinal diols. With the exception of ethylene glycol, monoamination of the vicinal diols occurred selectively and the corresponding amino alcohols were obtained in good yields, producing water as the only side product.

  15. Effect of aging on lazabemide binding, monoamine oxidase activity and monoamine metabolites in human frontal cortex.

    PubMed

    Galva, M D; Bondiolotti, G P; Olasmaa, M; Picotti, G B

    1995-01-01

    Age-related modifications of monoamine oxidase-A and -B (MAO-A and MAO-B) and amine metabolite concentrations were studied in human frontal cortex taken postmortem from 22 subjects of various ages (21-75 years). Qualitative and quantitative analysis for MAO-B was provided by kinetic studies with a specific radioligand, [3H]lazabemide. The data demonstrated a significant (P < 0.05) positive correlation between the density of [3H]lazabemide binding sites (Bmax) and age of the subject, without showing an apparent modification in the dissociation constant (KD) of the radioligand. In parallel experiments, MAO-B but not MAO-A activity was shown to correlate with age (P < 0.05). The concentrations of the amine metabolites 4-hydroxy-3-methoxyphenylacetic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol (DHPG) were all devoid of a correlation with age. Neither did the concentrations of these metabolites relate to the respective subject's MAO-B enzymatic activity nor to [3H]lazabemide Bmax. A correlation, though rather weak, was obtained between MAO-A activity and MHPG concentration (P = 0.045). The MAO-A and -B enzyme characteristics in subjects who had committed suicide (n = 9) did not differ from those of subjects deceased for other causes (n = 13). Among the measured monoamine metabolites the concentrations of DOPAC and HVA were higher in the suicide versus control group (P < 0.05). The present data confirm in a direct manner that the increase in MAO-B activity in aging brain is due to an enhancement of the number of active sites of the enzyme and not through modifications of its kinetic characteristics. Furthermore, that neither the characteristics nor the activity of the enzyme are changed in the frontal cortex of suicide victims compared to control subjects.

  16. Effect of Alkaloids Isolated from Phyllodium pulchellum on Monoamine Levels and Monoamine Oxidase Activity in Rat Brain

    PubMed Central

    Cai, Lu; Wang, Chao; Dong, Pei-pei; Zhang, Bao-jing; Zhang, Hou-Li; Huang, Shan-shan; Zhang, Bo; Yu, Sheng-ming; Zhong, Ming; Ma, Xiao-Chi

    2016-01-01

    Phyllodium pulchellum (P. pulchellum) is a folk medicine with a significant number of bioactivities. The aim of this study was to investigate the effects displayed by alkaloids fractions, isolated from the roots of P. pulchellum, on neurotransmitters monoamine levels and on monoamine oxidase (MAO) activity. Six alkaloids, which had indolealkylamine or β-carboline skeleton, were obtained by chromatographic technologies and identified by spectroscopic methods such as NMR and MS. After treatment with alkaloids of P. pulchellum, the reduction of DA levels (54.55%) and 5-HT levels (35.01%) in rat brain was observed by HPLC-FLD. The effect of alkaloids on the monoamines metabolism was mainly related to MAO inhibition, characterized by IC50 values of 37.35 ± 6.41 and 126.53 ± 5.39 μg/mL for MAO-A and MAO-B, respectively. The acute toxicity indicated that P. pulchellum extract was nontoxic. PMID:27195015

  17. Brain monoamine oxidase activity in schizophrenics and controls.

    PubMed

    Reveley, M A; Glover, V; Sandler, M; Spokes, E G

    1981-06-01

    Postmortem samples of caudate nucleus and frontal cortex from schizophrenic, schizophrenic-like, and control subjects were examined for monoamine oxidase activity using dopamine, phenylethylamine, and 5-hydroxytryptamine as substrates. There were no significant differences between the diagnostic groups with any of the three substrates. Neither was there a difference between the sexes, nor a consistent relationship of enzyme activity to age.

  18. Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters

    PubMed Central

    Bermingham, Daniel P.

    2016-01-01

    Modulation of neurotransmission by the monoamines dopamine (DA), norepinephrine (NE), and serotonin (5-HT) is critical for normal nervous system function. Precise temporal and spatial control of this signaling in mediated in large part by the actions of monoamine transporters (DAT, NET, and SERT, respectively). These transporters act to recapture their respective neurotransmitters after release, and disruption of clearance and reuptake has significant effects on physiology and behavior and has been linked to a number of neuropsychiatric disorders. To ensure adequate and dynamic control of these transporters, multiple modes of control have evolved to regulate their activity and trafficking. Central to many of these modes of control are the actions of protein kinases, whose actions can be direct or indirectly mediated by kinase-modulated protein interactions. Here, we summarize the current state of our understanding of how protein kinases regulate monoamine transporters through changes in activity, trafficking, phosphorylation state, and interacting partners. We highlight genetic, biochemical, and pharmacological evidence for kinase-linked control of DAT, NET, and SERT and, where applicable, provide evidence for endogenous activators of these pathways. We hope our discussion can lead to a more nuanced and integrated understanding of how neurotransmitter transporters are controlled and may contribute to disorders that feature perturbed monoamine signaling, with an ultimate goal of developing better therapeutic strategies. PMID:27591044

  19. The Designer Methcathinone Analogs, Mephedrone and Methylone, are Substrates for Monoamine Transporters in Brain Tissue

    PubMed Central

    Baumann, Michael H; Ayestas, Mario A; Partilla, John S; Sink, Jacqueline R; Shulgin, Alexander T; Daley, Paul F; Brandt, Simon D; Rothman, Richard B; Ruoho, Arnold E; Cozzi, Nicholas V

    2012-01-01

    The nonmedical use of ‘designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study. PMID:22169943

  20. Water Depletion Threatens Agriculture

    NASA Astrophysics Data System (ADS)

    Brauman, K. A.; Richter, B. D.; Postel, S.; Floerke, M.; Malsy, M.

    2014-12-01

    Irrigated agriculture is the human activity that has by far the largest impact on water, constituting 85% of global water consumption and 67% of global water withdrawals. Much of this water use occurs in places where water depletion, the ratio of water consumption to water availability, exceeds 75% for at least one month of the year. Although only 17% of global watershed area experiences depletion at this level or more, nearly 30% of total cropland and 60% of irrigated cropland are found in these depleted watersheds. Staple crops are particularly at risk, with 75% of global irrigated wheat production and 65% of irrigated maize production found in watersheds that are at least seasonally depleted. Of importance to textile production, 75% of cotton production occurs in the same watersheds. For crop production in depleted watersheds, we find that one half to two-thirds of production occurs in watersheds that have not just seasonal but annual water shortages, suggesting that re-distributing water supply over the course of the year cannot be an effective solution to shortage. We explore the degree to which irrigated production in depleted watersheds reflects limitations in supply, a byproduct of the need for irrigation in perennially or seasonally dry landscapes, and identify heavy irrigation consumption that leads to watershed depletion in more humid climates. For watersheds that are not depleted, we evaluate the potential impact of an increase in irrigated production. Finally, we evaluate the benefits of irrigated agriculture in depleted and non-depleted watersheds, quantifying the fraction of irrigated production going to food production, animal feed, and biofuels.

  1. Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in rats.

    PubMed

    Guillem, Karine; Vouillac, Caroline; Azar, Marc R; Parsons, Loren H; Koob, George F; Cador, Martine; Stinus, Luis

    2006-12-01

    Although nicotine is considered to be responsible for the addictive properties of tobacco, growing evidence underlines the importance of non-nicotine components in smoking reinforcement. It has been shown that tobacco smoke contains monoamine oxidase (MAO) A and B inhibitors and decreases MAO-A and MAO-B activity in smokers. Here, we investigated the effects of clorgyline hydrochloride (irreversible MAO-A inhibitor; 2 mg/kg/day), selegiline (irreversible MAO-B inhibitor; 4 mg/kg) and the beta-carboline norharmane hydrochloride (reversible MAO-B inhibitor; 5 mg/kg/day) treatments on nicotine self-administration (30 microg/kg/infusion, free base) in rats. Independent of the responsiveness to novelty and locomotor activity stimulation, only clorgyline hydrochloride treatment increased the intake of nicotine in a fixed-ratio schedule (FR5) of reinforcement. When a progressive-ratio schedule was implemented, both clorgyline hydrochloride and norharmane hydrochloride treatments potentiated the reinforcing effects of nicotine, whereas selegiline had no effect. Taken together, these results indicate that MAO-A inhibition interacts with nicotine to enhance its rewarding effects in rats and suggest that other compounds present in tobacco, such as beta-carboline, may also play an important role in sustaining smoking behavior in humans.

  2. Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: correlations between behavior and neurochemistry

    PubMed Central

    Murnane, Kevin Sean; Perrine, Shane Alan; Finton, Brendan James; Galloway, Matthew Peter; Howell, Leonard Lee; Fantegrossi, William Edward

    2011-01-01

    Rationale Considerable evidence indicates that amphetamine derivatives can deplete brain monoaminergic neurotransmitters. However, the behavioral and cognitive consequences of neurochemical depletions induced by amphetamines are not well established. Objectives In this study, mice were exposed to dosing regimens of 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH), or para-chloroamphetamine (PCA) known to deplete the monoamine neurotransmitters dopamine and serotonin, and the effects of these dosing regimens on learning and memory were assessed. Methods In the same animals, we determined deficits in learning and memory via passive avoidance (PA) behavior and changes in tissue content of monoamine neurotransmitters and their primary metabolites in the striatum, frontal cortex, cingulate, hippocampus, and amygdala via ex vivo high pressure liquid chromatography. Results Consistent with previous studies, significant reductions in tissue content of dopamine and serotonin were readily apparent. In addition, exposure to METH and PCA impaired PA performance and resulted in significant depletions of dopamine, serotonin, and their metabolites in several brain regions. Multiple linear regression analysis revealed that the tissue concentration of dopamine in the anterior striatum was the strongest predictor of PA performance, with an additional significant contribution by the tissue concentration of the serotonin metabolite 5-hydroxyindoleacetic acid in the cingulate. In contrast to the effects of METH and PCA, exposure to MDMA did not deplete anterior striatal dopamine levels or cingulate levels of 5-hydroxyindoleacetic acid, and it did not impair PA performance. Conclusions These studies demonstrate that certain amphetamines impair PA performance in mice and that these impairments may be attributable to specific neurochemical depletions. PMID:21993877

  3. Halo Star Lithium Depletion

    SciTech Connect

    Pinsonneault, M. H.; Walker, T. P.; Steigman, G.; Narayanan, Vijay K.

    1999-12-10

    The depletion of lithium during the pre-main-sequence and main-sequence phases of stellar evolution plays a crucial role in the comparison of the predictions of big bang nucleosynthesis with the abundances observed in halo stars. Previous work has indicated a wide range of possible depletion factors, ranging from minimal in standard (nonrotating) stellar models to as much as an order of magnitude in models that include rotational mixing. Recent progress in the study of the angular momentum evolution of low-mass stars permits the construction of theoretical models capable of reproducing the angular momentum evolution of low-mass open cluster stars. The distribution of initial angular momenta can be inferred from stellar rotation data in young open clusters. In this paper we report on the application of these models to the study of lithium depletion in main-sequence halo stars. A range of initial angular momenta produces a range of lithium depletion factors on the main sequence. Using the distribution of initial conditions inferred from young open clusters leads to a well-defined halo lithium plateau with modest scatter and a small population of outliers. The mass-dependent angular momentum loss law inferred from open cluster studies produces a nearly flat plateau, unlike previous models that exhibited a downward curvature for hotter temperatures in the 7Li-Teff plane. The overall depletion factor for the plateau stars is sensitive primarily to the solar initial angular momentum used in the calibration for the mixing diffusion coefficients. Uncertainties remain in the treatment of the internal angular momentum transport in the models, and the potential impact of these uncertainties on our results is discussed. The 6Li/7Li depletion ratio is also examined. We find that the dispersion in the plateau and the 6Li/7Li depletion ratio scale with the absolute 7Li depletion in the plateau, and we use observational data to set bounds on the 7Li depletion in main-sequence halo

  4. Monoamine-containing fiber plexuses in the spinal cord of guinea pigs during paralysis, recovery and relapse stages of chronic relapsing experimental allergic encephalomyelitis.

    PubMed

    White, S R; Vyas, D; Bieger, D; Samathanam, G

    1989-05-01

    Immunohistochemical techniques were used to examine the morphology and distribution of monoamine- and substance P-containing fibers in the spinal cords of guinea pigs in acute paralytic, remission and relapse stages of chronic relapsing experimental allergic encephalomyelitis. During the initial paralytic attack, focal regions of axonal distortion appeared in the white matter of the cervical and thoracic cord; and axon terminal depletion in the gray matter of the caudal spinal cord was pronounced. This neuropathology persisted throughout remission and was exacerbated during relapse of paralysis. These results suggest that axonal damage is an important component of the pathophysiology of this autoimmune disease.

  5. Monoamine oxidase activity in cultured human skin fibroblasts.

    PubMed

    Groshong, R; Gibson, D A; Baldessarini, R J

    1977-10-01

    Skin fibroblast cultures were prepared from 21 men, and found to contain types A and B activity of monoamine oxidase, with a possible slight predominance of type A, as evaluated by substrate preferences and differential inhibition by clorgyline and deprenyl. Three women had similar activities. There was a close correlation of activities with different substrates, but there was no quantitative correlation between fibroblast and blood platelet enzyme (type B) activities. The fibroblasts also contained catechol-O-methyltransferase activity exceeding, but poorly correlated with, that in erythrocytes. Fibroblasts may be advantageous in studies of monoamine oxidase in man by providing both types of enzyme as found, for example, in the central nervous system, and by providing a means of removing many in vivo chemical influences from the cells in culture. Nevertheless, great caution must be exercised in generalizing results of this "model" to other tissues, since activities of both enzymes correlated poorly with those in blood cells of the same individuals.

  6. Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon

    PubMed Central

    Szabó, C. Ákos; Patel, Mayuri; Uteshev, Victor V.

    2016-01-01

    The baboon represents a natural model for genetic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). In this retrospective study, cerebrospinal fluid (CSF) monoamine metabolites and scalp electroencephalography (EEG) were evaluated in 263 baboons of a pedigreed colony. CSF monoamine abnormalities have been linked to reduced seizure thresholds, behavioral abnormalities and SUDEP in various animal models of epilepsy. The levels of 3-hydroxy-4-methoxyphenylglycol, 5-hydroxyindolacetic acid and homovanillic acid in CSF samples drawn from the cisterna magna were analyzed using high-performance liquid chromatography. These levels were compared between baboons with seizures (SZ), craniofacial trauma (CFT) and asymptomatic, control (CTL) baboons, between baboons with abnormal and normal EEG studies. We hypothesized that the CSF levels of major monoaminergic metabolites (i.e., dopamine, serotonin and norepinephrine) associate with the baboons’ electroclinical status and thus can be used as clinical biomarkers applicable to seizures/epilepsy. However, despite apparent differences in metabolite levels between the groups, usually lower in SZ and CFT baboons and in baboons with abnormal EEG studies, we did not find any statistically significant differences using a logistic regression analysis. Significant correlations between the metabolite levels, especially between 5-HIAA and HVA, were preserved in all electroclinical groups. While we were not able to demonstrate significant differences in monoamine metabolites in relation to seizures or EEG markers of epilepsy, we cannot exclude the monoaminergic system as a potential source of pathogenesis in epilepsy and SUDEP. A prospective study evaluating serial CSF monoamine levels in baboons with recently witnessed seizures, and evaluation of abnormal expression and function of monoaminergic receptors and transporters within epilepsy-related brain regions, may impact the electroclinical status. PMID:26924854

  7. Platelet monoamine oxidase activity and the classification of depression.

    PubMed

    Davidson, J R; McLeod, M N; Turnbull, C D; White, H L; Feuer, E J

    1980-07-01

    An attempt was made to compare platelet monoamine oxidase (MAO) activity in descriptively based types of nonbipolar depression. Platelet MAO activity was significantly higher in depression secondary to chronic anxiety, compared with primary unipolar depression and depression secondary to borderline personality, and in women compared with men. No significant differences were observed between endogenous-nonendogenous, delusional-nondelusional, psychomotor states, or different age groups.

  8. [Monoamine-hormonal interactions in the pathogenesis of anxious depression].

    PubMed

    Uzbekov, M G; Maksimova, N M

    2015-01-01

    Biochemical aspects of the relationship between monoaminergic and hormonal systems in the pathogenesis of anxious depression are analyzed on the basis of literature and own results published earlier. Significant alterations in biogenic monoamine metabolism and changes in the hormonal status, that reflects homeostasis disturbance in whole, are inherent to anxious depression. The biochemical mechanisms of imbalance between serotonergic and noradrenergic systems and a role of cortisol in this process are discussed.

  9. Designing modulators of monoamine transporters using virtual screening techniques

    PubMed Central

    Mortensen, Ole V.; Kortagere, Sandhya

    2015-01-01

    The plasma-membrane monoamine transporters (MATs), including the serotonin (SERT), norepinephrine (NET) and dopamine (DAT) transporters, serve a pivotal role in limiting monoamine-mediated neurotransmission through the reuptake of their respective monoamine neurotransmitters. The transporters are the main target of clinically used psychostimulants and antidepressants. Despite the availability of several potent and selective MAT substrates and inhibitors the continuing need for therapeutic drugs to treat brain disorders involving aberrant monoamine signaling provides a compelling reason to identify novel ways of targeting and modulating the MATs. Designing novel modulators of MAT function have been limited by the lack of three dimensional structure information of the individual MATs. However, crystal structures of LeuT, a bacterial homolog of MATs, in a substrate-bound occluded, substrate-free outward-open, and an apo inward-open state and also with competitive and non-competitive inhibitors have been determined. In addition, several structures of the Drosophila DAT have also been resolved. Together with computational modeling and experimental data gathered over the past decade, these structures have dramatically advanced our understanding of several aspects of SERT, NET, and DAT transporter function, including some of the molecular determinants of ligand interaction at orthosteric substrate and inhibitor binding pockets. In addition progress has been made in the understanding of how allosteric modulation of MAT function can be achieved. Here we will review all the efforts up to date that has been made through computational approaches employing structural models of MATs to design small molecule modulators to the orthosteric and allosteric sites using virtual screening techniques. PMID:26483692

  10. Depleted Uranium: Technical Brief

    EPA Pesticide Factsheets

    This technical brief provides accepted data and references to additional sources for radiological and chemical characteristics, health risks and references for both the monitoring and measurement, and applicable treatment techniques for depleted uranium.

  11. Battery depletion monitor

    SciTech Connect

    Lee, Y.S.

    1982-01-26

    A cmos inverter is used to compare pacemaker battery voltage to a referenced voltage. When the reference voltage exceeds the measured battery voltage, the inverter changes state to indicate battery depletion.

  12. Addressing Ozone Layer Depletion

    EPA Pesticide Factsheets

    Access information on EPA's efforts to address ozone layer depletion through regulations, collaborations with stakeholders, international treaties, partnerships with the private sector, and enforcement actions under Title VI of the Clean Air Act.

  13. Quantitative distribution of monoamine oxidase A in brainstem monoamine nuclei is normal in major depression.

    PubMed

    Ordway, G A; Farley, J T; Dilley, G E; Overholser, J C; Meltzer, H Y; Balraj, E K; Stockmeier, C A; Klimek, V

    1999-11-13

    An abnormal expression of noradrenergic proteins (e.g., tyrosine hydroxylase, norepinephrine transporters) in the locus coeruleus has recently been demonstrated in subjects with major depression and/or victims of suicide. Monoamine oxidase A (MAO-A) is a key enzyme in the catabolism of biogenic amines and is expressed in brain noradrenergic neurons. In this study, the binding of [3H]Ro41-1049 to MAO-A was measured by quantitative autoradiography at multiple levels along the rostral-caudal axis of the noradrenergic locus coeruleus from subjects with major depression and age- and postmortem interval-matched control subjects who were psychiatrically normal. [3H]Ro41-1049 binding to MAO-A was unevenly distributed along the axis of the locus coeruleus, paralleling an uneven number of neuromelanin-containing (noradrenergic) neurons throughout the nucleus. Accordingly, there was a significant correlation between the number of neuromelanin-containing neurons per section and the specific binding of [3H]Ro41-1049 at any particular level of the locus coeruleus in control subjects (r(2)=0.25; p<0.001) and in subjects with major depression (r(2)=0.14; p<0. 001). Moderate levels of [3H]Ro41-1049 binding were observed in regions surrounding the locus coeruleus, including the central gray and the dorsal and median raphe nuclei. No significant differences in [3H]Ro41-1049 binding to MAO-A were observed at any level of the locus coeruleus, or raphe nuclei, comparing subjects with major depression to psychiatrically normal control subjects. These findings demonstrate that the pathophysiology of major depression is not likely to involve abnormalities in MAO-A.

  14. Monoamine mediation of the morphine-induced activation of mice

    PubMed Central

    Carroll, Bernard J.; Sharp, Peter T.

    1972-01-01

    1. The dose-response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established. 2. The activation response can be modified by drugs which affect either catecholamines or indoleamines. 3. The monoamine precursors L-DOPA and 5-hydroxytryptophan potentiate the response. 4. The monoamine synthesis inhibitors α-methyl-p-tyrosine and p-chlorophenylalanine reduce the response. 5. Inhibition of monoamine oxidase activity by pargyline caused a great increase in the response. The simultaneous administration of reserpine resulted in a further potentiation. 6. Reserpine blocked the response whenever it was given alone, either before, with or after the injection of morphine. 7. Blockade of α-adrenoceptors with phentolamine or phenoxybenzamine reduced the response. 8. Blockade of tryptaminergic receptors with methysergide or cinanserin also antagonized the response. 9. The major tranquillizers haloperidol and chlorpromazine reduced the response. Haloperidol was especially effective in this regard. 10. The tricyclic antidepressant drug imipramine potentiated the response. 11. The morphine antagonist nalorphine completely prevented the response. 12. The anticholinergic agent atropine and the antihistaminic drug mepyramine did not affect the response. 13. We conclude that dopamine, noradrenaline and 5-hydroxytryptamine are all involved in the normal activation response of grouped mice to morphine, with dopaminergic mechanisms being of primary importance. PMID:4263794

  15. Androgen receptor and monoamine oxidase polymorphism in wild bonobos

    PubMed Central

    Garai, Cintia; Furuichi, Takeshi; Kawamoto, Yoshi; Ryu, Heungjin; Inoue-Murayama, Miho

    2014-01-01

    Androgen receptor gene (AR), monoamine oxidase A gene (MAOA) and monoamine oxidase B gene (MAOB) have been found to have associations with behavioral traits, such as aggressiveness, and disorders in humans. However, the extent to which similar genetic effects might influence the behavior of wild apes is unclear. We examined the loci AR glutamine repeat (ARQ), AR glycine repeat (ARG), MAOA intron 2 dinucleotide repeat (MAin2) and MAOB intron 2 dinucleotide repeat (MBin2) in 32 wild bonobos, Pan paniscus, and compared them with those of chimpanzees, Pan troglodytes, and humans. We found that bonobos were polymorphic on the four loci examined. Both loci MAin2 and MBin2 in bonobos showed a higher diversity than in chimpanzees. Because monoamine oxidase influences aggressiveness, the differences between the polymorphisms of MAin2 and MBin2 in bonobos and chimpanzees may be associated with the differences in aggression between the two species. In order to understand the evolution of these loci and AR, MAOA and MAOB in humans and non-human primates, it would be useful to conduct future studies focusing on the potential association between aggressiveness, and other personality traits, and polymorphisms documented in bonobos. PMID:25606465

  16. Sleep Apneas are Increased in Mice Lacking Monoamine Oxidase A

    PubMed Central

    Real, Caroline; Popa, Daniela; Seif, Isabelle; Callebert, Jacques; Launay, Jean-Marie; Adrien, Joëlle; Escourrou, Pierre

    2007-01-01

    Study Objectives: Alterations in the serotonin (5-HT) system have been suggested as a mechanism of sleep apnea in humans and rodents. The objective is to evaluate the contribution of 5-HT to this disorder. Design: We studied sleep and breathing (whole-body plethysmography) in mutant mice that lack monoamine oxidase A (MAOA) and have increased concentrations of monoamines, including 5-HT. Measurements and Results: Compared to wild-type mice, the mutants showed similar amounts of slow wave sleep (SWS) and rapid eye movement sleep (REMS), but exhibited a 3-fold increase in SWS and REMS apnea indices. Acute administration of the MAOA inhibitor clorgyline decreased REMS amounts and increased the apnea index in wild-type but not mutant mice. Parachlorophenylalanine, a 5-HT synthesis inhibitor, reduced whole brain concentrations of 5-HT in both strains, and induced a decrease in apnea index in mutant but not wild-type mice. Conclusion: Our results show that MAOA deficiency is associated with increased sleep apnea in mice and suggest that an acute or chronic excess of 5-HT contributes to this phenotype. Citation: Real C; Popa D; Seif I; Callebert J; Launay JM; Adrien J; Escourrou P. Sleep apneas are increased in mice lacking monoamine oxidase A. PMID:17969463

  17. Stereoselective effects of MDMA on inhibition of monoamine uptake

    SciTech Connect

    Steele, T.D.; Nichols, D.E.; Yim, G.K.W.

    1986-03-05

    The R(-)-isomers of hallucinogenic phenylisopropylamines are most active, whereas the S(+)-enantiomers of amphetamine (AMPH) and methylenedioxymethamphetamine (MDMA) are more potent centrally. To determine if MDMA exhibits stereoselective effects at the biochemical level that resemble either those of amphetamine or the potent hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM), the ability of the isomers of MDMA, AMPH and DOM to inhibit uptake of radiolabelled monoamines into synaptosomes was measured. AMPH was more potent than MDMA in inhibiting uptake of /sup 3/H-norepinephrine (NE) into hypothalamic synaptosomes and /sup 3/H-dopamine (DA) into striatal synaptosomes. The S(+)-isomer was more active in each case. MDMA was more potent than AMPH in inhibiting uptake of /sup 3/H-serotonin (5-HT) into hippocampal synaptosomes and exhibited a high degree of stereoselectivity, in favor of the S(+)-isomer. DOM showed only minimal activity in inhibiting uptake of any monoamine (IC/sub 50/ > 10/sup -5/M). These results suggest that MDMA exhibits stereoselective effects similar to those of amphetamine on monoamine uptake inhibition, a parameter that is unrelated to the mechanism of action of the hallucinogen DOM.

  18. Revisiting the Monoamine Hypothesis of Depression: A New Perspective

    PubMed Central

    Goldberg, Joel S; Bell, Clifton E; Pollard, David A

    2014-01-01

    As the incidence of depression increases, depression continues to inflict additional suffering to individuals and societies and better therapies are needed. Based on magnetic resonance spectroscopy and laboratory findings, gamma aminobutyric acid (GABA) may be intimately involved in the pathophysiology of depression. The isoelectric point of GABA (pI = 7.3) closely approximates the pH of cerebral spinal fluid (CSF). This may not be a trivial observation as it may explain preliminary spectrophotometric, enzymatic, and HPLC data that monoamine oxidase (MAO) deaminates GABA. Although MAO is known to deaminate substrates such as catecholamines, indoleamines, and long chain aliphatic amines all of which contain a lipophilic moiety, there is very good evidence to predict that a low concentration of a very lipophilic microspecies of GABA is present when GABA pI = pH as in the CSF. Inhibiting deamination of this microspecies of GABA could explain the well-established successful treatment of refractory depression with MAO inhibitors (MAOI) when other antidepressants that target exclusively levels of monoamines fail. If further experimental work can confirm these preliminary findings, physicians may consider revisiting the use of MAOI for the treatment of non-intractable depression because the potential benefits of increasing GABA as well as the monoamines may outweigh the risks associated with MAOI therapy. PMID:24737931

  19. Cholesterol depletion induces autophagy

    SciTech Connect

    Cheng, Jinglei; Ohsaki, Yuki; Tauchi-Sato, Kumi; Fujita, Akikazu; Fujimoto, Toyoshi . E-mail: tfujimot@med.nagoya-u.ac.jp

    2006-12-08

    Autophagy is a mechanism to digest cells' own components, and its importance in many physiological and pathological processes is being recognized. But the molecular mechanism that regulates autophagy is not understood in detail. In the present study, we found that cholesterol depletion induces macroautophagy. The cellular cholesterol in human fibroblasts was depleted either acutely using 5 mM methyl-{beta}-cyclodextrin or 10-20 {mu}g/ml nystatin for 1 h, or metabolically by 20 {mu}M mevastatin and 200 {mu}M mevalonolactone along with 10% lipoprotein-deficient serum for 2-3 days. By any of these protocols, marked increase of LC3-II was detected by immunoblotting and by immunofluorescence microscopy, and the increase was more extensive than that caused by amino acid starvation, i.e., incubation in Hanks' solution for several hours. The induction of autophagic vacuoles by cholesterol depletion was also observed in other cell types, and the LC3-positive membranes were often seen as long tubules, >50 {mu}m in length. The increase of LC3-II by methyl-{beta}-cyclodextrin was suppressed by phosphatidylinositol 3-kinase inhibitors and was accompanied by dephosphorylation of mammalian target of rapamycin. By electron microscopy, autophagic vacuoles induced by cholesterol depletion were indistinguishable from those seen after amino acid starvation. These results demonstrate that a decrease in cholesterol activates autophagy by a phosphatidylinositol 3-kinase-dependent mechanism.

  20. Effect of rapid eye movement sleep deprivation on rat brain monoamine oxidases.

    PubMed

    Thakkar, M; Mallick, B N

    1993-08-01

    Monoamine oxidase, monoamine oxidase-A, and monoamine oxidase-B activities were compared in free moving, rapid eye movement sleep-deprived, recovered, and control rat brains. The activities were estimated in the whole brain, cerebrum, cerebellum, whole brainstem, medulla, pons, and midbrain. The flowerpot method was used for continuing deprivation for one, two, or four days. Monoamine oxidase activity decreased significantly in the cerebrum and the cerebellum of the sleep-deprived rats, whereas monoamine oxidase-A and monoamine oxidase-B were differentially affected. Medullary MAO-A was the first to be affected, showing an increase after just one day of rapid eye movement sleep deprivation, while longer deprivation decreased its activity. The activity of monoamine oxidase-B was not significantly affected in any brain areas of the deprived rats until after two days of rapid eye movement sleep deprivation. All the altered enzyme activities returned to control levels after recovery. Control experiments suggest that the decrease was primarily caused by the rapid eye movement sleep deprivation and was not due to nonspecific effects. These findings are consistent with past studies and may help to explain earlier observations. The results support the involvement of aminergic mechanisms in rapid eye movement sleep. The plausible reasons for the changes in the activities of monoamine oxidases, after rapid eye movement sleep deprivation, are discussed.

  1. Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis

    PubMed Central

    Wu, Jason Boyang; Shao, Chen; Li, Xiangyan; Li, Qinlong; Hu, Peizhen; Shi, Changhong; Li, Yang; Chen, Yi-Ting; Yin, Fei; Liao, Chun-Peng; Stiles, Bangyan L.; Zhau, Haiyen E.; Shih, Jean C.; Chung, Leland W.K.

    2014-01-01

    Tumors from patients with high-grade aggressive prostate cancer (PCa) exhibit increased expression of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines. Despite the association between MAOA and aggressive PCa, it is unclear how MAOA promotes PCa progression. Here, we found that MAOA functions to induce epithelial-to-mesenchymal transition (EMT) and stabilize the transcription factor HIF1α, which mediates hypoxia through an elevation of ROS, thus enhancing growth, invasiveness, and metastasis of PCa cells. Knockdown and overexpression of MAOA in human PCa cell lines indicated that MAOA induces EMT through activation of VEGF and its coreceptor neuropilin-1. MAOA-dependent activation of neuropilin-1 promoted AKT/FOXO1/TWIST1 signaling, allowing FOXO1 binding at the TWIST1 promoter. Importantly, the MAOA-dependent HIF1α/VEGF-A/FOXO1/TWIST1 pathway was activated in high-grade PCa specimens, and knockdown of MAOA reduced or even eliminated prostate tumor growth and metastasis in PCa xenograft mouse models. Pharmacological inhibition of MAOA activity also reduced PCa xenograft growth in mice. Moreover, high MAOA expression in PCa tissues correlated with worse clinical outcomes in PCa patients. These findings collectively characterize the contribution of MAOA in PCa pathogenesis and suggest that MAOA has potential as a therapeutic target in PCa. PMID:24865426

  2. Social modulation of brain monoamine levels in zebrafish.

    PubMed

    Teles, Magda C; Dahlbom, S Josefin; Winberg, Svante; Oliveira, Rui F

    2013-09-15

    In social species animals tend to adjust their social behaviour according to the available social information in the group, in order to optimize and improve their one social status. This changing environment requires for rapid and transient behavioural changes that relies primarily on biochemical switching of existing neural networks. Monoamines and neuropeptides are the two major candidates to mediate these changes in brain states underlying socially behavioural flexibility. In the current study we used zebrafish (Danio rerio) males to study the effects of acute social interactions on rapid regional changes in brain levels of monoamines (serotonin and dopamine). A behavioural paradigm under which male zebrafish consistently express fighting behaviour was used to investigate the effects of different social experiences: winning the interaction, losing the interaction, or fighting an unsolved interaction (mirror image). We found that serotonergic activity is significantly higher in the telencephalon of winners and in the optic tectum of losers, and no significant changes were observed in mirror fighters suggesting that serotonergic activity is differentially regulated in different brain regions by social interactions. Dopaminergic activity it was also significantly higher in the telencephalon of winners which may be representative of social reward. Together our data suggests that acute social interactions elicit rapid and differential changes in serotonergic and dopaminergic activity across different brain regions.

  3. Ammonia causes decreased brain monoamines in fathead minnows (Pimephales promelas)

    USGS Publications Warehouse

    Ronan, Patrick J.; Gaikowski, Mark P.; Hamilton, Steven J.; Buhl, Kevin J.; Summers, Cliff H.

    2007-01-01

    Hyperammonemia, arising from variety of disorders, leads to severe neurological dysfunction. The mechanisms of ammonia toxicity in brain are not completely understood. This study investigated the effects of ammonia on monoaminergic systems in brains of fathead minnows (Pimephales promelas). Fish serve as a good model system to investigate hyperammonemic effects on brain function since no liver manipulations are necessary to increase endogenous ammonia concentrations. Using high performance liquid chromatography with electrochemical detection, monoamines and some associated metabolites were measured from whole brain homogenate. Adult males were exposed for 48 h to six different concentrations of ammonia (0.01–2.36 mg/l unionized) which bracketed the 96-h LC50 for this species. Ammonia concentration-dependent decreases were found for the catecholamines (norepinephrine and dopamine) and the indoleamine serotonin (5-HT). After an initial increase in the 5-HT precursor 5-hydroxytryptophan it too decreased with increasing ammonia concentrations. There were also significant increases in the 5-HIAA/5-HT and DOPAC/DA ratios, often used as measures of turnover. There were no changes in epinephrine (Epi) or monoamine catabolites (DOPAC, 5-HIAA) at any ammonia concentrations tested. Results suggest that ammonia causes decreased synthesis while also causing increased release and degradation. Increased release may underlie behavioral reactions to ammonia exposure in fish. This study adds weight to a growing body of evidence demonstrating that ammonia leads to dysfunctional monoaminergic systems in brain which may underlie neurological symptoms associated with human disorders such as hepatic encephalopathy.

  4. A review of monoamine transporter-ligand interactions.

    PubMed

    Immadisetty, Kalyan; Madura, Jeffry D

    2013-12-01

    Transporters of the monoamines serotonin, dopamine, and norepinephrine are plasma membrane proteins belonging to the neurotransmitter sodium symporter family (NSS). Monoamine transporters (MATs) by facilitating reuptake of neurotransmitters from the synapse into the presynaptic nerve terminal, regulate neurotransmitter chemical signaling and maintain homeostasis. MATs are targets for several psychostimulants such as cocaine and amphetamine; and also for drugs treating several psychiatric disorders such as depression, attention deficit hyperactivity disorder, Parkinson's disease, and schizophrenia. Since, currently available treatment has several limitations and side effects, novel treatment is highly desired. Efforts to develop better treatment have been hampered by the lack of crystal structures for MATs. However, leucine transporter (LeuTAa), a bacterial protein from Aquifex aeolicus, belonging to the same NSS family as MATs has recently been crystallized. LeuTAa is used as a template to develop homology models of MATs, which facilitates understanding of the structure, function and pharmacology of MATs. Experimental methods for drug discovery demand a significant amount of time, effort and money. Efficient utilization of computational techniques hastens the process of drug discovery and also significantly reduces the cost. Assessing the binding affinity of drugs to the receptors is a key aspect of drug design. Free energy calculations compliment the experiment by quantitatively assessing the affinity of ligands to receptors. These methods are highly beneficial in the lead identification and optimization stages of rational drug design. We review the currently available free energy methods to treat protein-ligand interactions along with several free energy studies performed on MATs.

  5. Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis.

    PubMed

    Wu, Jason Boyang; Shao, Chen; Li, Xiangyan; Li, Qinlong; Hu, Peizhen; Shi, Changhong; Li, Yang; Chen, Yi-Ting; Yin, Fei; Liao, Chun-Peng; Stiles, Bangyan L; Zhau, Haiyen E; Shih, Jean C; Chung, Leland W K

    2014-07-01

    Tumors from patients with high-grade aggressive prostate cancer (PCa) exhibit increased expression of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines. Despite the association between MAOA and aggressive PCa, it is unclear how MAOA promotes PCa progression. Here, we found that MAOA functions to induce epithelial-to-mesenchymal transition (EMT) and stabilize the transcription factor HIF1α, which mediates hypoxia through an elevation of ROS, thus enhancing growth, invasiveness, and metastasis of PCa cells. Knockdown and overexpression of MAOA in human PCa cell lines indicated that MAOA induces EMT through activation of VEGF and its coreceptor neuropilin-1. MAOA-dependent activation of neuropilin-1 promoted AKT/FOXO1/TWIST1 signaling, allowing FOXO1 binding at the TWIST1 promoter. Importantly, the MAOA-dependent HIF1α/VEGF-A/FOXO1/TWIST1 pathway was activated in high-grade PCa specimens, and knockdown of MAOA reduced or even eliminated prostate tumor growth and metastasis in PCa xenograft mouse models. Pharmacological inhibition of MAOA activity also reduced PCa xenograft growth in mice. Moreover, high MAOA expression in PCa tissues correlated with worse clinical outcomes in PCa patients. These findings collectively characterize the contribution of MAOA in PCa pathogenesis and suggest that MAOA has potential as a therapeutic target in PCa.

  6. Maladaptive defensive behaviours in monoamine oxidase A-deficient mice

    PubMed Central

    Godar, Sean C.; Bortolato, Marco; Frau, Roberto; Dousti, Mona; Chen, Kevin; Shih, Jean C.

    2012-01-01

    Rich evidence indicates that monoamine oxidase (MAO) A, the major enzyme catalysing the degradation of monoamine neurotransmitters, plays a key role in emotional regulation. Although MAOA deficiency is associated with reactive aggression in humans and mice, the involvement of this enzyme in defensive behaviour remains controversial and poorly understood. To address this issue, we tested MAOA knockout (KO) mice in a spectrum of paradigms and settings associated with variable degrees of threat. The presentation of novel inanimate objects induced a significant reduction in exploratory approaches and increase in defensive behaviours, such as tail-rattling, biting and digging. These neophobic responses were context-dependent and particularly marked in the home cage. In the elevated plus- and T-mazes, MAOA KO mice and wild-type (WT) littermates displayed equivalent locomotor activity and time in closed and open arms; however, MAOA KO mice featured significant reductions in risk assessment, as well as unconditioned avoidance and escape. No differences between genotypes were observed in the defensive withdrawal and emergence test. Conversely, MAOA KO mice exhibited a dramatic reduction of defensive and fear-related behaviours in the presence of predator-related cues, such as predator urine or an anaesthetized rat, in comparison with those observed in their WT littermates. The behavioural abnormalities in MAOA KO mice were not paralleled by overt alterations in sensory and microvibrissal functions. Collectively, these results suggest that MAOA deficiency leads to a general inability to appropriately assess contextual risk and attune defensive and emotional responses to environmental cues. PMID:21156093

  7. Brain Monoamine Oxidase-A Activity Predicts Trait Aggression

    PubMed Central

    Alia-Klein, Nelly; Goldstein, Rita Z.; Kriplani, Aarti; Logan, Jean; Tomasi, Dardo; Williams, Benjamin; Telang, Frank; Shumay, Elena; Biegon, Anat; Craig, Ian W.; Henn, Fritz; Wang, Gene-Jack; Volkow, Nora D.; Fowler, Joanna S.

    2008-01-01

    The genetic deletion of monoamine oxidase A (MAO A, an enzyme which breaks down the monoamine neurotransmitters norepinephrine, serotonin and dopamine) produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, MIM 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidence linking the low MAOA genotype and violent behavior but only through interaction with severe environmental stressors during childhood. Here, we hypothesized that in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. Brain MAO A activity was measured in-vivo in healthy non-smoking men with positron emission tomography using a radioligand specific for MAO A (clorgyline labeled with carbon 11). Trait aggression was measured with the Multidimensional Personality Questionnaire (MPQ). Here we report for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits) such that the lower the MAO A activity in cortical and subcortical brain regions the higher the self-reported aggression (in both MAOA genotype groups) contributing to more than a third of the variability. Since trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression. PMID:18463263

  8. BEHAVIORAL OUTCOMES OF MONOAMINE OXIDASE DEFICIENCY: PRECLINICAL AND CLINICAL EVIDENCE

    PubMed Central

    Bortolato, Marco; Shih, Jean C.

    2012-01-01

    Monoamine oxidase (MAO) isoenzymes A and B are mitochondrial-bound proteins, catalyzing the oxidative deamination of monoamine neurotransmitters as well as xenobiotic amines. Although they derive from a common ancestral progenitor gene, are located at X-chromosome and display 70% structural identity, their substrate preference, regional distribution, and physiological role are divergent. In fact, while MAO-A has high affinity for serotonin and norepinephrine, MAO-B primarily serves the catabolism of 2-phenylethylamine (PEA) and contributes to the degradation of other trace amines and dopamine. Convergent lines of preclinical and clinical evidence indicate that variations in MAO enzymatic activity—due to either genetic or environmental factors—can exert a profound influence on behavioral regulation and play a role in the pathophysiology of a large spectrum of mental and neurodegenerative disorders, ranging from antisocial personality disorder to Parkinson’s disease. Over the past few years, numerous advances have been made in our understanding of the phenotypical variations associated with genetic polymorphisms and mutations of the genes encoding for both isoenzymes. In particular, novel findings on the phenotypes of MAO-deficient mice are highlighting novel potential implications of both isoenzymes in a broad spectrum of mental disorders, ranging from autism and anxiety to impulse-control disorders and ADHD. These studies will lay the foundation for future research on the neurobiological and neurochemical bases of these pathological conditions, as well as the role of gene × environment interactions in the vulnerability to several mental disorders. PMID:21971001

  9. Tocotrienols reverse IKAP and monoamine oxidase deficiencies in familial dysautonomia.

    PubMed

    Anderson, Sylvia L; Rubin, Berish Y

    2005-10-14

    Familial dysautonomia (FD), a recessive neurodegenerative disease, is caused by mutations in the IKBKAP gene that result in the production of nonfunctional IKAP protein. Manifestations of FD include autonomic crises characterized by hypertension, tachycardia, diaphoresis, and vomiting. Elevated plasma levels of norepinephrine (NE) and dopamine observed during autonomic crises and an exaggerated hypertensive response to low doses of NE prompted an examination of monoamine oxidase (MAO) levels, key isoenzymes responsible for degrading biogenic and dietary monoamines, in individuals with FD. Fetal tissue homozygous for the common FD-causing mutation and peripheral blood cells of individuals with FD have reduced MAO A mRNA levels. FD-derived cells, stimulated with tocotrienols or EGCG to produce increased levels of functional IKAP, express increased amounts of MAO A mRNA transcript and protein. Administration of tocotrienol to individuals with FD results in increased expression of both functional IKAP and MAO A transcripts in their peripheral blood cells. These findings provide new insight into the pathophysiology of FD and demonstrate the value of therapeutic approaches designed to elevate cellular levels of functional IKAP and MAO A.

  10. Monoamine oxidase A (MAO A) inhibitors decrease glioma progression

    PubMed Central

    Vaikari, Vijaya Pooja; Kota, Rajesh; Chen, Kevin; Yeh, Tzu-Shao; Jhaveri, Niyati; Groshen, Susan L.; Olenyuk, Bogdan Z.; Chen, Thomas C.; Hofman, Florence M.; Shih, Jean C.

    2016-01-01

    Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-alone drugs or as combination therapy with low dose TMZ for drug-resistant gliomas. NMI can also be used as a non-invasive imaging tool. Thus has a dual function for both therapy and diagnosis. PMID:26871599

  11. Depletion of Intense Fields

    NASA Astrophysics Data System (ADS)

    Seipt, D.; Heinzl, T.; Marklund, M.; Bulanov, S. S.

    2017-04-01

    The interaction of charged particles and photons with intense electromagnetic fields gives rise to multiphoton Compton and Breit-Wheeler processes. These are usually described in the framework of the external field approximation, where the electromagnetic field is assumed to have infinite energy. However, the multiphoton nature of these processes implies the absorption of a significant number of photons, which scales as the external field amplitude cubed. As a result, the interaction of a highly charged electron bunch with an intense laser pulse can lead to significant depletion of the laser pulse energy, thus rendering the external field approximation invalid. We provide relevant estimates for this depletion and find it to become important in the interaction between fields of amplitude a0˜1 03 and electron bunches with charges of the order of 10 nC.

  12. Effects of taurine deficiency and chronic methanol administration on rat retina, optic nerve and brain amino acids and monoamines.

    PubMed

    González-Quevedo, A; Obregón, F; Urbina, M; Roussó, T; Lima, L

    2003-08-01

    A chronic methanol (MeOH) intoxication scheme (2 g/kg/day ip for 2 weeks) was carried out in Sprague-Dawley rats, previously depleted of folates with methotrexate (MTX). beta-Alanine (beta-Ala), 5%, was also administered to some animals in the drinking water. Amino acids were determined in plasma, retina, optic nerve, hippocampus and posterior cortex by HPLC with fluorescence detection and monoamines in retina, hippocampus and posterior cortex by electrochemical detection. Beta-Ala administration reduced taurine (Tau) levels in plasma, hippocampus and posterior cortex, but not in retina and optic nerve. Aspartate (Asp) concentration in the optic nerve was increased in MTX-MeOH treated animals, and the administration of beta-Ala did not modify this elevation. The association of beta-Ala with MTX-MeOH produced an increase of threonine, and a decrease of 5-hydroxytryptamine (5-HT) in the retina without modifying 5-hydroxyindoleacetic acid, whereas in the hippocampus an elevation of asparagine was observed. We conclude that, in the retina, beta-Ala in combination with MTX-MeOH increased serotonin and decreased dopamine (DA) turnover rate, and resulted in changes in the amino acid balance, that could affect glycinergic activity. On the other hand, in the hippocampus, Asp metabolism could be affected by Tau depletion with beta-Ala.

  13. Effects of high-dose fenfluramine treatment on monoamine uptake sites in rat brain: Assessment using quantitative autoradiography

    SciTech Connect

    Appel, N.M.; Mitchell, W.M.; Contrera, J.F.; De Souza, E.B. )

    1990-01-01

    Fenfluramine is an amphetamine derivative that in humans is used primarily as an anorectic agent in the treatment of obesity. In rats, subchronic high-dose d,l-fenfluramine treatment (24 mg/kg subcutaneously, twice daily for 4 days) causes long-lasting decreases in brain serotonin (5HT), its metabolite 5-hydroxyindoleacetic acid, and high-affinity 5HT uptake sites. Moreover, this high-dose treatment regimen causes both selective long-lasting decreases in fine-caliber 5HT-immunoreactive axons and appearance of other 5HT-immunoreactive axons with morphology characteristic of degenerating axons. Determination of the potential neurotoxic effects of fenfluramine treatment using immunohistochemistry is limited from the perspectives that staining is difficult to quantify and that it relies on presence of the antigen (in this case 5HT), and the 5HT-depleting effects of fenfluramine are well known. In the present study, we used quantitative in vitro autoradiography to assess, in detail, the density and regional distribution of (3H)paroxetine-labeled 5HT and (3H)mazindol-labeled catecholamine uptake sites in response to the high-dose fenfluramine treatment described above. Because monoamine uptake sites are concentrated on monoamine-containing nerve terminals, decreases in uptake site density would provide a quantitative assessment of potential neurotoxicity resulting from this fenfluramine treatment regimen. Marked decreases in densities of (3H)paroxetine-labeled 5HT uptake sites occurred in brain regions in which fenfluramine treatment decreased the density of 5HT-like immunostaining when compared to saline-treated control rats. These included cerebral cortex, caudate putamen, hippocampus, thalamus, and medial hypothalamus.

  14. Disorders of consciousness and pharmaceuticals that act on oxygen based amino acid and monoamine neurotransmitter pathways of the brain.

    PubMed

    Clauss, Ralf

    2014-01-01

    Oxygen based neurotransmitters in the synapses of the brain are proposed to play an important role in the generation of consciousness. They include the amino acids glutamate and GABA which use Krebs cycle precursors for their synthesis, and the monoamines dopamine, noradrenalin, adrenalin and serotonin, which are derived from tyrosine and tryptophan. During ischemia after an acute brain injury, a GABA surge often initiates brain suppression. It has been proposed that with chronic ischemia, a secondary, possibly epigenetic response occurs when neurotransmitters deplete, a glucose and oxygen saving mechanism termed neurodormancy that may invoke alternative long term low energy metabolic pathways in the brain, encountered in Disorders of Consciousness. Some medications can reverse Disorders of Consciousness in some patients. Virtually all of them act on neurotransmitter systems that use oxygen as a building block or as an energy source within the brain. Pharmaceuticals that act in the oxygen based amino acid systems of the brain include the GABAergic medications zolpidem and baclofen, while those that act in the monoamine axes include the dopaminergic medications L Dopa, amantadine, bromocriptine, apomorphine and methylphenidate, and the noradrenergic and serotonergic medications desipramine, amitriptyline, protriptyline and fluoxetine. Another group are the cholinesterase inhibitors, responsible for increasing acetylcholine, which is synthesized from the Krebs cycle initiator, acetyl CoA. It appears that pharmaceuticals that are active in the oxygen based neurotransmitter pathways of the brain are successful to arouse to consciousness patients that suffer from its disorders. Research needs to be supported as foundation to understand the biochemical mechanisms that are involved in consciousness disorders and to explore further the pharmacological treatment possibilities for these devastating neurological conditions.

  15. The plasma membrane monoamine transporter (PMAT): Structure, function, and role in organic cation disposition.

    PubMed

    Wang, J

    2016-11-01

    Plasma membrane monoamine transporter (PMAT) is a new polyspecific organic cation transporter that transports a variety of biogenic amines and xenobiotic cations. Highly expressed in the brain, PMAT represents a major uptake2 transporter for monoamine neurotransmitters. At the blood-cerebrospinal fluid (CSF) barrier, PMAT is the principal organic cation transporter for removing neurotoxins and drugs from the CSF. Here I summarize our latest understanding of PMAT and its roles in monoamine uptake and xenobiotic disposition. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  16. Depleted uranium management alternatives

    SciTech Connect

    Hertzler, T.J.; Nishimoto, D.D.

    1994-08-01

    This report evaluates two management alternatives for Department of Energy depleted uranium: continued storage as uranium hexafluoride, and conversion to uranium metal and fabrication to shielding for spent nuclear fuel containers. The results will be used to compare the costs with other alternatives, such as disposal. Cost estimates for the continued storage alternative are based on a life-cycle of 27 years through the year 2020. Cost estimates for the recycle alternative are based on existing conversion process costs and Capital costs for fabricating the containers. Additionally, the recycle alternative accounts for costs associated with intermediate product resale and secondary waste disposal for materials generated during the conversion process.

  17. Tank depletion flow controller

    DOEpatents

    Georgeson, Melvin A.

    1976-10-26

    A flow control system includes two bubbler tubes installed at different levels within a tank containing such as radioactive liquid. As the tank is depleted, a differential pressure transmitter monitors pressure differences imparted by the two bubbler tubes at a remote, shielded location during uniform time intervals. At the end of each uniform interval, balance pots containing a dense liquid are valved together to equalize the pressures. The resulting sawtooth-shaped signal generated by the differential pressure transmitter is compared with a second sawtooth signal representing the desired flow rate during each time interval. Variations in the two signals are employed by a control instrument to regulate flow rate.

  18. Aggression and personality: association with amino acids and monoamine metabolites.

    PubMed

    Møller, S E; Mortensen, E L; Breum, L; Alling, C; Larsen, O G; Bøge-Rasmussen, T; Jensen, C; Bennicke, K

    1996-03-01

    Associations in 52 normal individuals were examined between plasma and cerebrospinal fluid (CSF) concentrations of tryptophan (Trp) and tyrosine, and concentrations of monoamine metabolites in the CSF, and scores on an aggression questionnaire, the Kinsey Institute Reaction List II, and the Eysenck Personality Questionnaire. There was a significantly positive correlation between CSF 5-hydroxyindoleacetic acid (5-HIAA) levels and extroverted aggression scores, and a significantly negative correlation between CSF 5-HIAA levels and introverted aggression scores. Males showed higher plasma Trp concentrations than females, and significantly positive correlations between plasma Trp concentrations and scores on extroverted aggression and the Eysenck E scale. Males, furthermore, showed a significantly negative correlation between CSF Trp levels and scores on the Eysenck P scale, and a significantly positive correlation between concentrations of 3-methoxy-4-hydroxy-phenylglycol in CSF and scores on moral aggression. These results suggest that central serotonin influences aggression in normal individuals through effects on personality.

  19. Human monoamine oxidase. Lack of brain and platelet correlation.

    PubMed

    Young, W F; Laws, E R; Sharbrough, F W; Weinshilboum, R M

    1986-06-01

    Monoamine oxidase (MAO) exists in two forms, MAO A and MAO B. Both are present in human brain, but the human platelet contains only MAO B. We studied whether individual variations in the activity of human platelet MAO B reflect individual variations in cerebral cortical MAO activities. Optimal conditions were determined for the measurement of MAO activities in both the platelet and cerebral cortex, obtained from 14 patients with epilepsy during clinically indicated neurosurgery. There was no significant correlation between the activities of MAO B in the cerebral cortex and platelets of these patients. Platelet MAO B activities also failed to correlate significantly with cerebral cortical MAO A activities. However, there was a significant positive correlation between cerebral cortical MAO A and MAO B activities. Individual variations in platelet MAO B activities do not reflect individual variations in either cerebral cortical MAO B or MAO A activities in patients with epilepsy who undergo neurosurgery.

  20. Monoamine oxidase inhibitors. A review of antidepressant effectiveness.

    PubMed

    Quitkin, F; Rifkin, A; Klein, D F

    1979-07-01

    Data from double-blind, placebo-controlled trials of the monoamine oxidase (MAO) inhibitors show that phenelzine is clearly effective in neurotic or atypical depressives, but the findings concerning its effect in endogenous depressives are inconclusive. Although few controlled studies have been done with tranylcypromine, similar conclusions are warranted. Studies have contrasted MAO inhibitors and tricyclic antidepressants (TCAs) to gain further information about the type of patients likely to respond to MAO inhibitors. We believe that simply contrasting the relative efficacy of TCAs and MAO inhibitors is outdated. Neurotic or atypical depression is probably a heterogeneous syndrome, and delineation of subtypes responsive to specific antidepressants is needed. The implications of fast acetylation, selective MAO inhibitors, types MAOA and MAOB, and measures of platelet MAO inhibition are discussed in this article.

  1. Psychiatric vulnerability, monoamine oxidase, and the average evoked potential.

    PubMed

    Haier, R J; Buchsbaum, M S; Murphy, D L; Gottesman, I I; Coursey, R D

    1980-03-01

    College students in two separate studies had platelet monoamine oxidase (MAO) activity determinations and average evoked potential (AEP) measurements taken. On the basis of Minnesota Muliphasic Personality Inventory (MMPI) or Research Diagnostic Criteria (RDC) evaluations, psychopathology, particularly affective disorder, was found to be more prevalent among both persons with the combination of low MAO activity and AEP augmenting and those with high MAO activity and AEP reducing. The same pattern is apparent whether students were selected for extremely high or low MAO activity (study 1) or for elevated or normal MMPI scores (study 2). Some psychiatric patient groups also show this pattern. An interactive model of sensation-seeking and sensory inhibition is presented.

  2. Amphetamines, new psychoactive drugs and the monoamine transporter cycle.

    PubMed

    Sitte, Harald H; Freissmuth, Michael

    2015-01-01

    In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit their actions: most amphetamines are substrates, which pervert the relay to elicit efflux of monoamines into the synaptic cleft. However, some amphetamines act as transporter inhibitors. Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse. Currently, a surge of new psychoactive substances occurs on a global scale. Chemists bypass drug bans by ingenuous structural variations, resulting in a rich pharmacology. A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects.

  3. Brofaromine: a monoamine oxidase-A and serotonin uptake inhibitor.

    PubMed

    Waldmeier, P C; Glatt, A; Jaekel, J; Bittiger, H

    1993-01-01

    Brofaromine is a tight-binding, reversible inhibitor of monoamine oxidase-A (MAO-A), with concomitant serotonin (5-HT) uptake-inhibiting properties. In psychopharmacologic investigations, the compound shows the properties expected of an MAO inhibitor, antagonizing the effects of reserpine, tetrabenazine, and 5-hydroxytryptophan in rats and mice, and suppressing rapid eye movement sleep in cats. Brofaromine showed antidepressant-like activity in a rat social conflict test. In radioligand binding assays, brofaromine exhibited weak or no interaction with alpha 1- and alpha 2-noradrenergic, 5-HT1, 5-HT2, 5-HT3, cholinergic, histamine H1 and H2, mu-opiate, GABAA, benzodiazepine, adenosine, neurotensin, and substance P receptors. Comparison of in vitro and in vivo potencies to inhibit 5-HT uptake with those of reference drugs, and direct evidence in patients and volunteers suggest that 5-HT uptake inhibition plays a role in the clinical profile of brofaromine.

  4. Low platelet monoamine oxidase activity in sensation-seeking bullfighters.

    PubMed

    Carrasco, J L; Sáiz-Ruiz, J; Díaz-Marsá, M; César, J; López-Ibor, J J

    1999-12-01

    In this study, we attempt to demonstrate an association between low platelet monoamine oxidase (MAO) activity, as assessed by isotopic methods, and the stable behavioral pattern of sensation- and risk-seeking of professional bullfighters. Sixteen professional bullfighters were studied and compared with a control group of 46 healthy control subjects who did not engage in risky jobs or activities. The group of bullfighters had significantly reduced platelet MAO activity compared with the control group (P<0.05). Bullfighters were shown to be significantly more extroverted and sensation-seeking than controls on various temperament scales. A predisposition to engage in risky activities (eg, bullfighting) and sensation-seeking could be partly conditioned by the presence of biological components of personality manifested by a significantly decreased platelet MAO activity.

  5. Translational neuroimaging: positron emission tomography studies of monoamine oxidase.

    PubMed

    Fowler, Joanna S; Logan, Jean; Volkow, Nora D; Wang, Gene-Jack

    2005-01-01

    Positron emission tomography (PET) using radiotracers with high molecular specificity is an important scientific tool in studies of monoamine oxidase (MAO), an important enzyme in the regulation of the neurotransmitters dopamine, norepinephrine, and serotonin as well as the dietary amine, tyramine. MAO occurs in two different subtypes, MAO A and MAO B, which have different substrate and inhibitor specificity and which are different gene products. The highly variable subtype distribution with different species makes human studies of special value. MAO A and B can be imaged in the human brain and certain peripheral organs using PET and carbon-11 (half-life 20.4 minutes) labeled mechanism-based irreversible inhibitors, clorgyline and L -deprenyl, respectively. In this article we introduce MAO and describe the development of these radiotracers and their translation from preclinical studies to the investigation of variables affecting MAO in the human brain and peripheral organs.

  6. Amphetamines, new psychoactive drugs and the monoamine transporter cycle

    PubMed Central

    Sitte, Harald H.; Freissmuth, Michael

    2015-01-01

    In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit their actions: most amphetamines are substrates, which pervert the relay to elicit efflux of monoamines into the synaptic cleft. However, some amphetamines act as transporter inhibitors. Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse. Currently, a surge of new psychoactive substances occurs on a global scale. Chemists bypass drug bans by ingenuous structural variations, resulting in a rich pharmacology. A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects. PMID:25542076

  7. Depletion of intense fields

    NASA Astrophysics Data System (ADS)

    Bulanov, S. S.; Seipt, D.; Heinzl, T.; Marklund, M.

    2017-03-01

    The problem of backreaction of quantum processes on the properties of the background field still remains on the list of outstanding questions of high intensity particle physics. Usually, photon emission by an electron or positron, photon decay into electron-positron pairs in strong electromagnetic fields, or electron-positron pair production by such fields are described in the framework of the external field approximation. It is assumed that the external field has infinite energy and is not affected by these processes. However, the above-mentioned processes have a multi-photon nature, i.e., they occur with the absorption of a significant number of field photons. As a result, the interaction of an intense electromagnetic field with either a highly charged electron bunch or a fast growing population of electrons, positrons, and gamma photons (as in the case of an electromagnetic cascade) may lead to a depletion of the field energy, thus making the external field approximation invalid. Taking the multi-photon Compton process as an example, we estimate the threshold of depletion and find it to become significant at field strengths (a0˜103) and electron bunch charge of about tens of nC.

  8. Mutations in human monoamine-related neurotransmitter pathway genes.

    PubMed

    Haavik, Jan; Blau, Nenad; Thöny, Beat

    2008-07-01

    Biosynthesis and metabolism of serotonin and catecholamines involve at least eight individual enzymes that are mainly expressed in tissues derived from the neuroectoderm, e.g., the central nervous system (CNS), pineal gland, adrenal medulla, enterochromaffin tissue, sympathetic nerves, and ganglia. Some of the enzymes appear to have additional biological functions and are also expressed in the heart and various other internal organs. The biosynthetic enzymes are tyrosine hydroxylase (TH), tryptophan hydroxylases type 1 and 2 (TPH1, TPH2), aromatic amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DbetaH), and phenylethanolamine N-methyltransferase (PNMT), and the specific catabolic enzymes are monoamine oxidase A (MAO-A) and catechol O-methyltransferase (COMT). For the TH, DDC, DBH, and MAOA genes, many single nucleotide polymorphisms (SNPs) with unknown function, and small but increasing numbers of cases with autosomal recessive mutations have been recognized. For the remaining genes (TPH1, TPH2, PNMT, and COMT) several different genetic markers have been suggested to be associated with regulation of mood, pain perception, and aggression, as well as psychiatric disturbances such as schizophrenia, depression, suicidality, and attention deficit/hyperactivity disorder. The genetic markers may either have a functional role of their own, or be closely linked to other unknown functional variants. In the future, molecular testing may become important for the diagnosis of such conditions. Here we present an overview on mutations and polymorphisms in the group of genes encoding monoamine neurotransmitter metabolizing enzymes. At the same time we propose a unified nomenclature for the nucleic acid aberrations in these genes. New variations or details on mutations will be updated in the Pediatric Neurotransmitter Disorder Data Base (PNDDB) database (www.bioPKU.org).

  9. Inhibition of monoamine oxidase activity by antidepressants and mood stabilizers.

    PubMed

    Fisar, Zdenek; Hroudová, Jana; Raboch, Jirí

    2010-01-01

    Monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters, has an important role in the brain development and function, and MAO inhibitors have a range of potential therapeutic uses. We investigated systematically in vitro effects of pharmacologically different antidepressants and mood stabilizers on MAO activity. Effects of drugs on the activity of MAO were measured in crude mitochondrial fraction isolated from cortex of pig brain, when radiolabeled serotonin (for MAO-A) or phenylethylamine (for MAO-B) was used as substrate. The several antidepressants and mood stabilizers were compared with effects of well known MAO inhibitors such as moclobemide, iproniazid, pargyline, and clorgyline. In general, the effect of tested drugs was found to be inhibitory. The half maximal inhibitory concentration, parameters of enzyme kinetic, and mechanism of inhibition were determined. MAO-A was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > desipramine > amitriptyline > imipramine > citalopram > venlafaxine > reboxetine > olanzapine > mirtazapine > tianeptine > moclobemide, cocaine > lithium, valproate. MAO-B was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > venlafaxine > amitriptyline > olanzapine > citalopram > desipramine > reboxetine > imipramine > tianeptine > mirtazapine, cocaine > moclobemide, lithium, valproate. The mechanism of inhibition of MAOs by several antidepressants was found various. It was concluded that MAO activity is acutely affected by pharmacologically different antidepressants at relatively high drug concentrations; this effect is inhibitory. There are differences both in inhibitory potency and in mechanism of inhibition between both several drugs and the two MAO isoforms. While MAO inhibition is not primary biochemical effect related to their therapeutic action, it can be supposed that decrease of MAO activity may be concerned in some effects of

  10. Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence.

    PubMed

    Bortolato, Marco; Shih, Jean C

    2011-01-01

    Monoamine oxidase (MAO) isoenzymes A and B are mitochondrial-bound proteins, catalyzing the oxidative deamination of monoamine neurotransmitters as well as xenobiotic amines. Although they derive from a common ancestral progenitor gene, are located at X-chromosome and display 70% structural identity, their substrate preference, regional distribution, and physiological role are divergent. In fact, while MAO-A has high affinity for serotonin and norepinephrine, MAO-B primarily serves the catabolism of 2-phenylethylamine (PEA) and contributes to the degradation of other trace amines and dopamine. Convergent lines of preclinical and clinical evidence indicate that variations in MAO enzymatic activity--due to either genetic or environmental factors--can exert a profound influence on behavioral regulation and play a role in the pathophysiology of a large spectrum of mental and neurodegenerative disorders, ranging from antisocial personality disorder to Parkinson's disease. Over the past few years, numerous advances have been made in our understanding of the phenotypical variations associated with genetic polymorphisms and mutations of the genes encoding for both isoenzymes. In particular, novel findings on the phenotypes of MAO-deficient mice are highlighting novel potential implications of both isoenzymes in a broad spectrum of mental disorders, ranging from autism and anxiety to impulse-control disorders and ADHD. These studies will lay the foundation for future research on the neurobiological and neurochemical bases of these pathological conditions, as well as the role of gene × environment interactions in the vulnerability to several mental disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Functional genetic variants in the vesicular monoamine transporter 1 (VMAT1) modulate emotion processing

    PubMed Central

    Lohoff, Falk W.; Hodge, Rachel; Narasimhan, Sneha; Nall, Aleksandra; Ferraro, Thomas N.; Mickey, Brian J.; Heitzeg, Mary M.; Langenecker, Scott A.; Zubieta, Jon-Kar; Bogdan, Ryan; Nikolova, Yuliya S.; Drabant, Emily; Hariri, Ahmad R.; Bevilacqua, Laura; Goldman, David; Doyle, Glenn A.

    2012-01-01

    SUMMARY Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits, and risk for psychopathology. PMID:23337945

  12. Stimulated Emission Depletion Microscopy.

    PubMed

    Blom, Hans; Widengren, Jerker

    2017-06-14

    Despite its short history, diffraction-unlimited fluorescence microscopy techniques have already made a substantial imprint in the biological sciences. In this review, we describe how stimulated emission depletion (STED) imaging originally evolved, how it compares to other optical super-resolution imaging techniques, and what advantages it provides compared to previous golden-standards for biological microscopy, such as diffraction-limited optical microscopy and electron microscopy. We outline the prerequisites for successful STED imaging experiments, emphasizing the equally critical roles of instrumentation, sample preparation, and photophysics, and describe major evolving strategies for how to push the borders of STED imaging even further in life science. Finally, we provide examples of how STED nanoscopy can be applied, within three different fields with particular potential for STED imaging experiments: neuroscience, plasma membrane biophysics, and subcellular clinical diagnostics. In these areas, and in many more, STED imaging can be expected to play an increasingly important role in the future.

  13. Effect of Oral Contraceptives on Depressive Mood Changes and on Endometrial Monoamine Oxidase and Phosphatases

    PubMed Central

    Grant, Ellen C. G.; Pryse-Davies, John

    1968-01-01

    Significant variations in the incidence of depression and loss of libido were found with the various types of oral contraceptives. The highest incidence occurred with strongly progestogenic compounds (especially with those containing a small amount of oestrogen) which have high monoamine oxidase activity for most of the cycle. The lowest incidence was found with the strongly oestrogenic sequential regimens which have weak monoamine oxidase activity for most of the cycle. PMID:5676714

  14. Black bile: are elevated monoamines an etiological factor in some cases of major depression?

    PubMed

    Fitzgerald, Paul J

    2013-06-01

    It was hypothesized decades ago that reduced levels of brain monoamines such as serotonin or norepinephrine form, at least in part, a pathophysiological basis for major depression. Consistent with this hypothesis, a conventional strategy used, with varying success, to treat major depression involves administering antidepressant drugs that are thought to boost the synaptic concentration of serotonin and/or norepinephrine. While the reduced monoamine hypothesis is well known but highly controversial and widely considered to be incomplete or simply incorrect, the possibility that elevated monoamines are an etiological factor in some cases of major depression (rather than or in addition to hypomania or mania) has received little attention at all. This paper puts forth the novel hypothesis elevated brain levels of three monoamines - serotonin, norepinephrine, dopamine - are each etiological factors in some cases of major depression. In support of this hypothesis, the paper very briefly reviews relevant data on each of these neurotransmitter systems, including: transporter knockout mice, human genetic association studies, and pharmaceutical studies that enhance or diminish transmitter signaling in either rodents or humans. While all of the published data do not support the hypothesis, there are studies that do for each of the three transmitter systems. The etiological basis of the putative effect of monoamines on depression may be mediated both through genetics and exposure to psychological stress. If the elevated monoamine hypothesis is correct for some persons, pharmaceutical treatment of depression may be significantly improved if the particular elevated monoamine(s) could be identified and then altered on a personalized basis, or perhaps for different putative subtypes of depression. One possibility is that atypical depression involves elevated noradrenergic signaling.

  15. [Comparative study of bacterial agmatinase inhibition by derivatives of putrescine and aliphatic monoamines].

    PubMed

    Khramov, V A

    1977-03-01

    Aliphatic monoamines and some putrescine derivatives (10(-3) M) are found to inhibit agmatinase from Proteus vulgaris. Constants and the type of inhibition are determined. Investigation of the temperature effect on the inhibition has revealed an exotermic character of this process. Some thermodinamic parameters of agmatinase-anylamine binding reaction are calculated. 1-Guanidobutane is obtained by means of 1-amidobutane guanidilation, and it is found to be more efficient inhibitor than monoamines.

  16. Ozone Depletion by Hydrofluorocarbons

    NASA Astrophysics Data System (ADS)

    Hurwitz, M.; Fleming, E. L.; Newman, P. A.; Li, F.; Mlawer, E. J.; Cady-Pereira, K. E.; Bailey, R.

    2015-12-01

    Hydrofluorocarbons (HFCs) are second-generation replacements for the chlorofluorocarbons (CFCs), halons and other substances that caused the 'ozone hole'. Atmospheric concentrations of HFCs are projected to increase dramatically in the coming decades. Coupled chemistry-climate simulations forced by these projections show that HFCs will impact the global atmosphere in 2050. As strong radiative forcers, HFCs modulate atmospheric temperature, thereby changing ozone-destroying catalytic cycles and enhancing the stratospheric circulation. These changes lead to a weak depletion of stratospheric ozone. Sensitivity simulations with the NASA Goddard Space Flight Center (GSFC) 2D model show that HFC-125 is the most important contributor to atmospheric change in 2050, as compared with HFC-23, HFC-32, HFC-134a and HFC-143a. Incorporating the interactions between chemistry, radiation and dynamics, for a likely 2050 climate, ozone depletion potentials (ODPs) for HFCs range from 4.3x10-4 to 3.5x10-2; previously HFCs were assumed to have negligible ODPs since these species lack chlorine or bromine atoms. The ozone impacts of HFCs are further investigated with the Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM). The GEOSCCM is a three-dimensional, fully coupled ocean-atmosphere model with interactive stratospheric chemistry. Sensitivity simulations in which CO2, CFC-11 and HCFC-22 are enhanced individually are used as proxies for the atmospheric response to the HFC concentrations expected by the mid-21st century. Sensitivity simulations provide quantitative estimates of the impacts of these greenhouse gases on global total ozone, and can be used to assess their effects on the recovery of Antarctic ozone.

  17. Validity of urinary monoamine assay sales under the "spot baseline urinary neurotransmitter testing marketing model".

    PubMed

    Hinz, Marty; Stein, Alvin; Uncini, Thomas

    2011-01-01

    Spot baseline urinary monoamine assays have been used in medicine for over 50 years as a screening test for monoamine-secreting tumors, such as pheochromocytoma and carcinoid syndrome. In these disease states, when the result of a spot baseline monoamine assay is above the specific value set by the laboratory, it is an indication to obtain a 24-hour urine sample to make a definitive diagnosis. There are no defined applications where spot baseline urinary monoamine assays can be used to diagnose disease or other states directly. No peer-reviewed published original research exists which demonstrates that these assays are valid in the treatment of individual patients in the clinical setting. Since 2001, urinary monoamine assay sales have been promoted for numerous applications under the "spot baseline urinary neurotransmitter testing marketing model". There is no published peer-reviewed original research that defines the scientific foundation upon which the claims for these assays are made. On the contrary, several articles have been published that discredit various aspects of the model. To fill the void, this manuscript is a comprehensive review of the scientific foundation and claims put forth by laboratories selling urinary monoamine assays under the spot baseline urinary neurotransmitter testing marketing model.

  18. 12. VIEW OF DEPLETED URANIUM INGOT AND MOLDS. DEPLETED URANIUM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. VIEW OF DEPLETED URANIUM INGOT AND MOLDS. DEPLETED URANIUM CASTING OPERATIONS CEASED IN 1988. (11/14/57) - Rocky Flats Plant, Non-Nuclear Production Facility, South of Cottonwood Avenue, west of Seventh Avenue & east of Building 460, Golden, Jefferson County, CO

  19. Depleted Uranium in Repositories

    SciTech Connect

    Haire, M.J.; Croff, A.G.

    1997-12-31

    For uranium to be useful in most fission nuclear reactors, it must be enriched (i.e. the concentration of the fissile isotope 235U must be increased). Therefore, depleted uranium (DU)-uranium which has less than naturally occurring concentrations of 235U-is a co-product of the enrichment process. Four to six tons of DU exist for every ton of fresh light water reactor fuel. There were 407,006 MgU 407,000 metric tons (t) of DU stored on U.S. Department of Energy (DOE) sites as of July 1993. If this DU were to be declared surplus, converted to a stable oxide form, and emplaced in a near surface disposal facility, the costs are estimated to be several billion dollars. However, the U.S. Nuclear Regulatory Commission has stated that near surface disposal of large quantities of DU tails is not appropriate. Thus, there is the possibility that disposition via disposal will be in a deep geological repository. One alternative that may significantly reduce the cost of DU disposition is to use it beneficially. In fact, DOE has begun the Beneficial Uses of DU Project to identify large scale uses of DU and to encourage its reuse. Several beneficial uses, many of which involve applications in the repository per se or in managing the wastes to go into the repository, are discussed in this report.

  20. The Toxicity of Depleted Uranium

    PubMed Central

    Briner, Wayne

    2010-01-01

    Depleted uranium (DU) is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed. PMID:20195447

  1. Ego depletion impairs implicit learning.

    PubMed

    Thompson, Kelsey R; Sanchez, Daniel J; Wesley, Abigail H; Reber, Paul J

    2014-01-01

    Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent.

  2. Ethanol Dependence Abolishes Monoamine and GIRK (Kir3) Channel Inhibition of Orbitofrontal Cortex Excitability.

    PubMed

    Nimitvilai, Sudarat; Lopez, Marcelo F; Mulholland, Patrick J; Woodward, John J

    2017-03-15

    Alcohol abuse disorders are associated with dysfunction of frontal cortical areas including the orbitofrontal cortex (OFC). The OFC is extensively innervated by monoamines, and drugs that target monoamine receptors have been used to treat a number of neuropsychiatric diseases, including alcoholism. However, little is known regarding how monoamines affect OFC neuron excitability or whether this modulation is altered by chronic exposure to ethanol. In this study, we examined the effect of dopamine, norepinephrine, and serotonin on lateral OFC neuronal excitability in naive mice and in those exposed to chronic intermittent ethanol (CIE) treatment. All three monoamines decreased current-evoked spike firing of lOFC neurons and this action required Giα-coupled D2, α2-adrenergic, and 5HT1A receptors, respectively. Inhibition of firing by dopamine or the D2 agonist quinpirole, but not norepinephrine or serotonin, was prevented by the GABAA receptor antagonist picrotoxin. GABA-mediated tonic current was enhanced by dopamine or the D1 agonist SKF81297 but not quinpirole, whereas the amplitude of spontaneous IPSCs was increased by quinpirole but not dopamine. Spiking was also inhibited by the direct GIRK channel activator ML297, whereas blocking these channels with barium increased firing and eliminated the inhibitory actions of monoamines. In the presence of ML297 or the G-protein blocker GDP-β-S, DA induced a further decrease in spike firing, suggesting the involvement of a non-GIRK channel mechanism. In neurons from CIE-treated mice, spike frequency was nearly doubled and inhibition of firing by monoamines or ML297 was lost. These effects occurred in the absence of significant changes in expression of Gi/o or GIRK channel proteins. Together, these findings show that monoamines are important modulators of lOFC excitability and suggest that disruption of this process could contribute to various deficits associated with alcohol dependence.Neuropsychopharmacology advance

  3. 3-Coumaranone derivatives as inhibitors of monoamine oxidase

    PubMed Central

    Van Dyk, Adriaan S; Petzer, Jacobus P; Petzer, Anél; Legoabe, Lesetja J

    2015-01-01

    The present study examines the monoamine oxidase (MAO) inhibitory properties of a series of 20 3-coumaranone [benzofuran-3(2H)-one] derivatives. The 3-coumaranone derivatives are structurally related to series of α-tetralone and 1-indanone derivatives, which have recently been shown to potently inhibit MAO, with selectivity for MAO-B (in preference to the MAO-A isoform). 3-Coumaranones are similarly found to selectively inhibit human MAO-B with half-maximal inhibitory concentration (IC50) values of 0.004–1.05 µM. Nine compounds exhibited IC50<0.05 µM for the inhibition of MAO-B. For the inhibition of human MAO-A, IC50 values ranged from 0.586 to >100 µM, with only one compound possessing an IC50<1 µM. For selected 3-coumaranone derivatives, it is established that MAO-A and MAO-B inhibition are reversible since dialysis of enzyme–inhibitor mixtures almost completely restores enzyme activity. On the basis of the selectivity profiles and potent action, it may be concluded that the 3-coumaranone derivatives are suitable leads for the development of selective MAO-B inhibitors as potential treatment for disorders such as Parkinson’s disease and Alzheimer’s disease. PMID:26491258

  4. Alcohol and violence: neuropeptidergic modulation of monoamine systems.

    PubMed

    Miczek, Klaus A; DeBold, Joseph F; Hwa, Lara S; Newman, Emily L; de Almeida, Rosa M M

    2015-09-01

    Neurobiological processes underlying the epidemiologically established link between alcohol and several types of social, aggressive, and violent behavior remain poorly understood. Acute low doses of alcohol, as well as withdrawal from long-term alcohol use, may lead to escalated aggressive behavior in a subset of individuals. An urgent task will be to disentangle the host of interacting genetic and environmental risk factors in individuals who are predisposed to engage in escalated aggressive behavior. The modulation of 5-hydroxytryptamine impulse flow by gamma-aminobutyric acid (GABA) and glutamate, acting via distinct ionotropic and metabotropic receptor subtypes in the dorsal raphe nucleus during alcohol consumption, is of critical significance in the suppression and escalation of aggressive behavior. In anticipation and reaction to aggressive behavior, neuropeptides such as corticotropin-releasing factor, neuropeptide Y, opioid peptides, and vasopressin interact with monoamines, GABA, and glutamate to attenuate and amplify aggressive behavior in alcohol-consuming individuals. These neuromodulators represent novel molecular targets for intervention that await clinical validation. Intermittent episodes of brief social defeat during aggressive confrontations are sufficient to cause long-lasting neuroadaptations that can lead to the escalation of alcohol consumption.

  5. A rational approach to elucidate human monoamine oxidase molecular selectivity.

    PubMed

    Mangiatordi, Giuseppe Felice; Alberga, Domenico; Pisani, Leonardo; Gadaleta, Domenico; Trisciuzzi, Daniela; Farina, Roberta; Carotti, Andrea; Lattanzi, Gianluca; Catto, Marco; Nicolotti, Orazio

    2017-04-01

    Designing highly selective human monoamine oxidase (hMAO) inhibitors is a challenging goal on the road to a more effective treatment of depression and anxiety (inhibition of hMAO-A isoform) as well as neurodegenerative diseases (inhibition of hMAO-B isoform). To uncover the molecular rationale of hMAOs selectivity, two recently prepared 2H-chromene-2-ones, namely compounds 1 and 2, were herein chosen as molecular probes being highly selective toward hMAO-A and hMAO-B, respectively. We performed molecular dynamics (MD) studies on four different complexes, cross-simulating one at a time the two hMAO-isoforms (dimer embedded in a lipid bilayer) with the two considered probes. Our comparative analysis on the obtained 100ns trajectories discloses a stable H-bond interaction between 1 and Gln215 as crucial for ligand selectivity toward hMAO-A whereas a water-mediated interaction might explain the observed hMAO-B selectivity of compound 2. Such hypotheses are further supported by binding free energy calculations carried out applying the molecular mechanics generalized Born surface area (MM-GBSA) method and allowing us to evaluate the contribution of each residue to the observed isoform selectivity. Taken as whole, this study represents the first attempt to explain at molecular level hMAO isoform selectivity and a valuable yardstick for better addressing the design of new and highly selective MAO inhibitors.

  6. Reye's syndrome: salicylate and mitochondrial monoamine oxidase function

    SciTech Connect

    Faraj, B.A.; Caplan, D.; Lolies, P.

    1986-03-01

    It has been suggested that aspirin is somehow linked with the onset of Reye's syndrome (RS). A general feature of Reye's syndrome is severe impairment of mitochondrial monoamine oxidase (MAO) function. The main objective of this investigation was to study the effect of salicylate on platelet mitochondrial MAO activity in three groups: group A (healthy children, n = 21) and group C (healthy adults, n = 10). Platelet MAO was measured by radio-enzymatic technique with /sup 14/C-tyramine as a substrate. The results showed that salicyclate (10 mM) had a 20 to 60 percent inhibitory effect on platelet MAO function in only 1, 3 and 2 of the subjects in group A, B and C. Furthermore, there was an association between low enzyme activity and salicylate MAO inhibitory effect in these subjects. These preliminary findings suggest that salicylate may induce deterioration in mitochondrial function in susceptible individuals and that the assessment of salicylate MAO inhibitory effect may identify those who may be at risk to develop aspirin poisoning and Reye's syndrome.

  7. Human monoamine oxidase A gene determines levels of enzyme activity.

    PubMed Central

    Hotamisligil, G S; Breakefield, X O

    1991-01-01

    Monoamine oxidase (MAO) is a critical enzyme in the degradative deamination of biogenic amines throughout the body. Two biochemically distinct forms of the enzyme, A and B, are encoded in separate genes on the human X chromosome. In these studies we investigated the role of the structural gene for MAO-A in determining levels of activity in humans, as measured in cultured skin fibroblasts. The coding sequence of the mRNA for MAO-A was determined by first-strand cDNA synthesis, PCR amplification, and direct dideoxy sequencing. Two single-basepair substitutions were observed in cDNAs from cells with a 30-fold difference in activity levels. These two substitutions were in the third base of a triplet codon and hence did not affect the deduced amino acid sequence but did affect the presence or absence of restriction-enzyme sites for EcoRV and Fnu4HI, which could be elucidated on PCR fragments derived from genomic DNA or cDNAs. A third polymorphism for MspI in the noncoding region of the MAOA gene was also evaluated by Southern blot analysis using genomic DNA. Statistically significant associations were observed between the alleles for MAOA and levels of MAO activity in human male fibroblast lines. This association indicates that the MAOA gene itself is a major determinant of activity levels, apparently, in part, through noncoding, regulatory elements. Images Figure 3 Figure 4 Figure 5 PMID:1678250

  8. 2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors

    PubMed Central

    Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2015-01-01

    Based on a previous report that substituted 2-acetylphenols may be promising leads for the design of novel monoamine oxidase (MAO) inhibitors, a series of C5-substituted 2-acetylphenol analogs (15) and related compounds (two) were synthesized and evaluated as inhibitors of human MAO-A and MAO-B. Generally, the study compounds exhibited inhibitory activities against both MAO-A and MAO-B, with selectivity for the B isoform. Among the compounds evaluated, seven compounds exhibited IC50 values <0.01 µM for MAO-B inhibition, with the most selective compound being 17,000-fold selective for MAO-B over the MAO-A isoform. Analyses of the structure–activity relationships for MAO inhibition show that substitution on the C5 position of the 2-acetylphenol moiety is a requirement for MAO-B inhibition, and the benzyloxy substituent is particularly favorable in this regard. This study concludes that C5-substituted 2-acetylphenol analogs are potent and selective MAO-B inhibitors, appropriate for the design of therapies for neurodegenerative disorders such as Parkinson’s disease. PMID:26203229

  9. Monoamine oxidases as sources of oxidants in the heart

    PubMed Central

    Kaludercic, Nina; Mialet-Perez, Jeanne; Paolocci, Nazareno; Parini, Angelo; Di Lisa, Fabio

    2014-01-01

    Oxidative stress can be generated at several sites within the mitochondria. Among these, monoamine oxidases (MAO) have been described as a prominent source. MAO are mitochondrial flavoenzymes responsible for the oxidative deamination of catecholamines, serotonin and biogenic amines, and during this process they generate H2O2 and aldehyde intermediates. The role of MAO in cardiovascular pathophysiology has only recently gathered some attention since it has been demonstrated that both H2O2 and aldehydes may target mitochondrial function and consequently affect function and viability of the myocardium. In the present review, we will discuss the role of MAO in catecholamine and serotonin clearance and cycling in relation to cardiac structure and function. The relevant contribution of each MAO isoform (MAO-A or -B) will be discussed in relation to mitochondrial dysfunction and myocardial injury. Finally, we will examine both beneficial effects of their pharmacological or genetic inhibition along with potential adverse effects observed at baseline in MAO knockout mice, as well as the deleterious effects following their over-expression specifically at cardiomyocyte level. PMID:24412580

  10. Alcohol and violence: neuropeptidergic modulation of monoamine systems

    PubMed Central

    Miczek, Klaus A.; DeBold, Joseph F.; Hwa, Lara S.; Newman, Emily L.; de Almeida, Rosa M. M.

    2015-01-01

    Neurobiological processes underlying the epidemiologically-established link between alcohol and several types of social, aggressive, and violent behavior remain poorly understood. Acute low doses of alcohol, as well as withdrawal from long-term alcohol use, may lead to escalated aggressive behavior in a subset of individuals. An urgent task will be to disentangle the host of interacting genetic and environmental risk factors in individuals that are predisposed to engage in escalated aggressive behavior. The modulation of 5-hydroxytryptamine impulse flow by gamma-aminobutyric acid (GABA) and glutamate, acting via distinct ionotropic and metabotropic receptor subtypes in the dorsal raphe nucleus during alcohol consumption, is of critical significance in the suppression and escalation of aggressive behavior. In anticipation and reaction to aggressive behavior, neuropeptides such as corticotropin-releasing factor, neuropeptide Y, opioid peptides, and vasopressin interact with monoamines, GABA, and glutamate to attenuate and amplify aggressive behavior in alcohol-consuming individuals. These neuromodulators represent novel molecular targets for intervention that await clinical validation. Intermittent episodes of brief social defeat during aggressive confrontations are sufficient to cause long-lasting neuroadaptations that can lead to the escalation of alcohol consumption. PMID:26285061

  11. Inhibition of Monoamine Oxidase by Stilbenes from Rheum palmatum

    PubMed Central

    Wei, Bo; Yang, Zhong-Duo; Shi, Dan-Feng; Yao, Xiao-Jun; Wang, Ming-Gang

    2016-01-01

    Seven stilbenes and one catechin were bioactivity-guidedly isolated from the rhizomes of Rheum palmatem. Their structures were identified as piceatannol (1), resveratrol (2), piceid (3), rhapontigenin (4), piceatannol-3´-O-β-D-glucopyranoside (5), rhaponticin (6), catechin (7) and desoxyrhapontigenin (8). Anti-monoamine oxidase (MAO) activities of compounds 1–8 were tested. Compounds 1 and 8 showed significant MAO inhibitory activities with IC50 values 16.4 ± 1.5 μM and 11.5 ± 1.1, respectively, when the IC50 value of iproniazid as a standard was 6.5 ± 0.5 μM. The selectivity of compounds 1-8 against MAO-A and MAO-B were also evaluated. The results showed that compounds 4˴6˴8 preferred to inhibit MAO-A rather than MAO-B with selectivity values ([IC50 of MAO-B]/ [IC50 of MAO-A]) of 4.74, 10.01 and 9.42, respectively. The preliminary structure–activity relationships (SARs) of these compounds were discussed and the molecular modeling was also performed to explore the binding mode of inhibitors at the active site of MAO-A and MAO-B. PMID:28243286

  12. Selected C7-substituted chromone derivatives as monoamine oxidase inhibitors.

    PubMed

    Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2012-12-01

    A series of C7-substituted chromone (1-benzopyran-4-one) derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The chromones are structurally related to a series of C7-functionalized coumarin (1-benzopyran-2-one) derivatives which has been reported to act as potent MAO inhibitors. The results of the current study document that the chromones are highly potent reversible inhibitors of MAO-B with IC(50) values ranging from 0.008 to 0.370 μM. While the chromone derivatives also exhibit affinities for MAO-A, with IC(50) values ranging from 0.495 to 8.03 μM, they are selective for the MAO-B isoform. Structure-activity relationships (SAR) show that 7-benzyloxy substitution of chromone is suitable for MAO-B inhibition with tolerance for a variety of substituents and substitution patterns on the benzyloxy ring. It may be concluded that 7-benzyloxychromones are appropriate lead compounds for the design of reversible and selective MAO-B inhibitors. With the aid of modeling studies, potential binding orientations and interactions of selected chromone derivatives in the MAO-A and -B active sites are examined. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Selected chromone derivatives as inhibitors of monoamine oxidase.

    PubMed

    Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2012-09-01

    A previous study has shown that a series of C6-benzyloxy substituted chromones exhibit high binding affinities for human monoamine oxidase (MAO) B. In an attempt to discover additional chromones with potent and selective MAO-B inhibitory potencies and to further examine the structure-activity relationships of MAO-B inhibition by chromones, the series was expanded with homologues containing polar functional groups on C3 of the chromone ring. The results demonstrate that 6-[(3-bromobenzyl)oxy]chromones containing acidic and aldehydic functional groups on C3 act as potent reversible MAO-B inhibitors with IC(50) values of 2.8 and 3.7 nM, respectively. Interestingly, a 2-hydroxy-2,3-dihydro-1-benzopyran-4-one derivative as well as open-ring 2-acetylphenol analogues of the chromones also were potent MAO-B inhibitors with IC(50) values ranging from 4 to 11 nM. Chromone derivatives containing the benzyloxy substituent on C5 of the chromone ring, however, exhibit MAO-B inhibition potencies that are several orders of magnitude weaker. High potency inhibitors of MAO-B may find application in the therapy of neurodegenerative disorders such as Parkinson's disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Monoamine oxidases as sources of oxidants in the heart.

    PubMed

    Kaludercic, Nina; Mialet-Perez, Jeanne; Paolocci, Nazareno; Parini, Angelo; Di Lisa, Fabio

    2014-08-01

    Oxidative stress can be generated at several sites within the mitochondria. Among these, monoamine oxidase (MAO) has been described as a prominent source. MAOs are mitochondrial flavoenzymes responsible for the oxidative deamination of catecholamines, serotonin and biogenic amines, and during this process they generate H2O2 and aldehyde intermediates. The role of MAO in cardiovascular pathophysiology has only recently gathered some attention since it has been demonstrated that both H2O2 and aldehydes may target mitochondrial function and consequently affect function and viability of the myocardium. In the present review, we will discuss the role of MAO in catecholamine and serotonin clearance and cycling in relation to cardiac structure and function. The relevant contribution of each MAO isoform (MAO-A or -B) will be discussed in relation to mitochondrial dysfunction and myocardial injury. Finally, we will examine both beneficial effects of their pharmacological or genetic inhibition along with potential adverse effects observed at baseline in MAO knockout mice, as well as the deleterious effects following their over-expression specifically at cardiomyocyte level. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System".

  15. Monoamine oxidases and alcoholism. II. Studies in alcoholic families

    SciTech Connect

    Suarez, B.K.; Hampe, C.L.; Parsian, A.; Cloninger, C.R.

    1995-10-09

    Thirty-five alcoholic families have been studied to investigate the relationship between DNA markers at the monoamine oxidase (MAO) loci and (1) platelet activity levels and (2) alcoholism. A quantitative linkage analysis failed to reveal any evidence that the variation in activity levels cosegregates with the DNA markers. A sib-pair analysis did not reveal a significant excess of MAO haplotype sharing among alcoholic sibs, although the deviation from random sharing was in the direction consistent with an X-linked component. A reanalysis of platelet MAO activity levels in a subset of these families revealed that the lower levels previously found in alcoholics is more likely due to the differences between males and females. Only among males and only when a {open_quotes}broad{close_quotes} definition of alcoholism is used (and MAO activity levels are transformed to normality) does it appear that alcoholics have depressed activities compared to nonalcoholics. Finally, when the confounding due to gender difference is removed, no differences between type I and type II alcoholics are found in these families. 63 refs., 6 tabs.

  16. The effects of two chronic intermittent stressors on brain monoamines.

    PubMed

    Campmany, L; Pol, O; Armario, A

    1996-03-01

    The effects of chronic exposure (27 days) to two different stressors on brain monoaminergic activity was studied in adult male rats. The stressors used were restraint in tubes (RES) and immobilization in wooden boards (IMO). Both chronically stressed and stress naive (control) rats were subjected to 0, 15, and 60 min of the same stressor to which they were chronically exposed. Previous chronic exposure to either RES or IMO significantly reduced ACTH response to the same stressor. Monoaminergic response to these stressors was studied by measuring the levels of noradrenaline (NA), serotonin (5-HT) and their metabolites: 3-methoxy,4-hydroxyphenyletileneglycol sulfate (MHPG-SO4) and 5-hydroxyindoleacetic acid (5-HIAA), respectively. The regions studied were: pons plus medulla, midbrain, hypothalamus, hippocampus, and frontal cortex. Previous chronic exposure to the stressors induced only few changes in the resting levels of the monoamines and their metabolites. In addition, monoaminergic response to the same stressor to which they were chronically exposed was always similar in control and chronically stressed rats. These data indicate that brain NA and 5-HT metabolism is less sensitive than ACTH to the process of habituation to a repeated stressor, at least in the gross areas of the brain analyzed in the present study.

  17. Monoamine Oxidase-A Occupancy by Moclobemide and Phenelzine: Implications for the Development of Monoamine Oxidase Inhibitors

    PubMed Central

    Chiuccariello, Lina; Cooke, Robert G; Miler, Laura; Levitan, Robert D; Baker, Glen B; Kish, Stephen J; Kolla, Nathan J; Rusjan, Pablo M; Houle, Sylvain; Wilson, Alan A

    2016-01-01

    Background: Monoamine oxidase inhibitors (MAOIs) are being developed for major depressive disorder, Alzheimer’s, and Parkinson’s Disease. Newer MAOIs have minimal sensitivity to tyramine, but a key limitation for optimizing their development is that standards for in vivo monoamine oxidase-A (MAO-A) occupancy in humans are not well established. The objectives were to determine the dose-occupancy relationship of moclobemide and the occupancy of phenelzine at typical clinical dosing. Methods: Major depressive episode (MDE) subjects underwent [11C]harmine positron emission tomography scanning prior to and following 6 weeks of treatment with moclobemide or phenelzine. Results: Mean brain MAO-A occupancies were 74.23±8.32% for moclobemide at 300–600mg daily (n = 11), 83.75±5.52% for moclobemide at 900–1200mg daily (n = 9), and 86.82±6.89% for phenelzine at 45–60mg daily (n = 4). The regional dose-occupancy relationship of moclobemide fit a hyperbolic function [F(x) = a(x/[b + x]); F(1,18) = 5.57 to 13.32, p = 0.002 to 0.03, mean ‘a’: 88.62±2.38%, mean ‘b’: 69.88±4.36 mg]. Multivariate analyses of variance showed significantly greater occupancy of phenelzine (45–60mg) and higher-dose moclobemide (900–1200mg) compared to lower-dose moclobemide [300–600mg; F(7,16) = 3.94, p = 0.01]. Conclusions: These findings suggest that for first-line MDE treatment, daily moclobemide doses of 300–600mg correspond to a MAO-A occupancy of 74%, whereas for treatment-resistant MDE, either phenelzine or higher doses of moclobemide correspond to a MAO-A occupancy of at least 84%. Therefore, novel MAO inhibitor development should aim for similar thresholds. The findings provide a rationale in treatment algorithm design to raise moclobemide doses to inhibit more MAO-A sites, but suggest switching from high-dose moclobemide to phenelzine is best justified by binding to additional targets. PMID:26316187

  18. Stratospheric ozone depletion.

    PubMed

    Rowland, F Sherwood

    2006-05-29

    Solar ultraviolet radiation creates an ozone layer in the atmosphere which in turn completely absorbs the most energetic fraction of this radiation. This process both warms the air, creating the stratosphere between 15 and 50 km altitude, and protects the biological activities at the Earth's surface from this damaging radiation. In the last half-century, the chemical mechanisms operating within the ozone layer have been shown to include very efficient catalytic chain reactions involving the chemical species HO, HO2, NO, NO2, Cl and ClO. The NOX and ClOX chains involve the emission at Earth's surface of stable molecules in very low concentration (N2O, CCl2F2, CCl3F, etc.) which wander in the atmosphere for as long as a century before absorbing ultraviolet radiation and decomposing to create NO and Cl in the middle of the stratospheric ozone layer. The growing emissions of synthetic chlorofluorocarbon molecules cause a significant diminution in the ozone content of the stratosphere, with the result that more solar ultraviolet-B radiation (290-320 nm wavelength) reaches the surface. This ozone loss occurs in the temperate zone latitudes in all seasons, and especially drastically since the early 1980s in the south polar springtime-the 'Antarctic ozone hole'. The chemical reactions causing this ozone depletion are primarily based on atomic Cl and ClO, the product of its reaction with ozone. The further manufacture of chlorofluorocarbons has been banned by the 1992 revisions of the 1987 Montreal Protocol of the United Nations. Atmospheric measurements have confirmed that the Protocol has been very successful in reducing further emissions of these molecules. Recovery of the stratosphere to the ozone conditions of the 1950s will occur slowly over the rest of the twenty-first century because of the long lifetime of the precursor molecules.

  19. Stratospheric ozone depletion

    PubMed Central

    Rowland, F. Sherwood

    2006-01-01

    Solar ultraviolet radiation creates an ozone layer in the atmosphere which in turn completely absorbs the most energetic fraction of this radiation. This process both warms the air, creating the stratosphere between 15 and 50 km altitude, and protects the biological activities at the Earth's surface from this damaging radiation. In the last half-century, the chemical mechanisms operating within the ozone layer have been shown to include very efficient catalytic chain reactions involving the chemical species HO, HO2, NO, NO2, Cl and ClO. The NOX and ClOX chains involve the emission at Earth's surface of stable molecules in very low concentration (N2O, CCl2F2, CCl3F, etc.) which wander in the atmosphere for as long as a century before absorbing ultraviolet radiation and decomposing to create NO and Cl in the middle of the stratospheric ozone layer. The growing emissions of synthetic chlorofluorocarbon molecules cause a significant diminution in the ozone content of the stratosphere, with the result that more solar ultraviolet-B radiation (290–320 nm wavelength) reaches the surface. This ozone loss occurs in the temperate zone latitudes in all seasons, and especially drastically since the early 1980s in the south polar springtime—the ‘Antarctic ozone hole’. The chemical reactions causing this ozone depletion are primarily based on atomic Cl and ClO, the product of its reaction with ozone. The further manufacture of chlorofluorocarbons has been banned by the 1992 revisions of the 1987 Montreal Protocol of the United Nations. Atmospheric measurements have confirmed that the Protocol has been very successful in reducing further emissions of these molecules. Recovery of the stratosphere to the ozone conditions of the 1950s will occur slowly over the rest of the twenty-first century because of the long lifetime of the precursor molecules. PMID:16627294

  20. Monoamines and ovarian hormone-linked sexual and emotional changes: A review.

    PubMed

    Janowsky, D S; Fann, W E; Davis, J M

    1971-09-01

    Emotional upsets related to changes in ovarian hormones are highly prevalent and are responsible for psychiatric morbidity and mortality. Significant increases in acute psychiatric hospitalizations, suicidal activity, and other psychopathology occur during the premenstruum and during menstruation. This paper reviews evidence indicating that menstrual cycle psychopathology may be mediated by the effects of estrogen, progesterone, and possibly the renin-angiotensin-aldosterone system on the brain monoamines, norepinephrine, dopamine, and serotonin. During the menstrual cycle, psychopathology often begins with the onset of luteal estrogen-progesterone-angiotensin-aldosterone secretion and intensifies as these hormone levels later fall, prior to and during menstruation. Aldosterone is reported elevated in cases of premenstrual tension syndrome. There are numerous reports of affective upsets occurring with the use of estrogen-progestin oral contraceptives and following their withdrawal. Contraceptives stimulate the renin-angiotensin-aldosterone system and are reported useful in alleviating premenstrual-menstrual emotional upsets and postpartum depressive episodes. Affective lability, prevalent at parturition, occurs when estrogen, progesterone, and aldosterone levels are first high and later falling. Exogenous estrogen and progesterone profoundly affect mating activity in castrated rhesus monkeys, and cyclic fluctuations in sexual activity in humans may occur during the menstrual cycle. Much information links manic and depressive reactions with alterations in brain monoamines. Lithium, monoamine oxidase inhibitors, and tricylic antidepressants, specifically used to treat affective disorders, are reported useful in treating ovarian hormone-linked upsets. Similarities exist between changes in animal behavior caused by drugs altering affective states and the effects of ovarian hormones. Like certain antidepressants, estrogen induces hyperactivity in rats. Like reserpine

  1. The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain.

    PubMed

    Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako

    2007-03-22

    We developed a reproducible, simple, and small-scale method for determining the re-uptake and release of monoamines (dopamine, serotonin (5-HT) and norepinephrine) using rat brain synaptosomes. These assays were then applied to study the effects of different kinds of non-medically used psychoactive drugs on monoamine re-uptake and release. The phenethylamine derivatives, 4-fluoroamphetamine, 2-methylamino-3,4-methylene-dioxy-propiophenone (methylone), 1-(1,3-benzodioxol-5-yl)-2-butanamine (BDB), and N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), had strong inhibitory effects on the re-uptake of dopamine, 5-HT and norepinephrine. 4-Fluoroamphetamine, methylone and BDB also strongly increased the release of the three monoamines, but MBDB increased 5-HT and norepinephrine release, but had little effect on dopamine release. However, 2,5-dimethoxy-4-iodophenethylamine (2C-I), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,4,5-trimethoxyamphetamine (TMA-2) and 2,4,6-trimethoxyamphetamine (TMA-6), which are methoxylated phenethylamine derivatives, slightly influenced the re-uptake and release of monoamines. Alpha-metyltryptamine (AMT), a tryptamine derivative, was one of the strongest re-uptake inhibitors and releasers of the three monoamines. The tryptamine derivative, 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), also strongly inhibited re-uptake and increased the release of the three monoamines. N,N-dipropyltryptamine (DPT), 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), 5-methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) inhibited monoamine re-uptake, but had a few effects on monoamine release. 1-(3-Chlorophenyl)piperazine (3CPP) and 1-(methoxyphenyl)piperazine (4MPP), which are piperazine derivatives, inhibited monoamine re-uptake and accelerated their release. The results suggest that some designer drugs strongly act on the central nerve system to the same

  2. Testing fully depleted CCD

    NASA Astrophysics Data System (ADS)

    Casas, Ricard; Cardiel-Sas, Laia; Castander, Francisco J.; Jiménez, Jorge; de Vicente, Juan

    2014-08-01

    The focal plane of the PAU camera is composed of eighteen 2K x 4K CCDs. These devices, plus four spares, were provided by the Japanese company Hamamatsu Photonics K.K. with type no. S10892-04(X). These detectors are 200 μm thick fully depleted and back illuminated with an n-type silicon base. They have been built with a specific coating to be sensitive in the range from 300 to 1,100 nm. Their square pixel size is 15 μm. The read-out system consists of a Monsoon controller (NOAO) and the panVIEW software package. The deafualt CCD read-out speed is 133 kpixel/s. This is the value used in the calibration process. Before installing these devices in the camera focal plane, they were characterized using the facilities of the ICE (CSIC- IEEC) and IFAE in the UAB Campus in Bellaterra (Barcelona, Catalonia, Spain). The basic tests performed for all CCDs were to obtain the photon transfer curve (PTC), the charge transfer efficiency (CTE) using X-rays and the EPER method, linearity, read-out noise, dark current, persistence, cosmetics and quantum efficiency. The X-rays images were also used for the analysis of the charge diffusion for different substrate voltages (VSUB). Regarding the cosmetics, and in addition to white and dark pixels, some patterns were also found. The first one, which appears in all devices, is the presence of half circles in the external edges. The origin of this pattern can be related to the assembly process. A second one appears in the dark images, and shows bright arcs connecting corners along the vertical axis of the CCD. This feature appears in all CCDs exactly in the same position so our guess is that the pattern is due to electrical fields. Finally, and just in two devices, there is a spot with wavelength dependence whose origin could be the result of a defectous coating process.

  3. Chronic scream sound exposure alters memory and monoamine levels in female rat brain.

    PubMed

    Hu, Lili; Zhao, Xiaoge; Yang, Juan; Wang, Lumin; Yang, Yang; Song, Tusheng; Huang, Chen

    2014-10-01

    Chronic scream sound alters the cognitive performance of male rats and their brain monoamine levels, these stress-induced alterations are sexually dimorphic. To determine the effects of sound stress on female rats, we examined their serum corticosterone levels and their adrenal, splenic, and thymic weights, their cognitive performance and the levels of monoamine neurotransmitters and their metabolites in the brain. Adult female Sprague-Dawley rats, with and without exposure to scream sound (4h/day for 21 day) were tested for spatial learning and memory using a Morris water maze. Stress decreased serum corticosterone levels, as well as splenic and adrenal weight. It also impaired spatial memory but did not affect the learning ability. Monoamines and metabolites were measured in the prefrontal cortex (PFC), striatum, hypothalamus, and hippocampus. The dopamine (DA) levels in the PFC decreased but the homovanillic acid/DA ratio increased. The decreased DA and the increased 5-hydroxyindoleacetic acid (5-HIAA) levels were observed in the striatum. Only the 5-HIAA level increased in the hypothalamus. In the hippocampus, stress did not affect the levels of monoamines and metabolites. The results suggest that scream sound stress influences most physiologic parameters, memory, and the levels of monoamine neurotransmitter and their metabolites in female rats. Copyright © 2014. Published by Elsevier Inc.

  4. Transequatorial Propagation and Depletion Precursors

    NASA Astrophysics Data System (ADS)

    Miller, E. S.; Bust, G. S.; Kaeppler, S. R.; Frissell, N. A.; Paxton, L. J.

    2014-12-01

    The bottomside equatorial ionosphere in the afternoon and evening sector frequently evolves rapidly from smoothly stratified to violently unstable with large wedges of depleted plasma growing through to the topside on timescales of a few tens of minutes. These depletions have numerous practical impacts on radio propagation, including amplitude scintillation, field-aligned irregularity scatter, HF blackouts, and long-distance transequatorial propagation at frequencies above the MUF. Practical impacts notwithstanding, the pathways and conditions under which depletions form remain a topic of vigorous inquiry some 80 years after their first report. Structuring of the pre-sunset ionosphere---morphology of the equatorial anomalies and long-wavelength undulations of the isodensity contours on the bottomside---are likely to hold some clues to conditions that are conducive to depletion formation. The Conjugate Depletion Experiment is an upcoming transequatorial forward-scatter HF/VHF experiment to investigate pre-sunset undulations and their connection with depletion formation. We will present initial results from the Conjugate Depletion Experiment, as well as a companion analysis of a massive HF propagation data set.

  5. Monoamines and their metabolites in the avian brain

    PubMed Central

    Juorio, A. V.; Vogt, Marthe

    1967-01-01

    1. In the avian brain, a high concentration of dopamine was found in a sharply contoured region of the nucleus basalis which may or may not have included the nucleus entopeduncularis, and therefore lay within the palaeostriatum of the nomenclature of Crosby and Huber. This was thus the only region which may be considered biochemically homologous to the mammalian corpus striatum. For purposes of macroscopic identification only, the region is described here as the `anterior part of the nucleus basalis'. The concentration of dopamine was 3 μg/g in the pigeon, about the same in the duck and chicken, and 7·5 μg/g in the finch. In the pigeon this region also contained some noradrenaline; the quantity of 5-hydroxytryptamine (1·4 μg/g) and 5-hydroxyindolylacetic acid (0·6 μg/g) was larger than in any other part of the brain. 2. In the brain of the pigeon and the chicken, the highest concentrations of noradrenaline (1·5 and 1·4 μg/g) were found in the hypothalamus. 3. The concentration of adrenaline was higher in the avian than in the mammalian brain. In the hypothalamus, it ranged from 0·4 μg/g in the pigeon to 1 μg/g in the chicken. 4. Fluorescence microscopy, using the formaldehyde condensation method, showed, in the anterior part of the nucleus basalis, a large area of diffuse green-yellow fluorescence, similar in appearance to the fluorescence of the striatum of the rat. In addition this part of the brain contained a small region of fluorescent fibres and varicosities. It is suggested that the diffuse fluorescence was produced by dopamine. It was absent from brains of reserpine-treated pigeons. 5. In the pigeon, reserpine, tetrabenazine and prenylamine produced a decrease in the concentration of brain monoamines, an effect which was comparable to that seen in mammals. Yet, none of these drugs raised the concentration of homovanillic acid, but they increased that of 5-hydroxyindolylacetic acid; these drugs raise the concentration of both acids in mammalian

  6. Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation

    PubMed Central

    Lominac, Kevin D.; McKenna, Courtney L.; Schwartz, Lisa M.; Ruiz, Paige N.; Wroten, Melissa G.; Miller, Bailey W.; Holloway, John J.; Travis, Katherine O.; Rajasekar, Ganesh; Maliniak, Dan; Thompson, Andrew B.; Urman, Lawrence E.; Phillips, Tamara J.; Szumlinski, Karen K.

    2014-01-01

    Methamphetamine (MA) is a highly addictive psychomotor stimulant, with life-time prevalence rates of abuse ranging from 5–10% world-wide. Yet, a paucity of research exists regarding MA addiction vulnerability/resiliency and neurobiological mediators of the transition to addiction that might occur upon repeated low-dose MA exposure, more characteristic of early drug use. As stimulant-elicited neuroplasticity within dopamine neurons innervating the nucleus accumbens (NAC) and prefrontal cortex (PFC) is theorized as central for addiction-related behavioral anomalies, we used a multi-disciplinary research approach in mice to examine the interactions between sub-toxic MA dosing, motivation for MA and mesocorticolimbic monoamines. Biochemical studies of C57BL/6J (B6) mice revealed short- (1 day), as well as longer-term (21 days), changes in extracellular dopamine, DAT and/or D2 receptors during withdrawal from 10, once daily, 2 mg/kg MA injections. Follow-up biochemical studies conducted in mice selectively bred for high vs. low MA drinking (respectively, MAHDR vs. MALDR mice), provided novel support for anomalies in mesocorticolimbic dopamine as a correlate of genetic vulnerability to high MA intake. Finally, neuropharmacological targeting of NAC dopamine in MA-treated B6 mice demonstrated a bi-directional regulation of MA-induced place-conditioning. These results extend extant literature for MA neurotoxicity by demonstrating that even subchronic exposure to relatively low MA doses are sufficient to elicit relatively long-lasting changes in mesocorticolimbic dopamine and that drug-induced or idiopathic anomalies in mesocorticolimbic dopamine may underpin vulnerability/resiliency to MA addiction. PMID:24847220

  7. Targeting monoamine oxidase A in advanced prostate cancer

    PubMed Central

    Flamand, Vincent; Zhao, Hongjuan

    2010-01-01

    Purpose Inhibitors of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine, are commonly used to treat neurological conditions including depression. Recently, we and others identified high expression of MAOA in normal basal prostatic epithelium and high-grade primary prostate cancer (PCa). In contrast, MAOA is low in normal secretory prostatic epithelium and low-grade PCa. An irreversible inhibitor of MAOA, clorgyline, induced secretory differentiation in primary cultures of normal basal epithelial cells and high-grade PCa. Furthermore, clorgyline inhibited several oncogenic pathways in PCa cells, suggesting clinical value of MAOA inhibitors as a pro-differentiation and anti-oncogenic therapy for high-risk PCa. Here, we extended our studies to a model of advanced PCa, VCaP cells, which were derived from castration-resistant metastatic PCa and express a high level of MAOA. Methods Growth of VCaP cells in the presence or absence of clorgyline was evaluated in vitro and in vivo. Gene expression changes in response to clorgyline were determined by microarray and validated by quantitative real-time polymerase chain reaction. Results Treatment with clorgyline in vitro inhibited growth and altered the transcriptional pattern of VCaP cells in a manner consistent with the pro-differentiation and anti-oncogenic effects seen in treated primary PCa cells. Src, beta-catenin, and MAPK oncogenic pathways, implicated in androgen-independent growth and metastasis, were significantly downregulated. Clorgyline treatment of mice bearing VCaP xenografts slowed tumor growth and induced transcriptome changes similar to those noted in vitro. Conclusion Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa. PMID:20204405

  8. Predicting Monoamine Oxidase Inhibitory Activity through Ligand-Based Models

    PubMed Central

    Vilar, Santiago; Ferino, Giulio; Quezada, Elias; Santana, Lourdes; Friedman, Carol

    2013-01-01

    The evolution of bio- and cheminformatics associated with the development of specialized software and increasing computer power has produced a great interest in theoretical in silico methods applied in drug rational design. These techniques apply the concept that “similar molecules have similar biological properties” that has been exploited in Medicinal Chemistry for years to design new molecules with desirable pharmacological profiles. Ligand-based methods are not dependent on receptor structural data and take into account two and three-dimensional molecular properties to assess similarity of new compounds in regards to the set of molecules with the biological property under study. Depending on the complexity of the calculation, there are different types of ligand-based methods, such as QSAR (Quantitative Structure-Activity Relationship) with 2D and 3D descriptors, CoMFA (Comparative Molecular Field Analysis) or pharmacophoric approaches. This work provides a description of a series of ligand-based models applied in the prediction of the inhibitory activity of monoamine oxidase (MAO) enzymes. The controlled regulation of the enzymes’ function through the use of MAO inhibitors is used as a treatment in many psychiatric and neurological disorders, such as depression, anxiety, Alzheimer’s and Parkinson’s disease. For this reason, multiple scaffolds, such as substituted coumarins, indolylmethylamine or pyridazine derivatives were synthesized and assayed toward MAO-A and MAO-B inhibition. Our intention is to focus on the description of ligand-based models to provide new insights in the relationship between the MAO inhibitory activity and the molecular structure of the different inhibitors, and further study enzyme selectivity and possible mechanisms of action. PMID:23231398

  9. IDPN-induced monoamine and hydroxyl radical changes in the rat brain.

    PubMed

    Wakata, N; Araki, Y; Sugimoto, H; Iguchi, H; Kinoshita, M

    2000-03-01

    beta-beta'-iminodipropionitrile (IDPN)-induced monoamine and hydroxyl radical changes in the rat brains were studied. IDPN caused decreases in 5-HT and 5-HIAA levels in all brain regions, strongly indicating that IDPN's neurotoxicity primarily affects 5-HT containing neurons. Dopamine and its metabolites' levels decreased in the some regions, most likely due to depression of dopamine metabolic turnover. Our results more clearly demonstrate IDPN-induced monoamine alterations in the rat brain more than previous reports. To clarify one of the pathogenesis of IDPN-induced neurological disorders, we measured hydroxyl radical levels. 2,3-DHBA increased at 1st day, and decreased in some regions at 7th days after discontinuing IDPN. We conclude, hydroxyl radical formation causes neuronal damage, and monoamine changes contribute to IDPN-induced neurological disorder.

  10. [Hydrazine derivative modification of the activity of brain mitochondrial monoamine oxidases].

    PubMed

    Kalninia, I E; Baumanas, E A; Kaĭrane, Ch B; Gorkin, V Z

    1981-01-01

    Treatment of bovine brain stem mitochondria with hydrazine derivatives, which inhibited the monoamine oxidase activity (substrate: 5-hydroxytryptamine), was accompanied by appearance of the properties to deaminate histamine and cadaverine at a high rate. The same phenomenon was observed in vivo after treatment of mice with the hydrazine derivatives. The dramatic increase in histamine deaminating activity in brain was accompanied by a decrease in the tissue concentration of histamine. The hydrazine derivatives are considered as prooxidants stimulating via a free-radical mechanism lipid peroxidation in methyloleate solutions and in biomembranes (ref. 5) and causing qualitative alteration (transformation) in catalytic properties of monoamine oxidases of the tyre A, which acquire the histamine deaminating activity. A certain correlation was noted between the prooxidant effect of the hydrazine derivatives and the modification of catalytic properties of the membrane bound monoamine oxidases of brain mitochondria in vitro and in vivo.

  11. Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder.

    PubMed

    Foley, Debra L; Eaves, Lindon J; Wormley, Brandon; Silberg, Judy L; Maes, Hermine H; Kuhn, Jonathan; Riley, Brien

    2004-07-01

    Very little is known about how different sets of risk factors interact to influence risk for psychiatric disorder. To replicate a recent report of a genotype-environment interaction that predicts risk for antisocial behavior in boys. Characterizing risk for conduct disorder in boys in association with monoamine oxidase A genotype and exposure to familial adversity, defined by interparental violence, parental neglect, and inconsistent discipline. A community-based sample of twin boys. Five hundred fourteen male twins aged 8 to 17 years. Conduct disorder. There was a main effect of adversity but not of monoamine oxidase A on risk for conduct disorder. Low monoamine oxidase A activity increased risk for conduct disorder only in the presence of an adverse childhood environment. Neither a passive nor an evocative genotype-environment correlation accounted for the interaction. This study replicates a recent report of a genotype-environment interaction that predicts individual variation in risk for antisocial behavior in boys.

  12. Ego Depletion Impairs Implicit Learning

    PubMed Central

    Thompson, Kelsey R.; Sanchez, Daniel J.; Wesley, Abigail H.; Reber, Paul J.

    2014-01-01

    Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent. PMID:25275517

  13. Dopamine depleters in the treatment of hyperkinetic movement disorders.

    PubMed

    Jankovic, Joseph

    2016-12-01

    Abnormal involuntary movements often improve in response to anti-dopaminergic drugs. In contrast to classic neuroleptics that block dopamine receptors, drugs that deplete presynaptic dopamine by blocking vesicular monoamine transporter type 2 (VMAT2) seem to be safer and have little or no risk of tardive dyskinesia. This is one reason why there has been a recent emergence of novel VMAT2 inhibitors. Areas covered: Since the approval of tetrabenazine, the classic VMAT2 inhibitor, in the treatment of chorea associated with Huntington disease (HD), other VMAT2 inhibitors (e.g. deutetrabenazine and valbenazine) have been studied in the treatment of HD-related chorea, tardive dyskinesia and tics associated with Tourette syndrome. This review, based largely on a detailed search of PubMed, will summarize the pharmacology and clinical experience with the various VMAT2 inhibitors. Expert commentary: Because of differences in pharmacology and pharmacokinetics these new VMAT2 inhibitors promise to be at least as effective as tetrabenazine but with a lower risk of adverse effects, such as sedation, insomnia, depression, parkinsonism, and akathisia.

  14. Befloxatone, a new reversible and selective monoamine oxidase-A inhibitor. II. Pharmacological profile.

    PubMed

    Caille, D; Bergis, O E; Fankhauser, C; Gardes, A; Adam, R; Charieras, T; Grosset, A; Rovei, V; Jarreau, F X

    1996-04-01

    The pharmacological profile of befloxatone, a reversible, selective and competitive inhibitor of monoamine oxidase-A has been investigated in rodents. In mice, befloxatone was more active at potentiating generalized tremors induced by L-5-hydroxytryptophan (ED50, 0.21 mg/kg p.o.) than phenylethylamine-induced stereotypies (ED50, 58 mg/kg p.o.), indicating a very high in vivo selectivity for inhibition of the A form of monoamine oxidase. Befloxatone showed potent activity in behavioral models in rodents predictive of antidepressant activity (forced swimming test, learned helplessness and reserpine reversal) with minimal effective doses of 0.1 to 0.2 mg/kg p.o. In these tests, befloxatone was much more potent (10- to 500-fold) than reference antidepressant compounds (reversible and irreversible monoamine oxidase inhibitors and monoamine reuptake inhibitors). In rats, befloxatone increased rapid eye movement sleep latency and decreased rapid eye movement sleep duration, without rebound effects. Potential anxiolytic activity was observed in the elevated-plus maze test in rats (minimal effective dose, 1-2 mg/kg p.o.). Befloxatone had no effect on motor performance, did not induce sedative or stimulant activity up to doses of 200 mg/kg p.o. and was devoid of anticholinergic activity in mice. Interaction studies with p.o. dietary tyramine (12 mg/kg), carried out in freely moving rats, demonstrated that, in contrast to irreversible monoamine oxidase inhibitors, befloxatone did not potentiate the pressor effect of this amine in the range of doses which showed pharmacological activity in antidepressant behavioral models. Furthermore, of the compounds tested (moclobemide, brofaromine, nialamide and phenelzine), comparison of doses active in antidepressant models and doses potentiating the pressor effects of tyramine demonstrated that befloxatone had the best therapeutic index. The results suggest that befloxatone will show clinical antidepressant activity at low doses and

  15. "When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect.

    PubMed

    Salmon, Stefanie J; Adriaanse, Marieke A; De Vet, Emely; Fennis, Bob M; De Ridder, Denise T D

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion.

  16. Catalytic Amine Oxidation under Ambient Aerobic Conditions: Mimicry of Monoamine Oxidase B**

    PubMed Central

    Murray, Alexander T; Dowley, Myles J H; Pradaux-Caggiano, Fabienne; Baldansuren, Amgalanbaatar; Fielding, Alistair J; Tuna, Floriana; Hendon, Christopher H; Walsh, Aron; Lloyd-Jones, Guy C; John, Matthew P; Carbery, David R

    2015-01-01

    The flavoenzyme monoamine oxidase (MAO) regulates mammalian behavioral patterns by modulating neurotransmitters such as adrenaline and serotonin. The mechanistic basis which underpins this enzyme is far from agreed upon. Reported herein is that the combination of a synthetic flavin and alloxan generates a catalyst system which facilitates biomimetic amine oxidation. Mechanistic and electron paramagnetic (EPR) spectroscopic data supports the conclusion that the reaction proceeds through a radical manifold. This data provides the first example of a biorelevant synthetic model for monoamine oxidase B activity. PMID:26087676

  17. Catalytic Amine Oxidation under Ambient Aerobic Conditions: Mimicry of Monoamine Oxidase B.

    PubMed

    Murray, Alexander T; Dowley, Myles J H; Pradaux-Caggiano, Fabienne; Baldansuren, Amgalanbaatar; Fielding, Alistair J; Tuna, Floriana; Hendon, Christopher H; Walsh, Aron; Lloyd-Jones, Guy C; John, Matthew P; Carbery, David R

    2015-07-27

    The flavoenzyme monoamine oxidase (MAO) regulates mammalian behavioral patterns by modulating neurotransmitters such as adrenaline and serotonin. The mechanistic basis which underpins this enzyme is far from agreed upon. Reported herein is that the combination of a synthetic flavin and alloxan generates a catalyst system which facilitates biomimetic amine oxidation. Mechanistic and electron paramagnetic (EPR) spectroscopic data supports the conclusion that the reaction proceeds through a radical manifold. This data provides the first example of a biorelevant synthetic model for monoamine oxidase B activity.

  18. Continuation and maintenance treatments in major depression: the neglected role of monoamine oxidase inhibitors.

    PubMed Central

    Kennedy, S H

    1997-01-01

    The importance of continuation and maintenance antidepressant therapy has been increasingly recognized, but usually focuses on tricyclic and selective serotonin reuptake inhibitor (SSRI) antidepressants. This review examines the evidence in support of classical monoamine oxidase inhibitor (MAOI) agents and the selective reversible monoamine oxidase type A inhibitor moclobemide in continuation and maintenance therapy. Phenelzine and tranylcypromine have demonstrated long-term efficacy but often cause intolerable side effects. Moclobemide is a well-tolerated alternative antidepressant, but there is a need for prospective controlled trials to evaluate its long-term efficacy. PMID:9074307

  19. Effects of 3,N,N'-trimethyl-2-phenyl-1,4-piperazine diastereomers on monoamine uptake and monoamine oxidase in rat brain.

    PubMed

    Smith, D F; Jensen, P N; Gelbcke, M; Tytgat, D

    1992-01-01

    The diastereomers of 3,N,N'-trimethyl-2-phenyl-1,4-piperazine dihydrochloride (TPP) were tested for their effects on NA, DA and 5-HT uptake in synaptosomes prepared from hypothalamus, corpus striatum, and frontal cortex, respectively. The diastereomers differed with respect to their inhibitory properties. (2 R, 3 R)-TPP was more potent than the other diastereomers on NA and DA uptake, whereas (2 S, 3 S)-TPP was least potent. In contrast, the (2 S, 3 S)- and (2 S, 3 R)-diastereomers of TPP were more potent than (2 R, 3 R)- and (2 R, 3 S)-TPP as inhibitors of 5-HT uptake. None of the diastereomers affected monoamine oxidase activity. The findings show that the diastereomers of TPP interact stereoselectively with neuronal mechanisms for monoamine uptake, and that the (S)-configuration at the 2 carbon is important for inhibitory actions of TPP on 5-HT uptake.

  20. Depleting depletion: Polymer swelling in poor solvent mixtures

    NASA Astrophysics Data System (ADS)

    Mukherji, Debashish; Marques, Carlos; Stuehn, Torsten; Kremer, Kurt

    A polymer collapses in a solvent when the solvent particles dislike monomers more than the repulsion between monomers. This leads to an effective attraction between monomers, also referred to as depletion induced attraction. This attraction is the key factor behind standard polymer collapse in poor solvents. Strikingly, even if a polymer exhibits poor solvent condition in two different solvents, it can also swell in mixtures of these two poor solvents. This collapse-swelling-collapse scenario is displayed by poly(methyl methacrylate) (PMMA) in aqueous alcohol. Using molecular dynamics simulations of a thermodynamically consistent generic model and theoretical arguments, we unveil the microscopic origin of this phenomenon. Our analysis suggests that a subtle interplay of the bulk solution properties and the local depletion forces reduces depletion effects, thus dictating polymer swelling in poor solvent mixtures.

  1. Monoamine oxidase A is highly expressed in classical Hodgkin lymphoma.

    PubMed

    Li, Pei Chuan; Siddiqi, Imran N; Mottok, Anja; Loo, Eric Y; Wu, Chieh Hsi; Cozen, Wendy; Steidl, Christian; Shih, Jean Chen

    2017-10-01

    Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines and produces H2 O2 . It facilitates the progression of gliomas and prostate cancer, but its expression and functional relevance have not been studied in lymphoma. Here, we evaluated MAOA in 427 cases of Hodgkin and non-Hodgkin lymphoma and in a spectrum of reactive lymphoid tissues by immunohistochemistry on formalin-fixed, paraffin-embedded specimens. MAOA was expressed by Hodgkin Reed-Sternberg (HRS) cells in the majority of classical Hodgkin lymphomas (cHLs) (181/241; 75%), with 34.8% showing strong expression. Weak MAOA was also noted in a minority of primary mediastinal large B-cell lymphomas (8/47; 17%) and in a mediastinal gray-zone lymphoma. In contrast, no MAOA was found in non-neoplastic lymphoid tissues, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL; 0/8) or any other non-Hodgkin lymphomas studied (0/123). MAOA was more common in Epstein-Barr virus (EBV)-negative compared to EBV-positive cHL (p < 0.0001) and was especially prevalent in the EBV-negative nodular sclerosing subtype. Similar to primary human lymphoma specimens, most cHL-derived cell lines displayed MAOA activity, whereas non-Hodgkin-lymphoma-derived cell lines did not. The MAOA inhibitor clorgyline reduced the growth of L1236 cells and U-HO1 cells, and shRNA knockdown of MAOA reduced the growth of L1236 cells. Conversely, ectopic overexpression of MAOA increased the growth of MAOA-negative HDLM2 cells. Combined treatment with clorgyline and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) was more effective in reducing cell growth than either regimen alone. In summary, MAOA is highly expressed in cHL and may reflect the distinct biology of this lymphoma. Further studies on the potential utility of MAOA as a diagnostic marker and therapeutic target are warranted. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John

  2. Changes in monoamine levels in mouse brain elicited by forced-swimming stress, and the protective effect of a new monoamine oxidase inhibitor, RS-8359.

    PubMed

    Miura, H; Naoi, M; Nakahara, D; Ohta, T; Nagatsu, T

    1993-01-01

    As a stress model, a forced swimming test was applied to mice; and a typical behavioral change, an immobile posture, was recognized. This affected the brain monoamine levels significantly. The norepinephrine concentration was reduced, while that of its product was increased; and in the case of dopamine, both the amount of the amine and its product were increased. Stress increased the levels of serotonin and its product in the brain. The effects of RS-8359, (+/-)-4-(4-cyanophenyl)amino-6,7-dihydro-7-hydroxy-5H-cyclopenta[d ]- pyrimidine, a new inhibitor of type A monoamine oxidase, on the behavioral and biochemical changes caused by forced swimming were also investigated. RS-8359 significantly improved the immobile posture elicited by the forced swimming test. It reduced the increased turnover of norepinephrine and serotonin systems caused by swimming. These results suggest that the effect of RS-8359 on behavioral and biochemical changes by stress may be mainly due to its effects on norepinephrine and serotonin systems, presumably by the inhibition of type A monoamine oxidase.

  3. Fully depleted back illuminated CCD

    DOEpatents

    Holland, Stephen Edward

    2001-01-01

    A backside illuminated charge coupled device (CCD) is formed of a relatively thick high resistivity photon sensitive silicon substrate, with frontside electronic circuitry, and an optically transparent backside ohmic contact for applying a backside voltage which is at least sufficient to substantially fully deplete the substrate. A greater bias voltage which overdepletes the substrate may also be applied. One way of applying the bias voltage to the substrate is by physically connecting the voltage source to the ohmic contact. An alternate way of applying the bias voltage to the substrate is to physically connect the voltage source to the frontside of the substrate, at a point outside the depletion region. Thus both frontside and backside contacts can be used for backside biasing to fully deplete the substrate. Also, high resistivity gaps around the CCD channels and electrically floating channel stop regions can be provided in the CCD array around the CCD channels. The CCD array forms an imaging sensor useful in astronomy.

  4. Charge depletion in organic heterojunction

    NASA Astrophysics Data System (ADS)

    Ng, T. W.; Lo, M. F.; Lee, S. T.; Lee, C. S.

    2012-03-01

    Until now two types of organic-organic heterojunction (OHJ) have been observed in P-N junctions formed between undoped-organic semiconductors. Charge-transfers across OHJs are either negligible or showing electron transfer from P-type to N-type materials, leading to charges accumulation near the interface. Here, we observed that junction of 4,4',4''-tris(2-methylphenyl-phenylamino)triphenylamine (m-MTDATA)/bathocuproine (BCP) show the third-behavior. Electrons in BCP (N-type) transfer to m-MTDATA (P-type), leading to depletion of mobile majority carriers near the junction. While "depletion junctions" are typical in inorganic semiconductors, there are no reports in undoped-OHJ. Formation mechanism of depletion OHJs and fundamental differences between inorganic and organic HJs are discussed.

  5. Monoamine Oxidase a Promoter Gene Associated with Problem Behavior in Adults with Intellectual/Developmental Disabilities

    ERIC Educational Resources Information Center

    May, Michael E.; Srour, Ali; Hedges, Lora K.; Lightfoot, David A.; Phillips, John A., III; Blakely, Randy D.; Kennedy, Craig H.

    2009-01-01

    A functional polymorphism in the promoter of the gene encoding monoamine oxidase A has been associated with problem behavior in various populations. We examined the association of MAOA alleles in adult males with intellectual/developmental disabilities with and without established histories of problem behavior. These data were compared with a…

  6. Discovery of two new classes of potent monoamine oxidase-B inhibitors by tricky chemistry.

    PubMed

    Cagide, F; Silva, T; Reis, J; Gaspar, A; Borges, F; Gomes, L R; Low, J N

    2015-02-18

    The discovery of potent and selective monoamine oxidase-B inhibitors for the management of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases is still a challenging endeavor. Herein, we report the discovery of two new classes of potent and selective MAO-B inhibitors based on chromane-2,4-dione and chromone-3-carboxamide scaffolds.

  7. Prepulse inhibition (PPI) disrupting effects of Glycyrrhiza glabra extract in mice: a possible role of monoamines.

    PubMed

    Michel, Haidy E; Tadros, Mariane G; Abdel-Naim, Ashraf B; Khalifa, Amani E

    2013-06-07

    Liquorice extract was reported to have nootropic and/or antiamnestic effects. Prepulse inhibition (PPI) of startle response is a multimodal, cross-species phenomenon used as a measure of sensorimotor gating. Previous studies indicated that liquorice/its constituents augmented mouse brain monoamine levels. Increased brain monoamines' transmission was suggested to underlie PPI disruption. However, the effect of antiamnestic dose(s) of the extract on PPI has not been investigated despite the coexistence of impaired memory and PPI deficit in some neurological disorders. The effect of administration of the antiamnestic dose of the extract (150 mg/kg for 7 days) was tested on PPI of acoustic startle response in mice. It resulted in PPI disruption and therefore its effect on monoamines' levels was investigated in a number of mouse brain areas involved in PPI response mediation. Results demonstrated that the extract antiamnestic dose augmented cortical, hippocampal and striatal monoamine levels. It was therefore concluded that liquorice extract (150 mg/kg)-induced PPI deficit was mediated through augmenting monoaminergic transmission in the cortex, hippocampus and striatum. These findings can be further investigated in experimental models for autism, psychosis and Huntington's disease to decide the safety of using liquorice extract in ameliorating memory disturbance in disorders manifesting PPI deficit. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Monoamine Oxidase a Promoter Gene Associated with Problem Behavior in Adults with Intellectual/Developmental Disabilities

    ERIC Educational Resources Information Center

    May, Michael E.; Srour, Ali; Hedges, Lora K.; Lightfoot, David A.; Phillips, John A., III; Blakely, Randy D.; Kennedy, Craig H.

    2009-01-01

    A functional polymorphism in the promoter of the gene encoding monoamine oxidase A has been associated with problem behavior in various populations. We examined the association of MAOA alleles in adult males with intellectual/developmental disabilities with and without established histories of problem behavior. These data were compared with a…

  9. Human platelet monoamine oxidase activity in health and disease: a review.

    PubMed Central

    Sandler, M; Reveley, M A; Glover, V

    1981-01-01

    The most readily available source of monoamine oxidase in man is the platelet, although only the B form of the enzyme is represented in this site. Platelet activity is higher in women than in men. The enzyme activity is generally stable and is partly under genetic control. There is some evidence that individuals with low activity have a higher psychiatric morbidity than those with high activity. Despite some negative studies, the consensus of publication dealing with schizophrenia, migraine, and alcoholism find that mean platelet monoamine oxidase activity in the patient group is lower than in the controls. Values are raised in unipolar depression. Technical differences, or patient or control group heterogeneity, might well account for the absence of unanimity in the literature. A considerable degree of overlap between patient and control values, whatever the clinical diagnosis, appears to be the standard finding. Apart from these neuropsychiatric disturbances, platelet monoamine oxidase activity is raised in megaloblastic anaemia and reduced in iron deficiency anaemia. Although altered enzyme activity values may be linked to abnormal platelet populations in some of the haematological disorders discussed, in general the causes of abnormal platelet monoamine oxidase activity are unknown. PMID:6453137

  10. [Analysis of correlation between occupational stress and serum monoamine neurotransmitters in nurses].

    PubMed

    Zhan, Yongguo; Tian, Honger; Zhang, Qingdong; Zhu, Xinyun; Cao, Lili; Su, Jingguo; Xu, Tian; Zhu, Huabin; Liu, Ling

    2014-02-01

    To investigate the impact of occupational stress on serum monoamine neurotransmitters in nurses. A total of 131 nurses were included as study subjects by stratified cluster sampling. The occupational health information collection system (based on the Internet of things) was used to measure occupational stress. Serum levels of monoamine neurotransmitters were also measured. Epinephrine (E) was negatively correlated with superior support (P < 0.05) and colleague support (P < 0.05). Negative correlation was also found between dopamine (DA) and job prospect (P < 0.05). Level of 5-hydroxytryptamine was negatively correlated with promotion opportunities (P < 0.05). Norepinephrine (NE), E, and DA were all negatively correlated with work satisfaction (P < 0.05) and positively correlated with daily stress (P < 0.01). NE and E were negatively correlated with sufficient confidence (P < 0.05) and positively correlated with physical complaints (P < 0.01). There was a negative correlation between NE and psychological satisfaction (P < 0.05). Occupational stress in nurses is correlated with serum monoamine neurotransmitters, and it may affect serum levels of monoamine neurotransmitters to a certain extent.

  11. Whole brain monoamine detection and manipulation in a stalk-eyed fly.

    PubMed

    Bubak, Andrew N; Swallow, John G; Renner, Kenneth J

    2013-09-30

    Understanding the physiological mechanisms that influence conflict resolution is of great importance because the outcome of contests over limited resources such as mates, territories, and food has significant fitness consequences. Male stalk-eyed flies (Teleopsis dalmanni) compete over territory and mates and provide an excellent model system to study aggression. To investigate potential effects of serotonin (5-HT) on aggressive behavior in these flies, we developed a dissection and sample preparation method sufficiently sensitive to measure monoamine concentrations from whole brain samples of small insects. This new method allows the detection of monoamines from a single fly brain using high performance liquid chromatography with electrochemical detection. The method allows for the detection and quantification of octopamine (OA), 5-hydroxytryptophan (5-HTP), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), tyramine (TA), and serotonin (5-HT) and provides a means for assessing changes in stalk-eyed fly brain monoamine concentrations in response to drug administration in food media. We successfully elevated 5-HT levels approximately 8-fold that of control levels in stalk-eyed fly brains by oral administration of the 5-HT precursor 5-HTP. Furthermore, in size-matched competitions for a food resource, flies that had elevated 5-HT in response to 5-HTP pretreatment exhibited a high probability of winning the contests. These results suggest that 5-HT enhances aggression in the stalk-eyed fly and highlight the potential of our method for testing putative roles of monoamines in modulating self and rival assessment in conflict resolution.

  12. Beyond Monoamines-Novel Targets for Treatment-Resistant Depression: A Comprehensive Review

    PubMed Central

    Rosenblat, Christian; McIntyre, Roger S.; Alves, Gilberto S.; Fountoulakis, Konstantinos N.; Carvalho, André F.

    2015-01-01

    Major depressive disorder (MDD) is a leading cause of disability worldwide. Current first line therapies target modulation of the monoamine system. A large variety of agents are currently available that effectively alter monoamine levels; however, approximately one third of MDD patients remain treatment refractory after adequate trials of multiple monoamine based therapies. Therefore, patients with treatment-resistant depression (TRD) may require modulation of pathways outside of the classic monoamine system. The purpose of this review was thus to discuss novel targets for TRD, to describe their potential mechanisms of action, the available clinical evidence for these targets, the limitations of available evidence as well as future research directions. Several alternate pathways involved in the patho-etiology of TRD have been uncovered including the following: inflammatory pathways, the oxidative stress pathway, the hypothalamic-pituitary-adrenal (HPA) axis, the metabolic and bioenergetics system, neurotrophic pathways, the glutamate system, the opioid system and the cholinergic system. For each of these systems, several targets have been assessed in preclinical and clinical models. Preclinical models strongly implicate these pathways in the patho-etiology of MDD. Clinical trials for TRD have been conducted for several novel targets; however, most of the trials discussed are small and several are uncontrolled. Therefore, further clinical trials are required to assess the true efficacy of these targets for TRD. As well, several promising novel agents have been clinically tested in MDD populations, but have yet to be assessed specifically for TRD. Thus, their applicability to TRD remains unknown. PMID:26467412

  13. Ciproxifan, a histamine H3 receptor antagonist, reversibly inhibits monoamine oxidase A and B

    PubMed Central

    Hagenow, S.; Stasiak, A.; Ramsay, R. R.; Stark, H.

    2017-01-01

    Ciproxifan is a well-investigated histamine H3 receptor (H3R) inverse agonist/antagonist, showing an exclusively high species-specific affinity at rodent compared to human H3R. It is well studied as reference compound for H3R in rodent models for neurological diseases connected with neurotransmitter dysregulation, e.g. attention deficit hyperactivity disorder or Alzheimer’s disease. In a screening for potential monoamine oxidase A and B inhibition ciproxifan showed efficacy on both enzyme isoforms. Further characterization of ciproxifan revealed IC50 values in a micromolar concentration range for human and rat monoamine oxidases with slight preference for monoamine oxidase B in both species. The inhibition by ciproxifan was reversible for both human isoforms. Regarding inhibitory potency of ciproxifan on rat brain MAO, these findings should be considered, when using high doses in rat models for neurological diseases. As the H3R and monoamine oxidases are all capable of affecting neurotransmitter modulation in brain, we consider dual targeting ligands as interesting approach for treatment of neurological disorders. Since ciproxifan shows only moderate activity at human targets, further investigations in animals are not of primary interest. On the other hand, it may serve as starting point for the development of dual targeting ligands. PMID:28084411

  14. In vivo relationship between monoamine oxidase type B and alcohol dehydrogenase: effects of ethanol and phenylethylamine

    SciTech Connect

    Aliyu, S.U.; Upahi, L.

    1988-01-01

    The role of acute ethanol and phenylethylamine on the brain and platelet monoamine oxidase activities, hepatic cytosolic alcohol dehydrogenase, redox state and motor behavior were studied in male rats. Ethanol on its own decreased the redox couple ratio, as well as, alcohol dehydrogenase activity in the liver while at the same time it increased brain and platelet monoamine oxidase activity due to lower Km with no change in Vmax. The elevation in both brain and platelet MAO activity was associated with ethanol-induced hypomotility in the rats. Co-administration of phenylethylamine and ethanol to the animals, caused antagonism of the ethanol-induced effects described above. The effects of phenylethylamine alone, on the above mentioned biochemical and behavioral indices, are more complex. Phenylethylamine on its own, like ethanol, caused reduction of the cytosolic redox, ratio and elevation of monoamine oxidase activity in the brain and platelets. However, in contrast to ethanol, this monoamine produced hypermotility and activation of the hepatic cytosolic alcohol dehydrogenase activity in the animals.

  15. Double-staining techniques allows electrophysiological identification of monoamine-containing neurons.

    PubMed

    Audesirk, T E; Audesirk, G J

    1985-08-01

    Electrophysiological recording provides important evidence for positive identification of many neurons in gastropods. We describe a technique which combines intracellular recording and injection of a persistent, non-fluorescent dye (Fast Green) with subsequent histofluorescence treatment using a modification of the wholemount glyoxylic acid procedure developed by Barber (1983) to establish the presence or absence of monoamine transmitters in positively identified single gastropod neurons.

  16. Ciproxifan, a histamine H3 receptor antagonist, reversibly inhibits monoamine oxidase A and B.

    PubMed

    Hagenow, S; Stasiak, A; Ramsay, R R; Stark, H

    2017-01-13

    Ciproxifan is a well-investigated histamine H3 receptor (H3R) inverse agonist/antagonist, showing an exclusively high species-specific affinity at rodent compared to human H3R. It is well studied as reference compound for H3R in rodent models for neurological diseases connected with neurotransmitter dysregulation, e.g. attention deficit hyperactivity disorder or Alzheimer's disease. In a screening for potential monoamine oxidase A and B inhibition ciproxifan showed efficacy on both enzyme isoforms. Further characterization of ciproxifan revealed IC50 values in a micromolar concentration range for human and rat monoamine oxidases with slight preference for monoamine oxidase B in both species. The inhibition by ciproxifan was reversible for both human isoforms. Regarding inhibitory potency of ciproxifan on rat brain MAO, these findings should be considered, when using high doses in rat models for neurological diseases. As the H3R and monoamine oxidases are all capable of affecting neurotransmitter modulation in brain, we consider dual targeting ligands as interesting approach for treatment of neurological disorders. Since ciproxifan shows only moderate activity at human targets, further investigations in animals are not of primary interest. On the other hand, it may serve as starting point for the development of dual targeting ligands.

  17. Simultaneous measurement of monoamine metabolites and 5-methyltetrahydrofolate in the cerebrospinal fluid of children.

    PubMed

    Akiyama, Tomoyuki; Hayashi, Yumiko; Hanaoka, Yoshiyuki; Shibata, Takashi; Akiyama, Mari; Nakamura, Kazuyuki; Tsuyusaki, Yu; Kubota, Masaya; Yoshinaga, Harumi; Kobayashi, Katsuhiro

    2017-02-01

    We describe a new method for simultaneous measurement of monoamine metabolites (3-O-methyldopa [3-OMD], 3-methoxy-4-hydroxyphenylethyleneglycol [MHPG], 5-hydroxyindoleacetic acid [5-HIAA], and homovanillic acid [HVA]) and 5-methyltetrahydrofolate (5-MTHF) and its use on cerebrospinal fluid (CSF) samples from pediatric patients. Monoamine metabolites and 5-MTHF were measured by high-performance liquid chromatography with fluorescence detection. CSF samples were prospectively collected from children according to a standardized collection protocol in which the first 1-ml fraction was used for analysis. Monoamine metabolites and 5-MTHF were separated within 10min. They showed linearity from the limit of detection to 1024nmol/l. The limit of quantification of each metabolite was sufficiently low for the CSF sample assay. In 42 CSF samples after excluding cases with possibly altered neurotransmitter profiles, the concentrations of 3-OMD, MHPG, 5-HIAA, HVA, and 5-MTHF showed significant age dependence and their ranges were comparable with the reference values in the literature. The metabolite profiles of aromatic l-amino acid decarboxylase deficiency, Segawa disease, and folate receptor α defect by this method were compatible with those in the literature. This method is a simple means of measuring CSF monoamine metabolites and 5-MTHF, and is especially useful for laboratories not equipped with electrochemical detectors. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. A combination of mirtazapine and milnacipran augments the extracellular levels of monoamines in the rat brain.

    PubMed

    Yamauchi, Miki; Imanishi, Taiichiro; Koyama, Tsukasa

    2012-06-01

    Mirtazapine, an antidepressant, antagonizes α(2)-adrenergic autoreceptors and heteroreceptors, which leads to enhanced noradrenergic and serotonergic transmission without inhibiting monoamine transporters. Using a microdialysis technique, we investigated whether co-administration of mirtazapine and a serotonin noradrenaline reuptake inhibitor (SNRI), milnacipran, augments the effects of each drug on the extracellular levels of monoamines by pharmacological synergy. Mirtazapine increased the extracellular levels of noradrenaline and serotonin in the dorsal hippocampus. In contrast, it increased the levels of noradrenaline and dopamine without changing serotonin levels in the prefrontal cortex. Milnacipran increased the levels of all monoamines evaluated in both areas, and the combined treatment with mirtazapine augmented these changes. The combined treatment with idazoxan, an α(2) adrenoceptor antagonist, and milnacipran also increased all monoamine levels in the prefrontal cortex. Ketanserin, a serotonin 5-HT(2A) receptor antagonist, showed no effect in combination with milnacipran, while SB242084, a 5-HT(2C) receptor antagonist, augmented the effects of milnacipran on the levels of serotonin and dopamine in the prefrontal cortex. These results suggest that combined treatment with mirtazapine and milnacipran augments the extracellular levels of noradrenaline, serotonin and dopamine through the blockade of α(2) adrenoceptors without regional specificity, whereas mirtazapine enhances serotonergic transmission in a region-specific manner. 5-HT(2C) receptor antagonism may also partly contribute to the amplification effects of mirtazapine on serotonin and dopamine levels. These neurochemical changes could play a role in reported advantageous clinical effects in patients treated with an SNRI and mirtazapine.

  19. Age-related ultrastructural and monoamine oxidase changes in the rat optic nerve.

    PubMed

    Taurone, S; Ripandelli, G; Minni, A; Lattanzi, R; Miglietta, S; Pepe, N; Fumagalli, L; Micera, A; Pastore, F S; Artico, M

    2016-01-01

    The aim of this paper is to study the morphology and the distribution of the monoamine oxidase enzymatic system in the optic nerve of 4 month-old Wistar (young) and 28 month-old Wistar (old) rats. The optic nerve was harvested from 20 young and old rats. The segment of optic nerve was divided longitudinally into two pieces, each 0.1 mm in length. The first piece was used for transmission electron microscopy. The second piece was stained with histochemical reaction for monoamine oxidase. The agerelated changes in the optic nerve of rats include micro-anatomical details, ultrastructure and monoamine oxidase histochemical staining. A strong decrease of the thin nerve fibers and a swelling of the thick ones can be observed in optic nerve fibers of old rats. Increased monoamine oxidase histochemical staining of the optic nerve of aged rats is well demonstrated. The increase of meningeal shealth and the decrease of thin nerve fibers of the optic nerve in old rats are well documented. Morphological, ultrastructural and histochemical changes observed in optic nerve fibers of the old rats show a close relation with aging.

  20. Lobelane analogues as novel ligands for the vesicular monoamine transporter-2.

    PubMed

    Zheng, Guangrong; Dwoskin, Linda P; Deaciuc, Agripina G; Zhu, Jun; Jones, Marlon D; Crooks, Peter A

    2005-06-02

    A series of lobelane analogues has been synthesized and their structure-activity relationships at the vesicular monoamine transporter-2 (VMAT2) have been evaluated. The most potent analogues in this series were the cis-2,6-piperidino analogues, 25b, 27b, 28b, and 30b, with K(i) values ranging from 430 to 580 nM.

  1. Alterations in central monoamine systems after postnatal lead acetate treatment in rats

    SciTech Connect

    Luthman, J. Univ. of Colorado Health Sciences Center, Denver, CO ); Lindqvist, E.; Olson, L. ); Gerhardt, G.A.; Hoffer, B.H. )

    1994-04-01

    The present study was undertaken to investigate the effect of postnatal lead exposure on central monoamine systems. Newborn male Sprague-Dawley rats were given 1 or 8 mg/kg lead acetate intraperitoneally for 20 days postnatally. Two groups of control rats received sodium acetate, or sodium acetate in oversized litters to compensate for lead-induced malnutrition in the high lead dose group, while nontreated animals also served as controls. At Day 21 or 51 regional tissue levels of monoamines were determined using HPLC techniques. No major changes were seen after the lead exposures in the levels of dopamine, noradrenaline, and serotonin, or metabolites of dopamine and serotonin, when compared to respective control groups. On the other hand, in the control group given sodium acetate in oversized litters some alterations of the monoamine levels were observed in frontal cortex and striatum at Day 21 compared to controls. At Day 51, the striatal homovanillic acid and 5-hydroxyindoleacetic acid levels were higher in the low lead dose group compared to those in the controls, No other changes in the monoamine levels were seen at Day 51. At 50-70 days postnatally, potassium-stimulated dopamine overflow was studied in striatum with in vivo chronoamperometry. In the high lead dose group the amplitudes of signals were lower in both the dorsal and ventral striatum compared to the controls, while no difference was seen in the clearance time of dopamine. The capacity of the dopamine terminals to respond to repeated stimulation was not affected by the lead exposure. Thus, the steady-state levels of monoamines were essentially unaltered after postnatal lead exposure in rats, while functional aspects of striatal dopamine transmission were affected after exposure to the higher dose of lead. These findings support the hypothesis that lead-induced changes in motor skills and exploratory behavior may be related to altered dopamine neurotransmission. 77 refs., 3 figs., 2 tabs.

  2. Insulin modulates cocaine-sensitive monoamine transporter function and impulsive behavior.

    PubMed

    Schoffelmeer, Anton N M; Drukarch, Benjamin; De Vries, Taco J; Hogenboom, François; Schetters, Dustin; Pattij, Tommy

    2011-01-26

    Because insulin acutely enhances the function of dopamine transporters, the tyrosine kinase receptors activated by this hormone may modulate transporter-dependent neurochemical and behavioral effects of psychoactive drugs. In this respect, we examined the effects of insulin on exocytotic monoamine release and the efficacy of the monoamine transporter blocker cocaine in rat nucleus accumbens. Whereas insulin reduced electrically evoked exocytotic [(3)H]dopamine release in nucleus accumbens slices, the hormone potentiated the release-enhancing effect of cocaine thereon. The phosphatidylinositol 3-kinase inhibitor LY294002 abolished these effects, indicating the involvement of insulin receptors. Similar insulin effects were observed on the release of [(3)H]norepinephrine in nucleus accumbens slices, but not on that of [(3)H]serotonin, and were also apparent in medial prefrontal cortex slices. As might then be expected, insulin also potentiated the dopamine and norepinephrine release-enhancing effects of the selective monoamine uptake inhibitors GBR12909 and desmethylimipramine, respectively. In subsequent behavioral experiments, we investigated the role of insulin in motor impulsivity that depends on monoamine neurotransmission in the nucleus accumbens. Intracranial administration of insulin in the nucleus accumbens alone reduced premature responses in the five-choice serial reaction time task and enhanced the stimulatory effect of peripheral cocaine administration on impulsivity, resembling the observed neurochemical effects of the hormone. In contrast, cocaine-induced locomotor activity remained unchanged by intra-accumbal insulin application. These data reveal that insulin presynaptically regulates cocaine-sensitive monoamine transporter function in the nucleus accumbens and, as a consequence, impulsivity. Therefore, insulin signaling proteins may represent targets for the treatment of inhibitory control deficits such as addictive behaviors.

  3. Maternal factors and monoamine changes in stress-resilient and susceptible mice: cross-fostering effects.

    PubMed

    Prakash, Priya; Merali, Zul; Kolajova, Miroslava; Tannenbaum, Beth M; Anisman, Hymie

    2006-09-21

    Genetic factors influence stressor-provoked monoamine changes associated with anxiety and depression, but such effects might be moderated by early life experiences. To assess the contribution of maternal influences in determining adult brain monoamine responses to a stressor, strains of mice that were either stressor-reactive or -resilient (BALB/cByJ and C57BL/6ByJ, respectively) were assessed as a function of whether they were raising their biological offspring or those of the other strain. As adults, offspring were assessed with respect to stressor-provoked plasma corticosterone elevations and monoamine variations within discrete stressor-sensitive brain regions. BALB/cByJ mice demonstrated poorer maternal behaviors than C57BL/6ByJ dams, irrespective of the pups being raised. In response to a noise stressor, BALB/cByJ mice exhibited higher plasma corticosterone levels and elevated monoamine turnover in several limbic and hypothalamic sites. The stressor-provoked corticosterone increase in BALB/cByJ mice was diminished among males (but not females) raised by a C57BL/6ByJ dam. Moreover, increased prefrontal cortical dopamine utilization was attenuated among BALB/cByJ mice raised by a C57BL/6ByJ dam. These effects were asymmetrical as a C57BL/6ByJ mice raised by a BALB/cByJ dam did not exhibit increased stressor reactivity. It appears that stressors influence multiple neurochemical systems that have been implicated in anxiety and affective disorders. Although monoamine variations were largely determined by genetic factors, maternal influences contributed to stressor-elicited neurochemical changes in some regions, particularly dopamine activation within the prefrontal cortex.

  4. Isolation and characterization of a monoamine oxidase B selective inhibitor from tobacco smoke.

    PubMed

    Khalil, Ashraf A; Davies, Bruce; Castagnoli, Neal

    2006-05-15

    It is well established that tobacco smokers have reduced levels of monoamine oxidase activities both in the brain and peripheral organs. Furthermore, extensive evidence suggests that smokers are less prone to develop Parkinson's disease. These facts, plus the observation that inhibition of monoamine oxidase B protects against the parkinsonian inducing effects of the nigrostriatal neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have prompted studies to identify monoamine oxidase inhibitors in the tobacco plant and tobacco cigarette smoke. Our previous efforts on cured tobacco leaf extracts have led to the characterization of 2,3,6-trimethyl-1,4-naphthoquinone, a non-selective monoamine oxidase inhibitor, and farnesylacetone, a selective monoamine oxidase B inhibitor. We now have extended these studies to tobacco smoke constituents. Fractionation of the smoke extracts has confirmed and extended the qualitative results of an earlier report [J. Korean Soc. Tob. Sci.1997, 19, 136] demonstrating the inhibitory activity of the terpene trans,trans-farnesol on rat brain MAO-B. In the present study, K(i) values for the inhibition of human, baboon, monkey, dog, rat, and mouse liver MAO-B have been determined. Noteworthy is the absence of inhibitory effects on human placental MAO-A and beef liver MAO-B. A limited structure-activity relationship study of analogs of trans,trans-farnesol is reported. Although the health hazards associated with the use of tobacco products preclude any therapeutic opportunities linked to smoking, these results suggest the possibility of identifying novel structures of compounds that could lead to the development of neuroprotective agents.

  5. Behavioral expression of opiate withdrawal is altered after prefrontocortical dopamine depletion in rats: monoaminergic correlates.

    PubMed

    Espejo, E F; Serrano, M I; Caillé, S; Stinus, L

    2001-08-01

    The objective of this study was to establish the effects of prefrontocortical dopamine depletion on opiate withdrawal and prefrontocortical neurochemical changes elicited by morphine dependence and withdrawal. The dopaminergic content was also measured in the nucleus accumbens during withdrawal, in order to detect reactive changes induced by prefrontocortical lesion. Withdrawal was induced by naloxone in morphine-dependent rats. Monoamine levels were analyzed post-mortem by high performance liquid cromatography. The results showed that chronic morphine dependence did not modify basal levels of monoamines in sham rats, revealing neuroadaptation of prefrontocortical dopamine, noradrenaline and serotonin systems to chronic morphine. The neuroadaptive phenomenon remained after prefrontocortical lesion (> 79% dopamine depletion). On the other hand, a strong increase of dopamine, noradrenaline, and serotonin contents in the medial prefrontal cortex of sham rats was detected during opiate withdrawal. However, in lesioned rats, the increase of prefrontocortical dopamine and serotonin content, but not that of noradrenaline, was much lower. In the nucleus accumbens, prefrontocortical lesion reactively enhanced the dopaminergic tone and, although opiate withdrawal reduced dopaminergic activity in both sham and lesioned rats, this reduction was less intense in the latter group. At a behavioral level, some symptoms of physical opiate withdrawal were exacerbated in lesioned rats (writhing, mastication, teeth-chattering, global score) and exploration was reduced. The findings hence indicate that: (i) prefrontocortical monoaminergic changes play a role in the behavioral expression of opiate withdrawal; (ii) the severity of some withdrawal signs are related to the dopaminergic and serotonergic tone of the medial prefrontal cortex rather than to the noradrenergic one, and (iii) an inverse relationship between mesocortical and mesolimbic dopaminergic systems exists.

  6. Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors with potential therapeutic utility in depression and pain.

    PubMed

    Lucas, Matthew C; Weikert, Robert J; Carter, David S; Cai, Hai-Ying; Greenhouse, Robert; Iyer, Pravin S; Lin, Clara J; Lee, Eun Kyung; Madera, Ann Marie; Moore, Amy; Ozboya, Kerem; Schoenfeld, Ryan C; Steiner, Sandra; Zhai, Yansheng; Lynch, Stephen M

    2010-09-15

    Two new series of monoamine triple reuptake inhibitors (TRIs) have been discovered through scaffold homologation of our recently reported series of 3,3-disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines demonstrated high levels of potency against all three monoamine transporters as well as good human in vitro stability, low drug-drug interaction potential and a decreased propensity for hERG channel binding. Representative compounds from these series displayed good in vivo pharmacokinetics and high monoamine receptor occupancies which are indicators of good brain penetration. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  7. Impaired reward learning and intact motivation after serotonin depletion in rats

    PubMed Central

    Izquierdo, Alicia; Carlos, Kathleen; Ostrander, Serena; Rodriguez, Danilo; McCall-Craddolph, Aaron; Yagnik, Gargey; Zhou, Feimeng

    2012-01-01

    Aside from the well-known influence of serotonin (5-hydroxytryptamine, 5-HT) on emotional regulation, more recent investigations have revealed the importance of this monoamine in modulating cognition. Parachlorophenylalanine (PCPA) depletes 5-HT by inhibiting tryptophan hydroxylase, the enzyme required for 5-HT synthesis and, if administered at sufficiently high doses, can result in a depletion of at least 90% of the brain s 5-HT levels. The present study assessed the long-lasting effects of widespread 5-HT depletions on two tasks of cognitive flexibility in Long Evans rats: effort discounting and reversal learning. We assessed performance on these tasks after administration of either 250 or 500 mg/kg PCPA or saline (SAL) on two consecutive days. Consistent with a previous report investigating the role of 5-HT on effort discounting, pretreatment with either dose of PCPA resulted in normal effortful choice: All rats continued to climb tall barriers to obtain large rewards and were not work-averse. Additionally, rats receiving the lower dose of PCPA displayed normal reversal learning. However, despite intact motivation to work for food rewards, rats receiving the largest dose of PCPA were unexpectedly impaired relative to SAL rats on the pretraining stages leading up to reversal learning, ultimately failing to approach and respond to the stimuli associated with reward. High performance liquid chromatography (HPLC) with electrochemical detection confirmed 5-HT, and not dopamine, levels in the ventromedial frontal cortex were correlated with this measure of associative reward learning. PMID:22652392

  8. Pharmacological analysis of monoamine synthesis and catabolism in the scallop, Placopecten magellanicus.

    PubMed

    Pani, A K; Croll, R P

    1998-07-01

    1. The efficacies of various agents that affect monoamine synthesis, oxidation and methylation were evaluated in the scallop, Placopecten magellanicus, through the use of high performance liquid chromatography with electrochemical detection. 2. Central ganglia, labial palps and feet from animals bathed in 10(-5) M or 10(-4) M alpha-methyl-p-tyrosine for 1 day followed by 3-6 day recovery in artificial sea water had significantly reduced concentrations of 3,4-dihydroxyphenylalanine, norepinephrine, epinephrine, dopamine and 3,4-dihydroxyphenylacetic acid. 3. Central ganglia, labial palps and feet from scallops incubated in 10(-5) M or 10(-4) M para-chlorophenylalanine for 1 day followed by a 3-6 day wash in artificial sea water had significantly reduced concentrations of 5-hydroxytryptophan, 5-hydroxytryptamine and 5-hydroxy-3-indoleacetic acid. 4. Monamine oxidase inhibitors (administered at 10(-4) M for 1 day followed by a 2-day recovery) significantly decreased the concentrations of 3,4-dihydroxyphenylalanine and 5-hydroxy-3-indolacetic acid and increased the concentrations of their corresponding precursors in tissues. Deprenyl, a monoamine oxidase type B inhibitor, generally had more potent effects than pargyline, which inhibits monoamine oxidase type B and type A. Clorgyline, a monoamine oxidase type A specific inhibitor, showed few significant effects on the levels of the monoamines or their precursors or metabolites. 5. Bath application of 10(-4) M 3,5-dinitrocatechol, a blocker of catechol-O-methyl transferase, resulted in significant decreases in the concentrations of normetanephrine and metanephrine in nervous and other tissues and increased the levels of their corresponding precursors, dopamine, norepinephrine and epinephrine. 6. Generally, treatments that appeared to directly cause changes in levels of catecholaminergic compounds indirectly resulted in inverse changes in levels of indolaminergic compounds, and vice versa. This suggests an interaction

  9. Role of monoamine oxidase, nitric oxide synthase and regional brain monoamines in the antidepressant-like effects of methylene blue and selected structural analogues.

    PubMed

    Harvey, Brian H; Duvenhage, Ingrid; Viljoen, Francois; Scheepers, Nellie; Malan, Sarel F; Wegener, Gregers; Brink, Christiaan B; Petzer, Jacobus P

    2010-11-15

    Dual action antidepressants have important therapeutic implications. Methylene blue (MB), a charged compound structurally related to tricyclic antidepressants, acts on both monoamine oxidase (MAO) and the nitric oxide (NO)-cGMP pathway, and has demonstrated antidepressant activity in rodents. We investigated the antidepressant properties of MB and selected structural analogues and whether their actions involve MAO, NO synthase (NOS) and regional brain monoamines. Acute imipramine (IMI, 15 mg/kg), saline, MB, acriflavine (ACR), methylene green (MG), methylene violet (MV), thionine (THI) and tacrine (TAC) (1-60 mg/kg i.p.) were tested for antidepressant activity in the forced swim test (FST), as well as MAO-A/B inhibitory activity. Active antidepressant compounds were subsequently studied at their most effective dose during sub-chronic treatment, followed by behavioural sampling in the FST and assay of cortico-limbic monoamines and hippocampal nitrate (for NOS activity). Only IMI, MB (15, 30, 60 mg/kg) and MG (7.5, 25, 40 mg/kg) reduced immobility in the acute FST. MB, MG and ACR were potent inhibitors of especially MAO-A. Following sub-chronic treatment, IMI (15 mg/kg) increased noradrenergic behaviour in the FST, while MB (15 mg/kg) and MG (15 mg/kg) enhanced serotonergic behaviour. MB and MG bolstered cortico-limbic serotonin (5HT) levels and to a lesser extent l-norepinephrine (l-NE), but did not significantly alter regional dopamine (DA) levels. MB, and to lesser degree MG, reduced hippocampal nitrate levels. MB and MG present with structure-specific antidepressant-like effects following acute and sub-chronic treatment, possibly involving NOS and MAO-A inhibition and cortico-limbic 5HT and l-NE release. A role for MAO-B and DA appears minimal. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Ozone Depletion from Nearby Supernovae

    NASA Technical Reports Server (NTRS)

    Gehrels, Neil; Laird, Claude M.; Jackman, Charles H.; Cannizzo, John K.; Mattson, Barbara J.; Chen, Wan; Bhartia, P. K. (Technical Monitor)

    2002-01-01

    Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made also in theoretical modeling of supernovae and of the resultant gamma ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma rays and cosmic rays. We find that for the combined ozone depletion from these effects roughly to double the 'biologically active' UV flux received at the surface of the Earth, the supernova must occur at approximately or less than 8 parsecs.

  11. Ozone depletion, paradigms, and politics

    SciTech Connect

    Iman, R.L.

    1993-10-01

    The destruction of the Earth`s protective ozone layer is a prime environmental concern. Industry has responded to this environmental problem by: implementing conservation techniques to reduce the emission of ozone-depleting chemicals (ODCs); using alternative cleaning solvents that have lower ozone depletion potentials (ODPs); developing new, non-ozone-depleting solvents, such as terpenes; and developing low-residue soldering processes. This paper presents an overview of a joint testing program at Sandia and Motorola to evaluate a low-residue (no-clean) soldering process for printed wiring boards (PWBs). Such processes are in widespread use in commercial applications because they eliminate the cleaning operation. The goal of this testing program was to develop a data base that could be used to support changes in the mil-specs. In addition, a joint task force involving industry and the military has been formed to conduct a follow-up evaluation of low-residue processes that encompass the concerns of the tri-services. The goal of the task force is to gain final approval of the low-residue technology for use in military applications.

  12. Validity of urinary monoamine assay sales under the “spot baseline urinary neurotransmitter testing marketing model”

    PubMed Central

    Hinz, Marty; Stein, Alvin; Uncini, Thomas

    2011-01-01

    Spot baseline urinary monoamine assays have been used in medicine for over 50 years as a screening test for monoamine-secreting tumors, such as pheochromocytoma and carcinoid syndrome. In these disease states, when the result of a spot baseline monoamine assay is above the specific value set by the laboratory, it is an indication to obtain a 24-hour urine sample to make a definitive diagnosis. There are no defined applications where spot baseline urinary monoamine assays can be used to diagnose disease or other states directly. No peer-reviewed published original research exists which demonstrates that these assays are valid in the treatment of individual patients in the clinical setting. Since 2001, urinary monoamine assay sales have been promoted for numerous applications under the “spot baseline urinary neurotransmitter testing marketing model”. There is no published peer-reviewed original research that defines the scientific foundation upon which the claims for these assays are made. On the contrary, several articles have been published that discredit various aspects of the model. To fill the void, this manuscript is a comprehensive review of the scientific foundation and claims put forth by laboratories selling urinary monoamine assays under the spot baseline urinary neurotransmitter testing marketing model. PMID:21912487

  13. Issues in Stratospheric Ozone Depletion.

    NASA Astrophysics Data System (ADS)

    Lloyd, Steven Andrew

    Following the announcement of the discovery of the Antarctic ozone hole in 1985 there have arisen a multitude of questions pertaining to the nature and consequences of polar ozone depletion. This thesis addresses several of these specific questions, using both computer models of chemical kinetics and the Earth's radiation field as well as laboratory kinetic experiments. A coupled chemical kinetic-radiative numerical model was developed to assist in the analysis of in situ field measurements of several radical and neutral species in the polar and mid-latitude lower stratosphere. Modeling was used in the analysis of enhanced polar ClO, mid-latitude diurnal variation of ClO, and simultaneous measurements of OH, HO_2, H_2 O and O_3. Most importantly, such modeling was instrumental in establishing the link between the observed ClO and BrO concentrations in the Antarctic polar vortex and the observed rate of ozone depletion. The principal medical concern of stratospheric ozone depletion is that ozone loss will lead to the enhancement of ground-level UV-B radiation. Global ozone climatology (40^circS to 50^ circN latitude) was incorporated into a radiation field model to calculate the biologically accumulated dosage (BAD) of UV-B radiation, integrated over days, months, and years. The slope of the annual BAD as a function of latitude was found to correspond to epidemiological data for non-melanoma skin cancers for 30^circ -50^circN. Various ozone loss scenarios were investigated. It was found that a small ozone loss in the tropics can provide as much additional biologically effective UV-B as a much larger ozone loss at higher latitudes. Also, for ozone depletions of > 5%, the BAD of UV-B increases exponentially with decreasing ozone levels. An important key player in determining whether polar ozone depletion can propagate into the populated mid-latitudes is chlorine nitrate, ClONO_2 . As yet this molecule is only indirectly accounted for in computer models and field

  14. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A

    SciTech Connect

    Brunner, H.G. ); Nelen, M.; Ropers, H.H.; van Oost, B.A. )

    1993-10-22

    Genetic and metabolic studies have been done on a large kindred in which several males are affected by a syndrome of borderline mental retardation and abnormal behavior. The types of behavior that occurred include impulsive aggression, arson, attempted rape, and exhibitionism. Analysis of 24-hour urine samples indicated markedly disturbed monoamine metabolism. This syndrome was associated with a complete and selective deficiency of enzymatic activity of monoamine oxidase A (MAOA). In each of five affected males, a point mutation was identified in the eighth exon of the MAOA structural gene, which changes a glutamine to a termination codon. Thus, isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.

  15. Frightening music triggers rapid changes in brain monoamine receptors: a pilot PET study.

    PubMed

    Zhang, Ying; Chen, Qiaozhen; Du, Fenglei; Hu, Yanni; Chao, Fangfang; Tian, Mei; Zhang, Hong

    2012-10-01

    Frightening music can rapidly arouse emotions in listeners that mimic those from actual life-threatening experiences. However, studies of the underlying mechanism for perceiving danger created by music are limited. We investigated monoamine receptor changes induced by frightening music using (11)C-N-methyl-spiperone ((11)C-NMSP) PET. Ten healthy male volunteers were included, and their psychophysiologic changes were evaluated. Compared with the baseline condition, listening to frightening music caused a significant decrease in (11)C-NMSP in the right and left caudate nuclei, right limbic region, and right paralimbic region; a particularly significant decrease in the right anterior cingulate cortex; but an increase in the right frontal occipital and left temporal lobes of the cerebral cortex. Transient fright triggers rapid changes in monoamine receptors, which decrease in the limbic and paralimbic regions but increase in the cerebral cortex.

  16. [Liver monoamine oxidase activity of the lamprey Lampetra fluviatilis. the substrate-inhibitory specificity].

    PubMed

    Iagodina, O V; Basova, I N

    2013-01-01

    Based on data of substrate-inhibitory analysis with use of specific inhibitors--deprenyl, chlorgi-lin--and specific substrates--serotonin, noradrenalin, benzylamine, beta-phenylethylamine, and N-methylhistamine--a suggestion is put forward about the possible existence of one molecular form of monoamine oxidase (MAO) in liver of mature individuals of the European lamprey Lampetra fluviatilis. There are determined kinetic parameters of monoamine oxidase deamination of eight substrates, which indicates the large spectrum of substrate specificity of the lamprey liver MAO. The studied enzyme does not deaminate histamine and putrescine and is not sensitive to 10(-2) M semicarbaside. Results of study of the substrate-inhibitor specificity allow us to suggest some resemblance of catalytic properties of the lamprey liver MAO and the mammalian form A MAO. The revealed low activity of the enzyme at deamination of all used substrates seems to be connected with low detoxational functional of the lamprey liver.

  17. [SENSITIVITY OF LIVER MONOAMINE OXIDASE IN THE LAMPREY LAMPETRA FLUVIATILIS TO SOME TRICYCLIC COMPOUNDS].

    PubMed

    Basova, L N; Basova, N E; Suvorov, A A; Yagodina, O V

    2015-01-01

    A comparative analysis of the effect of the five acridine, three phenothiazine and one xanten (pyronine G) derivatives on the activity of liver mitochondrial monoamine oxidase (MAO) in sexually mature male river lampreys Lampetra fluviatilis has been conducted. Tyramine, dopamine, serotonin, noradrenaline, benzylamine, β-phenylethylamine and N-methylhistamine have been used as substrates for analyzing the monoamine oxidase activity of heterocyclic compounds. The analyzed synthetic hexamerous tricyclic compounds exhibit irreversible inhibition of the enzyme but no specificity depending on the desaminated substrate. The number and identity of heteroatoms in the analyzed heterocyclic compounds have been established to influence their inhibitory efficiency. The data of substrate-inhibitory analysis obtained with the use of the specific substrates provide indirect evidence for the existence of a single MAO form in the lamprey liver.

  18. The neuroprotective role of vesicular monoamine transporter 2 in neurodegenerative diseases.

    PubMed

    Yulug, Burak; Hanoglu, Lutfu; Kilic, Ertugrul

    2015-01-01

    Neuropharmacological relation of religious belief supports the role of dopaminergic activation as the leading neurochemical feature. However, vesicular monoamine transporter-2 (VMAT-2) has been shown to be responsible for removing of neurotransmitters such as dopamine that may secondarily lead to a neuroprotective activity by different neurodegeneration models. Moreover, there are interesting data showing that VMAT-2 may play an important role during religious belief and experience. In the light of these findings, we aimed to review the preclinical and clinical neuroprotective data of Vesicular monoamine transporter (VMAT-2) in different neurodegenerative and neuropsychiatric diseases. In respect of rapidly increasing evidences about the neurobiological and neuroimaging correlates of religious belief, we hypothesized that there is a link between belief and neuroprotection.

  19. Distinct effects of the serotonin-noradrenaline reuptake inhibitors milnacipran and venlafaxine on rat pineal monoamines.

    PubMed

    Muneoka, Katsumasa; Kuwagata, Makiko; Ogawa, Tetsuo; Shioda, Seiji

    2015-06-17

    Monoamine systems are involved in the pathology and therapeutic mechanism of depression. The pineal gland contains large amounts of serotonin as a precursor for melatonin, and its activity is controlled by noradrenergic sympathetic nerves. Pineal diurnal activity and its release of melatonin are relevant to aberrant states observed in depression. We investigated the effects on pineal monoamines of serotonin-noradrenaline reuptake inhibitors, which are widely used antidepressants. Four days of milnacipran treatment led to an increase in noradrenaline and serotonin levels, whereas 4 days of venlafaxine treatment reduced 5-hydroxyindoleacetic acid levels; both agents induced an increase in dopamine levels. Our data suggest that milnacipran increases levels of the precursor for melatonin synthesis by facilitating the noradrenergic regulation of pineal activity and that venlafaxine inhibits serotonin reuptake into noradrenergic terminals on the pineal gland.

  20. [The effect of electromagnetic radiation on the monoamine oxidase A activity in the rat brain].

    PubMed

    Dolgacheva, L P; Semenova, T P; Abzhalelov, B B; Akoev, I G

    2000-01-01

    The effect of the ultralow power pulse-modulated electromagnetic radiation (EMR, power density 10 microW/cm2; carrying frequency 915 MHz; modulating pulses with frequency 2, 4, 6, 8, 12, 16 and 20 Hz) on activity of monoamine oxidase (MAO-A), enzyme involved in the oxidative deamination of monoamines, was investigated. It was established that the increase of activity MAO in hypothalamus reached the maximal meaning at modulation frequency of 6 Hz that corresponded 160% (p < 0.01) of the control level; and at modulation frequency of 20 Hz the decrease of enzyme activity up to 74% (p < 0.01) was found. Mainly the action of ultralow power pulse-modulated EMR on activity of MAO in hippocamp was activating; and the maximal increase of enzyme activity up to 174% (p < 0.01) was registered at modulation frequency of 4 Hz.

  1. Specificity study on concentration of monoamine transmitters at acupoint and effect of acupuncture on its distribution.

    PubMed

    Luo, Ting; Guo, Yi

    2014-01-01

    To investigate the distribution of monoamine transmitters at acupoints and effect of acupuncture on it. Take this experiment by means of microdialysis. Twenty rabbits were randomly assigned to two groups (Group A: acupuncture Guanyuan (RN4), Group B: acupuncture nonacupoint which is besides Guanyuan (RN4) 1 cm). Before and after acupuncture was taken, tissue fluids both at Zhongwan (RN12) which is on the same meridian as Guanyuan and at a nonacupoint 1 cm away from Zhongwan were collected through microdialysis, respectively. The collected samples were analyzed to determine concentrations of monoamine transmitters. Epinephrine and 5-HT were detected. An unknown substance was found. Its concentration at acupoint was significantly higher than that at nonacupoint and decreased after acupuncture. Its significant specificity at acupoints suggests that it may play an important role in meridian's activity.

  2. Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder

    SciTech Connect

    Lim, L.C.C.; Sham, P.; Castle, D.

    1995-08-14

    We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significantly only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant. 58 refs., 1 fig., 3 tabs.

  3. Potent and Selective Inhibition of Plasma Membrane Monoamine Transporter by HIV Protease Inhibitors

    PubMed Central

    Duan, Haichuan; Hu, Tao; Foti, Robert S.; Pan, Yongmei; Swaan, Peter W.

    2015-01-01

    Plasma membrane monoamine transporter (PMAT) is a major uptake-2 monoamine transporter that shares extensive substrate and inhibitor overlap with organic cation transporters 1–3 (OCT1–3). Currently, there are no PMAT-specific inhibitors available that can be used in in vitro and in vivo studies to differentiate between PMAT and OCT activities. In this study, we showed that IDT307 (4-(4-(dimethylamino)phenyl)-1-methylpyridinium iodide), a fluorescent analog of 1-methyl-4-phenylpyridinium (MPP+), is a transportable substrate for PMAT and that IDT307-based fluorescence assay can be used to rapidly identify and characterize PMAT inhibitors. Using the fluorescent substrate-based assays, we analyzed the interactions of eight human immunodeficiency virus (HIV) protease inhibitors (PIs) with human PMAT and OCT1–3 in human embryonic kidney 293 (HEK293) cells stably transfected with individual transporters. Our data revealed that PMAT and OCTs exhibit distinct sensitivity and inhibition patterns toward HIV PIs. PMAT is most sensitive to PI inhibition whereas OCT2 and OCT3 are resistant. OCT1 showed an intermediate sensitivity and a distinct inhibition profile from PMAT. Importantly, lopinavir is a potent PMAT inhibitor and exhibited >120 fold selectivity toward PMAT (IC50 = 1.4 ± 0.2 µM) over OCT1 (IC50 = 174 ± 40 µM). Lopinavir has no inhibitory effect on OCT2 or OCT3 at maximal tested concentrations. Lopinavir also exhibited no or much weaker interactions with uptake-1 monoamine transporters. Together, our results reveal that PMAT and OCTs have distinct specificity exemplified by their differential interaction with HIV PIs. Further, we demonstrate that lopinavir can be used as a selective PMAT inhibitor to differentiate PMAT-mediated monoamine and organic cation transport from those mediated by OCT1–3. PMID:26285765

  4. Synthesis, inhibition and binding of simple non-nitrogen inhibitors of monoamine transporters.

    PubMed

    Petersen, Mikkel Due; Boye, Søren Valdgård; Nielsen, Erik Holm; Willumsen, Jeanette; Sinning, Steffen; Wiborg, Ove; Bols, Mikael

    2007-06-15

    A series of simple truncated analogues of phenyl tropanes, 2-arylcycloalk-1-enyl carboxylic acid methylesters, were prepared and investigated for their activity towards the dopamine, serotonin and norepinephrine transporters. The compounds were prepared from cyclic ketoesters, which were converted to enolic triflates and reacted with arylboronates using the Suzuki coupling. For comparison the corresponding piperidines were also made and investigated. The new compounds inhibit monoamine-transporters with Ki values ranging from 0.1 to 1000 microM.

  5. Altered monoamine and acylcarnitine metabolites in HIV-positive and HIV-negative subjects with depression

    PubMed Central

    Cassol, Edana; Misra, Vikas; Morgello, Susan; Kirk, Gregory D.; Mehta, Shruti H.; Gabuzda, Dana

    2015-01-01

    Background Depression is a frequent comorbidity in HIV infection that has been associated with worse treatment outcomes and increased mortality. Recent studies suggest that increased innate immune activation and tryptophan catabolism are associated with higher risk of depression in HIV infection and other chronic inflammatory diseases, but the mechanisms leading to depression remain poorly understood. Methods The severity of depressive symptoms was assessed by Beck Depression Inventory or Center for Epidemiological Studies Depression Scale. Untargeted metabolomic profiling of plasma from 104 subjects (68 HIV-positive and 36 HIV-negative) across three independent cohorts was performed using liquid or gas chromatography followed by mass spectrometry. Cytokine profiling was by Bioplex array. Bioinformatic analysis was performed in Metaboanalyst and R. Results Decreased monoamine metabolites (phenylacetate, 4-hydroxyphenylacetate) and acylcarnitines (propionylcarnitine, isobutyrylcarnitine, isovalerylcarnitine, 2-methylbutyrylcarnitine) in plasma distinguished depressed subjects from controls in HIV-positive and HIV-negative cohorts, and these alterations correlated with the severity of depressive symptoms. In HIV-positive subjects, acylcarnitines and other markers of mitochondrial function correlated inversely with tryptophan catabolism, a marker of IFN responses, suggesting inter-relationships between inflammatory pathways, tryptophan catabolism, and metabolic alterations associated with depression. Altered metabolites mapped to pathways involved in monoamine metabolism, mitochondrial function, and inflammation, suggesting a model in which complex relationships between monoamine metabolism and mitochondrial bioenergetics contribute to biological mechanisms involved in depression that may be augmented by inflammation during HIV infection. Conclusions Integrated approaches targeting inflammation, monoamine metabolism, and mitochondrial pathways may be important for

  6. Mercurial induced brain monoamine oxidase inhibition in the teleost Channa punctatus (Bloch)

    SciTech Connect

    Ram, R.N.; Sathyanesan, A.G.

    1985-11-01

    Neurotoxic effects of mercurials are well established in a variety of animals including man. In mammals, mercury is known to alter brain monamine synthesis, high affinity uptake and central catecholamine development. However, such investigations on the fishes are meager. In the present communication, mercuric chloride (HgCl2) and organic mercurial fungicide Emisan induced changes in the brain monoamine oxidase (MAO) content in the fish C. punctatus are described.

  7. [Effects of acrylonitrile in drinking water on monoamine neurotransmitters and its metabolites in male rat brains].

    PubMed

    Lu, Rong-zhu; Chen, Zi-qiang; Jin, Fu-sheng

    2005-03-01

    To elucidate the possible involvement of monoamine neurotransmitters in the development of neurobehavioral damage produced by acrylonitrile in drinking water in male rat brains. Totally 30 male SD rats were randomly divided into three groups, the control group (n = 10), low dosage group (n = 10), and high dosage group (n = 10), which were respectively administered 0 mg/L, 50 mg/L, 200 mg/L acrylonitrile (AN) in drinking water. The treatment was lasted for 12 weeks. Seven animals were randomly selected from each group for determination of monoamine neurotransmitters in striatum and cerebellum by high performance liquid chromatography with electrochemical detector and activities of monoamine oxidase in cortex. The contents of dopamine in the striatum of low and high dosage groups were decreased to (2.2 +/- 0.7) and (3.2 +/- 2.0) microg/g wet tissue, respectively, and compared with that of control group (9.0 +/- 4.2) microg/g wet tissue, the differences were statistically significant. There were no statistical differences among the contents of dopamine in the cerebellum of all rats, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine in the cerebellum were (186 +/- 41), (245 +/- 90) and (115 +/- 65) ng/g wet tissue in the control, low and high dosage groups, respectively and in low-dosage group they were significantly higher than those in other groups. There was dosage-dependently decreasing of the contents of serotonin of striatum in the control (249 +/- 34) ng/g wet tissue, low dosage (155 +/- 95) ng/g wet tissue and high dosage groups (128 +/- 101) ng/g wet tissue. This study underlines the importance of alterations in the monoamine neurotransmitters system as a possible causative mechanism behind the behavioural and functional changes produced by acrylonitrile.

  8. Monoamine oxidase A gene promoter polymorphism affects novelty seeking and reward dependence in healthy study participants.

    PubMed

    Shiraishi, Hiroaki; Suzuki, Akihito; Fukasawa, Takashi; Aoshima, Toshiaki; Ujiie, Yukihiro; Ishii, Genki; Otani, Koichi

    2006-04-01

    It has been suggested that monoamine oxidase A plays an important role in the characterization of personality. Previous studies on the association between the polymorphism of variable number tandem repeat in the promoter region of the monoamine oxidase A gene and personality traits have, however, been unproductive. In the present study, the association between the monoamine oxidase A variable number tandem repeat polymorphism and personality traits assessed by the Temperament and Character Inventory was examined in 324 Japanese volunteers without psychiatric disorders. The low activity allele with three repeats (allele 3) and high activity allele with four repeats (allele 4) were determined by a polymerase chain reaction method. The carriers of allele 3 in males and the homozygotes of allele 3 in females were classified as the low activity group, the heterozygotes of alleles 3 and 4 in females as the medium activity group, and the carriers of allele 4 in males and the homozygotes of allele 4 in females as the high activity group. One-way analysis of variance showed that the scores of novelty seeking (P=0.006) and reward dependence (P=0.013) were significantly higher in the high activity group than in the low activity group. Multiple regression analysis demonstrated that the excess in the high activity allele was significantly associated with higher scores of novelty seeking (P=0.004) and reward dependence (P=0.003). The present study thus suggests that the monoamine oxidase A variable number tandem repeat polymorphism affects novelty seeking and reward dependence in healthy study participants.

  9. Peripheral blood gene expression profiles linked to monoamine metabolite levels in cerebrospinal fluid

    PubMed Central

    Luykx, J J; Olde Loohuis, L M; Neeleman, M; Strengman, E; Bakker, S C; Lentjes, E; Borgdorff, P; van Dongen, E P A; Bruins, P; Kahn, R S; Horvath, S; de Jong, S; Ophoff, R A

    2016-01-01

    The blood–brain barrier separates circulating blood from the central nervous system (CNS). The scope of this barrier is not fully understood which limits our ability to relate biological measurements from peripheral to central phenotypes. For example, it is unknown to what extent gene expression levels in peripheral blood are reflective of CNS metabolism. In this study, we examine links between central monoamine metabolite levels and whole-blood gene expression to better understand the connection between peripheral systems and the CNS. To that end, we correlated the prime monoamine metabolites in cerebrospinal fluid (CSF) with whole-genome gene expression microarray data from blood (N=240 human subjects). We additionally applied gene-enrichment analysis and weighted gene co-expression network analyses (WGCNA) to identify modules of co-expressed genes in blood that may be involved with monoamine metabolite levels in CSF. Transcript levels of two genes were significantly associated with CSF serotonin metabolite levels after Bonferroni correction for multiple testing: THAP7 (P=2.8 × 10−8, β=0.08) and DDX6 (P=2.9 × 10−7, β=0.07). Differentially expressed genes were significantly enriched for genes expressed in the brain tissue (P=6.0 × 10−52). WGCNA revealed significant correlations between serotonin metabolism and hub genes with known functions in serotonin metabolism, for example, HTR2A and COMT. We conclude that gene expression levels in whole blood are associated with monoamine metabolite levels in the human CSF. Our results, including the strong enrichment of brain-expressed genes, illustrate that gene expression profiles in peripheral blood can be relevant for quantitative metabolic phenotypes in the CNS. PMID:27959337

  10. Tianeptine in combination with monoamine oxidase inhibitors for major depressive disorder.

    PubMed

    Tobe, Edward H

    2012-10-09

    Major depressive disorder may respond to monotherapy with monoamine oxidase inhibitors (MAOIs) or tianeptine. Literature search showed no reports of MAOIs combined with tianeptine. The method included was clinical case history. A 59-year-old woman had partial improvement of depression with the MAOI tranylcypromine combined with topiramate, trazodone and ziprasidone. The patient had further improvement of depression symptoms after addition of tianeptine. No adverse events were evident. The combination of MAIOs and tianeptine may be effective for refractory major depressive disorder.

  11. Monoamine fluctuations during the reproductive cycle of the Pacific lion's paw scallop Nodipecten subnodosus.

    PubMed

    López-Sánchez, J Armando; Maeda-Martínez, Alfonso N; Croll, Roger P; Acosta-Salmón, Héctor

    2009-11-01

    The Pacific lion's paw scallop Nodipecten subnodosus has been one of the most important commercial species of mollusc in the Baja California peninsula in Mexico since 1990. This species is a functional hermaphrodite with tropical and sub-tropical distributions and experiences wide annual temperature oscillations influencing its physiological functions. We determined norepinephrine (NE), dopamine (DA), and serotonin (5-HT) concentrations in different organs (female and male gonads, digestive gland, adductor muscle, gill, mantle, and foot) of N. subnodosus, at 6 reproductive stages (resting, initial, maturing, mature, partially spent and fully spent). Monoamine concentrations were determined by HPLC fitted with an electrochemical detector. Results indicated that monoamine concentrations increased during maturing stage, peaked at mature stage and declined after spawning. NE concentrations were higher than the rest of monoamines followed by DA, and 5-HT. NE was present in all organs at all reproductive stages. DA concentrations were higher in the gill and digestive gland during all stages. 5-HT was only detectable in the male gonadic portion at all stages except at spent stage. NE was the most abundant neurotransmitter found in the female gonad of N. subnodosus, while 5-HT was the most abundant neurotransmitter found in the male gonad. Furthermore, these two neurotransmitters accumulated in the respective gonad tissues during the initial reproductive stages I to IV and then declined after spawning (stages V and VI). This suggests that this species utilized different neurotransmitters specific for each gender and that this utilization was related to the reproductive cycle.

  12. L-deprenyl in Alzheimer's disease. Preliminary evidence for behavioral change with monoamine oxidase B inhibition.

    PubMed

    Tariot, P N; Cohen, R M; Sunderland, T; Newhouse, P A; Yount, D; Mellow, A M; Weingartner, H; Mueller, E A; Murphy, D L

    1987-05-01

    Since monoamine neurotransmitter disturbances exist in some cases of dementia of the Alzheimer's type (DAT), monoamine-enhancing drugs may ameliorate some symptoms of DAT. L-Deprenyl is a monoamine oxidase (MAO) inhibitor that is generally free of undesired effects. At low doses (10 mg/d) it selectively inhibits MAO-B, an enzyme whose level is elevated in the brains of patients with DAT who are studied post mortem. At higher doses it has more complex effects, including inhibition of MAO-A plus MAO-B. We administered 10 mg/d and 40 mg/d of L-deprenyl to 17 patients with DAT in a double-blind, placebo-controlled, serial treatment. Total Brief Psychiatric Rating Scale scores decreased significantly during 10-mg/d treatment, with decreases in measures of anxiety/depression, tension, and excitement. Approximately one half of the patients' conditions were judged to be improved clinically, with evidence of increased activity and social interaction along with reduced tension and retardation. Similar but smaller changes were observed during 40-mg/d treatment. The behavioral changes were associated with improvement in performance on a complex cognitive task requiring sustained effort. There were minimal physiologic and side effects. The greater effect of low-dose L-deprenyl therapy suggests that it is the inhibition of MAO-B, and not MAO-A, that may be important in the behavioral effects of L-deprenyl administration to patients with DAT.

  13. Cloning, sequencing and heterologous expression of the monoamine oxidase gene from Aspergillus niger.

    PubMed

    Schilling, B; Lerch, K

    1995-05-20

    The gene encoding the flavin-containing monoamine oxidase (MAO-N) of the filamentous fungus Aspergillus niger was cloned. MAO-N is the first nonvertebrate monoamine oxidase described to date. Three partial cDNA clones, isolated from an expression library, were used to identify and clone the structural gene (maoN) from an A. niger genomic DNA library. The maoN gene was sequenced, and analysis revealed an open reading frame that codes for a protein of 495 amino acids with a calculated molecular mass of 55.6 kDa. Sequencing of an internal proteolytic fragment of the purified enzyme confirmed the derived amino acid sequence. Analysis of the deduced amino acid sequence indicates that MAO-N is structurally related to the human monoamine oxidases MAO-A and MAO-B. In particular, the regions known to be involved in the binding of the FAD cofactor show a high degree of homology; however, the conserved cysteine residue to which the flavin cofactor is covalently bound in the mammalian forms is absent in the fungal enzyme. MAO-N has the C-terminal tripeptide Ala-Arg-Leu, which corresponds to the consensus targeting sequence found in many peroxisomal enzymes. The full-length cDNA for MAO-N was expressed in Escherichia coli from the T7 promoter of the expression vector pET3a, yielding a soluble and fully active enzyme form.

  14. The monoamine hypothesis for the pathophysiology of paraphilic disorders: an update.

    PubMed

    Kafka, Martin P

    2003-06-01

    A monoamine hypothesis for the pathophysiology of paraphilic disorders was first articulated in 1997 by Kafka. This hypothesis was based on four converging lines of empirical evidence. First, the monoamine neurotransmitters, dopamine, norepinephrine, and serotonin serve a modulatory role in human and mammalian sexual motivation, appetitive, and consummatory behavior. Second, the sexual effects of pharmacological agents that affect monoamine neurotransmitters can have both significant facilitative and inhibitory effects on sexual behavior. Third, paraphilic disorders appear to have Axis I comorbid associations with nonsexual psychopathologies that are associated with monoaminergic dysregulation. Last, pharmacological agents that enhance central serotonergic function in particular, have been reported to ameliorate paraphilic sexual arousal and behavior. Contemporary data supporting or refuting a monoaminergic hypothesis as a biological component associated with paraphilic sex offending behaviors will be reviewed. Particular attention will be given to pharmacological-metabolic probe studies, reports of Axis I comorbidity, the proposed role of disinhibited sexual motivation or sexual appetitive behavior, and cumulative pharmacological treatment data sets.

  15. No association between a TPH2 promoter polymorphism and mood disorders or monoamine turnover.

    PubMed

    Mann, J John; Currier, Dianne; Murphy, Lauren; Huang, Yung-yu; Galfalvy, Hanga; Brent, David; Greenhill, Laurence; Oquendo, Maria

    2008-02-01

    Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. TPH2 is a recently discovered isoform that is expressed predominantly in serotonin neurons. Associations are reported of TPH2 polymorphisms with MDD, bipolar disorder and suicidal behavior. This study examines a single nucleotide polymorphism in the putative promoter region of the TPH2 gene. One hundred nine bipolar, 324 major depressive disorder, and 130 healthy volunteers were genotyped for the rs4131347 (-C8347G) promoter SNP. Association was assessed with diagnosis, suicide attempt status, severity of psychopathology and cerebrospinal fluid monoamine metabolite levels of 5-HIAA, HVA, and MHPG. General linear models and logistic regression tested the effect of genotype*childhood abuse interactions on psychopathology severity and suicide attempt. There was no association between genotype and either mood disorder, suicide attempt status, psychopathology severity or CSF monoamine metabolite levels. No association was detected between the rs4131347 (-C8347G) SNP in the promoter region of the TPH2 gene and mood disorders, suicidal behavior or monoamine function.

  16. Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B knockout mice.

    PubMed

    Singh, Chanpreet; Bortolato, Marco; Bali, Namrata; Godar, Sean C; Scott, Anna L; Chen, Kevin; Thompson, Richard F; Shih, Jean C

    2013-07-30

    The monoamine oxidase isoenzymes (MAOs) A and B play important roles in the homeostasis of monoaminergic neurotransmitters. The combined deficiency of MAO A and B results in significantly elevated levels of serotonin (5-hydroxytryptamine), norepinephrine, dopamine, and β-phenylethylamine; in humans and mice, these neurochemical changes are accompanied by neurodevelopmental perturbations as well as autistic-like responses. Ample evidence indicates that normal levels of monoamines in the hippocampus, amygdala, frontal cortex, and cerebellum are required for the integrity of learning and memory. Thus, in the present study, the cognitive status of MAO A/B knockout (KO) mice was examined with a wide array of behavioral tests. In comparison with male wild-type littermates, MAO A/B KO mice exhibited abnormally high and overgeneralized fear conditioning and enhanced eye-blink conditioning. These alterations were accompanied by significant increases in hippocampal long-term potentiation and alterations in the relative expression of NMDA glutamate receptor subunits. Our data suggest that chronic elevations of monoamines, because of the absence of MAO A and MAO B, cause functional alterations that are accompanied with changes in the cellular mechanisms underlying learning and memory. The characteristics exhibited by MAO A/B KO mice highlight the potential of these animals as a useful tool to provide further insight into the molecular bases of disorders associated with abnormal monoaminergic profiles.

  17. SDS-resistant aggregation of membrane proteins: application to the purification of the vesicular monoamine transporter.

    PubMed Central

    Sagné, C; Isambert, M F; Henry, J P; Gasnier, B

    1996-01-01

    The vesicular monoamine transporter, which catalyses a H+/ monoamine antiport in monoaminergic vesicle membrane, is a very hydrophobic intrinsic membrane protein. After solubilization, this protein was found to have a high tendency to aggregate, as shown by SDS/PAGE, especially when samples were boiled in the classical Laemmli buffer before electrophoresis. This behavior was analysed in some detail. The aggregation was promoted by high temperatures, organic solvents and acidic pH, suggesting that it resulted from the unfolding of structure remaining in SDS. The aggregates were very stable and could be dissociated only by suspension in anhydrous trifluoroacetic acid. This SDS-resistant aggregation behaviour was shared by very few intrinsic proteins of the chromaffin granule membrane. Consequently, a purification procedure was based on this property. A detergent extract of chromaffin granule membranes enriched in monoamine transporter was heated and the aggregates were isolated by size-exclusion HPLC in SDS. The aggregates, containing the transporter, were dissociated in the presence of trifluoroacetic acid and analysed on the same HPLC column. This strategy might be of general interest for the purification of membrane proteins that exhibit SDS-resistant aggregation. PMID:8670158

  18. Distribution of monoamines and metabolites in rabbit neostriatum, hippocampus and cortex.

    PubMed

    Reader, T A; Dewar, K M; Grondin, L

    1989-09-01

    The monoamines noradrenaline (NA), dopamine (DA), adrenaline (AD) and 5-hydroxytryptamine (5-HT) were assayed in the putamen (PUT), the lateral (lCAU) and medial (mCAU) portions of the caudate, the dorsal (dHIP) and ventral (vHIP) hippocampus, as well as in four cortical areas, i.e., anterior cingulate (CIN), entorhinal-piriform (EnPi), sensorimotor (SSC; somatosensory) and primary visual (VIS). The use of an HPLC procedure enabled us to perform these measurements in microdissected samples and to assay as well monoamine metabolites. The DA levels were highest in the neostriatum, moderate in the EnPi and CIN and very low in the SSC, VIS and hippocampus. The distribution of NA was more uniform, although higher concentrations were measured in the neostriatum, hippocampus and EnPi. The largest amounts of 5-HT were in the EnPi, while moderate concentrations were found in the other regions. The ratios between the neurotransmitters and their metabolites were used as an index of turnover and indicate that the terminal fields of the monoamine systems are heterogenous within the neostriatal, hippocampal and cortical subdivisions.

  19. Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury

    PubMed Central

    Kaludercic, Nina; Carpi, Andrea; Menabò, Roberta; Lisa, Fabio Di; Paolocci, Nazareno

    2010-01-01

    Recent evidence highlights monoamine oxidases (MAO) as another prominent source of oxidative stress. MAO are a class of enzymes located in the outer mitochondrial membrane, deputed to the oxidative breakdown of key neurotransmitters such as norepinephrine, epinephrine and dopamine, and in the process generate H2O2. All these monoamines are endowed with potent modulatory effects on myocardial function. Thus, when the heart is subjected to chronic neuro-hormonal and/or peripheral hemodynamic stress, the abundance of circulating/tissue monoamines can make MAO-derived H2O2 production particularly prominent. This is the case of acute cardiac damage due to ischemia/reperfusion injury or, on a more chronic stand, of the transition from compensated hypertrophy to overt ventricular dilation/pump failure. Here, we will first briefly discuss mitochondrial status and contribution to acute and chronic cardiac disorders. We will illustrate possible mechanisms by which MAO activity affects cardiac biology and function, along with a discussion as to their role as a prominent source of reactive oxygen species. Finally, we will speculate on why MAO inhibition might have therapeutic value for treating cardiac affections of ischemic and non-ischemic origin. PMID:20869994

  20. Vesicular monoamine transporter 2 (Vmat2) knockdown elicits anxiety-like behavior in zebrafish.

    PubMed

    Wang, Yali; Li, Siyue; Liu, Wenwen; Wang, Fen; Hu, Li-Fang; Zhong, Zhao-Min; Wang, Han; Liu, Chun-Feng

    2016-02-19

    Vesicular monoamine transporter 2 (Vmat2) is widely distributed in the central nervous system, and responsible for uptaking transmitters into the vesicles. However, whether Vmat2-deficiency is related to the anxiety is rarely investigated, especially in zebrafish. Here, we reported Vmat2 heterzygous mutant zebrafish displayed anxiety-like behavior. The mutants spent less time in the top area and took longer latency to the top in the novel tank test. Consistently, they showed dark avoidance in the light/dark box test, with longer duration in the light zone and increased number of crossing between the two zones. Monoamine concentration analysis showed that the levels of monoamine neurotransmitters including dopamine (DA), 5-hydroxy tryptamine (5-HT) and norepinephrine (NE), as well as their metabolites were decreased in VMAT mutants. Taken together, these findings suggest that Vmat2 heterzygous mutant zebrafish may serve as a new model of anxiety, which may be related with the low level of DA, 5-HT and NE.

  1. A Peroxidase-linked Spectrophotometric Assay for the Detection of Monoamine Oxidase Inhibitors.

    PubMed

    Zhi, Kangkang; Yang, Zhongduo; Sheng, Jie; Shu, Zongmei; Shi, Yin

    2016-01-01

    To develop a new more accurate spectrophotometric method for detecting monoamine oxidase inhibitors from plant extracts, a series of amine substrates were selected and their ability to be oxidized by monoamine oxidase was evaluated by the HPLC method and a new substrate was used to develop a peroxidase-linked spectrophotometric assay. 4-(Trifluoromethyl) benzylamine (11) was proved to be an excellent substrate for peroxidase-linked spectrophotometric assay. Therefore, a new peroxidase-linked spectrophotometric assay was set up. The principle of the method is that the MAO converts 11 into aldehyde, ammonia and hydrogen peroxide. In the presence of peroxidase, the hydrogen peroxide will oxidize 4-aminoantipyrine into oxidised 4-aminoantipyrine which can condense with vanillic acid to give a red quinoneimine dye. The production of the quinoneimine dye was detected at 490 nm by a microplate reader. The ⊿OD value between the blank group and blank negative control group in this new method is twice as much as that in Holt's method, which enables the procedure to be more accurate and avoids the produce of false positive results. The new method will be helpful for researchers to screening monoamine oxidase inhibitors from deep-color plant extracts.

  2. A Peroxidase-linked Spectrophotometric Assay for the Detection of Monoamine Oxidase Inhibitors

    PubMed Central

    Zhi, Kangkang; Yang, Zhongduo; Sheng, Jie; Shu, Zongmei; Shi, Yin

    2016-01-01

    To develop a new more accurate spectrophotometric method for detecting monoamine oxidase inhibitors from plant extracts, a series of amine substrates were selected and their ability to be oxidized by monoamine oxidase was evaluated by the HPLC method and a new substrate was used to develop a peroxidase-linked spectrophotometric assay. 4-(Trifluoromethyl) benzylamine (11) was proved to be an excellent substrate for peroxidase-linked spectrophotometric assay. Therefore, a new peroxidase-linked spectrophotometric assay was set up. The principle of the method is that the MAO converts 11 into aldehyde, ammonia and hydrogen peroxide. In the presence of peroxidase, the hydrogen peroxide will oxidize 4-aminoantipyrine into oxidised 4-aminoantipyrine which can condense with vanillic acid to give a red quinoneimine dye. The production of the quinoneimine dye was detected at 490 nm by a microplate reader. The ⊿OD value between the blank group and blank negative control group in this new method is twice as much as that in Holt’s method, which enables the procedure to be more accurate and avoids the produce of false positive results. The new method will be helpful for researchers to screening monoamine oxidase inhibitors from deep-color plant extracts. PMID:27610153

  3. Physiological implications of anthropogenic environmental calcium depletion

    Treesearch

    Catherine H. Borer; Paul G. Schaberg; Donald H. DeHayes; Gary J. Hawley

    2001-01-01

    Recent evidence indicates that numerous anthropogenic factors can deplete calcium (Ca) from forested ecosystems. Although it is difficult to quantify the extent of this depletion, some reports indicate that the magnitude of Ca losses may be substantial. The potential for Ca depletion raises important questions about tree health. Only a fraction of foliar Ca is...

  4. Exposure to nature counteracts aggression after depletion.

    PubMed

    Wang, Yan; She, Yihan; Colarelli, Stephen M; Fang, Yuan; Meng, Hui; Chen, Qiuju; Zhang, Xin; Zhu, Hongwei

    2017-08-31

    Acts of self-control are more likely to fail after previous exertion of self-control, known as the ego depletion effect. Research has shown that depleted participants behave more aggressively than non-depleted participants, especially after being provoked. Although exposure to nature (e.g., a walk in the park) has been predicted to replenish resources common to executive functioning and self-control, the extent to which exposure to nature may counteract the depletion effect on aggression has yet to be determined. The present study investigated the effects of exposure to nature on aggression following depletion. Aggression was measured by the intensity of noise blasts participants delivered to an ostensible opponent in a competition reaction-time task. As predicted, an interaction occurred between depletion and environmental manipulations for provoked aggression. Specifically, depleted participants behaved more aggressively in response to provocation than non-depleted participants in the urban condition. However, provoked aggression did not differ between depleted and non-depleted participants in the natural condition. Moreover, within the depletion condition, participants in the natural condition had lower levels of provoked aggression than participants in the urban condition. This study suggests that a brief period of nature exposure may restore self-control and help depleted people regain control over aggressive urges. © 2017 Wiley Periodicals, Inc.

  5. The Case of Ozone Depletion

    NASA Technical Reports Server (NTRS)

    Lambright, W. Henry

    2005-01-01

    While the National Aeronautics and Space Administration (NASA) is widely perceived as a space agency, since its inception NASA has had a mission dedicated to the home planet. Initially, this mission involved using space to better observe and predict weather and to enable worldwide communication. Meteorological and communication satellites showed the value of space for earthly endeavors in the 1960s. In 1972, NASA launched Landsat, and the era of earth-resource monitoring began. At the same time, in the late 1960s and early 1970s, the environmental movement swept throughout the United States and most industrialized countries. The first Earth Day event took place in 1970, and the government generally began to pay much more attention to issues of environmental quality. Mitigating pollution became an overriding objective for many agencies. NASA's existing mission to observe planet Earth was augmented in these years and directed more toward environmental quality. In the 1980s, NASA sought to plan and establish a new environmental effort that eventuated in the 1990s with the Earth Observing System (EOS). The Agency was able to make its initial mark via atmospheric monitoring, specifically ozone depletion. An important policy stimulus in many respects, ozone depletion spawned the Montreal Protocol of 1987 (the most significant international environmental treaty then in existence). It also was an issue critical to NASA's history that served as a bridge linking NASA's weather and land-resource satellites to NASA s concern for the global changes affecting the home planet. Significantly, as a global environmental problem, ozone depletion underscored the importance of NASA's ability to observe Earth from space. Moreover, the NASA management team's ability to apply large-scale research efforts and mobilize the talents of other agencies and the private sector illuminated its role as a lead agency capable of crossing organizational boundaries as well as the science-policy divide.

  6. Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour.

    PubMed

    Desbonnet, Lieve; Clarke, Gerard; Traplin, Alexander; O'Sullivan, Orla; Crispie, Fiona; Moloney, Rachel D; Cotter, Paul D; Dinan, Timothy G; Cryan, John F

    2015-08-01

    There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may

  7. (/sup 11/C)clorgyline and (/sup 11/C)-L-deprenyl and their use in measuring functional monoamine oxidase activity in the brain using positron emission tomography

    DOEpatents

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.

    1986-04-17

    This invention involves a new strategy for imaging the activity of the enzyme monoamine oxidase in the living body by using /sup 11/C-labeled enzyme inhibitors which bind irreversibly to an enzyme as a result of catalysis. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography. 2 figs.

  8. The mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway: a potential site of action of daidzin.

    PubMed

    Rooke, N; Li, D J; Li, J; Keung, W M

    2000-11-02

    Recent studies showed that daidzin suppresses ethanol intake in ethanol-preferring laboratory animals. In vitro, it potently and selectively inhibits the mitochondrial aldehyde dehydrogenase (ALDH-2). Further, it inhibits the conversion of monoamines such as serotonin (5-HT) and dopamine (DA) into their respective acid metabolites, 5-hydroxyindole-3-acetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in isolated hamster or rat liver mitochondria. Studies on the suppression of ethanol intake and inhibition of 5-HIAA (or DOPAC) formation by six structural analogues of daidzin suggested a potential link between these two activities. This, together with the finding that daidzin does not affect the rates of mitochondria-catalyzed oxidative deamination of these monoamines, raised the possibility that the ethanol intake-suppressive (antidipsotropic) action of daidzin is not mediated by the monoamines but rather by their reactive biogenic aldehyde intermediates such as 5-hydroxyindole-3-acetaldehyde (5-HIAL) and/or 3,4-dihydroxyphenylacetaldehyde (DOPAL) which accumulate in the presence of daidzin. To further evaluate this possibility, we synthesized more structural analogues of daidzin and tested and compared their antidipsotropic activities in Syrian golden hamsters with their effects on monoamine metabolism in isolated hamster liver mitochondria using 5-HT as the substrate. Effects of daidzin and its structural analogues on the activities of monoamine oxidase (MAO) and ALDH-2, the key enzymes involved in 5-HT metabolism in the mitochondria, were also examined. Results from these studies reveal a positive correlation between the antidipsotropic activities of these analogues and their abilities to increase 5-HIAL accumulation during 5-HT metabolism in isolated hamster liver mitochondria. Daidzin analogues that potently inhibit ALDH-2 but have no or little effect on MAO are most antidipsotropic, whereas those that also potently inhibit MAO exhibit little, if

  9. Kinetics of Inhibition of Monoamine Oxidase Using Curcumin and Ellagic Acid

    PubMed Central

    Khatri, Dharmendra Kumar; Juvekar, Archana Ramesh

    2016-01-01

    Background: Curcumin and ellagic are the natural polyphenols having a wide range of pharmacological actions. They have been reported to have their use in various neurological disorders. Objective: This study was aimed to evaluate the effect of curcumin and ellagic acid on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters which are pivotal for neuronal development and function. Materials and Methods: The in vitro effects of these selected polyphenols on MAO activities in mitochondria isolated from rat brains were examined. Brain mitochondria were assayed for MAO type-B (MAO-B) using benzylamine as substrates. Rat brain mitochondrial MAO preparation was used to study the kinetics of enzyme inhibition using double reciprocal Lineweaver–Burk plot. Results: MAO activity was inhibited by curcumin and ellagic acid; however, higher half maximal inhibitory concentrations of curcumin (500.46 nM) and ellagic acid (412.24 nM) were required compared to the known MAO-B inhibitor selegiline. It is observed that the curcumin and ellagic acid inhibit the MAO activity with both the competitive and noncompetitive type of inhibitions. Conclusions: Curcumin and ellagic acid can be considered a possible source of MAO inhibitor used in the treatment of Parkinson's and other neurological disorders. SUMMARY Monoamine oxidase (MAO) is involved in a variety of neurological disorders including Parkinson's disease (PD)Curcumin and ellagic acid inhibit the monoamine oxidase activityEllagic acid revealed more potent MAO type-B (MAO-B) inhibitory activity than curcuminKinetic studies of MAO inhibition using different concentrations of curcumin and ellagic acid were plotted as double reciprocal Lineweaver–Burk plotThe mode of inhibition of both compounds toward MAO-B is mixed (competitive and uncompetitive) type of inhibition with both the competitive and noncompetitive type of inhibitions. Abbreviations used: MAO: Monoamine oxidase

  10. Biomedical consequences of ozone depletion

    NASA Astrophysics Data System (ADS)

    Coohill, Thomas P.

    1994-07-01

    It is widely agreed that a portion of the earth's protective stratospheric ozone layer is being depleted. The major effect of this ozone loss will be an increase in the amount of ultraviolet radiation (UV reaching the biosphere. This increase will be completely contained within the UVB (290nm - 320nm). It is imperative that assessments be made of the effects of this additional UVB on living organisms. This requires a detailed knowledge of the UVB photobiology of these life forms. One analytical technique to aid in the approximations is the construction of UV action spectra for such important biological end-points as human skin cancer, cataracts, immune suppression; plant photosynthesis and crop yields; and aquatic organism responses to UVB, especially the phytoplankton. Combining these action spectra with the known solar spectrum (and estimates for various ozone depletion scenarios) can give rise to a series of effectiveness spectra for these parameters. This manuscript gives a first approximation, rough estimate, for the effectiveness spectra for some of these bioresponses, and a series of crude temporary values for how a 10% ozone loss would affect the above end-points. These are not intended to masquerade as final answers, but rather, to serve as beginning attempts for a process which should be continually refined. It is hoped that these estimates will be of some limited use to agencies, such as government and industry, that have to plan now for changes in human activities that might alter future atmospheric chemistry in a beneficial manner.

  11. Effect of co-administration of varenicline and antidepressants on extracellular monoamine concentrations in rat prefrontal cortex.

    PubMed

    Rollema, Hans; Wilson, Gary G; Lee, Theodore C; Folgering, Joost H A; Flik, Gunnar

    2011-01-01

    Since a substantial proportion of smokers have comorbid mood disorders, the smoking cessation aid varenicline might occasionally be prescribed to patients who are simultaneously treated with antidepressants. Given that varenicline is a selective nicotinic acetylcholine receptor partial agonist and not a substrate or inhibitor of drug metabolizing enzymes, pharmacokinetic interactions with various classes of antidepressants are highly unlikely. It is, however, conceivable that varenicline may have a pharmacodynamic effect on antidepressant-evoked increases in central monoamine release. Interactions resulting in excessive transmitter release could cause adverse events such as serotonin syndrome, while attenuation of monoamine release could impact the clinical efficacy of antidepressants. To investigate this we examined whether varenicline administration modulates the effects of the selective serotonin reuptake inhibitor sertraline and the monoamine oxidase inhibitor clorgyline, given alone and combined, on extracellular concentrations of the monoamines serotonin, dopamine, and norepinephrine in rat brain by microdialysis. Given the important role attributed to cortical monoamine release in serotonin syndrome as well as antidepressant activity, the effects on extracellular monoamine concentrations were measured in the medial prefrontal cortex. Responses to maximally effective doses of sertraline or clorgyline and of sertraline plus clorgyline were the same in the absence as in the presence of a relatively high dose of varenicline, which by itself had no significant effect on cortical monoamine release. This is consistent with the binding profile of varenicline that has insufficient affinity for receptors, enzymes, or transporters to inhibit or potentiate the pharmacologic effects of antidepressants. Since varenicline neither diminished nor potentiated sertraline- or clorgyline-induced increases in neurotransmitter levels, combining varenicline with serotonergic

  12. Monoamine Release in the Cat Lumbar Spinal Cord during Fictive Locomotion Evoked by the Mesencephalic Locomotor Region.

    PubMed

    Noga, Brian R; Turkson, Riza P; Xie, Songtao; Taberner, Annette; Pinzon, Alberto; Hentall, Ian D

    2017-01-01

    Spinal cord neurons active during locomotion are innervated by descending axons that release the monoamines serotonin (5-HT) and norepinephrine (NE) and these neurons express monoaminergic receptor subtypes implicated in the control of locomotion. The timing, level and spinal locations of release of these two substances during centrally-generated locomotor activity should therefore be critical to this control. These variables were measured in real time by fast-cyclic voltammetry in the decerebrate cat's lumbar spinal cord during fictive locomotion, which was evoked by electrical stimulation of the mesencephalic locomotor region (MLR) and registered as integrated activity in bilateral peripheral nerves to hindlimb muscles. Monoamine release was observed in dorsal horn (DH), intermediate zone/ventral horn (IZ/VH) and adjacent white matter (WM) during evoked locomotion. Extracellular peak levels (all sites) increased above baseline by 138 ± 232.5 nM and 35.6 ± 94.4 nM (mean ± SD) for NE and 5-HT, respectively. For both substances, release usually began prior to the onset of locomotion typically earliest in the IZ/VH and peaks were positively correlated with net activity in peripheral nerves. Monoamine levels gradually returned to baseline levels or below at the end of stimulation in most trials. Monoamine oxidase and uptake inhibitors increased the release magnitude, time-to-peak (TTP) and decline-to-baseline. These results demonstrate that spinal monoamine release is modulated on a timescale of seconds, in tandem with centrally-generated locomotion and indicate that MLR-evoked locomotor activity involves concurrent activation of descending monoaminergic and reticulospinal pathways. These gradual changes in space and time of monoamine concentrations high enough to strongly activate various receptors subtypes on locomotor activated neurons further suggest that during MLR-evoked locomotion, monoamine action is, in part, mediated by extrasynaptic neurotransmission in

  13. Protective effect of puerarin on lead-induced mouse cognitive impairment via altering activities of acetyl cholinesterase, monoamine oxidase and nitric oxide synthase.

    PubMed

    Liu, Chan-Min; Zheng, Gui-Hong; Ming, Qing-Lei; Sun, Jian-Mei; Cheng, Chao

    2013-05-01

    Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. The present study aimed to investigate the protective effects of puerarin on neurotoxicity in mice exposed to lead. ICR mice were exposed to lead acetate in the drinking water (500 ppm) with or without puerarin coadministration (100 and 200 mgPU/kg intragastrically once daily) for three months. We found puerarin significantly prevented Pb-induced neurotoxicity in a dose-dependent manner, indicated by behavioral indicators. Puerarin also decreased Pb contents in blood and brain. Puerarin increased activities of acetyl cholinesterase (AChE) and monoamine oxidase (MAO) in brain of Pb-treated mice. Moreover, Pb-induced profound elevation of oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of total antioxidant capacity in brain, were suppressed by treatment with puerarin. Puerarin markedly increased NO production and PKA activity in brain of Pb-treated mice. Western blot analysis showed that puerarin dramatically increased the expression levels of nNOS, eNOS and phosphor-Akt in brains of Pb-treated mice. In conclusion, these results suggested that puerarin can inhibit Pb-induced neurotoxicity, at least in part, by suppressing oxidative stress, reversing the Pb-induced alterations in transmitters and enzymes and modulating the PKA/Akt/NOS signaling pathway.

  14. Depleted Argon from Underground Sources

    SciTech Connect

    Back, H. O.; Galbiati, C.; Goretti, A.; Loer, B.; Montanari, D.; Mosteiro, P.; Alexander, T.; Alton, A.; Rogers, H.; Kendziora, C.; Pordes, S.

    2011-04-27

    Argon is a strong scintillator and an ideal target for Dark Matter detection; however {sup 39}Ar contamination in atmospheric argon from cosmic ray interactions limits the size of liquid argon dark matter detectors due to pile-up. Argon from deep underground is depleted in {sup 39}Ar due to the cosmic ray shielding of the earth. In Cortez, Colorado, a CO{sub 2} well has been discovered to contain approximately 600 ppm of argon as a contamination in the CO{sub 2}. We first concentrate the argon locally to 3% in an Ar, N{sub 2}, and He mixture, from the CO{sub 2} through chromatographic gas separation, and then the N{sub 2} and He will be removed by continuous distillation to purify the argon. We have collected 26 kg of argon from the CO{sub 2} facility and a cryogenic distillation column is under construction at Fermilab to further purify the argon.

  15. Depleted uranium disposal options evaluation

    SciTech Connect

    Hertzler, T.J.; Nishimoto, D.D.; Otis, M.D.

    1994-05-01

    The Department of Energy (DOE), Office of Environmental Restoration and Waste Management, has chartered a study to evaluate alternative management strategies for depleted uranium (DU) currently stored throughout the DOE complex. Historically, DU has been maintained as a strategic resource because of uses for DU metal and potential uses for further enrichment or for uranium oxide as breeder reactor blanket fuel. This study has focused on evaluating the disposal options for DU if it were considered a waste. This report is in no way declaring these DU reserves a ``waste,`` but is intended to provide baseline data for comparison with other management options for use of DU. To PICS considered in this report include: Retrievable disposal; permanent disposal; health hazards; radiation toxicity and chemical toxicity.

  16. Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

    PubMed Central

    Koulu, M; Scheinin, M; Kaarttinen, A; Kallio, J; Pyykkö, K; Vuorinen, J; Zimmer, R H

    1989-01-01

    1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A-type of the enzyme, were administered to eight young, healthy male volunteers in a double-blind, random-order, placebo-controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO-B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose-dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non-deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4-dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO-B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose-dependent and MAO-A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO-A inhibition in man. 4. Sympatho-adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose-dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged. PMID

  17. High-voltage-compatible, fully depleted CCDs

    SciTech Connect

    Holland, Stephen E.; Bebek, Chris J.; Dawson, Kyle S.; Emes, JohnE.; Fabricius, Max H.; Fairfield, Jessaym A.; Groom, Don E.; Karcher, A.; Kolbe, William F.; Palaio, Nick P.; Roe, Natalie A.; Wang, Guobin

    2006-05-15

    We describe charge-coupled device (CCD) developmentactivities at the Lawrence Berkeley National Laboratory (LBNL).Back-illuminated CCDs fabricated on 200-300 mu m thick, fully depleted,high-resistivity silicon substrates are produced in partnership with acommercial CCD foundry.The CCDs are fully depleted by the application ofa substrate bias voltage. Spatial resolution considerations requireoperation of thick, fully depleted CCDs at high substrate bias voltages.We have developed CCDs that are compatible with substrate bias voltagesof at least 200V. This improves spatial resolution for a given thickness,and allows for full depletion of thicker CCDs than previously considered.We have demonstrated full depletion of 650-675 mu m thick CCDs, withpotential applications in direct x-ray detection. In this work we discussthe issues related to high-voltage operation of fully depleted CCDs, aswell as experimental results on high-voltage-compatible CCDs.

  18. Changes of brain monoamine levels and physiological indexes during heat acclimation in rats.

    PubMed

    Nakagawa, Hikaru; Matsumura, Takeru; Suzuki, Kota; Ninomiya, Chisa; Ishiwata, Takayuki

    2016-05-01

    Brain monoamines, such as noradrenaline (NA), dopamine (DA), and serotonin (5-HT), regulate many important physiological functions including thermoregulation. The purpose of this study was to clarify changes in NA, DA, and 5-HT levels in several brain regions in response to heat acclimation while also recording body temperature (Tb), heart rate (HR), and locomotor activity (Act). Rats were exposed to a heated environment (32°C) for 3h (3H), 1 day (1D), 7 days, 14 days (14D), 21 days, or 28 days (28D). After heat exposure, each of the following brain regions were immediately extracted and homogenized: the caudate putamen (CPu), preoptic area (PO), dorsomedial hypothalamus (DMH), frontal cortex (FC), and hippocampus (Hip). NA, DA, and 5-HT levels in the extract were measured by high performance liquid chromatography. Although Tb increased immediately after heat exposure, it decreased about 14D later. HR was maintained at a low level throughout heat exposure, and Act tended to increase near the end of heat exposure. After 3H, we observed a marked increase in NA level in the CPu. Although this response vanished after 1D, the level increased again after 28D. DA level in the CPu decreased significantly from 1D to 28D. 5-HT level in the PO and DMH decreased from 1D to 14D. It returned to control levels after 28D with increment of DA level. 5-HT level in the FC decreased at the start of heat exposure, but recovered after 28D; a time point at which DA level also increased. Monoamine levels in the Hip were unchanged after early heat exposure, but both 5-HT and DA levels increased after 28D. These results provide definitive evidence of changes in monoamines in individual brain regions involved in thermoregulation and behavioral, cognitive, and memory function during both acute and chronic heat exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Binding Mode Selection Determines the Action of Ecstasy Homologs at Monoamine Transporters

    PubMed Central

    Sandtner, Walter; Stockner, Thomas; Hasenhuetl, Peter S.; Partilla, John S.; Seddik, Amir; Zhang, Yuan-Wei; Cao, Jianjing; Holy, Marion; Steinkellner, Thomas; Rudnick, Gary; Baumann, Michael H.; Ecker, Gerhard F.; Newman, Amy Hauck

    2016-01-01

    Determining the structural elements that define substrates and inhibitors at the monoamine transporters is critical to elucidating the mechanisms underlying these disparate functions. In this study, we addressed this question directly by generating a series of N-substituted 3,4-methylenedioxyamphetamine analogs that differ only in the number of methyl substituents on the terminal amine group. Starting with 3,4-methylenedioxy-N-methylamphetamine, 3,4-methylenedioxy-N,N-dimethylamphetamine (MDDMA) and 3,4-methylenedioxy-N,N,N-trimethylamphetamine (MDTMA) were prepared. We evaluated the functional activities of the compounds at all three monoamine transporters in native brain tissue and cells expressing the transporters. In addition, we used ligand docking to generate models of the respective protein-ligand complexes, which allowed us to relate the experimental findings to available structural information. Our results suggest that the 3,4-methylenedioxyamphetamine analogs bind at the monoamine transporter orthosteric binding site by adopting one of two mutually exclusive binding modes. 3,4-methylenedioxyamphetamine and 3,4-methylenedioxy-N-methylamphetamine adopt a high-affinity binding mode consistent with a transportable substrate, whereas MDDMA and MDTMA adopt a low-affinity binding mode consistent with an inhibitor, in which the ligand orientation is inverted. Importantly, MDDMA can alternate between both binding modes, whereas MDTMA exclusively binds to the low-affinity mode. Our experimental results are consistent with the idea that the initial orientation of bound ligands is critical for subsequent interactions that lead to transporter conformational changes and substrate translocation. PMID:26519222

  20. High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU).

    PubMed

    Winn, Shelley R; Scherer, Tanja; Thöny, Beat; Harding, Cary O

    2016-01-01

    Central nervous system (CNS) deficiencies of the monoamine neurotransmitters, dopamine and serotonin, have been implicated in the pathophysiology of neuropsychiatric dysfunction in phenylketonuria (PKU). Increased brain phenylalanine concentration likely competitively inhibits the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the rate limiting steps in dopamine and serotonin synthesis respectively. Tetrahydrobiopterin (BH4) is a required cofactor for TH and TPH activity. Our hypothesis was that treatment of hyperphenylalaninemic Pah(enu2/enu2) mice, a model of human PKU, with sapropterin dihydrochloride, a synthetic form of BH4, would stimulate TH and TPH activities leading to improved dopamine and serotonin synthesis despite persistently elevated brain phenylalanine. Sapropterin (20, 40, or 100mg/kg body weight in 1% ascorbic acid) was administered daily for 4 days by oral gavage to Pah(enu2/enu2) mice followed by measurement of brain biopterin, phenylalanine, tyrosine, tryptophan and monoamine neurotransmitter content. A significant increase in brain biopterin content was detected only in mice that had received the highest sapropterin dose, 100mg/kg. Blood and brain phenylalanine concentrations were unchanged by sapropterin therapy. Sapropterin therapy also did not alter the absolute amounts of dopamine and serotonin in brain but was associated with increased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), dopamine and serotonin metabolites respectively, in both wild type and Pah(enu2/enu2) mice. Oral sapropterin therapy likely does not directly affect central nervous system monoamine synthesis in either wild type or hyperphenylalaninemic mice but may stimulate synaptic neurotransmitter release and subsequent metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics.

    PubMed

    Riba, Jordi; Valle, Marta; Urbano, Gloria; Yritia, Mercedes; Morte, Adelaida; Barbanoj, Manel J

    2003-07-01

    The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting beta-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.

  2. Interplay between aggression, brain monoamines and fur color mutation in the American mink.

    PubMed

    Kulikov, A V; Bazhenova, E Y; Kulikova, E A; Fursenko, D V; Trapezova, L I; Terenina, E E; Mormede, P; Popova, N K; Trapezov, O V

    2016-11-01

    Domestication of wild animals alters the aggression towards humans, brain monoamines and coat pigmentation. Our aim is the interplay between aggression, brain monoamines and depigmentation. The Hedlund white mutation in the American mink is an extreme case of depigmentation observed in domesticated animals. The aggressive (-2.06 ± 0.03) and tame (+3.5 ± 0.1) populations of wild-type dark brown color (standard) minks were bred during 17 successive generations for aggressive or tame reaction towards humans, respectively. The Hedlund mutation was transferred to the aggressive and tame backgrounds to generate aggressive (-1.2 ± 0.1) and tame (+3.0 ± 0.2) Hedlund minks. Four groups of 10 males with equal expression of aggressive (-2) or tame (+5) behavior, standard or with the Hedlund mutation, were selected to study biogenic amines in the brain. Decreased levels of noradrenaline in the hypothalamus, but increased concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid and dopamine metabolite, homovanillic acid, in the striatum were measured in the tame compared with the aggressive standard minks. The Hedlund mutation increased noradrenaline level in the hypothalamus and substantia nigra, serotonin level in the substantia nigra and striatum and decreased dopamine concentration in the hypothalamus and striatum. Significant interaction effects were found between the Hedlund mutation and aggressive behavior on serotonin metabolism in the substantia nigra (P < 0.001), dopamine level in the midbrain (P < 0.01) and its metabolism in the striatum (P < 0.05). These results provide the first experimental evidence of the interplay between aggression, brain monoamines and the Hedlund mutation in the American minks. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  3. Monoamine transporter contributions to l-DOPA effects in hemi-parkinsonian rats.

    PubMed

    Conti, Melissa M; Meadows, Samantha M; Melikhov-Sosin, Mitchell; Lindenbach, David; Hallmark, Joy; Werner, David F; Bishop, Christopher

    2016-11-01

    l-DOPA is the standard treatment for Parkinson's disease (PD), but chronic treatment typically leads to abnormal involuntary movement or dyskinesia (LID) development. Although poorly understood, dyskinetic mechanisms involve a complex interaction between the remaining dopamine system and the semi-homologous serotonin and norepinephrine systems. Serotonin and norepinephrine transporters (SERT and NET, respectively) have affinity for dopamine uptake especially when dopamine transporters (DAT) are scant. Monoamine reuptake inhibitors have been reported to modulate l-DOPA's anti-parkinsonian effects, but DAT, SERT, and NET's contribution to dyskinesia has not been well delineated. The current investigation sought to uncover the differential expression and function of DAT, SERT, and NET in the l-DOPA-treated hemi-parkinsonian rat. Protein analysis of striatal monoamine transporters in unilateral sham or 6-hydroxydopamine-lesioned rats treated with l-DOPA (0 or 6 mg/kg) showed lesion-induced DAT loss and l-DOPA-induced gain in SERT:DAT and NET:DAT ratios in lesioned rats which positively correlated with dyskinesia expression, suggesting functional shifts among monoamine transporters in the dyskinetic state. SERT blockade with citalopram (3, 5 mg/kg) reduced LID while DAT and NET blockade with GBR-12909 (5, 10 mg/kg) and nisoxetine (5, 10 mg/kg), respectively, mildly exacerbated dyskinesia expression. Transporter inhibition did not significantly alter l-DOPA's ability to reverse motor deficit. Overall, DA and DAT loss with l-DOPA treatment appear to precipitate gain in SERT and NET function. Strong correlations with LID and direct behavioral comparisons of selective transporter blockade reveal novel implications for SERT, DAT, and NET as potential biomarkers and therapeutic targets in the hemi-parkinsonian model and dyskinetic PD patients.

  4. X-linked borderline mental retardation with prominent behavioral disturbance: Phenotype, genetic localization, and evidence for disturbed monoamine metabolism

    SciTech Connect

    Brunner, H.G.; Nelen, M.R.; Zandvoort, P. van; Abeling, N.G.G.M.; Gennip, A.H. van; Ropers, H.H.; Oost, B.A. van ); Wolters, E.C.; Kuiper, M.A. )

    1993-06-01

    The authors have identified a large Dutch kindred with a new form of X-linked nondysmorphic mild mental retardation. All affected males in this family show very characteristic abnormal behavior, in particular aggressive and sometimes violent behavior. Other types of impulsive behavior include arson, attempted rape, and exhibitionism. Attempted suicide has been reported in a single case. The locus for this disorder could be assigned to the Xp11-21 interval between DXS7 and DXS77 by linkage analysis using markers spanning the X chromosome. A maximal multipoint lod score of 3.69 was obtained at the monoamine oxidase type A (MAOA) monoamine metabolism. These data are compatible with a primary defect in the structural gene for MAOA and/or monoamine oxidase type B (MAOB). Normal platelet MAOB activity suggests that the unusual behavior pattern in this family may be caused by isolated MAOA deficiency. 34 refs., 4 figs., 4 tabs.

  5. CO depletion in the Gould Belt clouds

    NASA Astrophysics Data System (ADS)

    Christie, H.; Viti, S.; Yates, J.; Hatchell, J.; Fuller, G. A.; Duarte-Cabral, A.; Sadavoy, S.; Buckle, J. V.; Graves, S.; Roberts, J.; Nutter, D.; Davis, C.; White, G. J.; Hogerheijde, M.; Ward-Thompson, D.; Butner, H.; Richer, J.; Di Francesco, J.

    2012-05-01

    We present a statistical comparison of CO depletion in a set of local molecular clouds within the Gould Belt using Sub-millimetre Common User Bolometer Array (SCUBA) and Heterodyne Array Receiver Programme (HARP) data. This is the most wide-ranging study of depletion thus far within the Gould Belt. We estimate CO column densities assuming local thermodynamic equilibrium and, for a selection of sources, using the radiative transfer code RADEX in order to compare the two column density estimation methods. High levels of depletion are seen in the centres of several dust cores in all the clouds. We find that in the gas surrounding protostars, levels of depletion are somewhat lower than for starless cores with the exception of a few highly depleted protostellar cores in Serpens and NGC 2024. There is a tentative correlation between core mass and core depletion, particularly in Taurus and Serpens. Taurus has, on average, the highest levels of depletion. Ophiuchus has low average levels of depletion which could perhaps be related to the anomalous dust grain size distribution observed in this cloud. High levels of depletion are often seen around the edges of regions of optical emission (Orion) or in more evolved or less dynamic regions such as the bowl of L1495 in Taurus and the north-western region of Serpens.

  6. Ego depletion increases risk-taking.

    PubMed

    Fischer, Peter; Kastenmüller, Andreas; Asal, Kathrin

    2012-01-01

    We investigated how the availability of self-control resources affects risk-taking inclinations and behaviors. We proposed that risk-taking often occurs from suboptimal decision processes and heuristic information processing (e.g., when a smoker suppresses or neglects information about the health risks of smoking). Research revealed that depleted self-regulation resources are associated with reduced intellectual performance and reduced abilities to regulate spontaneous and automatic responses (e.g., control aggressive responses in the face of frustration). The present studies transferred these ideas to the area of risk-taking. We propose that risk-taking is increased when individuals find themselves in a state of reduced cognitive self-control resources (ego-depletion). Four studies supported these ideas. In Study 1, ego-depleted participants reported higher levels of sensation seeking than non-depleted participants. In Study 2, ego-depleted participants showed higher levels of risk-tolerance in critical road traffic situations than non-depleted participants. In Study 3, we ruled out two alternative explanations for these results: neither cognitive load nor feelings of anger mediated the effect of ego-depletion on risk-taking. Finally, Study 4 clarified the underlying psychological process: ego-depleted participants feel more cognitively exhausted than non-depleted participants and thus are more willing to take risks. Discussion focuses on the theoretical and practical implications of these findings.

  7. Monoamine oxidase A regulates neural differentiation of murine embryonic stem cells

    PubMed Central

    Wang, Zhi-qiang; Chen, Kevin; Ying, Qi-long; Li, Ping

    2012-01-01

    Monoamine oxidase (MAO) A is the major metabolizing enzyme of serotonin (5-hydroxytryptamine, 5-HT) which regulates early brain development. In this study, wild-type (WT) and MAO Aneo embryonic stem (ES) cell lines were established from the inner cell mass of murine blastocysts and their characteristics during ES and differentiating stages were studied. Our results show that the differentiation to neural cells in MAO Aneo ES cells was reduced compared to WT, suggesting MAO A played a regulatory role in stem cells neural differentiation. PMID:21607742

  8. Novel Phenotypes Detectable with PET in Mood Disorders: Elevated Monoamine Oxidase A and Translocator Protein Level.

    PubMed

    Meyer, Jeffrey

    2017-07-01

    As a result of high prevalence and high rates of treatment resistance, major depressive disorder has become the leading cause of death and disability in moderate-income to high-income nations. Poor targeting of phenotypes is a plausible reason for treatment resistance and PET imaging offers a unique role to identify phenotypes. Both increased monoamine oxidase A binding and greater translocator protein 18 kDa binding occur throughout the gray matter during major depressive episodes, including affect-modulating brain regions such as the prefrontal and anterior cingulate cortex, and are detectable with advanced radioligand technology for both of these targets. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Urinary output of endogenous monoamine oxidase inhibitor and isatin during acute migraine attacks.

    PubMed

    Jarman, J; Przyborowska, A; Glover, V; Halket, J; Davies, P T; Rose, F C; Sandler, M

    1991-01-01

    Urinary output of endogenous monoamine oxidase (MAO) inhibitory activity, was significantly raised in serial samples collected across a migraine attack compared with collections during attack-free periods and in healthy controls, which did not differ from each other. There was a highly significant correlation in output between isatin, a major fraction of the MAO inhibitory activity, and output of the MAO inhibitory activity itself. However, although there was a tendency towards increased isatin excretion during migraine attacks, it failed to reach statistical significance.

  10. Thermal inactivation of mouse brain monoamine oxidase type A and type B.

    PubMed

    Hall, T R; Figueroa, H R; Newton, D K; Yurgens, P B

    1983-01-01

    Mouse brain monoamine oxidase (MAO) type A and type B were incubated at 54 degrees C and samples removed for up to 60 min, and remaining MAO activity was determined. Total MAO activity, type A activity and type B activity all disappeared, presumably due to thermal denaturation, in a time-dependent fashion. The rate of disappearance of MAO type B was faster than that of type A both at pH 7.4 and at pH 9.2, though both types denatured faster at the higher pH compared to the lower pH.

  11. Effect of prenatal exposure to phenobarbital on the development of monoamine oxidase and glucocorticoids.

    PubMed

    Soliman, K F; Richardson, S D

    1983-01-01

    1. Fetal exposure to phenobarbital (PB, 30 mg/kg) 2-5 days prior to parturition was conducted in Sprague-Dawley rats. The fetal exposure to PB resulted in: (a) Significant increase (P less than 0.01) in body wt at 23 and 42 days of age; (b) Significant increase (P less than 0.01) in brain wt at all ages studied; (c) Significant decline (P less than 0.05) in liver monoamine oxidase at day 13 of age; (d) Significant (P less than 0.05) increase in plasma corticosterone levels at days 23 and 42.

  12. Monoamine oxidase B inhibitors from the fruits of Opuntia ficus-indica var. saboten.

    PubMed

    Han, Y N; Choo, Y; Lee, Y C; Moon, Y I; Kim, S D; Choi, J W

    2001-02-01

    Three varieties of methyl citrate and 1-methyl malate were isolated from the fruits of Opuntia ficus-indica var. saboten Makino through in vitro bioassay-guided isolation for the inhibition on monoamine oxidase(MAO). The IC50 values for MAO-B of 1-monomethyl citrate, 1,3-dimethyl citrate, trimethyl citrate and 1-methyl malate were 0.19, 0.23, 0.61 and 0.25 mM, respectively. However, on MAO-A, their inhibitions showed only marginal activity.

  13. Immunocytochemical Localization of Monoamine Oxidase Type B in Rat's Peripheral Nervous System.

    PubMed

    Chen, Qiang; Xu, Yang; Zhang, Hui; Tan, Xiao; Liu, Shu Hui; Yan, Fen

    2015-11-01

    Immunohistochemistry is used to investigate subcellular localization of monoamine oxidase type B (MAOB) in the axon of the rat's peripheral nervous system. Through light and electron microscopy, the presence of MAOB-immunoreactive structures in the propria lamina of tongue and on the outer membranes of mitochondria in both myelinated and unmyelinated axons can be detected. As a result, MAOB may potentially play a crucial role in the axons of the rat's peripheral nervous system and may be closely associated with both axonal transport and nerve conduction.

  14. Close encounters of the monoamine kind: immune cells betray their nervous disposition

    PubMed Central

    Meredith, Elizabeth J; Chamba, Anita; Holder, Michelle J; Barnes, Nicholas M; Gordon, John

    2005-01-01

    Here we review the evidence for immune cells expressing multiple components of the serotonergic and dopaminergic systems that are more commonly associated with the central nervous system (CNS). We discuss where and how peripheral encounters with these biogenic monoamines occur and posit reasons as to why the immune system would wish to deploy these pathways. A full taxonomy of serotonergic and dopaminergic constituents and their workings in component cells of the immune system should facilitate the formulation of novel therapeutic approaches in diseases characterized by immune dysfunction and potentially provide a range of surrogate peripheral markers for registering and monitoring disturbances within the CNS. PMID:15946246

  15. Close encounters of the monoamine kind: immune cells betray their nervous disposition.

    PubMed

    Meredith, Elizabeth J; Chamba, Anita; Holder, Michelle J; Barnes, Nicholas M; Gordon, John

    2005-07-01

    Here we review the evidence for immune cells expressing multiple components of the serotonergic and dopaminergic systems that are more commonly associated with the central nervous system (CNS). We discuss where and how peripheral encounters with these biogenic monoamines occur and posit reasons as to why the immune system would wish to deploy these pathways. A full taxonomy of serotonergic and dopaminergic constituents and their workings in component cells of the immune system should facilitate the formulation of novel therapeutic approaches in diseases characterized by immune dysfunction and potentially provide a range of surrogate peripheral markers for registering and monitoring disturbances within the CNS.

  16. Noncovalent Complexation of Monoamine Neurotransmitters and Related Ammonium Ions by Tetramethoxy Tetraglucosylcalix[4]arene

    NASA Astrophysics Data System (ADS)

    Torvinen, Mika; Kalenius, Elina; Sansone, Francesco; Casnati, Alessandro; Jänis, Janne

    2012-02-01

    The noncovalent complexation of monoamine neurotransmitters and related ammonium and quaternary ammonium ions by a conformationally flexible tetramethoxy glucosylcalix[4]arene was studied by electrospray ionization Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry. The glucosylcalixarene exhibited highest binding affinity towards serotonin, norepinephrine, epinephrine, and dopamine. Structural properties of the guests, such as the number, location, and type of hydrogen bonding groups, length of the alkyl spacer between the ammonium head-group and the aromatic ring structure, and the degree of nitrogen substitution affected the complexation. Competition experiments and guest-exchange reactions indicated that the hydroxyl groups of guests participate in intermolecular hydrogen bonding with the glucocalixarene.

  17. Chromone-2- and -3-carboxylic acids inhibit differently monoamine oxidases A and B.

    PubMed

    Alcaro, Stefano; Gaspar, Alexandra; Ortuso, Francesco; Milhazes, Nuno; Orallo, Francisco; Uriarte, Eugenio; Yáñez, Matilde; Borges, Fernanda

    2010-05-01

    Chromone carboxylic acids were evaluated as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. The biological data indicated that only chromone-3-carboxylic acid is a potent hMAO-B inhibitor, with a high degree of selectivity for hMAO-B compared to hMAO-A. Conversely the chromone-2-carboxylic acid resulted almost inactive against both MAO isoforms. Docking experiments were performed to elucidate the reasons of the different MAO IC(50) data and to explain the absence of activity versus selectivity, respectively. 2010 Elsevier Ltd. All rights reserved.

  18. Sex-dependent effects of maternal separation on plasma corticosterone and brain monoamines in response to chronic ethanol administration.

    PubMed

    Kawakami, S E; Quadros, I M H; Machado, R B; Suchecki, D

    2013-12-03

    Prolonged and repeated periods of maternal separation produce behavioral phenotype of increased vulnerability to neuropsychiatric disorders and drug abuse. Most of the changes in behavior, corticosterone (CORT) and monoamine levels induced by long maternal separation (LMS) are observed after a challenge, but not in basal conditions. LMS increases ethanol-induced locomotor response and self-administration, possibly due to changes in CORT release and/or monoamine concentrations. This study examined the effects of LMS in association with chronic ethanol treatment on plasma CORT and brain monoamine concentrations in male and female Swiss mice, which were kept undisturbed (animal facility rearing - AFR) or separated from their mothers for 3h/day, from 2 to 14 days of age (LMS). As adults, one set of male and female mice received no drug treatment to assess the effect of LMS per se. Another set of animals received saline injections for 20 days and one ethanol injection (2.2g/kg, i.p.) on day 21 (acute) or ethanol for 21 days (chronic). Locomotor activity, plasma CORT levels and monoamines in the frontal cortex, striatum and hippocampus of AFR and LMS mice were evaluated in non-treated, acute and chronic ethanol-treated animals. In non-treated mice, no differences were found in CORT or locomotor activity, with small changes in monoamines content. In LMS females, chronic ethanol increased dopamine and serotonin concentrations in the frontal cortex, relative to acute ethanol LMS and to chronic ethanol-treated AFR groups (p<0.05). In LMS males, chronic ethanol increased hippocampal noradrenaline, dopamine, serotonin and metabolites when compared to respective AFR controls, as well as acute LMS. Moreover, chronic ethanol treatment resulted in higher CORT concentrations in LMS than in AFR males. Overall, these results indicate that LMS mice were more susceptible to the effects of chronic ethanol administration on CORT and brain monoamine concentrations, and that these effects

  19. Impaired reward learning and intact motivation after serotonin depletion in rats.

    PubMed

    Izquierdo, Alicia; Carlos, Kathleen; Ostrander, Serena; Rodriguez, Danilo; McCall-Craddolph, Aaron; Yagnik, Gargey; Zhou, Feimeng

    2012-08-01

    Aside from the well-known influence of serotonin (5-hydroxytryptamine, 5-HT) on emotional regulation, more recent investigations have revealed the importance of this monoamine in modulating cognition. Parachlorophenylalanine (PCPA) depletes 5-HT by inhibiting tryptophan hydroxylase, the enzyme required for 5-HT synthesis and, if administered at sufficiently high doses, can result in a depletion of at least 90% of the brain's 5-HT levels. The present study assessed the long-lasting effects of widespread 5-HT depletions on two tasks of cognitive flexibility in Long Evans rats: effort discounting and reversal learning. We assessed performance on these tasks after administration of either 250 or 500 mg/kg PCPA or saline (SAL) on two consecutive days. Consistent with a previous report investigating the role of 5-HT on effort discounting, pretreatment with either dose of PCPA resulted in normal effortful choice: All rats continued to climb tall barriers to obtain large rewards and were not work-averse. Additionally, rats receiving the lower dose of PCPA displayed normal reversal learning. However, despite intact motivation to work for food rewards, rats receiving the largest dose of PCPA were unexpectedly impaired relative to SAL rats on the pretraining stages leading up to reversal learning, ultimately failing to approach and respond to the stimuli associated with reward. High performance liquid chromatography (HPLC) with electrochemical detection confirmed 5-HT, and not dopamine, levels in the ventromedial frontal cortex were correlated with this measure of associative reward learning. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Beneficial Uses of Depleted Uranium

    SciTech Connect

    Brown, C.; Croff, A.G.; Haire, M. J.

    1997-08-01

    Naturally occurring uranium contains 0.71 wt% {sup 235}U. In order for the uranium to be useful in most fission reactors, it must be enriched the concentration of the fissile isotope {sup 235}U must be increased. Depleted uranium (DU) is a co-product of the processing of natural uranium to produce enriched uranium, and DU has a {sup 235}U concentration of less than 0.71 wt%. In the United States, essentially all of the DU inventory is in the chemical form of uranium hexafluoride (UF{sub 6}) and is stored in large cylinders above ground. If this co-product material were to be declared surplus, converted to a stable oxide form, and disposed, the costs are estimated to be several billion dollars. Only small amounts of DU have at this time been beneficially reused. The U.S. Department of Energy (DOE) has begun the Beneficial Uses of DU Project to identify large-scale uses of DU and encourage its reuse for the primary purpose of potentially reducing the cost and expediting the disposition of the DU inventory. This paper discusses the inventory of DU and its rate of increase; DU disposition options; beneficial use options; a preliminary cost analysis; and major technical, institutional, and regulatory issues to be resolved.

  1. Depleted argon from underground sources

    SciTech Connect

    Back, H.O.; Alton, A.; Calaprice, F.; Galbiati, C.; Goretti, A.; Kendziora, C.; Loer, B.; Montanari, D.; Mosteiro, P.; Pordes, S.; /Fermilab

    2011-09-01

    Argon is a powerful scintillator and an excellent medium for detection of ionization. Its high discrimination power against minimum ionization tracks, in favor of selection of nuclear recoils, makes it an attractive medium for direct detection of WIMP dark matter. However, cosmogenic {sup 39}Ar contamination in atmospheric argon limits the size of liquid argon dark matter detectors due to pile-up. The cosmic ray shielding by the earth means that Argon from deep underground is depleted in {sup 39}Ar. In Cortez Colorado a CO{sub 2} well has been discovered to contain approximately 500ppm of argon as a contamination in the CO{sub 2}. In order to produce argon for dark matter detectors we first concentrate the argon locally to 3-5% in an Ar, N{sub 2}, and He mixture, from the CO{sub 2} through chromatographic gas separation. The N{sub 2} and He will be removed by continuous cryogenic distillation in the Cryogenic Distillation Column recently built at Fermilab. In this talk we will discuss the entire extraction and purification process; with emphasis on the recent commissioning and initial performance of the cryogenic distillation column purification.

  2. Depleted uranium--the growing concern.

    PubMed

    Abu-Qare, Aqel W; Abou-Donia, Mohamed B

    2002-01-01

    Recently, several studies have reported on the health and environmental consequences of the use of depleted uranium. Depleted uranium is a heavy metal that is also radioactive. It is commonly used in missiles as a counterweight because of its very high density (1.6 times more than lead). Immediate health risks associated with exposure to depleted uranium include kidney and respiratory problems, with conditions such as kidney stones, chronic cough and severe dermatitis. Long-term risks include lung and bone cancer. Several published reports implicated exposure to depleted uranium in kidney damage, mutagenicity, cancer, inhibition of bone, neurological deficits, significant decrease in the pregnancy rate in mice and adverse effects on the reproductive and central nervous systems. Acute poisoning with depleted uranium elicited renal failure that could lead to death. The environmental consequences of its residue will be felt for thousands of years. It is inhaled and passed through the skin and eyes, transferred through the placenta into the fetus, distributed into tissues and eliminated in urine. The use of depleted uranium during the Gulf and Kosovo Wars and the crash of a Boeing airplane carrying depleted uranium in Amsterdam in 1992 were implicated in a health concern related to exposure to depleted uranium.

  3. Depletion of brain norepinephrine: differential influence on anxiolyic treatment effects.

    PubMed

    Fontana, D J; McMiller, L V; Commissaris, R L

    1999-04-01

    Previous studies have demonstrated that anxiolytic-like anticonflict effects can be produced by either (1) acute administration of traditional anti-anxiety compounds (benzodiazepines or barbiturates) or (2) chronic administration of tricyclic (TCA) or monoamine oxidase inhibitor (MAOI) anti-depressants. The present study determined the effects of noradrenergic neuronal depletion on these distinct anticonflict treatments. After 3 weeks of training in a repeated measures drink suppression conflict paradigm, water-restricted rats consumed 11-14 ml water/session (unpunished responding) and accepted 25-40 shocks/session (punished responding) during control (i.e., non-drug) 10-min test sessions. The noradrenergic neurotoxin DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride; 65 mg/kg, IP] or its vehicle (saline; 1 ml/kg) was administered after 3 weeks of conflict testing. Conflict behavior was then evaluated for 8 weeks post-treatment. In separate groups of DSP4- and vehicle-pretreated subjects, the effects of acute administration (10-min pretreatment) of phenobarbital (5-40 mg/kg) or alprazolam (0.3-2.5 mg/kg) were determined. In a third experiment, the effects of chronic treatment with the TCA desipramine (DMI; 5 mg/kg, twice daily for 8 weeks) or the non-selective MAOI phenelzine (4.0 mg/kg, twice daily for 8 weeks) on conflict behavior were determined in additional groups of DSP4- or vehicle-pretreated subjects. DSP4 treatment produced a modest yet statistically significant decrease in punished responding (i.e., anxiogenic-like effect) relative to vehicle controls. DSP4 pretreatment did not alter the anticonflict effects of acute alprazolam or phenobarbital treatment. In contrast, DSP4 treatment completely abolished the anticonflict effects produced by chronic DMI or chronic phenelzine treatment. Thus, noradrenergic neuronal integrity appears to be required for the anxiolytic-like effects of chronic antidepressant treatment, but not for the anxiolytic

  4. Involvement of monoamine oxidase B on models of postoperative and neuropathic pain in mice.

    PubMed

    Villarinho, Jardel Gomes; Oliveira, Sara Marchesan; Silva, Cássia Regina; Cabreira, Thaíssa Nunes; Ferreira, Juliano

    2012-09-05

    In this study we assessed the involvement of monoamine oxidase B (MAO-B), a key enzyme implicated in monoamine metabolism, on postoperative (plantar incision) and neuropathic (partial sciatic nerve ligation) pain models in mice. Paw incision submitted mice showed a significant decrease in mechanical threshold compared with the sham-operated mice, characterizing the development of mechanical allodynia. The selective and irreversible MAO-B inhibitor selegiline, at a dose sufficient to selectively inhibit MAO-B activity (10 mg/kg), showed an anti-allodynic effect from 0.5 to 6 h after incision. Likewise, partial sciatic nerve ligation submitted mice also developed mechanical allodynia, which was reversed by selegiline (10 mg/kg) from 2 to 6 h after treatment. In addition, a significant increase on striatal MAO-B activity was observed in neuropathic mice compared with the sham-operated animals, which was reversed by selegiline treatment. Taken together, our results showed that MAO-B seems to exert a critical role in the development of postoperative and neuropathic pain. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Effects of Neonatal Methamphetamine and Stress on Brain Monoamines and Corticosterone in Preweanling Rats.

    PubMed

    Jablonski, Sarah A; Graham, Devon L; Vorhees, Charles V; Williams, Michael T

    2017-02-01

    Neonatal exposure to methamphetamine (MA) and developmental chronic stress significantly alter neurodevelopmental profiles that show a variety of long-term physiological and behavioral effects. In the current experiment, Sprague-Dawley rats were exposed to one of two housing conditions along with MA. Rats were given 0 (saline), 5, or 7.5 mg/kg MA, four times per day from postnatal day (P)11 to 15 or P11 to 20. Half of the litters were reared in cages with standard bedding and half with no bedding. Separate litters were assessed at P15 or P20 for organ weights (adrenals, spleen, thymus); corticosterone; and monoamine assessments (dopamine, serotonin, norepinephrine) and their metabolites within the neostriatum, hippocampus, and prefrontal cortex. Findings show neonatal MA altered monoamines, corticosterone, and organ characteristics alone, and as a function of developmental age and stress compared with controls. These alterations may in part be responsible for MA and early life stress-induced long-term learning and memory deficits.

  6. Monoamine Oxidase A gene polymorphisms and self reported aggressive behaviour in a Pakistani ethnic group.

    PubMed

    Shah, Syed Shoaib; Mohyuddin, Aisha; Colonna, Vincenza; Mehdi, Syed Qasim; Ayub, Qasim

    2015-08-01

    To investigate the association of monoamine oxidase Agene polymorphisms with aggression. The study was conducted in an ethnic community in Lahore, Pakistan, from August 2008 to December 2009 on the basis of data that was collected through a questionnaire between August 2004 and September 2005. It analysed 10 single nucleotide polymorphisms of monoamine oxidase A in unrelated males from the same ethnic background who were administered a Punjabi translation of the Buss and Perry aggression questionnaire. SPSS 13 was used for statistical analysis. Of the total 133 haplotypes studied, 52(39%) were Haplotype A, 58(43.6%) B, 8(6%) C, 3(2.3%) D, 9(6.8%) E and 3(2.3%) F. The six haplotypes were analysed for association with scores of the four subscales of the aggression questionnaire and multivariate analysis of variance showed no significant differences (p>0.05 each) in the error variances of the total scores and scores for three of the sub-scales across the haplotypes. The variance was significantly different only for the anger sub-scale (p<0.05). The association of an extended haplotype with low levels of self-reported aggression in this study should assist in characterisation of functional variants responsible for non-aggressive behaviour in male subjects.

  7. Potential of Natural Products of Herbal Origin as Monoamine Oxidase Inhibitors.

    PubMed

    Orhan, Ilkay Erdogan

    2016-01-01

    Monoamine oxidase (MAO, E.C. 1.4.3.4) is a flavin-adenine type of enzyme with two isoforms referred to MAO-A and MAO-B that function for oxidation of monoamines. While MAO-A inhibitors are effective as antidepressant and anxiolytic drugs (e.g. chlorgyline, moclobemide, and lazabemide), inhibitors of MAO-B (e.g. Ldeprenyl, pargyline, and rasagiline) are used against neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Considering the need for novel MAO inhibitors due to side effects of the current ones, natural products have become attractive targets for researchers. Up till now, many studies revealed strong MAO inhibitory activity of flavonoid, xanthone, alkaloid, and coumarin derivatives from herbal sources, which also become good models for the synthetic MAO inhibitors. For this purpose, the present review focuses on examples of in vitro and in vivo MAO-inhibiting natural compounds of plant origin from a wide variety of chemical classes isolated mainly between 2000 - 2015.

  8. Increased reactivity and monoamine dysregulation following stress in triploid Atlantic salmon (Salmo salar).

    PubMed

    Fraser, Thomas William Kenneth; Vindas, Marco Antonio; Fjelldal, Per Gunnar; Winberg, Svante; Thörnqvist, Per-Ove; Øverli, Øyvind; Skjæraasen, Jon-Egil; Hansen, Tom Jonny; Mayer, Ian

    2015-07-01

    Artificial triploid salmonids are sterile and therefore commercially bred to prevent genetic interactions between wild and domestic fish strains. The full biological effects of having an extra chromosome set are largely unknown, but triploids are considered to be more sensitive to sub-optimal environmental conditions and to be stressed by the presence of diploid conspecifics. Brain serotonergic and dopaminergic activity are known to regulate the stress response in vertebrates, but monoamine systems in diploid and triploid fish have yet to be compared. Here we study monoamine neurochemistry in the telencephalon and brain stem of juvenile diploid and triploid Atlantic salmon (Salmo salar) in response to stress (unstressed vs stressed individuals) and holding (separate- vs mixed-ploidy) conditions. Both diploids and triploids showed an increase in serotonergic activity following stress, but the increase was significantly greater in the telencephalon of triploids compared to diploids. Furthermore, while telencephalic dopaminergic activity was significantly increased in diploids following stress, there was no response in triploids. Holding conditions had a significant effect on dopaminergic activity in the brain stem of diploids only, with lower values in mixed- compared to separate-ploidy conditions. These results suggest artificially produced triploids experience increased reactivity and monoaminergic dysregulation following stress that may impede their welfare and performance.

  9. Platelet monoamine oxidase activity predicts alcohol sensitivity and voluntary alcohol intake in rhesus monkeys.

    PubMed

    Wargelius, Hanna-Linn; Fahlke, Claudia; Suomi, Stephen J; Oreland, Lars; Higley, James Dee

    2010-02-01

    Platelet monoamine oxidase B (MAO-B) has been proposed to be a biological marker for the properties of monoamine systems, with low activity being associated with vulnerability for high scores on personality traits such as sensation seeking, monotony avoidance, and impulsiveness, as well as for vulnerability for alcoholism. In the present study, platelet MAO-B activity was analysed in 78 rhesus macaques, and its relation to voluntary alcohol intake and behaviours after intravenous alcohol administration was observed. Monkeys with low platelet MAO-B activity had low levels of 5-hydroxyindole acetic acid in cerebrospinal fluid and showed excessive aggression after alcohol administration. A novel finding was that animals with low platelet MAO-B activity showed less intoxication following alcohol administration. As we have shown previously, they also voluntarily consumed more alcohol. We here replicate results from studies on both humans and non-human primates, showing the utility of platelet MAO as a marker for risk behaviours and alcohol abuse. Furthermore, we link platelet MAO activity to alcohol sensitivity.

  10. Cannabis extract, but not delta 1-tetrahydrocannabinol, inhibits human brain and liver monoamine oxidase.

    PubMed

    Schurr, A; Rigor, B M

    1984-01-01

    Mitochondrial monoamine oxidase (MAO) of human brain and liver was inhibited by low concentrations of cannabis extract (CE) and a cannabinoid fraction isolated from it. delta 1-Tetrahydrocannabinol (THC) did not elicit any inhibitory effect on the enzyme. The inhibition of MAO activity by CE and by its active fraction was more pronounced when the monoamine substrates 2-phenylethylamine (PEA) and benzylamine (BA) were used, as compared to the inhibition of the enzyme activity when 5-hydroxytryptamine was the substrate. The active cannabinoid fraction was found to be more potent than CE in inhibiting the activity of MAO with either substrate. The isolated fraction contains at least two cannabinoids with Rf values of 0.67 and 0.71 on silica gel thin layer chromatography (TLC), as determined with toluene/chloroform/methanol (100:10:1, by volume) as the solvent system. The findings of this study emphasize the need for further exploration of the potential of cannabis as a source for therapeutic agents.

  11. Selection for increased voluntary wheel-running affects behavior and brain monoamines in mice

    PubMed Central

    Waters, R.Parrish; Pringle, R.B.; Forster, G.L.; Renner, K.J.; Malisch, J.L.; Garland, T.; Swallow, J.G.

    2013-01-01

    Selective-breeding of house mice for increased voluntary wheel-running has resulted in multiple physiological and behavioral changes. Characterizing these differences may lead to experimental models that can elucidate factors involved in human diseases and disorders associated with physical inactivity, or potentially treated by physical activity, such as diabetes, obesity, and depression. Herein, we present ethological data for adult males from a line of mice that has been selectively bred for high levels of voluntary wheel-running and from a non-selected control line, housed with or without wheels. Additionally, we present concentrations of central monoamines in limbic, striatal, and midbrain regions. We monitored wheel-running for 8 weeks, and observed home-cage behavior during the last 5 weeks of the study. Mice from the selected line accumulated more revolutions per day than controls due to increased speed and duration of running. Selected mice exhibited more active behaviors than controls, regardless of wheel access, and exhibited less inactivity and grooming than controls. Selective-breeding also influenced the longitudinal patterns of behavior. We found statistically significant differences in monoamine concentrations and associated metabolites in brain regions that influence exercise and motivational state. These results suggest underlying neurochemical differences between selected and control lines that may influence the observed differences in behavior. Our results bolster the argument that selected mice can provide a useful model of human psychological and physiological diseases and disorders. PMID:23352668

  12. Selection for increased voluntary wheel-running affects behavior and brain monoamines in mice.

    PubMed

    Waters, R Parrish; Pringle, R B; Forster, G L; Renner, K J; Malisch, J L; Garland, T; Swallow, J G

    2013-05-01

    Selective-breeding of house mice for increased voluntary wheel-running has resulted in multiple physiological and behavioral changes. Characterizing these differences may lead to experimental models that can elucidate factors involved in human diseases and disorders associated with physical inactivity, or potentially treated by physical activity, such as diabetes, obesity, and depression. Herein, we present ethological data for adult males from a line of mice that has been selectively bred for high levels of voluntary wheel-running and from a non-selected control line, housed with or without wheels. Additionally, we present concentrations of central monoamines in limbic, striatal, and midbrain regions. We monitored wheel-running for 8 weeks, and observed home-cage behavior during the last 5 weeks of the study. Mice from the selected line accumulated more revolutions per day than controls due to increased speed and duration of running. Selected mice exhibited more active behaviors than controls, regardless of wheel access, and exhibited less inactivity and grooming than controls. Selective-breeding also influenced the longitudinal patterns of behavior. We found statistically significant differences in monoamine concentrations and associated metabolites in brain regions that influence exercise and motivational state. These results suggest underlying neurochemical differences between selected and control lines that may influence the observed differences in behavior. Our results bolster the argument that selected mice can provide a useful model of human psychological and physiological diseases and disorders. Published by Elsevier B.V.

  13. Behavioral and neurochemical effects of amphetamine analogs that release monoamines in the squirrel monkey.

    PubMed

    Kimmel, Heather L; Manvich, Daniel F; Blough, Bruce E; Negus, S Stevens; Howell, Leonard L

    2009-12-01

    To date, there are no effective pharmacotherapies for treating psychostimulant abuse. Previous preclinical and clinical studies have shown that continuous treatment with the monoamine releaser amphetamine reduces cocaine self-administration, but amphetamine selectively targets the dopamine system and is reinforcing. In the present study, we examined the consequences of administration of amphetamine and three structurally related analogs that vary in their potencies for releasing dopamine and serotonin on behavioral-stimulant effects and nucleus accumbens dopamine levels in squirrel monkeys. Amphetamine and PAL-353, which have relatively high selectivity for releasing dopamine vs. serotonin, increased accumbens dopamine levels and induced stimulant effects on behavior maintained by a fixed-interval schedule of reinforcement. PAL-313, which has a relatively low selectivity for releasing dopamine vs. serotonin, increased dopamine levels, but did not induce behavioral-stimulant effects. PAL-287, which is relatively nonselective in releasing dopamine and serotonin, did not increase dopamine levels or induce behavioral-stimulant effects. These results demonstrate that increasing serotonergic activity attenuates dopamine release and dopamine-mediated behavioral effects of monoamine releasers. In addition, these results support further investigation of PAL-313 and similar compounds as a potential medication for treating psychostimulant abuse.

  14. Purification and molecular analysis of a monoamine oxidase isolated from Narcissus tazetta.

    PubMed

    Cui, Zhifeng; Zhang, Yongming; Inoue, Hironori; Yogo, Syun; Hirasawa, Eiji

    2013-01-01

    Semicarbazide-sensitive amine oxidase activity was detected in Narcissus tazetta. The enzyme was purified to homogeneity by the criterion of native polyacrylamide gel electrophoresis (PAGE) with DEAE-Sephacel, hydroxyapatite, and phenyl-Sepharose columns. The molecular mass of the enzyme, determined using a GS-520 HQ column, was estimated to be 135 kDa. SDS-PAGE yielded two bands of, 75 kDa and 65 kDa. The enzyme, which had catalytic activity for some aliphatic and aromatic monoamines, belongs to a class of monoamine oxidases (MAOs). The K(m) value for n-propylamine was 5.9 × 10⁻⁵ M. A substrate analog, 2-bromoethylamine, inhibited enzyme activity. Redox-cycling staining detected a quinone in the MAO protein. By inductively coupled plasma mass analysis, it was determined that there were 2.44 moles of copper atoms per mole of the enzyme. Protein sequence analysis revealed that there was no identity between two N-terminal residues of the 75 kDa and 65 kDa proteins of narcissus MAO.

  15. An HPLC-ECD method for monoamines and metabolites quantification in cuttlefish (cephalopod) brain tissue.

    PubMed

    Bidel, Flavie; Corvaisier, Sophie; Jozet-Alves, Christelle; Pottier, Ivannah; Dauphin, François; Naud, Nadège; Bellanger, Cécile

    2016-08-01

    The cuttlefish belongs to the mollusk class Cephalopoda, considered as the most advanced marine invertebrates and thus widely used as models to study the biology of complex behaviors and cognition, as well as their related neurochemical mechanisms. Surprisingly, methods to quantify the biogenic monoamines and their metabolites in cuttlefish brain remain sparse and measure a limited number of analytes. This work aims to validate an HPLC-ECD method for the simultaneous quantification of dopamine, serotonin, norepinephrine and their main metabolites in cuttlefish brain. In comparison and in order to develop a method suitable to answer both ecological and biomedical questions, the validation was also carried out on a phylogenetically remote species: mouse (mammals). The method was shown to be accurate, precise, selective, repeatable and sensitive over a wide range of concentrations for 5-hydroxyindole-3-acetic acid, serotonin, dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine in the both extracts of cuttlefish and mouse brain, though with low precision and recovery for 4-hydroxy-3-methoxyphenylethylene glycol. Homovanillic acid, accurately studied in rodents, was not detectable in the brain of cuttlefish. Overall, we described here the first fully validated HPLC method for the routine measurement of both monoamines and metabolites in cuttlefish brain. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Nitric oxide interacts with monoamine oxidase to modulate aggression and anxiety-like behaviour.

    PubMed

    Gutiérrez, Héctor Carreño; O'Leary, Aet; Freudenberg, Florian; Fedele, Giorgio; Wilkinson, Rob; Markham, Eleanor; van Eeden, Freek; Reif, Andreas; Norton, William H J

    2017-09-23

    Nitric oxide (NO) is a gaseous neurotransmitter that has important behavioural functions in the vertebrate brain. In this study we compare the impact of decreased nitric NO signalling upon behaviour and neurobiology using both zebrafish and mouse. nitric oxide synthase mutant (nos1(-/-)) zebrafish show significantly reduced aggression and an increase in anxiety-like behaviour without altered production of the stress hormone cortisol. Nos1(-/-) mice also exhibit decreased aggression and are hyperactive in an open field test. Upon reduction of NO signalling, monoamine neurotransmitter metabolism is reduced as a consequence of decreased Monoamine oxidase activity. Treatment of nos1(-/-) zebrafish with the 5-HT receptor 1A agonist 8-OH-DPAT rescues aggression and some aspects of anxiety-like behaviour. Taken together, the interplay between NO and 5-HT appears to be critical to control behaviour. Our cross-species approach challenges the previous notion that reduced neuronal NOS leads to increased aggression. Rather, Nos1 knock-out can also lead to decreased aggression in some situations, a finding that may have implications for future translational research. Copyright © 2017. Published by Elsevier B.V.

  17. A Perspective on Monoamine Oxidase Enzyme as Drug Target: Challenges and Opportunities.

    PubMed

    Kumar, Bhupinder; Gupta, Vivek Prakash; Kumar, Vinod

    2017-01-01

    The monoamine oxidase (MAO) enzyme is responsible for the deamination of monoamine neurotransmitters and regulates their concentration in the central and peripheral nervous systems. Imbalance in the concentration of neurotransmitters in the brain and central nervous system is linked with the biochemical pathology of various neurogenic disorders. Irreversible MAO inhibitors were the first line drugs developed for the management of severe depression but most of these were withdrawn from the clinical practice due to their fatal side effects including food-drug interactions. New generations of MAO inhibitors were developed which were reversible and selective for one of the enzyme isoform and showed improved pharmacological profile. The discovery of crystal structure of MAO-A & MAO-B isoforms helped in understanding the drug-receptor interactions at the molecular level and designing of ligands with selectivity for either of the isoforms. The current article provides an overview on the MAO enzyme as potential drug target for different disease states. The article describes catalytic mechanism of MAO enzyme, crystal structures of the two MAO isoforms, traditional MAO inhibitors and various problems associated with their use, new developments in the MAO inhibitors and their potential as therapeutic agents especially in neurological disorders.

  18. Antidepressive-Like Property of Dichloromethane Fraction of Pimenta pseudocaryophyllus and Relevance of Monoamine Metabolic Enzymes

    PubMed Central

    Fajemiroye, James Oluwagbamigbe; Martins, José Luís Rodrigues; Ghedini, Paulo César; Galdino, Pablinny Morreira; de Paula, Joelma Abadia Marciano; Realino de Paula, José; Da Rocha, Fabio Fagundes; Costa, Elson Alves

    2013-01-01

    Pimenta pseudocaryophyllus popularly referred to as craveiro is considered as a calming agent in different local preparations. The present study attempted to examine antidepressant-like effect of dichloromethane fraction (DF) and role of monoamine oxidase (MAO), tryptophan, and tyrosine hydroxylase. Based on the research focus, tail suspension (TS), forced swimming (FS), and open field (OF) tests were conducted after oral administration of DF (125, 250, or 500 mg/Kg). Ex vivo assay of MAO was also conducted to evaluate inhibitory effect of DF (250 mg/Kg). Administration of DF elicits antidepressant-like response in the TS and FS. However, DF 500 mg/Kg did not alter mice performance in these models. The data obtained in the OF showed a reduction in total crossing and rearing activity; these effects suggest motor interference in TS and FS performance. Mice pretreatment with p-chlorophenylalanine methyl ester (PCPA) (100 mg/kg, i.p.—serotonin biosynthesis inhibitor) for 4 consecutive days or acute administration of α-methyl-p-tyrosine (AMPT) (100 mg/kg, i.p.—catecholamine synthesis inhibitor) blocked anti-immobility effect of DF in the FS. In ex vivo assay of MAO, DF did not inhibit catabolic activity of MAO. Our findings support antidepressant-like activity of DF and suggest an effect that depends on monoamine biosynthesis. PMID:23365611

  19. Functionally Important Carboxyls in a Bacterial Homologue of the Vesicular Monoamine Transporter (VMAT)*

    PubMed Central

    Yaffe, Dana; Vergara-Jaque, Ariela; Shuster, Yonatan; Listov, Dina; Meena, Sitaram; Singh, Satinder K.; Forrest, Lucy R.; Schuldiner, Shimon

    2014-01-01

    Transporters essential for neurotransmission in mammalian organisms and bacterial multidrug transporters involved in antibiotic resistance are evolutionarily related. To understand in more detail the evolutionary aspects of the transformation of a bacterial multidrug transporter to a mammalian neurotransporter and to learn about mechanisms in a milieu amenable for structural and biochemical studies, we identified, cloned, and partially characterized bacterial homologues of the rat vesicular monoamine transporter (rVMAT2). We performed preliminary biochemical characterization of one of them, Brevibacillus brevis monoamine transporter (BbMAT), from the bacterium B. brevis. BbMAT shares substrates with rVMAT2 and transports them in exchange with >1H+, like the mammalian transporter. Here we present a homology model of BbMAT that has the standard major facilitator superfamily fold; that is, with two domains of six transmembrane helices each, related by 2-fold pseudosymmetry whose axis runs normal to the membrane and between the two halves. The model predicts that four carboxyl residues, a histidine, and an arginine are located in the transmembrane segments. We show here that two of the carboxyls are conserved, equivalent to the corresponding ones in rVMAT2, and are essential for H+-coupled transport. We conclude that BbMAT provides an excellent experimental paradigm for the study of its mammalian counterparts and bacterial multidrug transporters. PMID:25336661

  20. Parasite manipulation of brain monoamines in California killifish (Fundulus parvipinnis) by the trematode Euhaplorchis californiensis

    PubMed Central

    Shaw, J.C.; Korzan, W.J.; Carpenter, R.E.; Kuris, A.M.; Lafferty, K.D.; Summers, C.H.; Øverli, Ø.

    2008-01-01

    California killifish (Fundulus parvipinnis) infected with the brain-encysting trematode Euhaplorchis californiensis display conspicuous swimming behaviours rendering them more susceptible to predation by avian final hosts. Heavily infected killifish grow and reproduce normally, despite having thousands of cysts inside their braincases. This suggests that E. californiensis affects only specific locomotory behaviours. We hypothesised that changes in the serotonin and dopamine metabolism, essential for controlling locomotion and arousal may underlie this behaviour modification. We employed micropunch dissection and HPLC to analyse monoamine and monoamine metabolite concentrations in the brain regions of uninfected and experimentally infected fish. The parasites exerted density-dependent changes in monoaminergic activity distinct from those exhibited by fish subjected to stress. Specifically, E. californiensis inhibited a normally occurring, stress-induced elevation of serotonergic metabolism in the raphae nuclei. This effect was particularly evident in the experimentally infected fish, whose low-density infections were concentrated on the brainstem. Furthermore, high E. californiensis density was associated with increased dopaminergic activity in the hypothalamus and decreased serotonergic activity in the hippocampus. In conclusion, the altered monoaminergic metabolism may explain behavioural differences leading to increased predation of the infected killifish by their final host predators. PMID:19129105

  1. The antidepressant venlafaxine disrupts brain monoamine levels and neuroendocrine responses to stress in rainbow trout.

    PubMed

    Melnyk-Lamont, Nataliya; Best, Carol; Gesto, Manuel; Vijayan, Mathilakath M

    2014-11-18

    Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is a widely prescribed antidepressant drug routinely detected in the aquatic environment. However, little is known about its impact on the physiology of nontarget organisms. We tested the hypothesis that venlafaxine perturbs brain monoamine levels and disrupts molecular responses essential for stress coping and feeding activity in fish. Rainbow trout (Oncorhynchus mykiss) were exposed to waterborne venlafaxine (0.2 and 1.0 μg/L) for 7 days. This treatment elevated norepinephrine, serotonin, and dopamine levels in the brain in a region-specific manner. Venlafaxine also increased the transcript levels of genes involved in stress and appetite regulation, including corticotropin releasing factor, pro-opiomelanocortin B, and glucose transporter type 2 in distinct brain regions of trout. The drug treatment reduced the total feed consumed per day, but did not affect the feeding behavior of the dominant and subordinate fish. However, the subordinate fish from the venlafaxine-exposed group had significantly higher plasma cortisol levels compared to the subordinate fish in the control group. Collectively, our results demonstrate that venlafaxine, at environmentally realistic levels, is a neuroendocrine disruptor, impacting the stress and feeding responses in rainbow trout. We propose the midbrain region as a key target for venlafaxine impact and the mode of action involves abnormal monoamine content in trout.

  2. Parasite manipulation of brain monoamines in California killifish (Fundulus parvipinnis) by the trematode Euhaplorchis californiensis

    USGS Publications Warehouse

    Shaw, J.C.; Korzan, W.J.; Carpenter, R.E.; Kuris, A.M.; Lafferty, K.D.; Summers, C.H.; Overli, O.

    2009-01-01

    California killifish (Fundulus parvipinnis) infected with the brain-encysting trematode Euhaplorchis californiensis display conspicuous swimming behaviours rendering them more susceptible to predation by avian final hosts. Heavily infected killifish grow and reproduce normally, despite having thousands of cysts inside their braincases. This suggests that E. californiensis affects only specific locomotory behaviours. We hypothesised that changes in the serotonin and dopamine metabolism, essential for controlling locomotion and arousal may underlie this behaviour modification. We employed micropunch dissection and HPLC to analyse monoamine and monoamine metabolite concentrations in the brain regions of uninfected and experimentally infected fish. The parasites exerted density-dependent changes in monoaminergic activity distinct from those exhibited by fish subjected to stress. Specifically, E. californiensis inhibited a normally occurring, stress-induced elevation of serotonergic metabolism in the raphae nuclei. This effect was particularly evident in the experimentally infected fish, whose low-density infections were concentrated on the brainstem. Furthermore, high E. californiensis density was associated with increased dopaminergic activity in the hypothalamus and decreased serotonergic activity in the hippocampus. In conclusion, the altered monoaminergic metabolism may explain behavioural differences leading to increased predation of the infected killifish by their final host predators. ?? 2008 The Royal Society.

  3. Monoamine oxidase B and free radical scavenging activities of natural flavonoids in Melastoma candidum D. Don.

    PubMed

    Lee, M H; Lin, R D; Shen, L Y; Yang, L L; Yen, K Y; Hou, W C

    2001-11-01

    Monoamine oxidase type B (MAO-B) activity and free radicals are elevated in certain neurological diseases. Four natural flavonoids, quercitrin, isoquercitrin, rutin, and quercetin, were isolated for the first time from the leaves of Melastoma candidum D. Don. They exhibited an inhibitory effect on MAO-B. These potent flavonoids were purified using bioassay-guided fractionation and were separated by Diaion, Sephadex LH-20, and MCI CHP20P columns. The IC(50) values of the four potent flavonoids, quercitrin, isoquercitrin, rutin, and quercetin on monoamine oxidase were 19.06, 11.64, 3.89, and 10.89 microM and enzyme kinetics analysis revealed apparent inhibition constants (K(i)) of 21.01, 2.72, 1.83, and 7.95 microM, respectively, on the substrate, benzylamine. The four potent compounds also exhibited hydroxyl radical scavenging activity as determined using a spin trapping electron spin resonance method. This suggests that the four flavonoids from M. candidum possess both MAO-B inhibitory and free radical scavenging activities. These important properties may be used for preventing some neurodegenerative diseases in the future.

  4. The monoamine reuptake inhibitor milnacipran does not affect nociception to acute visceral distension in rats.

    PubMed

    Shin, Sang-Wook; Eisenach, James C; Rao, Srinias G; Tong, Chuanyao

    2004-05-01

    The role of antidepressants in the treatment of visceral pain has not been extensively examined. Milnacipran, an antidepressant that inhibits monoamine reuptake, is widely used in the treatment of depression and fibromyalgia. In this study, we sought to determine the activity of milnacipran against acute visceral nociception. Female virgin rats were studied 7 days after bilateral ovariectomy. For uterine cervical distension (UCD), two metal rods were inserted into the cervical osses under general anesthesia for manual distension. Colorectal distension (CRD) was performed by insertion of a balloon catheter into the descending colon and rectum, followed by manual inflation. Two electrodes were inserted into the rectus abdominus muscle for recording UCD- or CRD-induced reflex contraction, which was quantified by electromyography (EMG). A dose response for milnacipran, administered intrathecally or i.v., was obtained for UCD and CRD stimulation. Milnacipran failed to inhibit the UCD-induced EMG response, whether administered i.v. or intrathecally. Similarly, i.v. milnacipran, administered either acutely or chronically, failed to inhibit the CRD-induced EMG response. CRD and UCD are well established animal models for the study of acute visceral pain. Milnacipran, although it provides some unique advantages compared with other antidepressants, is unlikely to produce analgesia after acute administration in the setting of acute visceral pain. Neither intrathecal nor i.v. milnacipran, a monoamine reuptake inhibitor, inhibits an acute visceral pain response induced by colorectal or uterine cervical distension.

  5. Potent Selective Inhibition of Monoamine Oxidase A by Alternariol Monomethyl Ether Isolated from Alternaria brassicae.

    PubMed

    Lee, Hyun Woo; Kim, Yeon Ji; Nam, Sang-Jip; Kim, Hoon

    2017-02-28

    Alternariol monomethyl ether (AME), a dibenzopyrone derivative, was isolated from Alternaria brassicae along with altertoxin II (ATX-II). The compounds were tested for the inhibitory activity of monoamine oxidase (MAO), which catalyzes neurotransmitting monoamines. AME was found to be a highly potent and selective inhibitor of human MAO-A with an IC50 value of 1.71 µM; however, it was found to be ineffective for MAO-B inhibition. ATX-II was not effective for the inhibition of either MAO-A or MAO-B. The inhibition of MAO-A using AME was apparently instantaneous. MAO-A activity was almost completely recovered after the dilution of the inhibited enzyme with an excess amount of AME, suggesting AME is a reversible inhibitor. AME showed mixed inhibition for MAO-A in Lineweaver-Burk plots with a Ki value of 0.34 µM. The findings of this study suggest that microbial metabolites and dibenzopyrone could be potent MAO inhibitors. In addition, AME could be a useful lead compound for developing reversible MAO-A inhibitors to treat depression, Parkinson's disease, and Alzheimer's disease.

  6. High homocysteine induces betaine depletion.

    PubMed

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J

    2015-04-28

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI-LC-MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte.

  7. High homocysteine induces betaine depletion

    PubMed Central

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J.

    2015-01-01

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI—LC–MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte. PMID:26182429

  8. Gulf war depleted uranium risks.

    PubMed

    Marshall, Albert C

    2008-01-01

    US and British forces used depleted uranium (DU) in armor-piercing rounds to disable enemy tanks during the Gulf and Balkan Wars. Uranium particulate is generated by DU shell impact and particulate entrained in air may be inhaled or ingested by troops and nearby civilian populations. As uranium is slightly radioactive and chemically toxic, a number of critics have asserted that DU exposure has resulted in a variety of adverse health effects for exposed veterans and nearby civilian populations. The study described in this paper used mathematical modeling to estimate health risks from exposure to DU during the 1991 Gulf War for both US troops and nearby Iraqi civilians. The analysis found that the risks of DU-induced leukemia or birth defects are far too small to result in an observable increase in these health effects among exposed veterans or Iraqi civilians. The analysis indicated that only a few ( approximately 5) US veterans in vehicles accidentally targeted by US tanks received significant exposure levels, resulting in about a 1.4% lifetime risk of DU radiation-induced fatal cancer (compared with about a 24% risk of a fatal cancer from all other causes). These veterans may have also experienced temporary kidney damage. Iraqi children playing for 500 h in DU-destroyed vehicles are predicted to incur a cancer risk of about 0.4%. In vitro and animal tests suggest the possibility of chemically induced health effects from DU internalization, such as immune system impairment. Further study is needed to determine the applicability of these findings for Gulf War exposure to DU. Veterans and civilians who did not occupy DU-contaminated vehicles are unlikely to have internalized quantities of DU significantly in excess of normal internalization of natural uranium from the environment.

  9. Specification for the VERA Depletion Benchmark Suite

    SciTech Connect

    Kim, Kang Seog

    2015-12-17

    CASL-X-2015-1014-000 iii Consortium for Advanced Simulation of LWRs EXECUTIVE SUMMARY The CASL neutronics simulator MPACT is under development for the neutronics and T-H coupled simulation for the pressurized water reactor. MPACT includes the ORIGEN-API and internal depletion module to perform depletion calculations based upon neutron-material reaction and radioactive decay. It is a challenge to validate the depletion capability because of the insufficient measured data. One of the detoured methods to validate it is to perform a code-to-code comparison for benchmark problems. In this study a depletion benchmark suite has been developed and a detailed guideline has been provided to obtain meaningful computational outcomes which can be used in the validation of the MPACT depletion capability.

  10. Action orientation overcomes the ego depletion effect.

    PubMed

    Dang, Junhua; Xiao, Shanshan; Shi, Yucai; Mao, Lihua

    2015-04-01

    It has been consistently demonstrated that initial exertion of self-control had negative influence on people's performance on subsequent self-control tasks. This phenomenon is referred to as the ego depletion effect. Based on action control theory, the current research investigated whether the ego depletion effect could be moderated by individuals' action versus state orientation. Our results showed that only state-oriented individuals exhibited ego depletion. For individuals with action orientation, however, their performance was not influenced by initial exertion of self-control. The beneficial effect of action orientation against ego depletion in our experiment results from its facilitation for adapting to the depleting task. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  11. Antidepressant-like activity of sildenafil following acute and subchronic treatment in the forced swim test in mice: effects of restraint stress and monoamine depletion.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Pieróg, Mateusz; Szuster-Ciesielska, Agnieszka; Wyska, Elżbieta; Wlaź, Piotr

    2016-10-01

    Sildenafil is a highly effective oral agent for the treatment of erectile dysfunction of multiple etiologies. Although in clinical practice sildenafil is often used in depressed patients, its influence on the pathophysiology of depression remains unclear. The aim of the present study was to evaluate the antidepressant-like activity following acute and subchronic treatment with sildenafil in naïve mice as well as in mice with reserpine- and restraint stress-induced depressive-like behavior. Since corticosterone is released in response to acute stress, we also aimed to assess the influence of sildenafil on serum corticosterone level in non-stressed and stressed animals. The antidepressant activity of sildenafil was assessed in the forced swim test. Corticosterone serum level was determined by using ELISA method, while brain and serum sildenafil level via HPLC method. Sildenafil administered acutely exerted an antidepressant-like effect. Subchronic (14 days) administration of sildenafil resulted only in a weak antidepressant-like effect when evaluated 24 h after the last dose. Acute but not subchronic sildenafil administration reversed the reserpine- and stress-induced immobility in the forced swim test. The lack of effects of sildenafil after subchronic treatment could have been related to its complete elimination from the brain within 24 h from the last injection. Interestingly, acute administration of sildenafil produced a marked increase in serum corticosterone level in both non-stressed and stressed animals. Sildenafil exerts differential effects in the forced swim test after acute and subchronic administration. Further studies on the antidepressant activity of sildenafil are required.

  12. Effects of lamotrigine on PCP-evoked elevations in monoamine levels in the medial prefrontal cortex of freely moving rats.

    PubMed

    Quarta, Davide; Large, Charles H

    2011-12-01

    Lamotrigine is suggested to have potential as an add-on treatment for patients with schizophrenia. Supporting evidence comes from the efficacy of the drug in models of psychotic-like behaviour induced by N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP). These drugs enhance levels of the monoamines in the cortex, which may contribute to their psychotomimetic effects. The ability of lamotrigine to prevent these neurochemical changes has not been examined. We studied PCP-evoked overflow of noradrenaline, dopamine and serotonin in the medial prefrontal cortex of awake rats using microdialysis. Rats were administered lamotrigine or vehicle, followed by PCP. Locomotor activity was also recorded before and after drug treatment. Lamotrigine did not have an influence on basal levels of the monoamines, but significantly reduced PCP-evoked overflow of dopamine and serotonin; PCP-evoked overflow of noradrenaline was also reduced by lamotrigine, but not to a significant degree. In contrast, PCP-induced hyperactivity was unaffected by lamotrigine. It is concluded that lamotrigine can modify PCP-evoked monoamine overflow in the cortex, consistent with an ability to prevent the psychotomimetic effects of NMDA receptor antagonists in rodents and humans. The dissociation between monoamine overflow and locomotor activity suggests the involvement of different brain circuits; relevance to the treatment of schizophrenia is also discussed.

  13. Monoamine content during the reproductive cycle of Perna perna depends on site of origin on the Atlantic Coast of Morocco

    PubMed Central

    Klouche, Mounia S.; De Deurwaerdère, Philippe; Dellu-Hagedorn, Françoise; Lakhdar-Ghazal, Nouria; Benomar, Soumaya

    2015-01-01

    Bivalve molluscs such as Perna perna display temporal cycles of reproduction that result from the complex interplay between endogenous and exogenous signals. The monoamines serotonin, dopamine and noradrenaline represent possible endocrine and neuronal links between these signals allowing the molluscs to modulate reproductive functions in conjunction with environmental constraints. Here, we report a disruption of the reproductive cycle of mussels collected from two of three sites along the Moroccan atlantic coast soiled by industrial or domestic waste. Using high pressure liquid chromatography, we show that the temporal pattern of monoamine content in the gonads, pedal and cerebroid ganglia varied throughout the reproductive cycle (resting, developing, maturing, egg-laying) of mussels from the unpolluted site. Marked modification of monoamine tissue content was found between sites, notably in noradrenaline content of the gonads. Discriminant statistics revealed a specific impact of mussel location on the temporal variations of noradrenaline and serotonin levels in gonads and cerebroid ganglia. Correlation analyses showed profound and temporal changes in the monoamine content between organs and ganglia, at the two sites where the reproduction was disrupted. We suggest that environmental constraints lead to profound changes of monoaminergic systems, which thereby compromises the entry of mussels into their reproductive cycle. PMID:26349428

  14. Low platelet monoamine oxidase activity in headache: no correlation with phenolsulphotransferase, succinate dehydrogenase, platelet preparation method or smoking.

    PubMed Central

    Littlewood, J; Glover, V; Sandler, M; Peatfield, R; Petty, R; Clifford Rose, F

    1984-01-01

    Platelet monoamine oxidase activity in male migrainous and cluster headache patients was significantly lower than in male controls, confirming our previous study. The activity range showed a normal distribution and low mean values could not be attributed to a subgroup with particularly low activity. When Corash 's platelet preparation method was used, with its high platelet yield, specific enzyme activities of a similar order were obtained. Thus, the low values encountered were not due to abnormal recovery within the platelet population. Two other enzyme activities, phenolsulphotransferase M and succinate dehydrogenase, were also measured in the same platelet samples. Although low succinate dehydrogenase activity was identified in the headache groups, it appeared to represent a separate phenomenon and there was no significant correlation between activity of either enzyme and that of monoamine oxidase. This shows that the low activity of platelet monoamine oxidase in headache is not related to a generalised platelet enzyme deficit. It was also shown that the low monoamine oxidase activity in the headache patients could not be attributed to smoking. PMID:6587008

  15. Identification of conformationally sensitive residues essential for inhibition of vesicular monoamine transport by the noncompetitive inhibitor tetrabenazine.

    PubMed

    Ugolev, Yelena; Segal, Tali; Yaffe, Dana; Gros, Yael; Schuldiner, Shimon

    2013-11-08

    Vesicular monoamine transporter 2 (VMAT2) transports monoamines into storage vesicles in a process that involves exchange of the charged monoamine with two protons. VMAT2 is a member of the DHA12 family of multidrug transporters that belongs to the major facilitator superfamily of secondary transporters. Tetrabenazine (TBZ) is a non-competitive inhibitor of VMAT2 that is used in the treatment of hyperkinetic disorders associated with Huntington disease and Tourette syndrome. Previous biochemical studies suggested that the recognition site for TBZ and monoamines is different. However, the precise mechanism of TBZ interaction with VMAT2 remains unknown. Here we used a random mutagenesis approach and selected TBZ-resistant mutants. The mutations clustered around the lumenal opening of the transporter and mapped to either conserved proline or glycine, or to residues immediately adjacent to conserved proline and glycine. Directed mutagenesis provides further support for the essential role of the latter residues. Our data strongly suggest that the conserved α-helix breaking residues identified in this work play an important role in conformational rearrangements required for TBZ binding and substrate transport. Our results provide a novel insight into the mechanism of transport and TBZ binding by VMAT2.

  16. Monoamine content during the reproductive cycle of Perna perna depends on site of origin on the Atlantic Coast of Morocco.

    PubMed

    Klouche, Mounia S; De Deurwaerdère, Philippe; Dellu-Hagedorn, Françoise; Lakhdar-Ghazal, Nouria; Benomar, Soumaya

    2015-09-09

    Bivalve molluscs such as Perna perna display temporal cycles of reproduction that result from the complex interplay between endogenous and exogenous signals. The monoamines serotonin, dopamine and noradrenaline represent possible endocrine and neuronal links between these signals allowing the molluscs to modulate reproductive functions in conjunction with environmental constraints. Here, we report a disruption of the reproductive cycle of mussels collected from two of three sites along the Moroccan atlantic coast soiled by industrial or domestic waste. Using high pressure liquid chromatography, we show that the temporal pattern of monoamine content in the gonads, pedal and cerebroid ganglia varied throughout the reproductive cycle (resting, developing, maturing, egg-laying) of mussels from the unpolluted site. Marked modification of monoamine tissue content was found between sites, notably in noradrenaline content of the gonads. Discriminant statistics revealed a specific impact of mussel location on the temporal variations of noradrenaline and serotonin levels in gonads and cerebroid ganglia. Correlation analyses showed profound and temporal changes in the monoamine content between organs and ganglia, at the two sites where the reproduction was disrupted. We suggest that environmental constraints lead to profound changes of monoaminergic systems, which thereby compromises the entry of mussels into their reproductive cycle.

  17. Effects of ractopamine feeding, gender and social rank on aggressiveness and monoamine concentrations in different brain areas of finishing pigs

    USDA-ARS?s Scientific Manuscript database

    This study evaluated the effects of the feed additive ractopamine (RAC), gender and social rank on aggressiveness and brain monoamines levels of serotonin (5HT), dopamine (DA), their metabolites, norepinephrine (NE) and epinephrine (EP) in finishing pigs. Thirty-two pigs (16 barrows/16 gilts) were a...

  18. Regional brain monoamine concentrations and their alterations in bovine hypomagnesaemic tetany experimentally induced by a magnesium-deficient diet.

    PubMed

    McCoy, M A; Young, P B; Hudson, A J; Davison, G; Kennedy, D G

    2000-12-01

    Monoamines are important brain neurotransmitters. An investigation was carried out to determine if hypomagnesaemic tetany was associated with alterations in regional brain monoamine concentrations in bovines. The results, established in cows with normal magnesium status, demonstrated that regional differences existed in the distribution and concentration of brain monoamines in the adult bovine, which were similar to those in other species. In magnesium-deficient cows, severe hypomagnesaemia and lowered cerebrospinal fluid (CSF) magnesium concentrations were associated with significant alterations in monoamine concentrations in some brain regions. Alterations in 3,4-dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC) concentrations in the corpus striatum, and dopamine (DA) in the cerebral cortex and cerebellum were recorded. These regions play an important role in both voluntary and involuntary motor function, and therefore these alterations may play a role in the aetiology of hypomagnesaemic tetany. However, there was no significant change in DA concentrations in the corpus striatum (the main dopaminergic region in the brain) associated with hypomagnesaemia. In addition, a significantly lower norepinephrine (NE) concentration in the corpus striatum of hypomagnesaemic animals was also recorded. Norephinephrine is generally excitatory and therefore lowered NE concentrations would be expected to result in depression rather than stimulation of motor function. Copyright 2000 Harcourt Publishers Ltd.

  19. Non-motor symptoms of Parkinson’s disease revealed in an animal model with reduced monoamine storage capacity

    PubMed Central

    Taylor, Tonya N.; Caudle, W. Michael; Shepherd, Kennie R.; Noorian, AliReza; Jackson, Chad R.; Iuvone, P. Michael; Weinshenker, David; Greene, James G.; Miller, Gary W.

    2010-01-01

    Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is characterized by the loss of dopamine neurons in the substantia nigra pars compacta, culminating in severe motor symptoms, including: resting tremor, rigidity, bradykinesia, and postural instability. In addition to motor deficits, there are a variety of non-motor symptoms associated with PD. These symptoms generally precede the onset of motor symptoms, sometimes by years, and include anosmia, problems with gastrointestinal motility, sleep disturbances, sympathetic denervation, anxiety, and depression. Previously, we have shown that mice with a 95% genetic reduction in vesicular monoamine transporter expression (VMAT2-deficient, VMAT2 LO) display progressive loss of striatal dopamine, L-DOPA responsive motor deficits, α-synuclein accumulation, and nigral dopaminergic cell loss. We hypothesized that since these animals exhibit deficits in other monoamine systems (norepinephrine, serotonin), which are known to regulate some of these behaviors that the VMAT2-deficient mice may display some of the non-motor symptoms associated with PD. Here we report that the VMAT2-deficient mice demonstrate progressive deficits in olfactory discrimination, delayed gastric emptying, altered sleep latency, anxiety-like behavior, and age-dependent depressive behavior. These results suggest that the VMAT2-deficient mice may be a useful model of the non-motor symptoms of PD. Furthermore, monoamine dysfunction may contribute to many of the non-motor symptoms of PD and interventions aimed at restoring monoamine function may be beneficial in treating the disease. PMID:19553450

  20. Genetic variation in the effect of monoamines on female mating receptivity and oviposition in the adzuki bean beetle, Callosobruchus chinensis (Coleoptera: Bruchidae).

    PubMed

    Yamane, Takashi

    2014-08-06

    Female mate choice after mating is a strong force in sexual selection and could lead to coevolution of mating traits between the sexes. How females of different genotypes respond to substances in the male ejaculate should be mediated by females' mate choices. Monoamines regulate animal physiology and behavior, including the post-mating behavior of females of the adzuki bean beetle, Callosobruchus chinensis (Coleoptera: Bruchidae). This study examined differences in females' response to four monoamines (dopamine, octopamine, tyramine, serotonin) between strains from different populations of C. chinensis. Injection with either octopamine or tyramine, two kinds of monoamines significantly reduced female receptivity in two strains with low remating frequencies. None of the four monoamines reduced female receptivity in one strain with high remating frequencies. However, all monoamines reduced it in another strain with high remating frequencies. Oviposition was activated by tyramine on days 1-5 or by serotonin on days 4 and 5 in the two strains with low remating frequencies, but only on day 1 or day 4 in the strains with high remating frequencies. These differences in female response to monoamines, especially tyramine and serotonin, correspond with results of previous studies. They indicate differences in female response to male substances that reduce receptivity and activate oviposition. These findings suggest relationships between the differences in female response to male substances among populations and mutations in the pathways of monoamine biosynthesis or transmission, which in turn determine female mate choice in response to male substances.

  1. Genetic variation in the effect of monoamines on female mating receptivity and oviposition in the adzuki bean beetle, Callosobruchus chinensis (Coleoptera: Bruchidae)

    PubMed Central

    2014-01-01

    Background Female mate choice after mating is a strong force in sexual selection and could lead to coevolution of mating traits between the sexes. How females of different genotypes respond to substances in the male ejaculate should be mediated by females’ mate choices. Monoamines regulate animal physiology and behavior, including the post-mating behavior of females of the adzuki bean beetle, Callosobruchus chinensis (Coleoptera: Bruchidae). This study examined differences in females’ response to four monoamines (dopamine, octopamine, tyramine, serotonin) between strains from different populations of C. chinensis. Results Injection with either octopamine or tyramine, two kinds of monoamines significantly reduced female receptivity in two strains with low remating frequencies. None of the four monoamines reduced female receptivity in one strain with high remating frequencies. However, all monoamines reduced it in another strain with high remating frequencies. Oviposition was activated by tyramine on days 1–5 or by serotonin on days 4 and 5 in the two strains with low remating frequencies, but only on day 1 or day 4 in the strains with high remating frequencies. Conclusion These differences in female response to monoamines, especially tyramine and serotonin, correspond with results of previous studies. They indicate differences in female response to male substances that reduce receptivity and activate oviposition. These findings suggest relationships between the differences in female response to male substances among populations and mutations in the pathways of monoamine biosynthesis or transmission, which in turn determine female mate choice in response to male substances. PMID:25098756

  2. Possible ozone depletions following nuclear explosions

    NASA Technical Reports Server (NTRS)

    Whitten, R. C.; Borucki, W. J.; Turco, R. P.

    1975-01-01

    The degree of depletion of the ozone layer ensuing after delivery of strategic nuclear warheads (5000 and 10,000 Mton) due to production of nitrogen oxides is theoretically assessed. Strong depletions are calculated for 16-km and 26-km altitudes, peaking 1-2 months after detonation and lasting for three years, while a significant depletion at 36 km would peak after one year. Assuming the explosions occur between 30 and 70 deg N, these effects should be much more pronounced in this region than over the Northern Hemisphere as a whole. It is concluded that Hampson's concern on this matter (1974) is well-founded.-

  3. Fully Depleted Charge-Coupled Devices

    SciTech Connect

    Holland, Stephen E.

    2006-05-15

    We have developed fully depleted, back-illuminated CCDs thatbuild upon earlier research and development efforts directed towardstechnology development of silicon-strip detectors used inhigh-energy-physics experiments. The CCDs are fabricated on the same typeof high-resistivity, float-zone-refined silicon that is used for stripdetectors. The use of high-resistivity substrates allows for thickdepletion regions, on the order of 200-300 um, with corresponding highdetection efficiency for near-infrared andsoft x-ray photons. We comparethe fully depleted CCD to thep-i-n diode upon which it is based, anddescribe the use of fully depleted CCDs in astronomical and x-ray imagingapplications.

  4. Possible ozone depletions following nuclear explosions

    NASA Technical Reports Server (NTRS)

    Whitten, R. C.; Borucki, W. J.; Turco, R. P.

    1975-01-01

    The degree of depletion of the ozone layer ensuing after delivery of strategic nuclear warheads (5000 and 10,000 Mton) due to production of nitrogen oxides is theoretically assessed. Strong depletions are calculated for 16-km and 26-km altitudes, peaking 1-2 months after detonation and lasting for three years, while a significant depletion at 36 km would peak after one year. Assuming the explosions occur between 30 and 70 deg N, these effects should be much more pronounced in this region than over the Northern Hemisphere as a whole. It is concluded that Hampson's concern on this matter (1974) is well-founded.-

  5. Monoamines tissue content analysis reveals restricted and site-specific correlations in brain regions involved in cognition.

    PubMed

    Fitoussi, A; Dellu-Hagedorn, F; De Deurwaerdère, P

    2013-01-01

    The dopamine (DA), noradrenalin (NA) and serotonin (5-HT) monoaminergic systems are deeply involved in cognitive processes via their influence on cortical and subcortical regions. The widespread distribution of these monoaminergic networks is one of the main difficulties in analyzing their functions and interactions. To address this complexity, we assessed whether inter-individual differences in monoamine tissue contents of various brain areas could provide information about their functional relationships. We used a sensitive biochemical approach to map endogenous monoamine tissue content in 20 rat brain areas involved in cognition, including 10 cortical areas and examined correlations within and between the monoaminergic systems. Whereas DA content and its respective metabolite largely varied across brain regions, the NA and 5-HT contents were relatively homogenous. As expected, the tissue content varied among individuals. Our analyses revealed a few specific relationships (10%) between the tissue content of each monoamine in paired brain regions and even between monoamines in paired brain regions. The tissue contents of NA, 5-HT and DA were inter-correlated with a high incidence when looking at a specific brain region. Most correlations found between cortical areas were positive while some cortico-subcortical relationships regarding the DA, NA and 5-HT tissue contents were negative, in particular for DA content. In conclusion, this work provides a useful database of the monoamine tissue content in numerous brain regions. It suggests that the regulation of these neuromodulatory systems is achieved mainly at the terminals, and that each of these systems contributes to the regulation of the other two. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Cocaine-like discriminative stimulus effects of "norepinephrine-preferring" monoamine releasers: time course and interaction studies in rhesus monkeys.

    PubMed

    Kohut, Stephen J; Jacobs, David S; Rothman, Richard B; Partilla, John S; Bergman, Jack; Blough, Bruce E

    2017-09-09

    The therapeutic potential of monoamine releasers with prominent dopaminergic effects is hindered by their high abuse liability. The present study examined the effects of several novel "norepinephrine (NE)-preferring" monoamine releasers relative to non-selective monoamine releasers, d-amphetamine and d-methamphetamine, in rhesus monkeys trained to discriminate cocaine. NE-preferring releasers were approximately 13-fold more potent for NE compared to dopamine release and ranged in potency for serotonin release (PAL-329 < l-methamphetamine < PAL-169). Adult rhesus macaques were trained to discriminate 0.4 mg/kg, IM cocaine on a 30-response fixed ratio schedule of food reinforcement. Substitution studies determined the extent to which test drugs produced cocaine-like discriminative stimulus effects and their time course. Drug interaction studies determined whether pretreatment with test drugs altered the discriminable effects of cocaine. Results show that cocaine, d-amphetamine, and d-methamphetamine dose-dependently substituted for cocaine with similar potencies. Among the "NE-preferring" releasers, PAL-329 and l-methamphetamine also dose-dependently substituted for cocaine but differed in potency. PAL-169 failed to substitute for cocaine up to a dose that disrupted responding. When administered prior to cocaine, only d-amphetamine and PAL-329 significantly shifted the cocaine dose-effect function leftward indicating enhancement of cocaine's discriminative stimulus effects. These data suggest that greater potency for NE relative to dopamine release (up to 13-fold) does not interfere with the ability of a monoamine releaser to produce cocaine-like discriminative effects but that increased serotonin release may have an inhibitory effect. Further characterization of these and other "NE-preferring" monoamine releasers should provide insight into their potential for the management of cocaine addiction.

  7. Activity wheel running reduces escape latency and alters brain monoamine levels after footshock.

    PubMed

    Dishman, R K; Renner, K J; Youngstedt, S D; Reigle, T G; Bunnell, B N; Burke, K A; Yoo, H S; Mougey, E H; Meyerhoff, J L

    1997-01-01

    We examined the effects of chronic activity wheel running on brain monoamines and latency to escape foot shock after prior exposure to uncontrollable, inescapable foot shock. Individually housed young (approximately 50 day) female Sprague-Dawley rats were randomly assigned to standard cages (sedentary) or cages with activity wheels. After 9-12 weeks, animals were matched in pairs on body mass. Activity wheel animals were also matched on running distance. An animal from each matched pair was randomly assigned to controllable or uncontrollable inescapable foot shock followed the next day by a foot shock escape test in a shuttle box. Brain concentrations of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) were assayed in the locus coeruleus (LC), dorsal raphe (DR), central amygdala (AC), hippocampus (CA1), arcuate nucleus, paraventricular nucleus (PVN), and midbrain central gray. After prior exposure to uncontrollable foot shock, escape latency was reduced by 34% for wheel runners compared with sedentary controls. The shortened escape latency for wheel runners was associated with 61% higher NE concentrations in LC and 44% higher NE concentrations in DR compared with sedentary controls. Sedentary controls, compared with wheel runners, had 31% higher 5-HIAA concentrations in CA1 and 30% higher 5-HIAA concentrations in AC after uncontrollable foot shock and had 28% higher 5-HT and 33% higher 5-HIAA concentrations in AC averaged across both foot shock conditions. There were no group differences in monoamines in the central gray or in plasma prolactin or ACTH concentrations, despite 52% higher DA concentrations in the arcuate nucleus after uncontrollable foot shock and 50% higher DOPAC/DA and 17% higher 5-HIAA/5-HT concentrations in the PVN averaged across both foot shock conditions for sedentary compared with activity wheel animals. The present results extend understanding of the

  8. Effect of dietary restriction on peripheral monoamines and anxiety symptoms in obese subjects with metabolic syndrome.

    PubMed

    Perez-Cornago, Aurora; Ramírez, María J; Zulet, M Ángeles; Martinez, J Alfredo

    2014-09-01

    Reduced circulating monoamines may have a role in the development of the metabolic syndrome (MetS), which is becoming a major health problem worldwide. Moreover, an association between anxiety disorder and MetS has been reported; however, it is not clear whether weight loss can diminish anxiety. This investigation is aimed to examine the effects of a weight loss intervention on peripheral monoamines levels and anxiety symptoms in subjects with metabolic syndrome (MetS). The study population encompassed subjects with MetS (age: 50±10 y.o. and BMI: 35.8±4.3 kg/m2) selected from the RESMENA study after they had completed the 6-month weight loss intervention (-30% energy). Anthropometric measurements, dietary records, anxiety symptoms, and blood monoamines levels were analysed before and after the intervention. Dopamine (DA) (+18.2%; 95% confidence interval (CI): -51.2 to -0.5) and serotonin (5-HT) (+16.1%; 95% CI: -26.3 to -2.2) blood levels were significantly increased after the intervention. Higher DA blood concentrations at the end of the study were inversely related with the carbohydrate intake during the study (B=-3.3; 95% CI: -8.4 to -0.4) and basal DA levels predicted a greater decrease in body weight and anthropometric parameters. Subjects with higher 5-HT concentrations after the weight loss intervention also showed a lower energy intake during the intervention (B=-0.04; 95% CI: -0.07 to -0.01). Additionally, anxiety symptoms decreased after the weight loss treatment (-28.3%; 95% CI: 6.2-20.4), which was parallel to a greater decrease in body weight and anthropometric markers, being related to lower 5-HT basal levels. Dietary restriction in patients with MetS may help in reducing anxiety symptoms, and also in increasing 5-HT and DA blood levels. These results provide further insights regarding emotional and neurological factors behind weight loss.

  9. The Benzopyrone Biochanin-A as a reversible, competitive, and selective monoamine oxidase B inhibitor.

    PubMed

    Zarmouh, Najla O; Eyunni, Suresh K; Soliman, Karam F A

    2017-01-10

    Monoamine oxidase-B (MAO-B) inhibitors are widely used in the treatment of Parkinson's disease. They increase vital monoamine neurotransmitters in the brain. However, there is a need for safer natural reversible MAO inhibitors with MAO-B selectivity. Our previous studies showed that Psoralea corylifolia seeds (PCS) extract contains compounds that inhibit monoamine oxidase-B. In this study, six of PCS constituents sharing a benzopyrone structure were investigated. The compounds Biochanin-A (BIO-A), isopsoralen, 6-prenylnaringenin, neobavaisoflavone, psoralen, and psoralidin, were tested for their ability to inhibit recombinant human MAO-A and B (hMAO-A and hMAO-B) isozymes. The ability of these compounds to inhibit MAO-A and MAO-B were compared to that of PCS ethanolic extract (PCSEE) using spectrophotometric assays and confirmed by luminescence assays. The highly potent and selective MAO-B inhibitor, BIO-A, was further investigated for both isozymes reversibility and enzyme kinetics. Molecular docking studies were used to predict the bioactive conformation and molecular interactions of BIO-A with both isozymes. The data obtained indicate that benzopyrones inhibited hMAO-A and hMAO-B with different degrees as confirmed with the luminescence assay. BIO-A inhibited hMAO-B with high potency and selectivity in the present study (IC50 = 0.003 μg/mL) and showing 38-fold more selectivity than PCSEE (hMAO-B IC50 = 3.03 μg/mL, 17-fold selectivity) without affecting hydrogen peroxide. Furthermore, BIO-A reversibly and competitively inhibited both hMAOs with significantly lower inhibitory constant (Ki) in hMAO-B (3.8 nM) than hMAO-A (99.3 nM). Our docking studies indicated that the H-bonds and hydrophobic interactions at the human MAO-A and MAO-B active sites contributed to the reversibility and selectivity of BIO-A. The data obtained indicate that BIO-A is a potent, reversible and selective MAO-B inhibitor and may be recommended for further investigation in its

  10. Effect of aspartame on oxidative stress and monoamine neurotransmitter levels in lipopolysaccharide-treated mice.

    PubMed

    Abdel-Salam, Omar M E; Salem, Neveen A; Hussein, Jihan Seid

    2012-04-01

    This study aimed at investigating the effect of the sweetener aspartame on oxidative stress and brain monoamines in normal circumstances and after intraperitoneal (i.p.) administration of lipopolysaccharide (LPS; 100 μg/kg) in mice. Aspartame (0.625-45 mg/kg) was given via subcutaneous route at the time of endotoxin administration. Mice were euthanized 4 h later. Reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid-reactive substances; TBARS), and nitrite concentrations were measured in brain and liver. Tumor necrosis factor-alpha (TNF-α) and glucose were determined in brain. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in liver. The administration of only aspartame (22.5 and 45 mg/kg) increased brain TBARS by 17.7-32.8%, decreased GSH by 25.6-31.6%, and increased TNF-α by 16.7-44%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline, and dopamine. Aspartame did not alter liver TBARS, nitrite, GSH, AST, ALT, or ALP. The administration of LPS increased nitrite in brain and liver by 26.8 and 37.1%, respectively; decreased GSH in brain and liver by 21.6 and 31.1%, respectively; increased brain TNF-α by 340.4%, and glucose by 39.9%, and caused marked increase in brain monoamines. LPS increased AST, ALT, and ALP in liver tissue by 84.4, 173.7, and 258.9%, respectively. Aspartame given to LPS-treated mice at 11.25 and 22.5 mg/kg increased brain TBARS by 15.5-16.9%, nitrite by 12.6-20.1%, and mitigated the increase in monoamines. Aspartame did not alter liver TBARS, nitrite, GSH, ALT, AST, or ALP. Thus, the administration of aspartame alone or in the presence of mild systemic inflammatory response increases oxidative stress and inflammation in the brain, but not in the liver.

  11. A definition of depletion of fish stocks

    USGS Publications Warehouse

    Van Oosten, John

    1949-01-01

    Attention was focused on the need of a common and better understanding of the term depletion as applied to the fisheries in order to eliminate if possible the existing inexactness of thought on the subject. Depletion has been confused at various times with at least ten different ideas associated with it but which, as has has heen pointed out, are not synonymous at all. In defining depletion we must recognize that the term represents a condition and must not he confounded with the cause (overfishing) that leads to this condition or with the symptoms that identify it. Depletion was defined as a reduction, through overfishing, in the level of abundance of the exploitable segment of a stock that prevents the realization of the maximum productive capacity.

  12. [Hepatomioneuropathy secondary to mitochondrial DNA depletion].

    PubMed

    Blanco-Barca, M O; Gómez-Lado, C; Campos-González, Y; Castro-Gago, M

    2007-04-01

    Mitochondrial DNA depletion (mtDNA) is an highly heterogeneous condition characterized by a decreased number of mtDNA copies. The patient is a 22-month-old girl with generalized hypotonia, marked weakness, respiratory failure, arterial hypertension, hyperlactacidemia, hepatosplenomegaly and mild hypertransaminasemia without hepatic failure neither hypoketotic hypoglycemia. Electromyographic findings were consistent with neuromyopathy and muscle biopsy suggested a neurogenic atrophy. Electron microscopy revealed lipid droplets, subsarcolemmal accumulation of mitochondrias and glycogen granules. Respiratory chain enzime activities were normal. Genetic study in muscle showed mtDNA depletion, and the diagnosis of spinal muscular atrophy caused by survival motoneuron gene deletion was excluded. This case might be a novel phenotype of mtDNA depletion which could be named hepatomioneuropatyc form. A normal result of respiratory chain enzimes in muscle doesn't excluded mtDNA depletion.

  13. Polar stratospheric clouds and ozone depletion

    NASA Technical Reports Server (NTRS)

    Toon, Owen B.; Turco, Richard P.

    1991-01-01

    A review is presented of investigations into the correlation between the depletion of ozone and the formation of polar stratospheric clouds (PSCs). Satellite measurements from Nimbus 7 showed that over the years the depletion from austral spring to austral spring has generally worsened. Approximately 70 percent of the ozone above Antarctica, which equals about 3 percent of the earth's ozone, is lost during September and October. Various hypotheses for ozone depletion are discussed including the theory suggesting that chlorine compounds might be responsible for the ozone hole, whereby chlorine enters the atmosphere as a component of chlorofluorocarbons produced by humans. The three types of PSCs, nitric acid trihydrate, slowly cooling water-ice, and rapidly cooling water-ice clouds act as important components of the Antarctic ozone depletion. It is indicated that destruction of the ozone will be more severe each year for the next few decades, leading to a doubling in area of the Antarctic ozone hole.

  14. Polar stratospheric clouds and ozone depletion

    NASA Technical Reports Server (NTRS)

    Toon, Owen B.; Turco, Richard P.

    1991-01-01

    A review is presented of investigations into the correlation between the depletion of ozone and the formation of polar stratospheric clouds (PSCs). Satellite measurements from Nimbus 7 showed that over the years the depletion from austral spring to austral spring has generally worsened. Approximately 70 percent of the ozone above Antarctica, which equals about 3 percent of the earth's ozone, is lost during September and October. Various hypotheses for ozone depletion are discussed including the theory suggesting that chlorine compounds might be responsible for the ozone hole, whereby chlorine enters the atmosphere as a component of chlorofluorocarbons produced by humans. The three types of PSCs, nitric acid trihydrate, slowly cooling water-ice, and rapidly cooling water-ice clouds act as important components of the Antarctic ozone depletion. It is indicated that destruction of the ozone will be more severe each year for the next few decades, leading to a doubling in area of the Antarctic ozone hole.

  15. Effects of Riverbed Conductance on Stream Depletion

    NASA Astrophysics Data System (ADS)

    Lackey, G.; Neupauer, R. M.; Pitlick, J.

    2012-12-01

    In the western United States and other regions of the world where growing population and changing climates are threatening water supplies, accurate modeling of potential human impacts on water resources is becoming more important. Stream depletion, the reduction of surface water flow due to the extraction of groundwater from a hydraulically connected aquifer, is one of the more direct ways that development can alter water availability, degrade water quality and endanger aquatic habitats. These factors have made the accurate modeling of stream depletion an important step in the process of installing groundwater wells in regions that are susceptible to this phenomenon. Proper estimation of stream depletion requires appropriate parameterization of aquifer and streambed hydraulic properties. Although many studies have conducted numerical investigations to determine stream depletion at specific sites, they typically do not measure streambed hydraulic conductivity (Kr), but rather assume a representative value. In this work, we establish a hypothetical model aquifer that is 2000 m by 1600 m and has a meandering stream running through its center. The Kr of the model stream is varied from 1.0x10-9 m s-1 to 1.0x10-2 m s-1 in order to determine the sensitivity of the stream depletion calculations to this parameter. It was found that when Kr is in the lower part of this range, slight changes in K¬r lead to significant impacts on the calculated stream depletion values. We vary Kr along the stream channel according to naturally occurring patterns and demonstrate that alterations of the parameter over a few orders of magnitude can affect the estimated stream depletion caused by a well at a specified location. The numerical simulations show that the mean value of Kr and its spatial variability along the channel should be realistic to develop an accurate model of stream depletion.

  16. Depleted uranium: A DOE management guide

    SciTech Connect

    1995-10-01

    The U.S. Department of Energy (DOE) has a management challenge and financial liability in the form of 50,000 cylinders containing 555,000 metric tons of depleted uranium hexafluoride (UF{sub 6}) that are stored at the gaseous diffusion plants. The annual storage and maintenance cost is approximately $10 million. This report summarizes several studies undertaken by the DOE Office of Technology Development (OTD) to evaluate options for long-term depleted uranium management. Based on studies conducted to date, the most likely use of the depleted uranium is for shielding of spent nuclear fuel (SNF) or vitrified high-level waste (HLW) containers. The alternative to finding a use for the depleted uranium is disposal as a radioactive waste. Estimated disposal costs, utilizing existing technologies, range between $3.8 and $11.3 billion, depending on factors such as applicability of the Resource Conservation and Recovery Act (RCRA) and the location of the disposal site. The cost of recycling the depleted uranium in a concrete based shielding in SNF/HLW containers, although substantial, is comparable to or less than the cost of disposal. Consequently, the case can be made that if DOE invests in developing depleted uranium shielded containers instead of disposal, a long-term solution to the UF{sub 6} problem is attained at comparable or lower cost than disposal as a waste. Two concepts for depleted uranium storage casks were considered in these studies. The first is based on standard fabrication concepts previously developed for depleted uranium metal. The second converts the UF{sub 6} to an oxide aggregate that is used in concrete to make dry storage casks.

  17. Anatomy of Depleted Interplanetary Coronal Mass Ejections

    NASA Astrophysics Data System (ADS)

    Kocher, M.; Lepri, S. T.; Landi, E.; Zhao, L.; Manchester, W. B., IV

    2017-01-01

    We report a subset of interplanetary coronal mass ejections (ICMEs) containing distinct periods of anomalous heavy-ion charge state composition and peculiar ion thermal properties measured by ACE/SWICS from 1998 to 2011. We label them “depleted ICMEs,” identified by the presence of intervals where C6+/C5+ and O7+/O6+ depart from the direct correlation expected after their freeze-in heights. These anomalous intervals within the depleted ICMEs are referred to as “Depletion Regions.” We find that a depleted ICME would be indistinguishable from all other ICMEs in the absence of the Depletion Region, which has the defining property of significantly low abundances of fully charged species of helium, carbon, oxygen, and nitrogen. Similar anomalies in the slow solar wind were discussed by Zhao et al. We explore two possibilities for the source of the Depletion Region associated with magnetic reconnection in the tail of a CME, using CME simulations of the evolution of two Earth-bound CMEs described by Manchester et al.

  18. A new definition of maternal depletion syndrome.

    PubMed Central

    Winkvist, A; Rasmussen, K M; Habicht, J P

    1992-01-01

    BACKGROUND. Although the term "maternal depletion syndrome" has been commonly used to explain poor maternal and infant health, whether such a syndrome actually exists remains unclear. This uncertainty may be due to the lack of a clear definition of the syndrome and the absence of theoretical frameworks that account for the many factors related to reproductive nutrition. METHODS. We propose a new definition of maternal depletion syndrome within a framework that accounts for potential confounding factors. RESULTS. Our conceptual framework distinguishes between childbearing pattern and inadequate diet as causes of poor maternal health; hence, our definition of maternal depletion syndrome has both biological and practical meaning. The new definition is based on overall change in maternal nutritional status over one reproductive cycle in relation to possible depletion and repletion phases and in relation to initial nutritional status. CONCLUSIONS. The empirical application of this approach should permit the testing of the existence of maternal depletion syndrome in the developing world, and the distinction between populations where family planning will alleviate maternal depletion and those in which an improved diet is also necessary. PMID:1566948

  19. Monoamine Oxidase A Gene (MAOA) Associated with Attitude Towards Longshot Risks

    PubMed Central

    Zhong, Songfa; Israel, Salomon; Xue, Hong; Ebstein, Richard P.; Chew, Soo Hong

    2009-01-01

    Decision making often entails longshot risks involving a small chance of receiving a substantial outcome. People tend to be risk preferring (averse) when facing longshot risks involving significant gains (losses). This differentiation towards longshot risks underpins the markets for lottery as well as for insurance. Both lottery and insurance have emerged since ancient times and continue to play a useful role in the modern economy. In this study, we observe subjects' incentivized choices in a controlled laboratory setting, and investigate their association with a widely studied, promoter-region repeat functional polymorphism in monoamine oxidase A gene (MAOA). We find that subjects with the high activity (4-repeat) allele are characterized by a preference for the longshot lottery and also less insurance purchasing than subjects with the low activity (3-repeat) allele. This is the first result to link attitude towards longshot risks to a specific gene. It complements recent findings on the neurobiological basis of economic risk taking. PMID:20046877

  20. [CATALITICAL PROPERTIES OF LIVER MONOAMINE OXIDASE IN THE CHUM SALMON ONCORHYNCHUS KETA].

    PubMed

    Basova, I N; Basova, N E; Yagodina, O V

    2015-01-01

    The substrate and inhibitory specificity of mitochondrial monoamine oxidase (MAO) in the liver of males of the summer form of the chum salmon Oncorhynchus keta was studied. As to the spectrum of deaminated substrates, the hepatic MAO of the chum salmon is similar to MAO of most terrestrial mammals, for eight classical MAO substrates similarity in their substrate characteristics were found. Analysis of the antimonoamine oxidase activity of two derivaties of 2-propinilamine, five derivatives of acridine as well as of pyronine G revealed significant qualitative and quantitative differences as compared to the hepatic enzyme of tuna and whitefish. The compounds tested manifested themselves as irreversible inhibitors of chum salmon's hepatic MAO possessing various efficacy, but lacking the selectivity of action as dependent on the deaminated substrate. The obtained data on the substrate and inhibitory analysis provide an indirect evidence for the presence of a single molecular form of MAO in the chum salmon liver.

  1. Human recombinant monoamine oxidase B as reliable and efficient enzyme source for inhibitor screening.

    PubMed

    Novaroli, Laura; Reist, Marianne; Favre, Elisabeth; Carotti, Angelo; Catto, Marco; Carrupt, Pierre-Alain

    2005-11-15

    Interest in inhibitors of monoamine oxidase type B (MAO B) has grown in recent years, due to their therapeutic potential in aging-related neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. This study is devoted to the use of human recombinant MAO B obtained from a Baculovirus expression system (Supersomes MAO B, BD Gentest, MA, USA) as reliable and efficient enzyme source for MAO B inhibitor screening. Comparison of inhibition potencies (pIC50 values) determined with human cloned and human platelet MAO B for the two series of MAO B inhibitors, coumarin and 5H-indeno[1,2-c]pyridazin-5-one derivatives, showed that the difference between pIC50 values obtained with the two enzyme sources was not significant (P>0.05, Student's t-test). Hence, recombinant enzyme is validated as convenient enzyme source for MAO B inhibitor screening.

  2. Treatment of hyperactive children with monoamine oxidase inhibitors. I. Clinical efficacy.

    PubMed

    Zametkin, A; Rapoport, J L; Murphy, D L; Linnoila, M; Ismond, D

    1985-10-01

    Fourteen boys (mean age, 9.2 +/- 1.5 years) with Attention Deficit Disorder (ADD) With Hyperactivity were treated with dextroamphetamine sulfate or a monoamine oxidase inhibitor (MAOI) (six received clorgyline, eight received tranylcypromine sulfate) for four weeks each in a double-blind, cross-over study that included a two-week placebo washout between active drug periods. The MAOIs had immediate, clinically significant benefit and were clinically indistinguishable from dextroamphetamine. Most children responded to both stimulant and MAOI. These findings of equivalent efficacy of MAOIs in ADD are in contrast to our previous studies with neurotransmitter system selective agents, which showed only weak effects, and suggest that multiple neurotransmitter alterations may be required for stimulant drug effects in ADD. The immediate response to MAOIs indicates a different mechanism from that mediating antidepressant effect. The MAOIs may be useful alternate treatments in selected cases of ADD.

  3. Decreased platelet monoamine oxidase activity in chronic schizophrenia, shown with novel substrates.

    PubMed

    Berrettini, W H; Prozialeck, W; Vogel, W H

    1978-05-01

    Platelet monoamine oxidase (MAO) was kinetically evaluated in chronic schizophrenics and matched controls, using substrates of major physiologic importance and substrates of particular interest in the study of schizophrenia, such as serotonin (5-ht), N,N-dimethyltryptamine (DMT), 5-methoxytryptamine (5-MT), and dopamine (DA). Substrates were measured at six concentrations; values for maximal velocity (Vmax) and Michaelis constant (Km) were obtained by using Lineweaver-Burk plots. The Vmax was decreased for all substrates in chronic schizophrenia and the Km was decreased for DA, 5-HT, and DMT, but remained unchanged for 5-MT. The value of Km/Vmax was similar for schizophrencis and normal persons when DA, 5-HT, and DMT were used as substrates, which may indicate that "uncompetitive" inhibition is responsible for the observed decrease in activity among chronic schizophrenics. The finding of a decreased Vmax but unchanged Km with 5-MT would be consistent with noncompetitive inhibition.

  4. The effects of acute and extended monoamine oxidase inhibition upon 5-hydroxyindoles in maturing mouse brain.

    PubMed

    Baker, P C; Hoff, K M

    1991-01-01

    1. Mice of four ages between newborn and adult were exposed to the monoamine oxidase inhibitor amiflamine both acutely and in an extended (5 day) regimen. Brains were then assayed at various times following amiflamine for changes in the levels of serotonin (5-HT, 5-hydroxytryptamine) and 5-hydroxyindole acetic acid (5-HIAA). 2. Although both metabolites initially changed as might be expected, with 5-HT elevating and 5-HIAA decreasing, the younger brains recovered their 5-HT levels slower than older brains and eventually young brains had levels of 5-HIAA that were in excess of normal. At some times both metabolites were in excess of normal at younger ages. 3. These results are compared to changes seen with the 5-HT uptake inhibitor citalopram and it is concluded that in young brain 5-HIAA levels lack firm regulatory control and are not passive reflections of 5-HT changes.

  5. Parkin degrades estrogen-related receptors to limit the expression of monoamine oxidases

    PubMed Central

    Ren, Yong; Jiang, Houbo; Ma, Dingyuan; Nakaso, Kazuhiro; Feng, Jian

    2011-01-01

    Parkin, whose mutations cause Parkinson disease (PD), controls oxidative stress by limiting the expression of monoamine oxidases (MAO)—mitochondrial enzymes responsible for the oxidative de-amination of dopamine. Here, we show that parkin performed this function by increasing the ubiquitination and degradation of estrogen-related receptors (ERR), orphan nuclear receptors that play critical roles in the transcription regulation of many nuclear-encoded mitochondrial proteins. All three ERRs (α, β and γ) increased the transcription of MAOs A and B; the effects were abolished by parkin, but not by its PD-linked mutants. Parkin bound to ERRs and increased their ubiquitination and degradation. In fibroblasts from PD patients with parkin mutations or brain slices from parkin knockout mice, degradation of ERRs was significantly attenuated. The results reveal the molecular mechanism by which parkin suppresses the transcription of MAOs to control oxidative stress induced by dopamine oxidation. PMID:21177257

  6. Platelet monoamine oxidase and serum dopamine-beta-hydroxylase activity in chronic alcoholics.

    PubMed

    Sullivan, J L; Stanfield, C N; Schanberg, S; Cavenar, J

    1978-10-01

    Previous independent reports suggest that low platelet monoamine oxidase (MAO) activity and high serum dopamine-beta-hydroxylase (DBH) activity may be associated with alcoholism or vulnerability toward alcoholism. However, there are also contradictory reports in the literature with regard to each of these two enzymes. We measured both platelet MAO and serum DBH activity in alcoholics followed up at periodic intervals for 12 months after hospitalization for acute alcoholism. Platelet MAO activity in the alcoholics was significantly lower compared to that of nonpsychiatric controls throughout the 12-month period, whereas serum DBH activity in the alcoholics was essentially the same as control values. Thus, low platelet MAO activity, previously reported in a spectrum of clinical psychiatric disorders, appears to be a relatively stable phenomenon in chronic alcoholics irrespective of acute intoxication or pathophysiological factors associated with acute decompensation in individuals vulnerable to alcoholism.

  7. Platelet monoamine oxidase activity in relatives of alcoholics. Preliminary study with matched control subjects.

    PubMed

    Schuckit, M A; Shaskan, E; Duby, J; Vega, R; Moss, M

    1982-02-01

    Platelet monoamine oxidase (MAO) activity levels were determined before and 180 minutes after ingestion of ethyl alcohol in 30 healthy men aged 21 to 25 years. The subjects included 15 men with alcoholic first-degree relatives who were matched by demography, height-weight ratio, and drinking history with 15 control subjects who had no family history of alcoholism. There was a nonsignificant trend toward lower platelet MAO activities at baseline and after ethyl alcohol ingestion in the group with alcoholic relatives when compared with the control subjects who had no family history of alcoholism. With an arbitrary MAO cutoff of 5.24 nmole/mg of protein per hour, eight of the 15 subjects with alcoholic relatives and 12 of the 15 without alcoholic relatives were correctly identified. However, because of the number of false-positive and false-negative findings, the results have limited clinical usefulness.

  8. Monoamine oxidase B layer-by-layer film fabrication and characterization toward dopamine detection.

    PubMed

    Miyazaki, Celina Massumi; Pereira, Tamyris Paschoal; Mascagni, Daniela Branco Tavares; de Moraes, Marli Leite; Ferreira, Marystela

    2016-01-01

    In this work nanostructured film composites of the monoamine oxidase B (MAO-B) enzyme, free or encapsulated in liposomes, were fabricated by the layer-by-layer (LbL) self-assembly technique, employing polyethylene imine (PEI) as polycation. Initially, the MAO-B enzyme was incorporated into liposomes in order to preserve its enzymatic structure ensuring their activity and catalytic stability. The LbL film growth was monitored by surface plasmon resonance (SPR) by gold resonance angle shift analysis after each bilayer deposition. Subsequently, the films were applied as amperometric biosensors for dopamine detection using Prussian Blue (PB) as the electron mediator. The biosensor fabricated by MAO-B incorporated into liposomes composed of DPPG:POPG in the ratio (1:4) (w/w) showed the best performance with a sensitivity of 0.86 (μA cm(-2))/(mmol L(-1)) and a detection limit of 0.33 mmol L(-1).

  9. [Substrate-inhibitory analysis of monoamine oxidase from hepatopancreas of the octopus Bathypolypus arcticus].

    PubMed

    Basova, I N; Iagodina, O V

    2012-01-01

    Study of the substrate-inhibitory specificity of mitochondrial monoamine oxidase (MAO) of hepatopancreas of the octopus Bathypolypus arcticus revealed distinctive peculiarities of catalytic properties of this enzyme. The studied enzyme, on one hand, like the classic MAO of homoiothermal animals, is able to deaminate tyramine, serotonin, benzylamine, tryptamine, beta-phenylethylamine, while, on the other hand, deaminates histamine and does not deaminate putrescine--classic substrates of diamine oxidase (DAO). Results of the substrate-inhibitory analysis with use of chlorgiline and deprenyl are indirect proofs of the existence in the octopus hepatopancreas of one molecular MAO form. Semicarbazide and pyronine G turned out to be weak irreversible inhibitors, four derivatives of acridine--irreversible inhibitors of the intermediate effectiveness with respect to the octopus hepatopancreas MAO; specificity of action of inhibitors at deamination of different substrates was equal.

  10. [Comparative sensitivity of liver monoamine oxidases of frog and whitefish to some tricyclic compounds].

    PubMed

    Basova, I N; Iagodina, O V

    2011-01-01

    There is performed a comparative analysis of action of four acridine derivatives and of one xanthene derivative (pyronine G) on activity of liver monoamine oxidase (MAO) of two species of poikilothermal freshwater animals: a representative of amphibians--the common frog Rana temnporaria and a representative of the order Salmonidae--the European whitefish Coregonus lavaretus. The studied synthetic hexamerous tricyclic compounds show the irreversible character of inhibition of intermediate potency towards the enzyme from both biological sources. There are obtained qualitative and quantitative differences in the reactional ability and selectivity of action of the studied inhibitors for liver MAO of frog and whitefish. The obtained data of the inhibitory analysis with use of specific substrates are an indirect proof for the existence in liver of the studies frog species of two molecular forms, whereas in the whitefish liver--single molecular MAO form.

  11. Improved Method for HPLC Analysis of Polyamines, Agmatine and Aromatic Monoamines in Plant Tissue

    PubMed Central

    Slocum, Robert D.; Flores, Hector E.; Galston, Arthur W.; Weinstein, Leonard H.

    1989-01-01

    The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucus carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues. Images Figure 4 Figure 5 PMID:11537449

  12. “Ping-pong gaze” secondary to monoamine oxidase inhibitor overdose

    PubMed Central

    Attaway, Amy; Sroujieh, Laila; Mersfelder, Tracey L.; Butler, Christopher; Ouellette, Daniel

    2016-01-01

    An infrequent manifestation of monoamine oxidase inhibitor (MAOI) toxicity is “ping-pong gaze” (PPG). We describe the case of a 26-year-old female who was found unresponsive after taking 40 tablets of phenelzine. On presentation to the hospital, her eyes were moving in characteristic “ping pong” fashion. After 6 hours her gaze terminated. The following day her neurologic exam was benign and she had no long-term sequelae. While the etiology of PPG is unknown, it is most often seen with irreversible structural brain damage. However, a detailed literature review revealed that previous cases of MAOI toxicity where the patient survived have all had complete neurologic recovery. PMID:27127395

  13. Combination monoamine oxidase inhibitor and beta-blocker treatment of migraine, with anxiety and depression.

    PubMed

    Merikangas, K R; Merikangas, J R

    1995-11-01

    This paper presents the results of a study comparing the effectiveness of a beta-adrenergic blocking agent, atenolol, a monoamine oxidase inhibitor (MAO-I), phenelzine, and the combination in treatment of 61 adults with migraine headache. The goals of the study are (1) to investigate the safety of concomitant treatment of migraine with beta-blockers and phenelzine, (2) to assess whether orthostatic hypertension and other side effects would be relieved, and (3) to compare the results of this open trial of phenelzine to those of a previous study using similar methods. Phenelzine was associated with a large decrease in the frequency and severity of migraine attacks. Anxiety and depression were also reduced by phenelzine both alone, and in combination with a beta-blocker. The results show that the combination of MAO-I's and beta-blockers can be administered safely, and can lead to the reduction in the side effects with either drug alone.

  14. Improved method for HPLC analysis of polyamines, agmatine and aromatic monoamines in plant tissue

    NASA Technical Reports Server (NTRS)

    Slocum, R. D.; Flores, H. E.; Galston, A. W.; Weinstein, L. H.

    1989-01-01

    The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucas carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues.

  15. Improved method for HPLC analysis of polyamines, agmatine and aromatic monoamines in plant tissue

    NASA Technical Reports Server (NTRS)

    Slocum, R. D.; Flores, H. E.; Galston, A. W.; Weinstein, L. H.

    1989-01-01

    The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucas carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues.

  16. Monoamines and sexual function in rats bred for increased catatonic reactivity.

    PubMed

    Klochkov, D V; Alekhina, T A; Kuznetsova, E G; Barykina, N N

    2009-07-01

    Body weight, ovary and uterus weight, the nature of estral cycles, and hypothalamus dopamine and noradrenaline levels and plasma testosterone levels were studied in female GC rats, bred for increased catatonic reactivity, at different stages of the estral cycle (estrus, proestrus). The outbred Wistar strain served as controls. On the background of decreased body weight, GC females showed impairments to the morphological cyclical changes in the ovaries and uterus, with a reduction in ovary weight in diestrus (p < 0.01) and a smaller estrogen-dependent increase in uterus weight in estrus as compared with Wistar females. On the background of decreases in dopamine and noradrenaline contents in the hypothalamus, GC rats showed higher levels of these monoamines in estrus and lower levels in diestrus. Plasma testosterone levels in female GC rats were higher in diestrus than in estrus and in Wistar rats.

  17. Lack of platelet monoamine oxidase activity in Cebus monkeys (Cebus albifrons).

    PubMed

    Heintz, R; Richardson, M A; Perumal, A S; Casey, D E

    1989-01-01

    1. Recent evidence suggests that monoamine oxidase (MAO) plays an important role modulating the extrapyramidal syndromes produced by neuroleptic drugs in both human and nonhuman primates. 2. To evaluate the possibility of using peripheral blood platelet MAO-B levels as indices of central nervous system MAO-B effects, we measured platelet MAO-B levels in Cebus monkeys that were previously tested with neuroleptics (N = 36) or drug naive (N = 6). 3. No platelet MAO-B was consistently detectable in these blood samples. 4. Thus platelet measures of MAO-B do not reliably reflect brain MAO-B function in nonhuman primates and do not offer a useful model for studying blood-brain MAO-B relationships.

  18. Platelet monoamine oxidase activity levels in subgroups of alcoholics: diagnostic, temporal, and clinical correlates.

    PubMed

    Anthenelli, R M; Smith, T L; Craig, C E; Tabakoff, B; Schuckit, M A

    1995-09-15

    Platelet monoamine oxidase (MAO) activity levels were measured in 47 male inpatient alcoholics to determine whether this biological marker might be useful in differentiating subtypes of alcoholics. Of the subgrouping methods tested, only type 2 alcoholics defined by the criteria of Gilligan et al had significantly lower platelet MAO activity than type 1 alcoholics at intake, but this finding was not stable over time in a subset of subjects. Neither separating male veteran alcoholics into either of two other variations of the type 1/type 2 subtypes, nor classifying the sample into primary alcoholics versus primary ASPD with secondary alcoholism categories, yielded significant differences between subgroups. Generally, enzyme activity levels (Vmax) were higher about 10 days after stopping drinking compared to platelet MAO values determined in thrombocytes obtained after approximately 4 weeks abstinence; these levels remained relatively stable 3 months later in a cohort of subjects. Tobacco smoking was significantly negatively correlated to platelet MAO activity levels.

  19. Exclusion of close linkage between the synaptic vesicular monoamine transporter locus and schizophrenia spectrum disorders

    SciTech Connect

    Persico, A.M.; Uhl, G.R.; Wang, Zhe Wu

    1995-12-18

    The principal brain synaptic vesicular monoamine transporter (VMAT2) is responsible for the reuptake of serotonin, dopamine, norepinephrine, epinephrine, and histamine from the cytoplasm into synaptic vesicles, thus contributing to determination of the size of releasable neurotransmitter vesicular pools. Potential involvement of VMAT2 gene variants in the etiology of schizophrenia and related disorders was tested using polymorphic VMAT2 gene markers in 156 subjects from 16 multiplex pedigrees with schizophrenia, schizophreniform, schizoaffective, and schizotypal disorders and mood incongruent psychotic depression. Assuming genetic homogeneity, complete ({theta} = 0.0) linkage to the schizophrenia spectrum was excluded under both dominant and recessive models. Allelic variants at the VMAT2 locus do not appear to provide major genetic contributions to the etiology of schizophrenia spectrum disorders in these pedigrees. 16 refs.

  20. Inhibition of Human Monoamine Oxidase: Biological and Molecular Modeling Studies on Selected Natural Flavonoids.

    PubMed

    Carradori, Simone; Gidaro, Maria Concetta; Petzer, Anél; Costa, Giosuè; Guglielmi, Paolo; Chimenti, Paola; Alcaro, Stefano; Petzer, Jacobus P

    2016-11-30

    Naturally occurring flavonoids display a plethora of different biological activities, but emerging evidence suggests that this class of compounds may also act as antidepressant agents endowed with multiple mechanisms of action in the central nervous system, increasing central neurotransmission, limiting the reabsorption of bioamines by synaptosomes, and modulating the neuroendocrine and GABAA systems. Due to their presence in foods, food-derived products, and nutraceuticals, we established their role and structure-activity relationships as reversible and competitive human monoamine oxidase (MAO) inhibitors. In addition, molecular modeling studies, which evaluated their modes of MAO inhibition, are presented. These findings could provide pivotal implications in the quest of novel drug-like compounds and for the establishment of harmful drug-dietary supplement interactions commonly reported in the therapy with antidepressant agents.

  1. Association analysis of the functional monoamine oxidase A gene promotor polymorphism in migraine.

    PubMed

    Marziniak, M; Mössner, R; Benninghoff, J; Syagailo, Y V; Lesch, K-P; Sommer, C

    2004-05-01

    Migraine affects about 15% of the adult population. Serotonergic and dopaminergic systems are believed to be involved in its pathophysiology. One of the key enzymes in the degradation of serotonin and to a lesser extent of dopamine is monoamine oxidase A (MAO-A). In this study we investigated a functionally relevant gene-linked polymorphic repetitive sequence (LPR) located approximately 1.2 kb upstream of the ATG codon in the MAO-A-promotor gene. 119 patients with migraine and 229 controls were tested. The allelic distribution of the controls and the migraine patients did not show significant differences with respect to the low- and high-activity alleles. Moreover, effectiveness of the potent serotonergic antimigraine agents, triptans, which are metabolized by MAO-A, was clinically not affected by the MAO-A-LPR in our patients. These findings thus indicate that there is no association between the functional MAO-A-LPR and susceptibility to migraine.

  2. [Effects of Kaixin San formulas on behavioristics and central monoamine neurotransmitters of chronic stress rats].

    PubMed

    Liu, Wan-wan; Xu, Lu; Dong, Xian-zhe; Tan, Xiao; Wang, Shi; Zhu, Wei-yu; Liu, Ping

    2015-06-01

    The efficacy of Chinese herbal formula in treating depression has been proved in many studies. In this study, six different Kaixin San formulas were compared to investigate their effects on central monoamine neurotransmitters of chronic stress rats and against depression based on their different components in plasma, in order to discuss the efficacy-comparability relationship and the possible efficacy mechanism. The classic isolation method and the chronic unpredictable mild stress (CUMS) depression model were combined to investigate the changes in contents in hippocampus and monoamine neurotransmitters (NE, DA, 5-HT) and the components of some formulas in plasma with HPLC and UPLC-Q-TOF-MSE methods. As a result, Dingzhi Xiaowan recorded in Essential Recipes for Emergent Use Worth A Thousand significantly increased the behavioral scores, NE and 5-HT contents in hippocampus and NE, DA and 5-HT contents in cortex, with the best anti-depressant effect. Dingzhi Xiaowan recorded in Complete Records of Ancient and Modern Medical Works showed a notable increase in sucrose preference and open field score in model rats, NE content in hippocampus and NE, DA and 5-HT contents in cortex, with a certain anti anti-depressant effect. Kaixin San recorded in Ishinpo showed remarkable rise in weight of model rats. NE content in hippocampus and DA content in cortex. Puxin Decoction recorded in A Supplement to Recipes Worth A Thousand Gold showed 5-HT content in hippocampus and DA content in cortex. Kaixin San recorded in Yimenfang only showed DA content in cortex. Kaixin Wan recorded in Essential Recipes for Emergent Use Worth A Thousand did not mention the antidepressant effect. According to the results, the formulas' different anti-depressant effects may be related to the different plasma components.

  3. (+)-Methamphetamine-induced monoamine reductions and impaired egocentric learning in adrenalectomized rats is independent of hyperthermia.

    PubMed

    Herring, Nicole R; Gudelsky, Gary A; Vorhees, Charles V; Williams, Michael T

    2010-10-01

    Methamphetamine (MA) is widely abused and implicated in residual cognitive deficits. In rats, increases in plasma corticosterone and egocentric learning deficits are observed after a 1-day binge regimen of MA (10 mg/kg x 4 at 2-h intervals). The purpose of this experiment was to determine if adrenal inactivation during and following MA exposure would attenuate the egocentric learning deficits in the Cincinnati water maze (CWM). In the first experiment, the effects of adrenalectomy (ADX) or sham surgery (SHAM) on MA-induced neurotoxicity at 72 h were determined. SHAM-MA animals showed typical patterns of hyperthermia, whereas ADX-MA animals were normothermic. Both SHAM-MA- and ADX-MA-treated animals showed increased neostriatal glial fibrillary acidic protein and decreased monoamines in the neostriatum, hippocampus, and entorhinal cortex. In the second experiment, SHAM-MA- and ADX-MA-treated groups showed equivalently impaired CWM performance 2 weeks post-treatment (increased latencies, errors, and start returns) compared to SHAM-saline (SAL) and ADX-SAL groups with no effects on novel object recognition, elevated zero maze, or acoustic startle/prepulse inhibition. Post-testing, monoamine levels remained decreased in both MA-treated groups in all three brain regions, but were not as large as those observed at 72-h post-treatment. The data demonstrate that MA-induced learning deficits can be dissociated from drug-induced increases in plasma corticosterone or hyperthermia, but co-occur with dopamine and serotonin reductions. (c) 2010 Wiley-Liss, Inc.

  4. Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys.

    PubMed

    Shively, Carol A; Register, Thomas C; Higley, J Dee; Willard, Stephanie L

    2014-04-01

    Although widely prescribed, little is known about the effects of selective serotonin reuptake inhibitors (SSRIs) on social behavior and cerebrospinal fluid (CSF) monoamines in female primates. The objective of this study was to determine the effects of sertraline on agonistic and affiliative behavior. Twenty-one adult female cynomolgus monkeys were housed in small, stable social groups, trained to participate in oral dosing, and began a 5-week cumulative dose-response study. Serial doses of 0, 5, 10, 15, and 20 mg/kg of sertraline were administered orally for 1 week each. Behavior was recorded daily during 10-min observations before and 4 h after dosing. On the seventh day of dosing, circulating sertraline/desmethylsertraline and CSF monoamines/metabolites were determined 4 h after the last dose. At 20 mg/kg, circulating sertraline/desmethylsertraline was in the therapeutic range. CSF 5-hydroxyindole acetic acid decreased by 33 % (p < 0.05). Overall aggression, submission, locomotion, and time alone decreased, whereas affiliative behaviors (body contact, grooming) increased (all p values <0.05). Effects of sertraline on aggression and submission were social status-dependent, reducing aggression in dominants and submission in subordinates. A clinically relevant oral dose of sertraline resulted in CSF metabolite changes similar to those observed in patients and altered the socioemotional behavior of female monkeys. Changes in CSF 5-HT and dopamine are novel observations that may be sex-specific. The robust effects of sertraline on aggression and affiliation may explain the efficacy of SSRIs on a range of human behavioral pathologies that share the characteristics of increased aggression and decreased sociality.

  5. DRD4 dopamine receptor genotype and CSF monoamine metabolites in Finnish alcoholics and controls

    SciTech Connect

    Adamson, M.D.; Dean, M.; Goldman, D.

    1995-06-19

    The DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in having a highly polymorphic gene structure that has been reported to produce altered receptor functioning. These allelic variations are caused by a 48-bp segment in exon III of the coding region which may be repeated from 2-10 times. Varying the numbers of repeated segments changes the length, structure, and, possibly, the functional efficiency of the receptor, which makes this gene an intriguing candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated for association with schizophrenia, bipolar disorder, Parkinson`s disease, and chronic alcoholism, and all have been largely negative for a direct association. We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were alcoholics, many of the early onset type with features of impulsivity and antisocial traits. Genotype frequencies were compared to 113 Finnish controls who were free of alcohol abuse, substance abuse, and major mental illness. In 70 alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). No association was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF concentrations of the monoamine metabolites showed no significant difference among the DRD4 genotypes. This study of the DRD4 dopamine receptor in alcoholics is the first to be conducted in a clinically and ethnically homogeneous population and to relate the DRD4 genotype to CSF monoamine concentrations. The results indicate that there is no association of the DRD4 receptor with alcoholism. 52 refs., 3 figs., 1 tab.

  6. Binding of the Amphetamine-like 1-Phenyl-piperazine to Monoamine Transporters

    PubMed Central

    2012-01-01

    The human serotonin transporter (hSERT), the human dopamine transporter (hDAT), and the human norepinephrine transporter (hNET) facilitate the active uptake of the neurotransmitters serotonin, dopamine, and norepinephrine from the synaptic cleft. Drugs of abuse such as MDMA (streetname “ecstasy”) and certain 1-phenyl-piperazine (PP) analogs such as 1-(3-chlorophenyl)-piperazine (mCPP) elicit their stimulatory effect by elevating the synaptic concentration of serotonin by blocking or reversing the normal transport activity of hSERT. Recent data suggest that certain analogs of PP may be able to counteract the addictive effect of cocaine. Little is still known about the precise mechanism by which MDMA and PP analogs function at hSERT, hDAT, and hNET and even less is known about the specific protein–ligand interactions. In this study, we provide a comprehensive biochemical examination of a repertoire of PP analogs in hSERT, hDAT, and hNET. Combined with induced fit docking models and molecular dynamics simulations of PP and 1-(3-hydroxyphenyl)-piperazine (3-OH-PP) bound to hSERT and hDAT, we present detailed molecular insight into the promiscuous binding of PP analogs in the monoamine transporters. We find that PP analogs inhibit uptake as well as induce release in all three monoamine transporters. We also find that the selectivity of the PP analogs can be adjusted by carefully selecting substituents on the PP skeleton. PMID:23019496

  7. Transtelephonic home blood pressure to assess the monoamine oxidase-B inhibitor rasagiline in Parkinson disease.

    PubMed

    White, William B; Salzman, Phyllis; Schwid, Steven R

    2008-09-01

    Monoamine oxidase inhibitors are associated with dietary tyramine interactions that can induce hypertensive crises. Rasagiline mesylate is a novel irreversible selective monoamine oxidase type B inhibitor for Parkinson disease that may have a low risk of interaction with dietary tyramine because of its selectivity. To study interactions of rasagiline with diets unrestricted in tyramine-containing foods, we incorporated transtelephonic, self-monitoring of the blood pressure (BP) into a randomized, placebo-controlled trial of rasagiline 0.5 and 1.0 mg daily in 414 levodopa-treated Parkinson patients with motor fluctuations. The proportion of patients with a systolic BP increase of >30 mm Hg was the primary BP end point. In 13 968 self-measured readings at baseline, the proportion of systolic BP values that increased by >30 mm Hg after a meal ranged from 9.5% to 12.9% in the 3 treatment groups. In 25 733 BPs obtained postrandomization, the proportion of values with a >30-mm Hg systolic postprandial increase was 15% in the placebo group, 15% in the rasagiline 0.5-mg group, and 11% in the rasagiline 1-mg group after 3 weeks of double-blind therapy and 13%, 14%, and 12%, respectively, after 26 weeks of treatment (P value was not significant for all of the comparisons among treatment groups). A postprandial increase in systolic BP to >180 mm Hg at any time after randomization was seen in 3.3%, 2.6%, and 2.9% of the placebo, 0.5-mg, and 1.0-mg rasagiline groups, respectively. These data demonstrate that rasagiline did not induce postprandial hypertension in patients with Parkinson disease who were on an unrestricted diet.

  8. Brain-encysting trematodes and altered monoamine activity in naturally infected killifish Fundulus parvipinnis.

    PubMed

    Shaw, J C; Øverli, Ø

    2012-12-01

    This paper presents novel evidence to address mechanisms by which trematode parasites effect behavioural changes in naturally infected fish hosts. California killifish Fundulus parvipinnis infected with the brain-encysting trematode Euhaplorchis californiensis display conspicuous swimming behaviours that render them 30 times more likely to be eaten by birds, the parasite's final host. Prevalence of E. californiensis reaches nearly 100% in most F. parvipinnis populations, with parasite biomass constituting almost 2% of F. parvipinnis biomass in some locations. Despite having thousands of cysts on their brains, infected fish grow and mature at rates comparable to those of uninfected populations. The lack of general pathology combined with the specificity of the altered behaviours suggests that the behavioural changes are due to parasite manipulation. The monoamine neurotransmitters serotonin and dopamine, which control locomotion and social behaviour in fishes and other vertebrates, were examined to explore the underlying mechanisms of this behaviour modification. Whereas previous studies were similarly conducted with experimentally infected fish, in this study, brain dopaminergic and serotonergic activity were analysed in naturally infected fish to assess how E. californiensis may alter F. parvipinnis monoamines in a naturally occurring system. A parasite density-associated decrease in serotonergic activity occurred in the hippocampus of naturally infected fish, as well as a decrease in dopaminergic activity in the raphe nuclei, suggesting that E. californiensis inhibits serotonin and dopamine signaling in naturally infected F. parvipinnis. The neurochemical profile of infected fish is consistent with the hypothesis that E. californiensis affects brain monoaminergic systems in order to induce impulse-driven, active, and aggressive behaviour in its hosts.

  9. Sertraline Effects on Cerebrospinal Fluid Monoamines and Species-typical Socioemotional Behavior of Female Cynomolgus Monkeys

    PubMed Central

    Shively, Carol A.; Register, Thomas C.; Higley, J. Dee; Willard, Stephanie L.

    2013-01-01

    Rationale Although widely prescribed, little is known about selective serotonin reuptake inhibitors (SSRIs) effects on social behavior and cerebrospinal fluid (CSF) monoamines in female primates. Objective To determine the effects of sertraline on agonistic and affiliative behavior. Methods 21 adult female cynomolgus monkeys were housed in small, stable social groups, trained to participate in oral dosing, and began a 5-week cumulative dose response study. Serial doses of 0, 5, 10, 15, and 20 mg/kg of sertraline were administered orally for one week each. Behavior was recorded daily during 10-minute observations before and 4 hours after dosing. On the 7th day of dosing, circulating sertraline/desmethylsertraline and CSF monoamines/metabolites were determined 4 hours after the last dose. Results At 20 mg/kg, circulating sertraline/desmethylsertraline was in the therapeutic range. CSF 5-hydroxyindole acetic acid decreased 33% (p<0.05). Overall aggression, submission, locomotion and time alone decreased, whereas affiliative behaviors (body contact, grooming) increased (all p’s<0.05). Effects of sertraline on aggression and submission were social status-dependent, reducing aggression in dominants and submission in subordinates. Conclusions A clinically relevant oral dose of sertraline resulted in CSF metabolite changes similar to those observed in patients, and altered the socioemotional behavior of female monkeys. Changes in CSF 5-HT and dopamine are novel observations that may be sex-specific. The robust effects of sertraline on aggression and affiliation may explain the efficacy of SSRIs on a range of human behavioral pathologies that share the characteristics of increased aggression and decreased sociality. PMID:24193371

  10. Effect of Zuogui Pill () on monoamine neurotransmitters and sex hormones in climacteric rats with panic attack.

    PubMed

    Li, Xiao-Yu; Wang, Xiao-Yun

    2017-03-01

    To explore the effects of Chinese medicine prescription Zuogui Pill (, ZGP) on monoamine neurotransmitters and sex hormones in climacteric rats with induced panic attacks. Forty-eight climacteric female rats were randomized into 6 groups with 8 rats in each group: the control group, the model group, the low-, medium- and high-dose ZGP groups and the alprazolam group. Rats in the low-, medium- and high-dose ZGP groups were administered 4.725, 9.45, or 18.9 g/kg ZGP by gastric perfusion, respectively. The alprazolam group was treated by gastric perfusion with 0.036 mg/kg alprazolam. The control and model groups were treated with distilled water. The animals were pretreated once daily for 8 consecutive weeks. The behaviors of rats in the open fifield test and the elevated T-maze (ETM) were observed after induced panic attack, and the levels of brain monoamine neurotransmitters and the plasma levels of sex hormones were measured. Compared with the control group, the mean ETM escape time and the levels of 5-hydroxytryptamine (5-HT) and noradrenalin (NE) of the model group were signifificantly reduced (P<0.05), Compared with the model group, the mean ETM escape time and the 5-HT and NE levels of all the ZGP groups increased signifificantly (P<0.05 or P<0.01). However, no signifificant difference was observed in the levels of sex hormones between the groups. Pretreatment with ZGP in climacteric rats may improve the behavior of panic attack, which may be related to increased 5-HT and NE in the brain.

  11. Nicotine-induced monoamine neurotransmitter changes in the brain of young rats.

    PubMed

    Shearman, E; Fallon, S; Sershen, H; Lajtha, A

    2008-08-15

    A number of studies in various species including man indicated a greater risk of drug preference and addictive behavior in young as compared to adults. Such age dependent preference was also found with nicotine. To examine possible mechanisms for this difference in our continuing study of reward mechanisms, we compared nicotine-induced neurotransmitter changes in the brain regions of adult and young Sprague-Dawley rats, assaying the transmitters via microdialysis in conscious freely moving animals. In general, nicotine-induced changes were significantly less in the regions measured in the young. Nicotine-induced effects on dopamine in the dorsal and ventral hippocampus (VH), prefrontal and medial temporal cortex, and superior cerebral peduncle were lower in the young than in adult, the same in the ventral tegmental area (VTA) and lateral septal nucleus (LS), and somewhat higher in the nucleus accumbens shell (NAccS). Norepinephrine levels in the young were lower in all areas except in the VH where they were the same, and serotonin levels were lower except in the VTA and LS where they remained the same, and higher in the NAccS. Age-dependent differences in the metabolites measured were more mixed. We conclude that the greater nicotine preference in young is not paralleled by a greater effect of nicotine on the release of monoamines at least in most of the brain areas assayed. Thus, increases of nicotine reward are not likely due to increases of monoamines in reward and cognitive areas. The small increase of dopamine (DA) and more significant increase of serotonin (5-HT) only in the NAccS are of significance, and would indicate a more significant role of 5-HT than of DA at least in the age difference in nicotine preference. Developmental changes in receptor composition and distribution involving several transmitter systems and other components such as neuropeptides are also likely to play a role.

  12. Valproic acid induces monoamine oxidase A via Akt/forkhead box O1 activation.

    PubMed

    Wu, Jason Boyang; Shih, Jean C

    2011-10-01

    Valproic acid (VPA) has been widely used in clinics for the treatment of multiple neuropsychiatric disorders, such as epilepsy and bipolar disorder. One of the mechanisms by which VPA exerts its effect is through regulating the brain levels of serotonin. However, the molecular basis of this VPA action is not fully understood. Here, we report for the first time that VPA activates monoamine oxidase (MAO) A catalytic activity, mRNA level, and promoter activity. MAO A is a key enzyme that degrades a number of monoamine neurotransmitters, including serotonin. Our results show that VPA increased the phosphorylation of both Akt and Forkhead box O1 (FoxO1), whereas pretreatment of cells with 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) (a phosphoinositide 3-kinase inhibitor) reduced the VPA activation of MAO A. Overexpression of FoxO1 dramatically repressed both the basal and VPA-induced MAO A catalytic and promoter activities to 30 to 60%. Small interfering RNA knockdown of FoxO1 attenuated the stimulating effect of VPA on MAO A. Moreover, introduction of a constitutively active form of FoxO1 abolished the activation of MAO A by VPA and Akt. These results suggest that FoxO1 is a repressor for MAO A transcription, and its phosphorylation is involved in VPA activation of MAO A. Sequence analysis, electrophoretic mobility shift and chromatin immunoprecipitation assays further showed the presence of a functional FoxO1-binding site in MAO A core promoter. Taken together, these results demonstrate that MAO A is a novel target for VPA via Akt/FoxO1 signaling pathway. This information provides new insights into the pharmacological mechanisms and therapeutic implications of VPA action.

  13. Valproic Acid Induces Monoamine Oxidase A via Akt/Forkhead Box O1 ActivationS⃞

    PubMed Central

    Wu, Jason Boyang

    2011-01-01

    Valproic acid (VPA) has been widely used in clinics for the treatment of multiple neuropsychiatric disorders, such as epilepsy and bipolar disorder. One of the mechanisms by which VPA exerts its effect is through regulating the brain levels of serotonin. However, the molecular basis of this VPA action is not fully understood. Here, we report for the first time that VPA activates monoamine oxidase (MAO) A catalytic activity, mRNA level, and promoter activity. MAO A is a key enzyme that degrades a number of monoamine neurotransmitters, including serotonin. Our results show that VPA increased the phosphorylation of both Akt and Forkhead box O1 (FoxO1), whereas pretreatment of cells with 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) (a phosphoinositide 3-kinase inhibitor) reduced the VPA activation of MAO A. Overexpression of FoxO1 dramatically repressed both the basal and VPA-induced MAO A catalytic and promoter activities to 30 to 60%. Small interfering RNA knockdown of FoxO1 attenuated the stimulating effect of VPA on MAO A. Moreover, introduction of a constitutively active form of FoxO1 abolished the activation of MAO A by VPA and Akt. These results suggest that FoxO1 is a repressor for MAO A transcription, and its phosphorylation is involved in VPA activation of MAO A. Sequence analysis, electrophoretic mobility shift and chromatin immunoprecipitation assays further showed the presence of a functional FoxO1-binding site in MAO A core promoter. Taken together, these results demonstrate that MAO A is a novel target for VPA via Akt/FoxO1 signaling pathway. This information provides new insights into the pharmacological mechanisms and therapeutic implications of VPA action. PMID:21775495

  14. A brief history of the development of antidepressant drugs: From monoamines to glutamate

    PubMed Central

    Hillhouse, Todd M.; Porter, Joseph H.

    2015-01-01

    Major depressive disorder (MDD) is a chronic, recurring, and debilitating mental illness that is the most common mood disorder in the United States. It has been almost 50 years since the monoamine hypothesis of depression was articulated, and just over 50 years since the first pharmacological treatment for MDD was discovered. Several monoamine-based pharmacological drug classes have been developed and approved for the treatment of MDD; however, remission rates are low (often less than 60%) and there is a delayed onset before remission of depressive symptoms is achieved. As a result of a “proof-of-concept” study in 2000 with the noncompetitive NMDA antagonist ketamine, a number of studies have examined the glutamatergic systems as viable targets for the treatment of MDD. This review will provide a brief history on the development of clinically available antidepressant drugs, and then review the possible role of glutamatergic systems in the pathophysiology of MDD. Specifically, the glutamatergic review will focus on the N-methyl-D-aspartate (NMDA) receptor and the efficacy of drugs that target the NMDA receptor for the treatment of MDD. The noncompetitive NMDA receptor antagonist ketamine, which has consistently produced rapid and sustained antidepressant effects in MDD patients in a number of clinical studies, has shown the most promise as a novel glutamatergic-based treatment for MDD. However, compounds that target other glutamatergic mechanisms, such as GLYX-13 (a glycine-site partial agonist at NMDA receptors) appear promising in early clinical trials. Thus, the clinical findings to date are encouraging and support the continued search for and the development of novel compounds that target glutamatergic mechanisms. PMID:25643025

  15. Reduced vesicular monoamine transport disrupts serotonin signaling but does not cause serotonergic degeneration

    PubMed Central

    Alter, Shawn P.; Stout, Kristen A.; Lohr, Kelly M.; Taylor, Tonya N.; Shepherd, Kennie R.; Wang, Minzheng; Guillot, Thomas S.; Miller, Gary W.

    2016-01-01

    We previously demonstrated that mice with reduced expression of the vesicular monoamine transporter 2 (VMAT2 LO) undergo age-related degeneration of the catecholamine-producing neurons of the substantia nigra pars compacta and locus ceruleus and exhibit motor disturbances and depressive-like behavior. In this work, we investigated the effects of reduced vesicular transport on the function and viability of serotonin neurons in these mice. Adult (4–6 months of age), VMAT2 LO mice exhibit dramatically reduced (90%) serotonin release capacity, as measured by fast scan cyclic voltammetry. We observed changes in serotonin receptor responsivity in in vivo pharmacological assays. Aged (months) VMAT2 LO mice exhibited abolished 5-HT1A autoreceptor sensitivity, as determined by 8-OH-DPAT (0.1 mg/kg) induction of hypothermia. When challenged with the 5HT2 agonist, 2,5-dimethoxy-4-iodoamphetamine (1 mg/kg), VMAT2 LO mice exhibited a marked increase (50%) in head twitch responses. We observed sparing of serotonergic terminals in aged mice (18–24 months) throughout the forebrain by SERT immunohistochemistry and [3H]-paroxetine binding in striatal homogenates of aged VMAT2 LO mice. In contrast to their loss of catecholamine neurons of the substantia nigra and locus ceruleus, aged VMAT2 LO mice do not exhibit a change in the number of serotonergic (TPH2 +) neurons within the dorsal raphe, as measured by unbiased stereology at 26–30 months. Collectively, these data indicate that reduced vesicular monoamine transport significantly disrupts serotonergic signaling, but does not drive degeneration of serotonin neurons. PMID:26428905

  16. Spontaneous recurrent seizures in rats: amino acid and monoamine determination in the hippocampus.

    PubMed

    Cavalheiro, E A; Fernandes, M J; Turski, L; Naffah-Mazzacoratti, M G

    1994-01-01

    Rats subjected to structural brain damage induced by sustained convulsions triggered by systemic administration of pilocarpine (PILO) are a useful model for investigation of the mechanisms essential for seizure generation and spread in rodents. After PILO administration, three distinct phases are observed: (a) an acute period of 1-2 days' duration corresponding to a pattern of repetitive limbic seizures and status epilepticus; (b) a seizure-free (silent) period characterized by a progressive return to normal EEG and behavior of 4-44 days' duration; and (c) a period of spontaneous recurrent seizures (SRS) starting 5-45 days after PILO administration and lasting throughout the animal's life. PILO (320-350 mg/kg intraperitoneally, i.p.) was administered to rats, and the content of hippocampal monoamines and amino acids was measured in the acute, silent, and SRS periods by liquid chromatography. Norepinephrine (NE) level was decreased during all periods whereas dopamine (DA) content was increased. Serotonin (5-hydroxytryptamine, 5-HT) was increased only in the acute period. Utilization rate measurement of monoamines showed increased NE consumption and decreased DA consumption during all phases. 5-HT utilization rate was increased only in the acute period. Amino acid content showed a decrease in aspartate (ASP) and glutamate (GLU) concentrations associated with increased gamma-aminobutyric acid (GABA) level during the acute period. The silent phase was characterized by a decrease in glycine (GLY) and GABA levels and an increase in GLU concentration. The SRS period showed an increase in all amino acid concentrations. These findings show important neurochemical changes in the course of establishment of an epileptic focus after brain damage induced by status epilepticus triggered by pilocarpine.

  17. Phase I metabolites of mephedrone display biological activity as substrates at monoamine transporters

    PubMed Central

    Mayer, F P; Wimmer, L; Dillon‐Carter, O; Partilla, J S; Burchardt, N V; Mihovilovic, M D; Baumann, M H

    2016-01-01

    Background and Purpose 4‐Methyl‐N‐methylcathinone (mephedrone) is a synthetic stimulant that acts as a substrate‐type releaser at transporters for dopamine (DAT), noradrenaline (NET) and 5‐HT (SERT). Upon systemic administration, mephedrone is metabolized to several phase I compounds: the N‐demethylated metabolite, 4‐methylcathinone (nor‐mephedrone); the ring‐hydroxylated metabolite, 4‐hydroxytolylmephedrone (4‐OH‐mephedrone); and the reduced keto‐metabolite, dihydromephedrone. Experimental Approach We used in vitro assays to compare the effects of mephedrone and synthetically prepared metabolites on transporter‐mediated uptake and release in HEK293 cells expressing human monoamine transporters and in rat brain synaptosomes. In vivo microdialysis was employed to examine the effects of i.v. metabolite injection (1 and 3 mg·kg−1) on extracellular dopamine and 5‐HT levels in rat nucleus accumbens. Key Results In cells expressing transporters, mephedrone and its metabolites inhibited uptake, although dihydromephedrone was weak overall. In cells and synaptosomes, nor‐mephedrone and 4‐OH‐mephedrone served as transportable substrates, inducing release via monoamine transporters. When administered to rats, mephedrone and nor‐mephedrone produced elevations in extracellular dopamine and 5‐HT, whereas 4‐OH‐mephedrone did not. Mephedrone and nor‐mephedrone, but not 4‐OH‐mephedrone, induced locomotor activity. Conclusions and Implications Our results demonstrate that phase I metabolites of mephedrone are transporter substrates (i.e. releasers) at DAT, NET and SERT, but dihydromephedrone is weak in this regard. When administered in vivo, nor‐mephedrone increases extracellular dopamine and 5‐HT in the brain whereas 4‐OH‐mephedrone does not, suggesting the latter metabolite does not penetrate the blood–brain barrier. Future studies should examine the pharmacokinetics of nor‐mephedrone to determine its possible

  18. Reduced vesicular monoamine transport disrupts serotonin signaling but does not cause serotonergic degeneration.

    PubMed

    Alter, Shawn P; Stout, Kristen A; Lohr, Kelly M; Taylor, Tonya N; Shepherd, Kennie R; Wang, Minzheng; Guillot, Thomas S; Miller, Gary W

    2016-01-01

    We previously demonstrated that mice with reduced expression of the vesicular monoamine transporter 2 (VMAT2 LO) undergo age-related degeneration of the catecholamine-producing neurons of the substantia nigra pars compacta and locus ceruleus and exhibit motor disturbances and depressive-like behavior. In this work, we investigated the effects of reduced vesicular transport on the function and viability of serotonin neurons in these mice. Adult (4-6 months of age), VMAT2 LO mice exhibit dramatically reduced (90%) serotonin release capacity, as measured by fast scan cyclic voltammetry. We observed changes in serotonin receptor responsivity in in vivo pharmacological assays. Aged (months) VMAT2 LO mice exhibited abolished 5-HT1A autoreceptor sensitivity, as determined by 8-OH-DPAT (0.1 mg/kg) induction of hypothermia. When challenged with the 5HT2 agonist, 2,5-dimethoxy-4-iodoamphetamine (1 mg/kg), VMAT2 LO mice exhibited a marked increase (50%) in head twitch responses. We observed sparing of serotonergic terminals in aged mice (18-24 months) throughout the forebrain by SERT immunohistochemistry and [(3)H]-paroxetine binding in striatal homogenates of aged VMAT2 LO mice. In contrast to their loss of catecholamine neurons of the substantia nigra and locus ceruleus, aged VMAT2 LO mice do not exhibit a change in the number of serotonergic (TPH2+) neurons within the dorsal raphe, as measured by unbiased stereology at 26-30 months. Collectively, these data indicate that reduced vesicular monoamine transport significantly disrupts serotonergic signaling, but does not drive degeneration of serotonin neurons.

  19. (+)-Methamphetamine-induced monoamine reductions and impaired egocentric learning in adrenalectomized rats is independent of hyperthermia

    PubMed Central

    Herring, Nicole R.; Gudelsky, Gary A.; Vorhees, Charles V.; Williams, Michael T.

    2010-01-01

    Methamphetamine (MA) is widely abused and implicated in residual cognitive deficits. In rats, increases in plasma corticosterone and egocentric learning deficits are observed after a one-day binge regimen of MA (10 mg/kg × 4 at 2 h intervals). The purpose of this experiment was to determine if adrenal inactivation during and following MA exposure would attenuate the egocentric learning deficits in the Cincinnati water maze (CWM). In the first experiment, the effects of adrenalectomy (ADX) or sham surgery (SHAM) on MA-induced neurotoxicity at 72 h was determined. SHAM-MA animals showed typical patterns of hyperthermia whereas ADX-MA animals were normothermic. SHAM-MA and ADX-MA treated animals both showed increased neostriatal glial fibrillary acidic protein and decreased monoamines in the neostriatum, hippocampus, and entorhinal cortex. In the second experiment, SHAM-MA and ADX-MA treated groups showed equivalently impaired CWM impairments two weeks post-treatment (increased latencies, errors, and start returns) compared to SHAM-saline (SAL) and ADX-SAL groups with no effects on novel object recognition, elevated zero maze, or acoustic startle/prepulse inhibition. Post-testing, monoamine levels remained decreased in both MA-treated groups in all three brain regions, but were not as large as those observed at 72 h post-treatment. The data demonstrate that MA-induced learning deficits can be dissociated from drug-induced increases in plasma corticosterone or hyperthermia, but co-occur with dopamine and serotonin reductions. PMID:20698032

  20. Relationship of monoamine oxidase A binding to adaptive and maladaptive personality traits.

    PubMed

    Soliman, A; Bagby, R M; Wilson, A A; Miler, L; Clark, M; Rusjan, P; Sacher, J; Houle, S; Meyer, J H

    2011-05-01

    Monoamine oxidase A (MAOA) is an important enzyme that metabolizes monoamines such as serotonin, norepinephrine and dopamine in the brain. In prefrontal cortex, low MAOA binding is associated with aggression and high binding is associated with major depressive disorder (MDD) and also risk for recurrence of depressive episodes. In rodent models, low MAOA levels are associated with increased aggression and fear conditioning, and decreased social and exploratory investigative behaviors. Our objective was to measure MAOA binding in prefrontal cortex and concurrently evaluate a broad range of validated personality traits. We hypothesized that prefrontal MAOA binding would correlate negatively with angry-hostility, a trait related to aggression/anger, and positively with traits intuitively related to adaptive investigative behavior. Participants were aged 19-49 years, healthy and non-smoking. MAOA binding was measured with [11C]harmine positron emission tomography (PET) in prefrontal brain regions and personality traits were measured with the NEO Personality Inventory Revised (NEO PI-R). Prefrontal MAOA binding correlated negatively with angry-hostility (r=-0.515, p=0.001) and positively with deliberation (r=0.514, p=0.001). In a two-factor regression model, these facets explained 38% of variance in prefrontal MAOA binding. A similar relationship was found in prefrontal cortex subregions. We propose a new continuum describing the relationship between personality and MAOA: deliberate/thoughtful contrasting aggressive/impulsive. Additionally, the association between high MAOA binding and greater deliberation may explain why some people have moderately high levels of MAOA, although very high levels occur during MDD. In health, higher MAOA binding is associated with an adaptive personality facet.

  1. Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication.

    PubMed

    Feinberg, S Shalom

    2004-11-01

    Among antidepressant augmentation strategies, the addition of a stimulant to a monoamine oxidase inhibitor (MAOI) has received little attention in the literature in recent years because of the diminished clinical use of the latter and concerns of precipitating a hypertensive crisis or other serious complication. Despite that fact, experienced clinicians continue to use this combination for a variety of indications after other options have failed. This article reviews these reported uses and presents a case suggesting another possible indication. A MEDLINE search was conducted for articles published from 1962 to December 2003 using relevant search terms (psychostimulant, stimulant, amphetamine, dextroamphetamine, pemoline or methylphenidate, atomoxetine, bupropion, monoamine oxidase inhibitor, and selegiline). A manual search was conducted of cross-references and other relevant recent psychiatric sources (2000-2003). The described uses of the MAOI-stimulant combination have included treatment of refractory depression and the MAOI-related side effects of orthostatic hypotension and daytime sedation. No documented reports were found in the recent literature of hypertensive crises or fatalities occurring when the stimulant was cautiously added to the MAOI. Also presented here is another possible indication for this therapeutic regimen: treatment of attention-deficit/hyperactivity disorder in an adult patient whose major depression had uniquely responded to the MAOI tranylcypromine. As in other fields of medicine, potentially hazardous medication combinations are utilized in psychiatry after cautiously weighing the danger of the treatment against the morbidity and risk of not adequately addressing the illness. Particularly, as the potential arrival of the apparently safer transdermal selegiline may increase the use of MAOIs, we feel this combination deserves additional controlled study.

  2. Valeriana wallichii root extract improves sleep quality and modulates brain monoamine level in rats.

    PubMed

    Sahu, Surajit; Ray, Koushik; Yogendra Kumar, M S; Gupta, Shilpa; Kauser, Hina; Kumar, Sanjeev; Mishra, Kshipra; Panjwani, Usha

    2012-07-15

    The present study was performed to investigate the effects of Valeriana wallichi (VW) aqueous root extract on sleep-wake profile and level of brain monoamines on Sprague-Dawley rats. Electrodes and transmitters were implanted to record EEG and EMG in freely moving condition and the changes were recorded telemetrically after oral administration of VW in the doses of 100, 200 and 300 mg/kg body weight. Sleep latency was decreased and duration of non-rapid eye movement (NREM) sleep was increased in a dose dependent manner. A significant decrease of sleep latency and duration of wakefulness were observed with VW at doses of 200 and 300 mg/kg. Duration of NREM sleep as well as duration of total sleep was increased significantly after treatment with VW at the doses of 200 and 300 mg/kg. VW also increased EEG slow wave activity during NREM sleep at the doses of 200 and 300 mg/kg. Level of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT) and hydroxy indole acetic acid (HIAA) were measured in frontal cortex and brain stem after VW treatment at the dose of 200mg/kg. NE and 5HT level were decreased significantly in both frontal cortex and brain stem. DA and HIAA level significantly decreased only in cortex. DOPAC level was not changed in any brain region studied. In conclusion it can be said that VW water extract has a sleep quality improving effect which may be dependent upon levels of monoamines in cortex and brainstem.

  3. Elevated brain monoamine oxidase A binding in the early postpartum period.

    PubMed

    Sacher, Julia; Wilson, Alan A; Houle, Sylvain; Rusjan, Pablo; Hassan, Sabrina; Bloomfield, Peter M; Stewart, Donna E; Meyer, Jeffrey H

    2010-05-01

    The early postpartum period is a time of high risk for a major depressive episode (or postpartum depression), with a prevalence of 13%. During this time, there is a heightened vulnerability for low mood because postpartum blues is common. Severe postpartum blues can herald the onset of postpartum depression. The neurobiological mechanisms to explain postpartum blues and the high risk for the onset of postpartum depression in the first few weeks after delivery are unclear. Estrogen levels drop 100- to 1000-fold during the first 3 to 4 days postpartum, and changes in estrogen levels have an inverse relationship with monoamine oxidase A (MAO-A) density. However, MAO-A levels have never been measured in the early postpartum period. To determine whether brain MAO-A binding is elevated in the early postpartum period. Case-control study. Tertiary care academic psychiatric hospital in Toronto, Ontario, Canada. Fifteen healthy women who were 4 to 6 days postpartum and 15 healthy women who had not recently been postpartum underwent carbon 11-labeled harmine positron emission tomography scanning. All women were nonsmoking and medication free. MAO-A total distribution volume, an index of MAO-A density, was measured in prefrontal cortex, anterior cingulate cortex, anterior temporal cortex, thalamus, dorsal putamen, hippocampus, and midbrain. MAO-A total distribution volume was significantly elevated (mean, 43%) throughout all analyzed brain regions during the early postpartum period. Elevated MAO-A levels in the early postpartum period can be interpreted as a marker of a monoamine-lowering process that contributes to the mood change of postpartum blues. Rather than a purely psychosocial model, we propose a neurobiological model of estrogen decline, followed by elevated MAO-A binding, low mood, and subsequently a period of high risk for major depressive episodes. Our model has important implications for preventing postpartum depression and for developing therapeutic strategies

  4. The MAO-B inhibitor deprenyl reduces the oral tremor and the dopamine depletion induced by the VMAT-2 inhibitor tetrabenazine.

    PubMed

    Podurgiel, Samantha J; Yohn, Samantha E; Dortche, Kristina; Correa, Merce; Salamone, John D

    2016-02-01

    Tetrabenazine (TBZ) is prescribed for the treatment of chorea associated with Huntington's disease. Via inhibition of the vesicular monoamine transporter (VMAT-2), TBZ blocks dopamine (DA) storage and depletes striatal DA; this drug also has been shown to induce Parkinsonian motor side effects in patients. Recently, TBZ was shown to induce tremulous jaw movements (TJMs) in rats and mice. TJMs are an oral tremor that has many of the characteristics of Parkinsonian tremor in humans. The present study focused upon the ability of the well-established antiparkinsonian agent deprenyl to attenuate the behavioral and neurochemical effects of 2.0mg/kg TBZ. Deprenyl is a selective and irreversible inhibitor of monoamine oxidase-B, and administration of deprenyl produced a dose-related suppression of TBZ-induced TJMs. A second experiment employed in vivo microdialysis to examine extracellular DA levels in the ventrolateral striatum, the neostriatal region most closely associated with the production of TJMs, after administration of TBZ and deprenyl. Consistent with the behavioral data, TBZ alone produced a biphasic effect on extracellular DA, with an initial increases followed by a prolonged decrease during the period in which TJMs are displayed. Co-administration of deprenyl with TBZ increased DA levels compared to rats treated with TBZ alone. These results provide support for use of TBZ as a rodent model of Parkinsonism, and future studies should utilize this model to evaluate putative anti-Parkinsonian agents.

  5. New Approach For Prediction Groundwater Depletion

    NASA Astrophysics Data System (ADS)

    Moustafa, Mahmoud

    2017-01-01

    Current approaches to quantify groundwater depletion involve water balance and satellite gravity. However, the water balance technique includes uncertain estimation of parameters such as evapotranspiration and runoff. The satellite method consumes time and effort. The work reported in this paper proposes using failure theory in a novel way to predict groundwater saturated thickness depletion. An important issue in the failure theory proposed is to determine the failure point (depletion case). The proposed technique uses depth of water as the net result of recharge/discharge processes in the aquifer to calculate remaining saturated thickness resulting from the applied pumping rates in an area to evaluate the groundwater depletion. Two parameters, the Weibull function and Bayes analysis were used to model and analyze collected data from 1962 to 2009. The proposed methodology was tested in a nonrenewable aquifer, with no recharge. Consequently, the continuous decline in water depth has been the main criterion used to estimate the depletion. The value of the proposed approach is to predict the probable effect of the current applied pumping rates on the saturated thickness based on the remaining saturated thickness data. The limitation of the suggested approach is that it assumes the applied management practices are constant during the prediction period. The study predicted that after 300 years there would be an 80% probability of the saturated aquifer which would be expected to be depleted. Lifetime or failure theory can give a simple alternative way to predict the remaining saturated thickness depletion with no time-consuming processes such as the sophisticated software required.

  6. Inhibition of type A and B monoamine oxidase by 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines and their N-methylated derivatives.

    PubMed

    Minami, M; Maruyama, W; Dostert, P; Nagatsu, T; Naoi, M

    1993-01-01

    6,7-Dihydroxy-1,2,3,4-tetrahydroisoquinoline (norsalsolinol) and 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), and their N-methylated derivatives were found to inhibit type A and B monoamine oxidase isolated from human brain synaptosomal mitochondria. N-Methyl-norsalsolinol, (R) and (S) enantiomer of salsolinol, and N-methyl-salsolinols inhibited type A monoamine oxidase competitively to the substrate, kynuramine, and R enantiomers were more potent inhibitors than S enantiomers. The inhibition was reversible. Norsalsolinol induced positive cooperativity toward kynuramine. Both norsalsolinol and N-methyl-norsalsolinol inhibited type B oxidase non-competitively to the substrate, and their Ki values were much higher than those to type A. Types of inhibition of type A monoamine oxidase depended on the enzyme sources. Inhibition of monoamine oxidase by 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines is discussed in relation to their chemical structures.

  7. Groundwater depletion embedded in international food trade.

    PubMed

    Dalin, Carole; Wada, Yoshihide; Kastner, Thomas; Puma, Michael J

    2017-03-29

    Recent hydrological modelling and Earth observations have located and quantified alarming rates of groundwater depletion worldwide. This depletion is primarily due to water withdrawals for irrigation, but its connection with the main driver of irrigation, global food consumption, has not yet been explored. Here we show that approximately eleven per cent of non-renewable groundwater use for irrigation is embedded in international food trade, of which two-thirds are exported by Pakistan, the USA and India alone. Our quantification of groundwater depletion embedded in the world's food trade is based on a combination of global, crop-specific estimates of non-renewable groundwater abstraction and international food trade data. A vast majority of the world's population lives in countries sourcing nearly all their staple crop imports from partners who deplete groundwater to produce these crops, highlighting risks for global food and water security. Some countries, such as the USA, Mexico, Iran and China, are particularly exposed to these risks because they both produce and import food irrigated from rapidly depleting aquifers. Our results could help to improve the sustainability of global food production and groundwater resource management by identifying priority regions and agricultural products at risk as well as the end consumers of these products.

  8. The New MCNP6 Depletion Capability

    SciTech Connect

    Fensin, Michael Lorne; James, Michael R.; Hendricks, John S.; Goorley, John T.

    2012-06-19

    The first MCNP based inline Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology.

  9. Depletion sensitivity predicts unhealthy snack purchases.

    PubMed

    Salmon, Stefanie J; Adriaanse, Marieke A; Fennis, Bob M; De Vet, Emely; De Ridder, Denise T D

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose weight on snack purchase behavior were explored. Participants included in the study were instructed to report every snack they bought over the course of one week. The dependent variables were the number of healthy and unhealthy snacks purchased. The results of the present study demonstrate that depletion sensitivity predicts the amount of unhealthy (but not healthy) snacks bought. The more sensitive people are to depletion, the more unhealthy snacks they buy. Moreover, there was some tentative evidence that this relation is more pronounced for people with a weak as opposed to a strong goal to lose weight, suggesting that a strong goal to lose weight may function as a motivational buffer against self-control failures. All in all, these findings provide evidence for the external validity of depletion sensitivity and the relevance of this construct in the domain of eating behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Groundwater depletion embedded in international food trade

    NASA Astrophysics Data System (ADS)

    Dalin, Carole; Wada, Yoshihide; Kastner, Thomas; Puma, Michael J.

    2017-03-01

    Recent hydrological modelling and Earth observations have located and quantified alarming rates of groundwater depletion worldwide. This depletion is primarily due to water withdrawals for irrigation, but its connection with the main driver of irrigation, global food consumption, has not yet been explored. Here we show that approximately eleven per cent of non-renewable groundwater use for irrigation is embedded in international food trade, of which two-thirds are exported by Pakistan, the USA and India alone. Our quantification of groundwater depletion embedded in the world’s food trade is based on a combination of global, crop-specific estimates of non-renewable groundwater abstraction and international food trade data. A vast majority of the world’s population lives in countries sourcing nearly all their staple crop imports from partners who deplete groundwater to produce these crops, highlighting risks for global food and water security. Some countries, such as the USA, Mexico, Iran and China, are particularly exposed to these risks because they both produce and import food irrigated from rapidly depleting aquifers. Our results could help to improve the sustainability of global food production and groundwater resource management by identifying priority regions and agricultural products at risk as well as the end consumers of these products.

  11. The new MCNP6 depletion capability

    SciTech Connect

    Fensin, M. L.; James, M. R.; Hendricks, J. S.; Goorley, J. T.

    2012-07-01

    The first MCNP based in-line Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology. (authors)

  12. Ego depletion in visual perception: Ego-depleted viewers experience less ambiguous figure reversal.

    PubMed

    Wimmer, Marina C; Stirk, Steven; Hancock, Peter J B

    2017-02-22

    This study examined the effects of ego depletion on ambiguous figure perception. Adults (N = 315) received an ego depletion task and were subsequently tested on their inhibitory control abilities that were indexed by the Stroop task (Experiment 1) and their ability to perceive both interpretations of ambiguous figures that was indexed by reversal (Experiment 2). Ego depletion had a very small effect on reducing inhibitory control (Cohen's d = .15) (Experiment 1). Ego-depleted participants had a tendency to take longer to respond in Stroop trials. In Experiment 2, ego depletion had small to medium effects on the experience of reversal. Ego-depleted viewers tended to take longer to reverse ambiguous figures (duration to first reversal) when naïve of the ambiguity and experienced less reversal both when naïve and informed of the ambiguity. Together, findings suggest that ego depletion has small effects on inhibitory control and small to medium effects on bottom-up and top-down perceptual processes. The depletion of cognitive resources can reduce our visual perceptual experience.

  13. The modality effect of ego depletion: Auditory task modality reduces ego depletion.

    PubMed

    Li, Qiong; Wang, Zhenhong

    2016-08-01

    An initial act of self-control that impairs subsequent acts of self-control is called ego depletion. The ego depletion phenomenon has been observed consistently. The modality effect refers to the effect of the presentation modality on the processing of stimuli. The modality effect was also robustly found in a large body of research. However, no study to date has examined the modality effects of ego depletion. This issue was addressed in the current study. In Experiment 1, after all participants completed a handgrip task, one group's participants completed a visual attention regulation task and the other group's participants completed an auditory attention regulation task, and then all participants again completed a handgrip task. The ego depletion phenomenon was observed in both the visual and the auditory attention regulation task. Moreover, participants who completed the visual task performed worse on the handgrip task than participants who completed the auditory task, which indicated that there was high ego depletion in the visual task condition. In Experiment 2, participants completed an initial task that either did or did not deplete self-control resources, and then they completed a second visual or auditory attention control task. The results indicated that depleted participants performed better on the auditory attention control task than the visual attention control task. These findings suggest that altering task modality may reduce ego depletion. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  14. Ozone depletion and chlorine loading potentials

    NASA Technical Reports Server (NTRS)

    Pyle, John A.; Wuebbles, Donald J.; Solomon, Susan; Zvenigorodsky, Sergei; Connell, Peter; Ko, Malcolm K. W.; Fisher, Donald A.; Stordal, Frode; Weisenstein, Debra

    1991-01-01

    The recognition of the roles of chlorine and bromine compounds in ozone depletion has led to the regulation or their source gases. Some source gases are expected to be more damaging to the ozone layer than others, so that scientific guidance regarding their relative impacts is needed for regulatory purposes. Parameters used for this purpose include the steady-state and time-dependent chlorine loading potential (CLP) and the ozone depletion potential (ODP). Chlorine loading potentials depend upon the estimated value and accuracy of atmospheric lifetimes and are subject to significant (approximately 20-50 percent) uncertainties for many gases. Ozone depletion potentials depend on the same factors, as well as the evaluation of the release of reactive chlorine and bromine from each source gas and corresponding ozone destruction within the stratosphere.

  15. Depletion performance of layered reservoirs without crossflow

    SciTech Connect

    Fetkovich, M.J.; Works, A.M.; Thrasher, T.S. ); Bradley, M.D. )

    1990-09-01

    This paper presents a study of the rate/time and pressure/cumulative-production depletion performance of a two-layered gas reservoir producing without crossflow. The gas reservoir has produced for more than 20 years at an effectively constant wellbore pressure, thus giving continuously declining rate/time and pressure/cumulative-production data for analysis. The field data demonstrates that Arps depletion-decline exponents between 0.5 and 1 can be obtained with a no-crossflow, layered reservoir description. Rate-vs.-time and pressure-vs.-cumulative-production predictions were developed from both 2D numerical and simplified tank models of a two layered, no-crossflow system. These results demonstrate the effects of changes in reservoir layer volumes, permeability, and skin on the depletion performance.

  16. Neutral depletion and the helicon density limit

    SciTech Connect

    Magee, R. M.; Galante, M. E.; Carr, J. Jr.; Lusk, G.; McCarren, D. W.; Scime, E. E.

    2013-12-15

    It is straightforward to create fully ionized plasmas with modest rf power in a helicon. It is difficult, however, to create plasmas with density >10{sup 20} m{sup −3}, because neutral depletion leads to a lack of fuel. In order to address this density limit, we present fast (1 MHz), time-resolved measurements of the neutral density at and downstream from the rf antenna in krypton helicon plasmas. At the start of the discharge, the neutral density underneath the antenna is reduced to 1% of its initial value in 15 μs. The ionization rate inferred from these data implies that the electron temperature near the antenna is much higher than the electron temperature measured downstream. Neutral density measurements made downstream from the antenna show much slower depletion, requiring 14 ms to decrease by a factor of 1/e. Furthermore, the downstream depletion appears to be due to neutral pumping rather than ionization.

  17. Global Warming: Lessons from Ozone Depletion

    NASA Astrophysics Data System (ADS)

    Hobson, Art

    2010-11-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of Arkansas have developed a conceptual understanding of energy and of electromagnetism, including the electromagnetic spectrum, I devote a lecture (and a textbook section) to ozone depletion and another lecture (and section) to global warming. Humankind came together in 1986 and quickly solved, to the extent that humans can solve it, ozone depletion. We could do the same with global warming, but we haven't and as yet there's no sign that we will. The parallel between the ozone and global warming cases, and the difference in outcomes, are striking and instructive.

  18. Self-regulation, ego depletion, and inhibition.

    PubMed

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Effect of low-dose clorgyline on 24-hour urinary monoamine excretion in patients with rapidly cycling bipolar affective disorder.

    PubMed

    Linnoila, M; Karoum, F; Potter, W Z

    1982-05-01

    Effects of clorgyline on urinary excretion of norepinephrine, dopamine, tyramine, and their major metabolites, 5-hydroxyindoleacetic acid and phenylethylamine, were studied in four women who suffered from primary, bipolar affective disorder. All patients had rapid mood cycles and were nonresponsive to lithium carbonate. During placebo administration, a strong correlation was found between the excretion rates of norepinephrine and dopamine and their respective metabolites. Clorgyline, 5 to 10 mg every or every other day, reduced overall-body norepinephrine turnover by 55% and increased tyramine but did not alter 5-hydroxyindoleacetic acid, phenylethylamine, or p-hydroxyphenylacetic acid excretion. These findings demonstrate the clinical actions of low-dose clorgyline and clorgyline's specificity as a monoamine oxidase A (MAO-A) inhibitor in vivo in humans, as well as the effects of specific MAO-A inhibition on monoamine metabolism.

  20. Effects of N- and C-terminal fragments of substance P on ATPase and monoamine oxidase activities in rat brain.

    PubMed

    Wojtkowiak, R; Turska, E; Lachowicz, L; Koziołkiewicz, W

    1990-01-01

    The in vitro influence of substance P (SP) C- and N-terminal fragments on the Na+,K(+)-ATPase and Ca2+,Mg2(+)-ATPase and monoamine oxidase (MAO) from synaptosomal membrane and extra-synaptosomal mitochondria were studied. The obtained results indicate: 1. C-terminal fragment of SP (SP6-11) in 10 microM concentration stimulates the Ca2+,Mg2(+)-ATPase activities from cerebral cortex and hippocampus. Na+,K(+)-ATPase from cerebral cortex is hardly sensitive to the action of this fragment. 2. N-terminal fragment of SP (SP1-5) in 10 microM concentration increases Na+,K(+)-ATPase activity from cerebral cortex and hippocampus. 3. N-terminal tetrapeptide (SP1-4) exerts no influence on ATPases independently from their brain localization. 4. The activity of monoamine oxidase after use of C- and N-terminal fragments is unchanged.

  1. [Changes in the monoamine content in different parts of hypothalamus depending on the stages of the estrous cycle].

    PubMed

    Babichev, V N; Adamskaia, E I

    1976-01-01

    Fluorimetric determination of monoamines in various regions of the hypothalamus and at different stages of the estral cycle in rats showed that the serotonin, noradrenaline, and particularly dophamine content changed both in the course of the cycle and at different time (10, 15 and 18 hours) of the same stage of the cycle. Dophamine concentration in the arcuate area--the centre of the tonic activity--reached its maximum at 18 hours of the diestrus-2 (D2) and fell to the minimum at 10 hours of the proestrus (P). Noradrenaline level in the preoptic area increased at 18 hours of the D2 and fell at 10 hours of the P. It is supposed that in the hypothalamic regulation of the estral cycle at least two monoamines (dopamine and noradrenaline) took part; the trigger role belongs to noradrenaline of the preoptic area (the cyclic centre).

  2. Structural insights into monoamine oxidase inhibitory potency and selectivity of 7-substituted coumarins from ligand- and target-based approaches.

    PubMed

    Catto, Marco; Nicolotti, Orazio; Leonetti, Francesco; Carotti, Andrea; Favia, Angelo Danilo; Soto-Otero, Ramón; Méndez-Alvarez, Estefanía; Carotti, Angelo

    2006-08-10

    A new series of 3-, 4-, 7-polysubstituted coumarins have been designed and evaluated for their monoamine oxidase A and monoamine oxidase B (MAO-A and MAO-B) inhibitory potency. Substituents at position 7 consisted of a bridge of different physicochemical nature linking a phenyl ring to the coumarin scaffold. Structure-affinity and structure-selectivity relationships, derived through CoMFA-GOLPE and docking studies, revealed the key physicochemical interactions responsible for the observed MAO-B and MAO-A inhibitory potency and suggested the main structural determinants for high selectivity toward one of the two enzymatic isoforms. The predictive power of our models was proved with the design of a new inhibitor demonstrating an outstanding MAO-B affinity (pIC50 = 8.29) and the highest MAO-B selectivity (DeltapIC50 = 3.39) within the entire series of ligands examined herein.

  3. The influence of manganese supplementation on seizure onset and severity, and brain monoamines in the genetically epilepsy prone rat.

    PubMed

    Critchfield, J W; Carl, G F; Keen, C L

    1993-01-01

    Human and experimental animal studies suggest a relationship between low Mn status and seizures. The genetically epilepsy prone rat (GEPR), which has low tissue Mn levels, was studied in the context of Mn supplementation. Manganese was provided at 45 micrograms/g diet (control) or 1000 micrograms/g diet (supplemented) to dams during pregnancy and lactation, then to the offspring after weaning. Offspring were tested for seizure susceptibility as young adults; tissue trace elements, brain monoamines and brain glutamine synthetase activity were measured as endpoint biochemical indices. Supplementation, although developmentally encompassing and highly effective in elevating tissue Mn levels, had no effect on seizure latency or severity. Similarly, brain monoamine concentrations and glutamine synthetase activities were resistant to Mn supplementation. Notably, the GEPR was confirmed to have low whole brain glutamine synthetase activity. These findings suggest that seizure activity in the GEPR does not stem from an increased nutritional/metabolic need for Mn.

  4. Prediction of battery depletion in implanted pacemakers

    PubMed Central

    Davies, Geoffrey; Siddons, Harold

    1973-01-01

    By the use of a measuring oscilloscope and the standard electrocardiogram limb leads the degree of battery depletion in an implanted pacemaker can be estimated. A formula based on readings obtained by this means has been used to determine when Devices fixed rate pacemakers should be removed. Laboratory tests show that 90% of their useful life is obtained by this means and it proved possible to extend the period of implantation from an arbitrary 24 months to 25 to 34 months without failure from battery depletion. PMID:4731110

  5. Seasonal oxygen depletion in Chesapeake Bay

    SciTech Connect

    Taft, J.L.; Hartwig, E.O.; Loftus, R.

    1980-12-01

    The spring freshet increases density stratification in Chesapeake Bay and minimizes oxygen transfer from the surface to the deep layer so that waters below 10 m depth experience oxygen depletion which may lead to anoxia during June to September. Respiration in the water of the deep layer is the major factor contributing to oxygen depletion. Benthic respiration seems secondary. Organic matter from the previous year which has settled into the deep layer during winter provides most of the oxygen demand but some new production in the surface layer may sink and thus supplement the organic matter accumulated in the deep layer.

  6. Low Sulfur Depletion in Photodissociation Regions

    NASA Astrophysics Data System (ADS)

    Goicoechea, J. R.; Pety, J.; Gerin, M.; Teyssier, D.; Roueff, E.; Hily-Blant, P.

    2006-06-01

    Sulfur is an abundant element which remains undepleted in diffuse interstellar gas but it is historically assumed to deplete (by factors of ˜1000) on grains at higher densities. Photodissociation regions (PDRs) are an interesting intermediate medium between translucent and dark clouds where the energetics and dynamics are dominated by an illuminating FUV radiation field, and thus they can provide some new insights about the sulfur depletion problem. In this work we present our latest studies on CS and HCS^+ photochemistry, excitation and radiative transfer in the Horsehead PDR, allowing us to infer the sulfur abundance.

  7. Effect of disease and drug treatment on blood serotonin and monoamine oxidase B activity in Parkinson's disease.

    PubMed

    van Kempen, G M; Janjua, R; Roos, R A

    1995-05-01

    Serotonin (5-hydroxytryptamine, 5HT) content and monoamine oxidase (MAO) activity were determined in whole blood of patients with Parkinson's disease (PD) with and without drug treatment and compared with controls. From that comparison a significant reduction in platelet 5HT became apparent in PD. Selegiline, which was always used in combination with L-dopa, not only inhibited MAO activity, as expected, but it also appeared to induce an increase in 5HT content.

  8. Linezolid-induced serotonin toxicity in a patient not taking monoamine oxidase inhibitors or serotonin receptor antagonists

    PubMed Central

    Sutton, Jacob; Stroup, Jeff

    2016-01-01

    Linezolid is an oxazolidinone antibiotic with weak monoamine oxidase (MAO) type A and MAO type B inhibitory effects. Linezolid has been associated with serotonin toxicity when used concomitantly with multiple medications that are known to increase serotonin concentrations. We report the case of a 65-year-old woman with signs and symptoms of serotonin toxicity following administration of linezolid for treatment of methicillin-resistant Staphylococcus aureus pneumonia. PMID:27034576

  9. Comparison of time-dependent effects of (+)-methamphetamine or forced swim on monoamines, corticosterone, glucose, creatine, and creatinine in rats.

    PubMed

    Herring, Nicole R; Schaefer, Tori L; Tang, Peter H; Skelton, Matthew R; Lucot, James P; Gudelsky, Gary A; Vorhees, Charles V; Williams, Michael T

    2008-05-30

    Methamphetamine (MA) use is a worldwide problem. Abusers can have cognitive deficits, monoamine reductions, and altered magnetic resonance spectroscopy findings. Animal models have been used to investigate some of these effects, however many of these experiments have not examined the impact of MA on the stress response. For example, numerous studies have demonstrated (+)-MA-induced neurotoxicity and monoamine reductions, however the effects of MA on other markers that may play a role in neurotoxicity or cell energetics such as glucose, corticosterone, and/or creatine have received less attention. In this experiment, the effects of a neurotoxic regimen of (+)-MA (4 doses at 2 h intervals) on brain monoamines, neostriatal GFAP, plasma corticosterone, creatinine, and glucose, and brain and muscle creatine were evaluated 1, 7, 24, and 72 h after the first dose. In order to compare MA's effects with stress, animals were subjected to a forced swim test in a temporal pattern similar to MA administration [i.e., (30 min/session) 4 times at 2 h intervals]. MA increased corticosterone from 1-72 h with a peak 1 h after the first treatment, whereas glucose was only increased 1 h post-treatment. Neostriatal and hippocampal monoamines were decreased at 7, 24, and 72 h, with a concurrent increase in GFAP at 72 h. There was no effect of MA on regional brain creatine, however plasma creatinine was increased during the first 24 h and decreased by 72 h. As with MA treatment, forced swim increased corticosterone more than MA initially. Unlike MA, forced swim reduced creatine in the cerebellum with no change in other brain regions while plasma creatinine was decreased at 1 and 7 h. Glucose in plasma was decreased at 7 h. Both MA and forced swim increase demand on energy substrates but in different ways, and MA has persistent effects on corticosterone that are not attributable to stress alone.

  10. 48 CFR 52.223-11 - Ozone-Depleting Substances.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Ozone-Depleting Substances....223-11 Ozone-Depleting Substances. As prescribed in 23.804(a), insert the following clause: Ozone-Depleting Substances (MAY 2001) (a) Definition. Ozone-depleting substance, as used in this clause, means...

  11. 48 CFR 52.223-11 - Ozone-Depleting Substances.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Ozone-Depleting Substances....223-11 Ozone-Depleting Substances. As prescribed in 23.804(a), insert the following clause: Ozone-Depleting Substances (MAY 2001) (a) Definition. Ozone-depleting substance, as used in this clause, means...

  12. 48 CFR 52.223-11 - Ozone-Depleting Substances.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Ozone-Depleting Substances....223-11 Ozone-Depleting Substances. As prescribed in 23.804(a), insert the following clause: Ozone-Depleting Substances (MAY 2001) (a) Definition. Ozone-depleting substance, as used in this clause, means...

  13. 48 CFR 52.223-11 - Ozone-Depleting Substances.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Ozone-Depleting Substances....223-11 Ozone-Depleting Substances. As prescribed in 23.804(a), insert the following clause: Ozone-Depleting Substances (MAY 2001) (a) Definition. Ozone-depleting substance, as used in this clause, means...

  14. 48 CFR 52.223-11 - Ozone-Depleting Substances.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Ozone-Depleting Substances....223-11 Ozone-Depleting Substances. As prescribed in 23.804(a), insert the following clause: Ozone-Depleting Substances (MAY 2001) (a) Definition. Ozone-depleting substance, as used in this clause, means...

  15. Two-step production of monoamines in monoenzymatic cells in the spinal cord: a different control strategy of neurotransmitter supply?

    PubMed

    Zhang, Mengliang

    2016-12-01

    Monoamine neurotransmitters play an important role in the modulation of sensory, motor and autonomic functions in the spinal cord. Although traditionally it is believed that in mammalian spinal cord, monoamine neurotransmitters mainly originate from the brain, accumulating evidence indicates that especially when the spinal cord is injured, they can also be produced in the spinal cord. In this review, I will present evidence for a possible pathway for two-step synthesis of dopamine and serotonin in the spinal cord. Published data from different sources and unpublished data from my own ongoing projects indicate that monoenzymatic cells expressing aromatic L-amino acid decarboxylase (AADC), tyrosine hydroxylase (TH) or tryptophan hydroxylase (TPH) are present in the spinal cord and that these TH and THP cells often lie in close proximity to AADC cells. Prompted by the above evidence, I hypothesize that dopamine and serotonin could be synthesized sequentially in two monoenzymatic cells in the spinal cord via a TH-AADC and a TPH-AADC cascade respectively. The monoamines synthesized through this pathway may compensate for lost neurotransmitters following spinal cord injury and also may play specific roles in the recovery of sensory, motor and autonomic functions.

  16. Analysis of microdialysate monoamines, including noradrenaline, dopamine and serotonin, using capillary ultra-high performance liquid chromatography and electrochemical detection.

    PubMed

    Ferry, Barbara; Gifu, Elena-Patricia; Sandu, Ioana; Denoroy, Luc; Parrot, Sandrine

    2014-03-01

    Electrochemical methods are very often used to detect catecholamine and indolamine neurotransmitters separated by conventional reverse-phase high performance liquid chromatography (HPLC). The present paper presents the development of a chromatographic method to detect monoamines present in low-volume brain dialysis samples using a capillary column filled with sub-2μm particles. Several parameters (repeatability, linearity, accuracy, limit of detection) for this new ultrahigh performance liquid chromatography (UHPLC) method with electrochemical detection were examined after optimization of the analytical conditions. Noradrenaline, adrenaline, serotonin, dopamine and its metabolite 3-methoxytyramine were separated in 1μL of injected sample volume; they were detected above concentrations of 0.5-1nmol/L, with 2.1-9.5% accuracy and intra-assay repeatability equal to or less than 6%. The final method was applied to very low volume dialysates from rat brain containing monoamine traces. The study demonstrates that capillary UHPLC with electrochemical detection is suitable for monitoring dialysate monoamines collected at high sampling rate.

  17. X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism.

    PubMed Central

    Brunner, H G; Nelen, M R; van Zandvoort, P; Abeling, N G; van Gennip, A H; Wolters, E C; Kuiper, M A; Ropers, H H; van Oost, B A

    1993-01-01

    We have identified a large Dutch kindred with a new form of X-linked nondysmorphic mild mental retardation. All affected males in this family show very characteristic abnormal behavior, in particular aggressive and sometimes violent behavior. Other types of impulsive behavior include arson, attempted rape, and exhibitionism. Attempted suicide has been reported in a single case. The locus for this disorder could be assigned to the Xp11-21 interval between DXS7 and DXS77 by linkage analysis using markers spanning the X chromosome. A maximal multipoint lod score of 3.69 was obtained at the monoamine oxidase type A (MAOA) locus in Xp11.23-11.4. Results of 24-h urine analysis in three affected males indicated a marked disturbance of monoamine metabolism. These data are compatible with a primary defect in the structural gene for MAOA and/or monoamine oxidase type B (MAOB). Normal platelet MAOB activity suggests that the unusual behavior pattern in this family may be caused by isolated MAOA deficiency. PMID:8503438

  18. CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters.

    PubMed

    Malm, J; Kristensen, B; Ekstedt, J; Adolfsson, R; Wester, P

    1991-03-01

    Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a subgroup of MID patients characterised by dilated ventricles and disturbed CSF hydrodynamics. These data suggest that a low CSF outflow conductance may facilitate the clearance of acidic substances from the arachnoid space at the probenecid sensitive active transport site. Alternative explanations would be that a pathologically low CSF outflow conductance is accompanied by an inverse caudorostral flow of CSF or a compromised trans-ependymal diffusion.

  19. CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters.

    PubMed Central

    Malm, J; Kristensen, B; Ekstedt, J; Adolfsson, R; Wester, P

    1991-01-01

    Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a subgroup of MID patients characterised by dilated ventricles and disturbed CSF hydrodynamics. These data suggest that a low CSF outflow conductance may facilitate the clearance of acidic substances from the arachnoid space at the probenecid sensitive active transport site. Alternative explanations would be that a pathologically low CSF outflow conductance is accompanied by an inverse caudorostral flow of CSF or a compromised trans-ependymal diffusion. PMID:1709421

  20. Changes in Brain Monoamines Underlie Behavioural Disruptions after Zebrafish Diet Exposure to Polycyclic Aromatic Hydrocarbons Environmental Mixtures.

    PubMed

    Vignet, Caroline; Trenkel, Verena M; Vouillarmet, Annick; Bricca, Giampiero; Bégout, Marie-Laure; Cousin, Xavier

    2017-03-04

    Zebrafish were exposed through diet to two environmentally relevant polycyclic aromatic hydrocarbons (PAHs) mixtures of contrasted compositions, one of pyrolytic (PY) origin and one from light crude oil (LO). Monoamine concentrations were quantified in the brains of the fish after six month of exposure. A significant decrease in noradrenaline (NA) was observed in fish exposed to both mixtures, while a decrease in serotonin (5HT) and dopamine (DA) was observed only in LO-exposed fish. A decrease in metabolites of 5HT and DA was observed in fish exposed to both mixtures. Several behavioural disruptions were observed that depended on mixtures, and parallels were made with changes in monoamine concentrations. Indeed, we observed an increase in anxiety in fish exposed to both mixtures, which could be related to the decrease in 5HT and/or NA, while disruptions of daily activity rhythms were observed in LO fish, which could be related to the decrease in DA. Taken together, these results showed that (i) chronic exposures to PAHs mixtures disrupted brain monoamine contents, which could underlie behavioural disruptions, and that (ii) the biological responses depended on mixture compositions.

  1. Two-step production of monoamines in monoenzymatic cells in the spinal cord: a different control strategy of neurotransmitter supply?

    PubMed Central

    Zhang, Mengliang

    2016-01-01

    Monoamine neurotransmitters play an important role in the modulation of sensory, motor and autonomic functions in the spinal cord. Although traditionally it is believed that in mammalian spinal cord, monoamine neurotransmitters mainly originate from the brain, accumulating evidence indicates that especially when the spinal cord is injured, they can also be produced in the spinal cord. In this review, I will present evidence for a possible pathway for two-step synthesis of dopamine and serotonin in the spinal cord. Published data from different sources and unpublished data from my own ongoing projects indicate that monoenzymatic cells expressing aromatic L-amino acid decarboxylase (AADC), tyrosine hydroxylase (TH) or tryptophan hydroxylase (TPH) are present in the spinal cord and that these TH and THP cells often lie in close proximity to AADC cells. Prompted by the above evidence, I hypothesize that dopamine and serotonin could be synthesized sequentially in two monoenzymatic cells in the spinal cord via a TH-AADC and a TPH-AADC cascade respectively. The monoamines synthesized through this pathway may compensate for lost neurotransmitters following spinal cord injury and also may play specific roles in the recovery of sensory, motor and autonomic functions. PMID:28197177

  2. Changes in Brain Monoamines Underlie Behavioural Disruptions after Zebrafish Diet Exposure to Polycyclic Aromatic Hydrocarbons Environmental Mixtures

    PubMed Central

    Vignet, Caroline; Trenkel, Verena M.; Vouillarmet, Annick; Bricca, Giampiero; Bégout, Marie-Laure; Cousin, Xavier

    2017-01-01

    Zebrafish were exposed through diet to two environmentally relevant polycyclic aromatic hydrocarbons (PAHs) mixtures of contrasted compositions, one of pyrolytic (PY) origin and one from light crude oil (LO). Monoamine concentrations were quantified in the brains of the fish after six month of exposure. A significant decrease in noradrenaline (NA) was observed in fish exposed to both mixtures, while a decrease in serotonin (5HT) and dopamine (DA) was observed only in LO-exposed fish. A decrease in metabolites of 5HT and DA was observed in fish exposed to both mixtures. Several behavioural disruptions were observed that depended on mixtures, and parallels were made with changes in monoamine concentrations. Indeed, we observed an increase in anxiety in fish exposed to both mixtures, which could be related to the decrease in 5HT and/or NA, while disruptions of daily activity rhythms were observed in LO fish, which could be related to the decrease in DA. Taken together, these results showed that (i) chronic exposures to PAHs mixtures disrupted brain monoamine contents, which could underlie behavioural disruptions, and that (ii) the biological responses depended on mixture compositions. PMID:28273853

  3. Transcriptional activation of vesicular monoamine transporter 2 in the pre-B cell line Ea3.123.

    PubMed Central

    Watson, F; Deavall, D G; Macro, J A; Kiernan, R; Dimaline, R

    1999-01-01

    Uptake and storage of monoamines in secretory granules is accomplished by vesicular monoamine transporters, and it is likely that vesicular monoamine transporter 2 (VMAT2) is important for histamine transport in vivo. In the present study we have used the pre-B-cell line Ea3.123 to investigate the mechanisms involved in the transcriptional activation of the VMAT2 gene. In Ea3.123 cells, VMAT2 mRNA abundance was increased following mobilization of intracellular calcium, and this increased mRNA expression was paralleled by changes in l-histidine decarboxylase mRNA, suggesting that VMAT2 may be responsible for sequestration of histamine into secretory vesicles in this cell line. We cloned the 5'-flanking region of the VMAT2 gene and determined its transcriptional start site by primer extension of rat VMAT2 mRNA. There was no TATA or TATA-like sequence upstream of this region; instead there were GC-rich elements, Ca2+/cAMP-response-element- and SP1-binding motifs. Approx. 900 bp upstream of the transcriptional start site was a purine-pyrimidine repeat sequence that may form a Z-DNA structure. A series of 5'-deletional VMAT2-promoter segments cloned upstream of a luciferase reporter were capable of driving transcription and indicated the presence of multiple regulatory elements, while stimulation with ionomycin or PMA resulted in an increased level of the transcriptional activity of the 5'-promoter segments studied. PMID:9882615

  4. Mild Traumatic Brain Injury with Social Defeat Stress Alters Anxiety, Contextual Fear Extinction, and Limbic Monoamines in Adult Rats

    PubMed Central

    Davies, Daniel R.; Olson, Dawne; Meyer, Danielle L.; Scholl, Jamie L.; Watt, Michael J.; Manzerra, Pasquale; Renner, Kenneth J.; Forster, Gina L.

    2016-01-01

    Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM), or for contextual fear conditioning and extinction. Brains were collected 24 h after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes. PMID:27147992

  5. [Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression].

    PubMed

    Wang, Tao; Qin, Feng

    2010-11-01

    To investigate the effects of Xiaoyao Powder, a compound traditional Chinese herbal medicine for treatment of depression, on monoamine neurotransmitters in hippocampus of rats with postpartum depression (PPD). Ovariectomized Sprague-Dawley rats were randomly divided into 4 groups: control group, untreated group, fluoxetine hydrochloride group and Xiaoyao Powder group. Except for the control group, the rats in the other 3 groups were injected subcutaneously with estrogen for 23 successive days to induce the "pregnancy" state. In the next 30 successive days, rats were given test drugs respectively and the concentrations of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). PPD was induced in rats of untreated group, and compared with rats of control group, the concentrations of NE, DA and 5-HT in the hippocampus significantly reduced (P<0.01), while the concentration of 5-HIAA significantly increased (P<0.01). Xiaoyao Powder treatment significantly improved the behavior indexes and levels of monoamine neurotransmitters in hippocampus (P<0.01). Xiaoyao Powder and fluoxetine hydrochloride produced similar effects in rats with PPD. Xiaoyao Powder produces an antidepression effect in rats by regulating the levels of monoamine neurotransmitters in hippocampus.

  6. Monoamines in the albumen gland, plasma, and central nervous system of the snail Biomphalaria glabrata during egg-laying.

    PubMed

    Boyle, Jon P; Yoshino, Timothy P

    2002-06-01

    The potential role of selected biogenic monoamines and related compounds in the reproductive physiology of the freshwater snail Biomphalaria glabrata was investigated. Extracts of the albumen gland (AG), plasma, and central nervous system (CNS) were subjected to high pressure liquid chromatography with electrochemical detection (HPLC-ED), and under the extraction and separation conditions employed the following amines were detected: tyrosine, dihydroxyphenylalanine (DOPA), dopamine, and tryptophan in the AG; DOPA, tyrosine, and tryptophan in the plasma; DOPA, tyrosine, dopamine and 5-hydroxytryptamine in the CNS. These compounds were then quantified in individual samples taken from snails known to be in a particular stage of the egg-laying process. AG dopamine levels were highest in snails in the first stage of the reproductive process, when the AG is secreting perivitelline fluid around each fertilized ovum. Significant decreases in AG protein content during the later stages of the egg-laying process were also evident. Plasma tyrosine and DOPA levels were lowest in snails that contained a fully packaged egg mass, while no changes in monoamine content were observed in the CNS. These data provide insights into the role(s) that monoamines, especially catecholamine-related compounds, may play in B. glabrata reproductive physiology.

  7. Genetic KCa3.1-Deficiency Produces Locomotor Hyperactivity and Alterations in Cerebral Monoamine Levels

    PubMed Central

    Sivasaravanaparan, Mithula; Ditzel, Nicholas; Sevelsted-Møller, Linda Maria; Oliván-Viguera, Aida; Rabjerg, Maj; Wulff, Heike; Köhler, Ralf

    2012-01-01

    Background The calmodulin/calcium-activated K+ channel KCa3.1 is expressed in red and white blood cells, epithelia and endothelia, and possibly central and peripheral neurons. However, our knowledge about its contribution to neurological functions and behavior is incomplete. Here, we investigated whether genetic deficiency or pharmacological activation of KCa3.1 change behavior and cerebral monoamine levels in mice. Methodology/Principal Findings In the open field test, KCa3.1-deficiency increased horizontal activity, as KCa3.1−/− mice travelled longer distances (≈145% of KCa3.1+/+) and at higher speed (≈1.5-fold of KCa3.1+/+). Working memory in the Y-maze was reduced by KCa3.1-deficiency. Motor coordination on the rotarod and neuromuscular functions were unchanged. In KCa3.1−/− mice, HPLC analysis revealed that turn-over rates of serotonin were reduced in frontal cortex, striatum and brain stem, while noradrenalin turn-over rates were increased in the frontal cortex. Dopamine turn-over rates were unaltered. Plasma catecholamine and corticosterone levels were unaltered. Intraperitoneal injections of 10 mg/kg of the KCa3.1/KCa2-activator SKA-31 reduced rearing and turning behavior in KCa3.1+/+ but not in KCa3.1−/− mice, while 30 mg/kg SKA-31 caused strong sedation in 50% of the animals of either genotypes. KCa3.1−/− mice were hyperactive (≈+60%) in their home cage and SKA-31-administration reduced nocturnal physical activity in KCa3.1+/+ but not in KCa3.1−/− mice. Conclusions/Significance KCa3.1-deficiency causes locomotor hyperactivity and altered monoamine levels in selected brain regions, suggesting a so far unknown functional link of KCa3.1 channels to behavior and monoaminergic neurotransmission in mice. The tranquilizing effects of low-dose SKA-31 raise the possibility to use KCa3.1/KCa2 channels as novel pharmacological targets for the treatment of neuropsychiatric hyperactivity disorders. PMID:23077667

  8. Monoamine Oxidase and Dopamine β-Hydroxylase Inhibitors from the Fruits of Gardenia jasminoides

    PubMed Central

    Kim, Ji Ho; Kim, Gun Hee; Hwang, Keum Hee

    2012-01-01

    This research was designed to determine what components of Gardenia jasminoides play a major role in inhibiting the enzymes related antidepressant activity of this plant. In our previous research, the ethyl acetate fraction of G. jasminosides fruits inhibited the activities of both monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B), and oral administration of the ethanolic extract slightly increased serotonin concentrations in the brain tissues of rats and decreased MAO-B activity. In addition, we found through in vitro screening test that the ethyl acetate fraction showed modest inhibitory activity on dopamine-β hydroxylase (DBH). The bioassay-guided fractionation led to the isolation of five bio-active compounds, protocatechuic acid (1), geniposide (2), 6'-O-trans-p-coumaroylgeniposide (3), 3,5-d-ihydroxy-1,7-bis (4-hydroxyphenyl) heptanes (4), and ursolic acid (5), from the ethyl acetate fraction of G. jasminoides fruits. The isolated compounds showed different inhibitory potentials against MAO-A, -B, and DBH. Protocatechuic acid showed potent inhibition against MAO-B (IC50 300 μmol/L) and DBH (334 μmol/L), exhibiting weak MAO-A inhibition (2.41 mmol/L). Two iridoid glycosides, geniposide (223 μmol/L) and 6'-O-trans-p-coumaroylgeniposide (127μmol/L), were selective MAO-B inhibitor. Especially, 6'-O-trans-p-coumaroylgeniposide exhibited more selective MAO-B inhibition than deprenyl, well-known MAO-B inhibitor for the treatment of early-stage Parkinson’s disease. The inhibitory activity of 3,5-di-hydroxy-1,7-bis (4-hydroxyphenyl) heptane was strong for MAO-B (196 μmol/L), modest for MAO-A (400 μmol/L), and weak for DBH (941 μmol/L). Ursolic acid exhibited significant inhibition of DBH (214 μmol/L), weak inhibition of MAO-B (780 μmol/L), and no inhibition against MAO-A. Consequently, G. jasminoides fruits are considerable for development of biofunctional food materials for the combination treatment of depression and neurodegenerative disorders

  9. Blood Levels of Monoamine Precursors and Smoking in Patients with Schizophrenia

    PubMed Central

    Mathai, Ashwin Jacob; Kanwar, Jyoti; Okusaga, Olaoluwa; Fuchs, Dietmar; Lowry, Christopher A.; Peng, Xiaoqing; Giegling, Ina; Hartmann, Annette M.; Konte, Bettina; Friedl, Marion; Gragnoli, Claudia; Reeves, Gloria M.; Groer, Maureen W.; Rosenthal, Richard N.; Rujescu, Dan; Postolache, Teodor T.

    2016-01-01

    Smoking is highly prevalent in patients with schizophrenia and exerts a negative impact on cardiovascular mortality in these patients. Smoking has complex interactions with monoamine metabolism through the ability of cigarette smoke to suppress Type 1 T helper cell (Th1) type immunity, the immunophenotype that is implicated in phenylalanine hydroxylase (PAH) dysfunction and tryptophan (Trp) breakdown to kynurenine (Kyn) via indoleamine 2,3-dioxygenase. Nicotine also induces tyrosine hydroxylase (TH) gene expression, leading to increased synthesis of catecholamines. Furthermore, there is evidence for PAH dysfunction in schizophrenia. This study aimed to compare the plasma levels of selected monoamine precursors and their metabolites in smokers vs. non-smokers in a large sample of patients with schizophrenia. We measured plasma phenylalanine (Phe), tyrosine (Tyr), Trp, and Kyn levels using high-performance liquid chromatography and calculated Phe:Tyr and Kyn:Trp ratios in 920 patients with schizophrenia. Analysis of variance and linear regression analyses were used to compare these endpoints between three groups of patients with schizophrenia: (1) current smokers, (2) past smokers, and (3) non-smokers. There were significant differences among the three groups with regards to Tyr levels [F(2,789) = 3.77, p = 0.02], with current smokers having lower Tyr levels when compared with non-smokers (p = 0.02). Kyn levels and Kyn:Trp ratio were different among the three groups [F(2,738) = 3.17, p = 0.04, F(2,738) = 3.61, p = 0.03] with current smokers having lower Kyn levels (p = 0.04) and higher Kyn:Trp ratio (p = 0.02) when compared with past smokers. These findings need to be replicated with protocols that include healthy controls to further elucidate the neurobiological underpinnings of altered Tyr and Kyn levels in smokers. Results do suggest potential molecular links between schizophrenia and smoking that may represent biomarkers and

  10. Kinetic evaluation of [11C]dihydrotetrabenazine by dynamic PET: measurement of vesicular monoamine transporter.

    PubMed

    Koeppe, R A; Frey, K A; Vander Borght, T M; Karlamangla, A; Jewett, D M; Lee, L C; Kilbourn, M R; Kuhl, D E

    1996-11-01

    (+)-alpha-[11C]Dihydrotetrabenazine (DTBZ) binds to the vesicular monoamine transporter (VMAT2) located in presynaptic vesicles. The purpose of this work was to evaluate various model configurations for analysis of [11C]DTBZ with the aim of providing the optimal measure of monoamine vesicular transporter density obtainable from a single dynamic PET study. PET studies on seven young normal volunteer subjects, ages 20-35, were performed following i.v. injection of 666 +/- 37 MBq (18 +/- 1 mCi) of (+)-alpha-[11C]DTBZ. Dynamic acquisition consisted of a 15-frame sequence over 1 h. Analysis methods included both creation of pixel-by-pixel functional images of transport (K1) and binding (DVtot) and nonlinear least-squares analysis of volume-of-interest data. Pixel-by-pixel calculations were performed for both two-compartment weighted integral calculations and slope-intercept estimations from Logan plots. Nonlinear least-squares analysis was performed applying model configurations with both two-compartments, estimating K1 and DVtot and three compartments, estimating K1-k4. For the more complex configuration, we examined the stability of various binding-related parameters including k3 (konBmax'), k3/k4 (Bmax'/Kd), DVsp[(K1/k2)(k3/k4)], and DVtot [K1/k2(1 + k3/k4)]. The three-compartment model provided significantly improved goodness-of-fit compared to the two-compartment model, yet did not increase the uncertainty in the estimate of the DVtot. Without constraining parameters in the three-compartment model fits, DVtot was found to provide a more stable estimate of binding density than either k3, k3/k4, or DVsp. The two-compartment least-squares analysis yielded approximately 10% underestimations of the total distribution. However, this bias was found to be very consistent from region to region as well as across subjects as indicated by the correlation between two- and three-compartment DVtot estimates of 0.997. We conclude that (+)-alpha-[11C]DTBZ and PET can provide

  11. Lobeline analogs with enhanced affinity and selectivity for plasmalemma and vesicular monoamine transporters.

    PubMed

    Miller, Dennis K; Crooks, Peter A; Zheng, Guangrong; Grinevich, Vladimir P; Norrholm, Seth D; Dwoskin, Linda P

    2004-09-01

    Lobeline attenuates the behavioral effects of psychostimulants in rodents and inhibits the function of nicotinic receptors (nAChRs), dopamine transporters (DATs), and vesicular monoamine transporters (VMAT2s). Monoamine transporters are considered valid targets for drug development for the treatment of methamphetamine abuse. In the current study, a series of lobeline analogs were evaluated for affinity and selectivity at these targets. None of the analogs was more potent than nicotine at the [3H]methyllycaconitine binding site (alpha7* nAChR subtype). Lobeline tosylate was equipotent with lobeline in inhibiting [3H]nicotine binding but 70-fold more potent in inhibiting nicotine-evoked 86Rb+ efflux, demonstrating antagonism of alpha4beta2* nAChRs. Compared with lobeline, the defunctionalized analogs lobelane, mesotransdiene, and (-)-trans-transdiene showed dramatically reduced affinity at alpha4beta2* nAChRs and a 15- to 100-fold higher affinity (Ki = 1.95, 0.58, and 0.26 microM, respectively) at DATs. Mesotransdiene and (-)-trans-transdiene competitively inhibited DAT function, whereas lobelane and lobeline acted noncompetitively. 10S/10R-MEPP [N-methyl-2R-(2R/2S-hydroxy-2-phenylethyl)6S-(2-phenylethyl)piperidine] and 10R-MESP [N-methyl-2R-(2R-hydroxy-2-phenylethyl)6S-(2-phenylethen-1-yl)piperidine] were 2 to 3 orders of magnitude more potent (Ki = 0.01 and 0.04 microM, respectively) than lobeline in inhibiting [3H]serotonin uptake; 10S/10R-MEPP showed a 600-fold selectivity for this transporter. Uptake results using hDATs and human serotonin transporters expressed in human embryonic kidney-293 cells were consistent with native transporter assays. Lobelane and ketoalkene were 5-fold more potent (Ki = 0.92 and 1.35 microM, respectively) than lobeline (Ki = 5.46 microM) in inhibiting [3H]methoxytetrabenazine binding to VMAT2 in vesicle preparations. Thus, structural modification (defunctionalization) of the lobeline molecule markedly decreases affinity for alpha4beta

  12. Simplified dietary acute tryptophan depletion: effects of a novel amino acid mixture on the neurochemistry of C57BL/6J mice

    PubMed Central

    Sánchez, Cristina L.; Van Swearingen, Amanda E. D.; Arrant, Andrew E.; Biskup, Caroline S.; Kuhn, Cynthia M.; Zepf, Florian D.

    2015-01-01

    Background Diet and nutrition can impact on the biological processes underpinning neuropsychiatric disorders. Amino acid (AA) mixtures lacking a specific neurotransmitter precursor can change the levels of brain serotonin (5-HT) or dopamine (DA) in the central nervous system. The availability of these substances within the brain is determined by the blood–brain barrier (BBB) that restricts the access of peripheral AA into the brain. AA mixtures lacking tryptophan (TRP) compete with endogenous TRP for uptake into the brain across the BBB, which in turn leads to a decrease in central nervous 5-HT synthesis. Objective The present study compared the effects of a simplified acute tryptophan depletion (SATD) mixture in mice on blood and brain serotonergic and dopaminergic metabolites to those of a commonly used acute tryptophan depletion mixture (ATD Moja-De) and its TRP-balanced control (BAL). Design The SATD formula is composed of only three large neutral AAs: phenylalanine (PHE), leucine (LEU), and isoleucine (ILE). BAL, ATD Moja-De, or SATD formulas were delivered to adult male C57BL/6J mice by gavage. TRP, monoamines, and their metabolites were quantified in blood and brain regions (hippocampus, frontal cortex, amygdala, caudate putamen, and nucleus accumbens). Results Both ATD Moja-De and SATD significantly decreased levels of serum and brain TRP, as well as brain 5-HIAA and 5-HT compared with BAL. SATD reduced HVA levels in caudate but did not alter total DA levels or DOPAC. SATD decreased TRP and serotonergic metabolites comparably to ATD Moja-De administration. Conclusion A simplified and more palatable combination of AAs can manipulate serotonergic function and might be useful to reveal underlying monoamine-related mechanisms contributing to different neuropsychiatric disorders. PMID:26278978

  13. Direct Visualization of an Impurity Depletion Zone

    NASA Technical Reports Server (NTRS)

    Chernov, Alex A.; Garcia-Ruiz, Juan Ma; Thomas, Bill R.

    2000-01-01

    When a crystal incorporates more impurity per unit of its volume than the impurity concentration in solution, the solution in vicinity of the growing crystal is depleted with respect to the impurity I,2. With a stagnant solution, e. g. in microgravity or gels, an impurity depletion zone expands as the crystal grows and results in greater purity in most of the outer portion of the crystal than in the core. Crystallization in gel provides an opportunity to mimic microgravity conditions and visualize the impurity depletion zone. Colorless, transparent apoferritin (M congruent to 450 KDa) crystals were grown in the presence of red holoferritin dimer as a microheterogeneous impurity (M congruent to 900 KDa) within agarose gel by counterdiffusion with Cd(2+) precipitant. Preferential trapping of dimers, (distribution coefficient K = 4 (exp 1,2)) results in weaker red color around the crystals grown in the left tube in the figure as compared to the control middle tube without crystals. The left and the middle tubes contain colored ferritin dimers, the right tube contains colored trimers. The meniscus in the left tube separate gel (below) and liquid solution containing Cd(2+) (above). Similar solutions, though without precipitants, were present on top of the middle and right tube allowing diffusion of dimers and trimers. The area of weaker color intensity around crystals directly demonstrates overlapped impurity depletion zones.

  14. Global Warming: Lessons from Ozone Depletion

    ERIC Educational Resources Information Center

    Hobson, Art

    2010-01-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of…

  15. Global Warming: Lessons from Ozone Depletion

    ERIC Educational Resources Information Center

    Hobson, Art

    2010-01-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of…

  16. Kinetics of the depletion of trichloroethene

    SciTech Connect

    Barrio-Lage, G.; Parson, F.Z.; Nassar, R.S.

    1987-04-01

    The depletion of trichloroethene (TCE) was studied in microcosms containing water and three types of natural sediment ranging in composition from highly organic to a calcareous sedimentary rock. The depletion rates varied slightly in the different sediments. The first-order rate constant k/sub 1/ for the depletion of TCE ranged from 8.7 x 10/sup -4/ and 4.9 x 10/sup -4/ h/sup -1/ in soils contaminated with TCE prior to microcosm preparation to 3.4 x 10/sup -4/ and 4.6 x 10/sup -4/ h/sup -1/ for soils with a large organic content to 3.2 x 10/sup -4/ h/sup -1/ for crushed rock microcosms. Depletion was found to follow nonlinear forms of Michaelis-Menten kinetics in the organic sediments; however, microcosms containing crushed rock and water followed a linear form of the equation. K/sub m/ values were found to be dependent on the percent of total organic carbon in the sediment. 16 references, 4 figures, 2 tables.

  17. Neutral depletion versus repletion due to ionization

    SciTech Connect

    Fruchtman, A.; Makrinich, G.; Raimbault, J.-L.; Liard, L.; Rax, J.-M.; Chabert, P.

    2008-05-15

    Recent theoretical analyses which predicted unexpected effects of neutral depletion in both collisional and collisionless plasmas are reviewed. We focus on the depletion of collisionless neutrals induced by strong ionization of a collisionless plasma and contrast this depletion with the effect of strong ionization on thermalized neutrals. The collisionless plasma is analyzed employing a kinetic description. The collisionless neutrals and the plasma are coupled through volume ionization and wall recombination only. The profiles of density and pressure both of the plasma and of the neutral-gas and the profile of the ionization rate are calculated. It is shown that for collisionless neutrals the ionization results in neutral depletion, while when neutrals are thermalized the ionization induces a maximal neutral-density at the discharge center, which we call neutral repletion. The difference between the two cases stems from the relation between the neutral density and pressure. The pressure of the collisionless neutral-gas turns out to be maximal where its density is minimal, in contrast to the case of a thermalized neutral gas.

  18. Soil moisture depletion patterns around scattered trees

    Treesearch

    Robert R. Ziemer

    1968-01-01

    Soil moisture was measured around an isolated mature sugar pine tree (Pinus lambertiana Dougl.) in the mixed conifer forest type of the north central Sierra Nevada, California, from November 1965 to October 1966. From a sequence of measurements, horizontal and vertical soil moisture profiles were developed. Estimated soil moisture depletion from the 61-foot radius plot...

  19. Demonstration of jackhammer incorporating depleted uranium

    SciTech Connect

    Fischer, L E; Hoard, R W; Carter, D L; Saculla, M D; Wilson, G V

    2000-04-01

    The United States Government currently has an abundance of depleted uranium (DU). This surplus of about 1 billion pounds is the result of an enrichment process using gaseous diffusion to produce enriched and depleted uranium. The enriched uranium has been used primarily for either nuclear weapons for the military or nuclear fuel for the commercial power industry. Most of the depleted uranium remains at the enrichment process plants in the form of depleted uranium hexafluoride (DUF{sub 6}). The Department of Energy (DOE) recently began a study to identify possible commercial applications for the surplus material. One of these potential applications is to use the DU in high-density strikers/hammers in pneumatically driven tools, such as jack hammers and piledrivers to improve their impulse performance. The use of DU could potentially increase tunneling velocity and excavation into target materials with improved efficiency. This report describes the efforts undertaken to analyze the particulars of using DU in two specific striking applications: the jackhammer and chipper tool.

  20. Dissolution Treatment of Depleted Uranium Waste

    SciTech Connect

    Gates-Anderson, D D; Laue, C A; Fitch, T E

    2004-02-09

    Researchers at LLNL have developed a 3-stage process that converts pyrophoric depleted uranium metal turnings to a solidified final product that can be transported to and buried at a permitted land disposal site. The three process stages are: (1) pretreatment; (2) dissolution; and (3) solidification. Each stage was developed following extensive experimentation. This report presents the results of their experimental studies.

  1. Contrasts between Antarctic and Arctic ozone depletion.

    PubMed

    Solomon, Susan; Portmann, Robert W; Thompson, David W J

    2007-01-09

    This work surveys the depth and character of ozone depletion in the Antarctic and Arctic using available long balloon-borne and ground-based records that cover multiple decades from ground-based sites. Such data reveal changes in the range of ozone values including the extremes observed as polar air passes over the stations. Antarctic ozone observations reveal widespread and massive local depletion in the heart of the ozone "hole" region near 18 km, frequently exceeding 90%. Although some ozone losses are apparent in the Arctic during particular years, the depth of the ozone losses in the Arctic are considerably smaller, and their occurrence is far less frequent. Many Antarctic total integrated column ozone observations in spring since approximately the 1980s show values considerably below those ever observed in earlier decades. For the Arctic, there is evidence of some spring season depletion of total ozone at particular stations, but the changes are much less pronounced compared with the range of past data. Thus, the observations demonstrate that the widespread and deep ozone depletion that characterizes the Antarctic ozone hole is a unique feature on the planet.

  2. “When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

    PubMed Central

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion. PMID:25009523

  3. How Depleted is the MORB mantle?

    NASA Astrophysics Data System (ADS)

    Hofmann, A. W.; Hart, S. R.

    2015-12-01

    Knowledge of the degree of mantle depletion of highly incompatible elements is critically important for assessing Earth's internal heat production and Urey number. Current views of the degree of MORB source depletion are dominated by Salters and Stracke (2004), and Workman and Hart (2005). The first is based on an assessment of average MORB compositions, whereas the second considers trace element data of oceanic peridotites. Both require an independent determination of one absolute concentration, Lu (Salters & Stracke), or Nd (Workman & Hart). Both use parent-daughter ratios Lu/Hf, Sm/Nd, and Rb/Sr calculated from MORB isotopes combined with continental-crust extraction models, as well as "canonical" trace element ratios, to boot-strap the full range of trace element abundances. We show that the single most important factor in determining the ultimate degree of incompatible element depletion in the MORB source lies in the assumptions about the timing of continent extraction, exemplified by continuous extraction versus simple two-stage models. Continued crust extraction generates additional, recent mantle depletion, without affecting the isotopic composition of the residual mantle significantly. Previous emphasis on chemical compositions of MORB and/or peridotites has tended to obscure this. We will explore the effect of different continent extraction models on the degree of U, Th, and K depletion in the MORB source. Given the uncertainties of the two most popular models, the uncertainties of U and Th in DMM are at least ±50%, and this impacts the constraints on the terrestrial Urey ratio. Salters, F.J.M. and Stracke, A., 2004, Geochem. Geophys. Geosyst. 5, Q05004. Workman, R.K. and Hart, S.R., 2005, EPSL 231, 53-72.

  4. Brain monoamine oxidase A binding in major depressive disorder: relationship to selective serotonin reuptake inhibitor treatment, recovery, and recurrence.

    PubMed

    Meyer, Jeffrey H; Wilson, Alan A; Sagrati, Sandra; Miler, Laura; Rusjan, Pablo; Bloomfield, Peter M; Clark, Michael; Sacher, Julia; Voineskos, Aristotle N; Houle, Sylvain

    2009-12-01

    Highly significant elevations in regional brain monoamine oxidase A (MAO-A) binding were recently reported during major depressive episodes (MDEs) of major depressive disorder (MDD). The relationship between MAO-A levels and selective serotonin reuptake inhibitor (SSRI) treatment, recovery, and recurrence in MDD is unknown. To determine whether brain MAO-A binding changes after SSRI treatment, whether brain MAO-A binding normalizes in subjects with MDD in recovery, and whether there is a relationship between prefrontal and anterior cingulate cortex MAO-A binding in recovery and subsequent recurrence of MDE. Case-control study. Tertiary care psychiatric hospital. Twenty-eight healthy subjects, 16 subjects with an MDE secondary to MDD, and 18 subjects with MDD in recovery underwent carbon 11-labeled harmine positron emission tomography scans. Subjects with MDE were scanned before and after 6 weeks of SSRI treatment. All were otherwise healthy, nonsmoking, and medication free. Subjects with MDD in recovery were followed up for 6 months after MAO-A binding measurement. Monoamine oxidase A V(T), an index of MAO-A density, was measured in the prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, dorsal putamen, ventral striatum, thalamus, anterior temporal cortex, midbrain, and hippocampus. Monoamine oxidase A V(T) was significantly elevated in each brain region both during MDE and after SSRI treatment as compared with healthy controls. During recovery, MAO-A V(T) was significantly elevated in each brain region; however, those who went on to recurrence had significantly higher MAO-A V(T) in the prefrontal and anterior cingulate cortex than those who did not. Elevated MAO-A binding after SSRI treatment indicates persistence of a monoamine-lowering process not present in health. This provides a strong conceptual rationale for continuing SSRI treatment during early remission. Greater MAO-A binding in the prefrontal and anterior cingulate cortex in

  5. Beta-phenylethylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain.

    PubMed

    Xie, Zhihua; Miller, Gregory M

    2008-05-01

    Brain monoamines include common biogenic amines (dopamine, norepinephrine, and serotonin) and trace amines [beta-phenylethylamine (beta-PEA), tyramine, tryptamine, and octopamine]. Common biogenic amines are well established as neurotransmitters, but the roles and functional importance of trace amines remain elusive. Here, we re-evaluated the interaction of trace amines with trace amine-associated receptor 1 (TAAR1) and investigated effects of beta-PEA on monoamine transporter function and influence of monoamine autoreceptors on TAAR1 signaling. We confirmed that TAAR1 was activated by trace amines and demonstrated that TAAR1 activation by beta-PEA significantly inhibited uptake and induced efflux of [3H]dopamine, [3H]norepinephrine, and [3H]serotonin in transfected cells. In brain synaptosomes, beta-PEA significantly inhibited uptake and induced efflux of [3H]dopamine and [3H]serotonin in striatal and [3H]norepinephrine in thalamic synaptosomes of rhesus monkeys and wild-type mice, but it lacked the same effects in synaptosomes of TAAR1 knockout mice. The effect of beta-PEA on efflux was blocked by transporter inhibitors in either the transfected cells or wild-type mouse synaptosomes. We also demonstrated that TAAR1 signaling was not affected by monoamine autoreceptors at exposure to trace amines that we show to have poor binding affinity for the autoreceptors relative to common biogenic amines. These results reveal that beta-PEA alters monoamine transporter function via interacting with TAAR1 but not monoamine autoreceptors. The functional profile of beta-PEA may reveal a common mechanism by which trace amines exert modulatory effects on monoamine transporters in brain.

  6. Naproxen, a Nonsteroidal Anti-Inflammatory Drug, Can Affect Daily Hypobaric Hypoxia-Induced Alterations of Monoamine Levels in Different Areas of the Brain in Male Rats.

    PubMed

    Goswami, Ananda Raj; Dutta, Goutam; Ghosh, Tusharkanti

    2016-06-01

    Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH)-induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS.

  7. Monoamine oxidase A and A/B knockout mice display autistic-like features

    PubMed Central

    Bortolato, Marco; Godar, Sean C.; Alzghoul, Loai; Zhang, Junlin; Darling, Ryan D.; Simpson, Kimberly L.; Bini, Valentina; Chen, Kevin; Wellman, Cara L.; Lin, Rick C. S.; Shih, Jean C.

    2012-01-01

    Converging lines of evidence show that a sizable subset of autism-spectrum disorders (ASDs) is characterized by increased blood levels of serotonin (5-hydroxytryptamine, 5-HT), yet the mechanistic link between these two phenomena remains unclear. The enzymatic degradation of brain 5-HT is mainly mediated by monoamine oxidase (MAO)A and, in the absence of this enzyme, by its cognate isoenzyme MAOB. MAOA and A/B knockout (KO) mice display high 5-HT levels, particularly during early developmental stages. Here we show that both mutant lines exhibit numerous behavioural hallmarks of ASDs, such as social and communication impairments, perseverative and stereotypical responses, behavioural inflexibility, as well as subtle tactile and motor deficits. Furthermore, both MAOA and A/B KO mice displayed neuropathological alterations reminiscent of typical ASD features, including reduced thickness of the corpus callosum, increased dendritic arborization of pyramidal neurons in the prefrontal cortex and disrupted microarchitecture of the cerebellum. The severity of repetitive responses and neuropathological aberrances was generally greater in MAOA/B KO animals. These findings suggest that the neurochemical imbalances induced by MAOAdeficiency (either by itself or in conjunction with lack of MAOB) may result in an array of abnormalities similar to those observed in ASDs. Thus, MAOA and A/B KO mice may afford valuable models to help elucidate the neurobiological bases of these disorders and related neurodevelopmental problems. PMID:22850464

  8. Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signaling.

    PubMed

    Liechti, Matthias

    2015-01-01

    Novel psychoactive substances are newly used designer drugs ("internet drugs", "research chemicals", "legal highs") potentially posing similar health risks to classic illicit substances. Chemically, many novel psychoactive substances can be classified as phenethylamines, amphetamines, synthetic cathinones, piperazines, pipradrols/piperidines, aminoindanes benzofurans, and tryptamines. Pharmacologically, these substances interact with various monoaminergic targets. Typically, stimulants inhibit the transport of dopamine and noradrenaline (pipradrols, pyrovalerone cathinones) or induce the release of these monoamines (amphetamines and methamphetamine-like cathinones), entactogens predominantly enhance serotonin release (phenylpiperazines, aminoindanes, para-substituted amphetamines, and MDMA-like cathinones) similar to MDMA (ecstasy), and hallucinogens (tryptamines, hallucinogenic phenethylamines) are direct agonists at serotonergic 5-HT2A receptors. Synthetic cannabinoids are another group of novel substances which all act as agonists at the cannabinoid CB1 receptor similar to THC but are chemically diverse. In particular, the relative serotonergic vs dopaminergic activity (determined by the dopamine/serotonin transporter inhibition ratio in vitro) can be helpful to predict the desired psychotropic but also the toxic effects of novel substances as well as their potential for addiction. Although the use of novel psychoactive substances mostly produces minor or moderate poisonings, serious complications occur. Serotonergic drugs (entactogens and hallucinogens) are associated with acute serotonin syndrome, hyperthermia, seizures, and hyponatremia. Dopaminergic drugs are highly addictive and acute toxicity includes prolonged stimulation, insomnia, agitation, and psychosis. Agitation, anxiety, paranoia, hypertension, and rarely myocardial infarction and renal failure are seen with synthetic cannabinoids. Treatment is supportive.

  9. Mono-amine functionalized phthalocyanines: microwave-assisted solid-phase synthesis and bioconjugation strategies.

    PubMed

    Erdem, S Sibel; Nesterova, Irina V; Soper, Steven A; Hammer, Robert P

    2009-12-18

    Phthalocyanines (Pcs) are excellent candidates for use as fluors for near-infrared (near-IR) fluorescent tagging of biomolecules for a wide variety of bioanalytical applications. Monofunctionalized Pcs, having two different types of peripheral substitutents, one for covalent conjugation of the Pc to biomolecules and others to improve the solubility of the macrocycle, are ideally suited for the desired applications. To date, difficulties faced during the purification of monofunctionalized Pcs limited their usage in various types of applications. Herein are reported a new synthetic method for rapid synthesis of the target Pcs and bioconjugation techniques for labeling of the oligonucleotides with the near-IR fluors. A novel synthetic route was developed utilizing a hydrophilic, poly(ethylene glycol) (PEG)-based support with an acid-labile Rink Amide linker. The Pcs were functionalized with an amine group for covalent conjugation purposes and were decorated with short PEG chains, serving as solubilizing groups. Microwave-assisted solid-phase synthetic method was successfully applied to obtain pure asymmetrically substituted monoamine functionalized Pcs in a short period of time. Three different bioconjugation techniques, reductive amination, amidation, and Huisgen cycloaddition, were employed for covalent conjugation of Pcs to oligonucleotides. The described microwave-assisted bioconjugation methods give an opportunity to synthesize and isolate the Pc-oligonucleotide conjugate in a few hours.

  10. Modulation of monoamine neurotransmitters in fighting fish Betta splendens exposed to waterborne phytoestrogens.

    PubMed

    Clotfelter, Ethan D; McNitt, Meredith M; Carpenter, Russ E; Summers, Cliff H

    2010-12-01

    Endogenous estrogens are known to affect the activity of monoamine neurotransmitters in vertebrate animals, but the effects of exogenous estrogens on neurotransmitters are relatively poorly understood. We exposed sexually mature male fighting fish Betta splendens to environmentally relevant and pharmacological doses of three phytoestrogens that are potential endocrine disruptors in wild fish populations: genistein, equol, and β-sitosterol. We also exposed fish to two doses of the endogenous estrogen 17β-estradiol, which we selected as a positive control because phytoestrogens are putative estrogen mimics. Our results were variable, but the effects were generally modest. Genistein increased dopamine levels in the forebrains of B. splendens at both environmentally relevant and pharmacological doses. The environmentally relevant dose of equol increased dopamine levels in B. splendens forebrains, and the pharmacological dose decreased norepinephrine (forebrain), dopamine (hindbrain), and serotonin (forebrain) levels. The environmentally relevant dose of β-sitosterol decreased norepinephrine and dopamine in the forebrain and hindbrain, respectively. Our results suggest that sources of environmental phytoestrogens, such as runoff or effluent from agricultural fields, wood pulp mills, and sewage treatment plants, have the potential to modulate neurotransmitter activity in free-living fishes in a way that could interfere with normal behavioral processes.

  11. Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

    PubMed Central

    Suri, Deepika; Teixeira, Cátia M; Cagliostro, Martha K Caffrey; Mahadevia, Darshini; Ansorge, Mark S

    2015-01-01

    Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system development, such sensitive periods shape the formation of neurocircuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint as well as the environmental context. While allowing for adaptation, such sensitive periods are also vulnerability windows during which external and internal factors can confer risk to disorders by derailing otherwise resilient developmental programs. Here we review developmental periods that are sensitive to monoamine signaling and impact adult behaviors of relevance to psychiatry. Specifically, we review (1) a serotonin-sensitive period that impacts sensory system development, (2) a serotonin-sensitive period that impacts cognition, anxiety- and depression-related behaviors, and (3) a dopamine- and serotonin-sensitive period affecting aggression, impulsivity and behavioral response to psychostimulants. We discuss preclinical data to provide mechanistic insight, as well as epidemiological and clinical data to point out translational relevance. The field of translational developmental neuroscience has progressed exponentially providing solid conceptual advances and unprecedented mechanistic insight. With such knowledge at hand and important methodological innovation ongoing, the field is poised for breakthroughs elucidating the developmental origins of neuropsychiatric disorders, and thus understanding pathophysiology. Such knowledge of sensitive periods that determine the developmental trajectory of complex behaviors is a necessary step towards improving prevention and treatment approaches for neuropsychiatric disorders. PMID:25178408

  12. Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo.

    PubMed

    Lohr, Kelly M; Bernstein, Alison I; Stout, Kristen A; Dunn, Amy R; Lazo, Carlos R; Alter, Shawn P; Wang, Minzheng; Li, Yingjie; Fan, Xueliang; Hess, Ellen J; Yi, Hong; Vecchio, Laura M; Goldstein, David S; Guillot, Thomas S; Salahpour, Ali; Miller, Gary W

    2014-07-08

    Disruption of neurotransmitter vesicle dynamics (transport, capacity, release) has been implicated in a variety of neurodegenerative and neuropsychiatric conditions. Here, we report a novel mouse model of enhanced vesicular function via bacterial artificial chromosome (BAC)-mediated overexpression of the vesicular monoamine transporter 2 (VMAT2; Slc18a2). A twofold increase in vesicular transport enhances the vesicular capacity for dopamine (56%), dopamine vesicle volume (33%), and basal tissue dopamine levels (21%) in the mouse striatum. The elevated vesicular capacity leads to an increase in stimulated dopamine release (84%) and extracellular dopamine levels (44%). VMAT2-overexpressing mice show improved outcomes on anxiety and depressive-like behaviors and increased basal locomotor activity (41%). Finally, these mice exhibit significant protection from neurotoxic insult by the dopaminergic toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as measured by reduced dopamine terminal damage and substantia nigra pars compacta cell loss. The increased release of dopamine and neuroprotection from MPTP toxicity in the VMAT2-overexpressing mice suggest that interventions aimed at enhancing vesicular capacity may be of therapeutic benefit in Parkinson disease.

  13. Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreas

    PubMed Central

    Saisho, Yoshifumi; Harris, Paul E.; Butler, Alexandra E.; Galasso, Ryan; Gurlo, Tatyana; Rizza, Robert A.

    2008-01-01

    Vesicular monoamine transporter 2 (VMAT2) is expressed in pancreatic beta cells and has recently been proposed as a target for measurement of beta cell mass in vivo. We questioned, (1) What proportion of beta cells express VMAT2? (2) Is VMAT2 expressed by other pancreatic endocrine or non-endocrine cells? (3) Is the relationship between VMAT2 and insulin expression disturbed in type 1 (T1DM) or type 2 diabetes (T2DM)? Human pancreas (7 non-diabetics, 5 T2DM, 10 T1DM) was immunostained for insulin, VMAT2 and other pancreatic hormones. Most beta cells expressed VMAT2. VMAT2 expression was not changed by the presence of diabetes. In tail of pancreas VMAT2 immunostaining closely correlated with insulin staining. However, VMAT2 was also expressed in some pancreatic polypeptide (PP) cells. Although VMAT2 was not excluded as a target for beta cell mass measurement, expression of VMAT2 in PP cells predicts residual VMAT2 expression in human pancreas even in the absence of beta cells. Electronic supplementary material The online version of this article (doi:10.1007/s10735-008-9195-9) contains supplementary material, which is available to authorized users. PMID:18791800

  14. The properties of B-form monoamine oxidase in mitochondria from monkey platelet.

    PubMed

    Obata, Toshio; Aomine, Masahiro

    The present study was examined the effect of the properties of monkey platelet monoamine oxidase (MAO) based on inhibitor sensitivity. Monkey platelet showed a high MAO activity with beta-phenylethylamine (beta-PEA) as substrate and a very low A-form MAO activity with 5 hydroxytryptamine (5-HT) as substrate. Moreover, monkey platelet MAO was sensitive to the drugs deprenyl as B-form MAO inhibitor and less sensitive to clorgyline and harmaline as A form MAO inhibitor with beta-PEA as the B-form MAO substrate. B-form MAO from monkey platelet was more stable against heat treatment at 55 degrees C than B-form MAO in brain. After digestion with trypsin at 37 degrees C for 4 hrs, it was found that MAO from platelet was inhibited about 70% with beta-PEA as substrate with brain. The tricyclic antidepressant imipramine and nortriptyline inhibited B-form MAO activity more potency than B-form MAO in brain. However, when the noncyclic antidepressant nomifensine was used, monkey platelet B-form MAO activities were less potently inhibited. All these reagents were noncompetitive inhibitors of B form MAO in monkey platelet. The present studies demonstrated that monkey platelet MAO is a single of B-form MAO and sensitive to tricyclic antidepressants.

  15. Monoamine oxidase A gene DNA hypomethylation - a risk factor for panic disorder?

    PubMed

    Domschke, Katharina; Tidow, Nicola; Kuithan, Henriette; Schwarte, Kathrin; Klauke, Benedikt; Ambrée, Oliver; Reif, Andreas; Schmidt, Hartmut; Arolt, Volker; Kersting, Anette; Zwanzger, Peter; Deckert, Jürgen

    2012-10-01

    The monoamine oxidase A (MAOA) gene has been suggested as a prime candidate in the pathogenesis of panic disorder. In the present study, DNA methylation patterns in the MAOA regulatory and exon 1/intron 1 region were investigated for association with panic disorder with particular attention to possible effects of gender and environmental factors. Sixty-five patients with panic disorder (44 females, 21 males) and 65 healthy controls were analysed for DNA methylation status at 42 MAOA CpG sites via direct sequencing of sodium bisulfate treated DNA extracted from blood cells. The occurrence of recent positive and negative life events was ascertained. Male subjects showed no or only very minor methylation with some evidence for relative hypomethylation at one CpG site in intron 1 in patients compared to controls. Female patients exhibited significantly lower methylation than healthy controls at 10 MAOA CpG sites in the promoter as well as in exon/intron 1, with significance surviving correction for multiple testing at four CpG sites (p≤0.001). Furthermore, in female subjects the occurrence of negative life events was associated with relatively decreased methylation, while positive life events were associated with increased methylation. The present pilot data suggest a potential role of MAOA gene hypomethylation in the pathogenesis of panic disorder particularly in female patients, possibly mediating a detrimental influence of negative life events. Future studies are warranted to replicate the present finding in independent samples, preferably in a longitudinal design.

  16. Selective and nonselective monoamine oxidase inhibitors: behavioral disturbances during their administration to depressed patients.

    PubMed

    Pickar, D; Murphy, D L; Cohen, R M; Campbell, I C; Lipper, S

    1982-05-01

    The occurrence of behavioral disturbances during four-week treatment of depressed patients with the nonselective monoamine oxidase (MAO) inhibitor, phenelzine sulfate (N = 14), the selective MAO-type A inhibitor, clorgyline (N = 12), and the partially selective MAO-type B inhibitor, pargyline hydrochloride (N = 13), was studied. Behavioral disturbances were encountered during treatment with each of the MAO-inhibiting drugs, with an overall incidence of 15% (six of 39 patients). All but one episode met criteria for mania or hypomania. Patients with bipolar illness experienced significantly greater incidences of behavioral disturbances in comparison with patients with unipolar illness (35.3% v 4.5%, respectively). The earliest latency to onset of a behavioral disturbances was 18 days, whereas the mean latencies were 22 to 26 days. Episodes of hypomania were observed after discontinuation of drug treatment in individual patients with unipolar and bipolar illness. Repeated MAO-inhibitor treatment, as part of a crossover study of clorgyline and pargyline, produced an increased severity of behavioral disturbances and a significantly shortened latency to onset.

  17. Platelet monoamine oxidase (MAO) activity: evidence for a single major locus.

    PubMed Central

    Rice, J; McGuffin, P; Goldin, L R; Shaskan, E G; Gershon, E S

    1984-01-01

    Monoamine oxidase (MAO), a mitochondrial enzyme involved in the degradation of biogenic amines, has been associated with psychiatric morbidity. Although twin and family studies have indicated that MAO activity is familial, the exact mode of transmission is unclear. We performed segregation analysis on 154 nuclear families containing 419 individuals using the mixed model, which allows for a single major locus with a polygenic background. We were able to reject a dominant and additive locus with or without a heritable background and a recessive locus without background. The acceptable models were: (1) a codominant model without background where the mean of the heterozygote distribution was 30% of the distance from the low to the high homozygote distributions, and (2) a recessive locus with heritable background. In both cases, the gene frequency for the high-MAO allele is approximately .25--at odds with suggestions that low-MAO represents a genetic marker for a disorder such as schizophrenia with a lifetime risk of only 0.85%. To ensure that results were not artifacts from a familial, skewed distribution, the data were also analyzed after power transformation. In addition, hypotheses were tested using both the joint and conditional likelihoods to examine for possible misspecification of the model with respect to intergenerational differences. Finally, we allowed for non-Mendelian transmission probabilities to provide another class of alternatives against which to test the hypothesis of a major locus. All these approaches provided additional confirmation for the presence of a major locus segregating within these families. PMID:6695924

  18. Effect of caroxazone, a new antidepressant drug, on monoamine oxidases in healthy volunteers

    PubMed Central

    Moretti, A.; Caccia, C.; Martini, A.; Bonollo, L.; Amico, A.; Sega, R.; Nicolella, V.; Nicolis, F. B.

    1981-01-01

    1 Caroxazone is a new antidepressant drug with a reversible inhibitory effect on monoamine oxidases (MAO) as previously shown experimentally in animals. 2 The effect of caroxazone on MAO was explored in healthy volunteers and compared with that of tranylcypromine and imipramine. Daily urinary excretion of tryptamine and MAO activity in platelets were assayed at various times during and after treatment and the differences from basal values were statistically analysed. In addition, caroxazone plasma levels were determined. 3 Caroxazone administered orally at doses of 300 or 600 mg/day for 12 days induced a significant, dose-dependent increase in urinary tryptamine excretion. Tranylcypromine (20 mg/day for 8 days) was even more active in this respect; imipramine (50 mg/day for 12 days) was completely inactive. 4 MAO activity in platelets was not affected by caroxazone or imipramine, but was completely inhibited by tranylcypromine. 5 Mean steady-state plasma levels of caroxazone were about 6 μg/ml and 11-12 μg/ml with the dose of 300 mg/day and 600 mg/day respectively. 6 It can be concluded that caroxazone is a MAO inhibitor in man too, at a clinically effective dose such as 600 mg/day. The fact that its MAO inhibition is not apparent in platelet preparation may be explained by its reversibility. 7 Tranylcypromine confirmed its potent irreversible MAO inhibitory effect, while imipramine lacked any effect at the tested dose. PMID:7272163

  19. Determination of isatin, an endogenous monoamine oxidase inhibitor, in urine and tissues of rats by HPLC.

    PubMed

    Hamaue, N; Yamazaki, N; Minami, M; Endo, T; Hirahuji, M; Monma, Y; Togashi, H

    1998-03-01

    1. We have previously identified isatin as one of the endogenous monoamine oxidase (MAO) inhibitors in the urine and the brain of stroke-prone spontaneously hypertensive rats (SHRSP), using gas chromatography-mass spectrometry (GC-MS). 2. In this study, we attempted to develop a convenient assay to determine isatin using high performance liquid chromatography with an ultraviolet detector (HPLC-UV). The standard curve for authentic isatin was linear at a range from 2 to 20 nmol per ml. The coefficient of variance was within 3% for both intra-assay and inter-assay. The sensitivity was 20 pmol per 10 microl of urine sample. 3. Isatin concentration correlated significantly and positively with endogenous MAO activity (tribulin-like activity) in both urine (r=0.924, P<0.001) and kidney extracts (r=0.862, P<0.01). There was a significant difference in urinary isatin between Wistar Kyoto rats (WKY) and SHRSP. Oral administration of isatin increased urinary isatin concentration and systolic blood pressure in WKY. 4. Determination of isatin using HPLC-UV may be useful for elucidating role of isatin in various conditions of stress and disease.

  20. Dopamine metabolism and neurotransmission in primate brain in relationship to monoamine oxidase A and B inhibition.

    PubMed

    Youdim, M B; Riederer, P

    1993-01-01

    The "cheese effect", potentiation of sympathomimetic action of indirectly acting amines such as tyramine, the main side effect of irreversible non-selective and selective monoamine oxidase (MAO) A inhibitors, has largely been eliminated in the new generation of reversible selective MAO-A and B and irreversible MAO-B inhibitors. These selective inhibitors are demonstrating unique pharmacology and initial controlled clinical studies are providing evidence to support their action as anti-depressants and anti-Parkinson's disease drugs and possibly as neuroprotectors. Thirty years of experience with non-selective MAO inhibitors has resulted in a better understanding and management of the new generation of MAO inhibitors. Because of their selective action on the specific forms of MAO, which results in selective elevation of brain noradrenaline and serotonin on the one hand and dopamine and phenylethylamine on the other, it is hoped that these drugs will be able to elucidate the functional roles of MAO-A and B subtypes with regards to dopamine metabolism in the human brain.

  1. The development of a MIP-optosensor for the detection of monoamine naphthalenes in drinking water.

    PubMed

    Valero-Navarro, Angel; Salinas-Castillo, Alfonso; Fernández-Sánchez, Jorge F; Segura-Carretero, Antonio; Mallavia, Ricardo; Fernández-Gutiérrez, Alberto

    2009-03-15

    To enhance the advantages of fluorescent flow-through sensing for drinking water we have designed a novel sensing matrix based on molecularly imprinted polymers (MIPs). The synergic combination of a tailor-made MIP recognition with a selective room temperature fluorescence detection is a novel concept for optosensing devices and is assessed here for the simple and selective determination of pollutants in water. We describe a simple approach to preparing synthetic receptors for monoamine naphthalene compounds (MA-NCs) using non-covalent molecular imprinting techniques and naphthalene as template. We examine in detail the binding characteristics of the imprinted polymer and describe the flow-through sensor of MA-NCs by solid-surface fluorescence. Its detection limits for recognizing 1-naphthylamine (1-NA) and 2-naphthylamine (2-NA) separately are 26 ngmL(-1) and 50 ngmL(-1), respectively, and it also determines 1-NA and 2-NA simultaneously with a detection limit of 45 ngmL(-1). All the instrumental, chemical and flow variables were carefully optimized and an interference study was carried out to demonstrate its applicability and selectivity. Finally, we applied it to the analysis of 1-NA and 2-NA in tap and mineral waters, obtaining a 98% average recovery rate.

  2. Mono-Amine Functionalized Phthalocyanines: Mwave-Assisted Solid-Phase Synthesis and Bioconjugation Strategies

    PubMed Central

    Erdem, S. Sibel; Nesterova, Irina V.; Soper, Steven A.; Hammer, Robert P.

    2009-01-01

    Phthalocyanines (Pcs) are excellent candidates for use as fluors for near-infrared (near-IR) fluorescent tagging of biomolecules for a wide variety of bioanalytical applications. Mono-functionalized Pcs, having two different types of peripheral substitutents; one for covalent conjugation of the Pc to biomolecules and others to improve the solubility of the macrocycle, ideally suit for the desired applications. To date, difficulties faced during the purification of the mono-functionalized Pcs limited their usage in various types of applications. Herein are reported a new synthetic method for rapid synthesis of the target Pcs and bioconjugation techniques for labeling of the oligonucleotides with the near-IR flours. A novel synthetic route was developed utilizing a hydrophilic, polyethylene glycol-based (PEG) support with an acid labile Rink Amide linker. The Pcs were functionalized with an amine group for covalent conjugation purposes and were decorated with short PEG chains, serving as solubilizing groups. Mwave-assisted solid-phase synthetic method was successfully applied to obtain pure asymmetrically-substituted mono-amine functionalized Pcs in a short period of time. Three different bioconjugation techniques, reductive amination, amidation and Huisgen cycloaddition, were employed for covalent conjugation of Pcs to oligonucleotides. The described μwave-assisted bioconjugation methods give an opportunity to synthesize and isolate the Pc-oligonucleotide conjugate in a few hours. PMID:19911767

  3. [Comparative study of substrate and inhibitory specificity of monoamine oxidase in the optic ganglia of squids].

    PubMed

    Iagodina, O V

    2010-01-01

    Comparative study of substrate specificity of monoamine oxidase (MAO) of optic ganglia of the Pacific squid Todarodes pacificus and the Commander squid Berryteuthis magister has been carried out. The enzyme of the Pacific squid, unlike that of the Commander squid, has been established to be able to deaminate not only tyramine, tryptamine, serotonin, benzylamine, and beta-phenylethylamine, but also histamine--substrate of diamine oxidase (DAO). In relation to all studied substrates, the MAO activity of optic ganglia of T. pacificus is several times higher as compared with B. magister. In the case of deamination of serotonin this difference was the greatest and amounted to 5 times. Semicarbazide, the classic DAO inhibitor, at a concentration of 10 mM did not inhibit catalytic activity of both studied enzymes. The substrate-inhibitory analysis with use of deprenyl and chlorogiline, specific inhibitors of different MAO forms, indicates homogeneity of the enzyme of the Pacific squid and heterogeneity of the Commander squid enzyme whose composition seems probably to contain at least two MAO forms. There are obtained quantitative differences in substrate specificity and reaction capability with respect to the inhibitors chlorgiline and deprenyl for MAO of optic ganglia of the studied squid species. These differences probably can be explained by significant differences in the evolutionary level of these biological species.

  4. Phentermine inhibition of recombinant human liver monoamine oxidases A and B.

    PubMed

    Nandigama, Ravi K; Newton-Vinson, Paige; Edmondson, Dale E

    2002-03-01

    Recent studies with rat tissue preparations have suggested that the anorectic drug phentermine inhibits serotonin degradation by inhibition of monoamine oxidase (MAO) A with a K(I) value of 85-88 microM, a potency suggested to be similar to that of other reversible MAO inhibitors (Ulus et al., Biochem Pharmacol 2000;59:1611-21). Since there are known differences between rats and humans in substrate and inhibitor specificities of MAOs, the interactions of phentermine with recombinant human purified preparations of MAO A and MAO B were determined. Human MAO A was competitively inhibited by phentermine with a K(I) value of 498+/-60 microM, a value approximately 6-fold weaker than that observed for the rat enzyme. Phentermine was also observed to be a competitive inhibitor of recombinant human liver MAO B with a K(I) value of 375+/-42 microM, a value similar to that observed with the rat enzyme (310-416 microM). In contrast to the behavior with rat tissue preparations, no slow time-dependent behavior was observed for phentermine inhibition of purified soluble human MAO preparations. Difference absorption spectral studies showed similar perturbations of the covalent FAD moieties of both human MAO A and MAO B, which suggests a similar mode of binding in both enzymes. These data suggest that phentermine inhibition of human MAO A (or of MAO B) is too weak to be of pharmacological relevance.

  5. Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans

    PubMed Central

    Dlugos, Andrea M.; Palmer, Abraham A.

    2013-01-01

    Monoamine oxidase A and B (MAOA and MAOB) appear to be involved in the pathogenesis of Major Depression, and vulnerability of Major Depression is associated with personality traits relating to positive and negative affect. This study aimed to investigate associations between MAOA and MAOB polymorphisms and personality traits of positive and negative emotionality in healthy volunteers, to elucidate mechanisms underlying personality and the risk for depression. Healthy Caucasian volunteers (N = 150) completed the Multiphasic Personality Questionnaire (MPQ), which includes independent superfactors of Positive Emotionality and Negative Emotionality. Participants were genotyped for 8 MAOA and 12 MAOB single nucleotide polymorphisms (SNPs). Association analyses for both SNPs and haplotypes were performed using the permutation approach implemented in PLINK. Negative Emotionality was significantly associated with the two highly linked MAOB polymorphisms rs10521432 and rs6651806 (p < 0.002). Findings were extended in haplotype analyses. For MAOB the 4-SNP haplotype GACG formed from rs1799836, rs10521432, rs6651806 and rs590551 was significantly related to lower Negative Emotionality scores (p < 0.002). MAOA was not related to personality in this study. Our finding provides the first evidence that MAOB polymorphisms influence levels of negative emotionality in healthy human volunteers. If confirmed, these results could lead to a better understanding of personality traits and inter-individual susceptibility developing psychiatric disorders such as major depression. PMID:19657584

  6. Serotonin immunoreactivity in auditory brainstem neurons of the postnatal monoamine oxidase-A knockout mouse.

    PubMed

    Thompson, Ann M

    2008-09-04

    Altered levels of extracellular serotonin (5-HT) during development cause structural abnormalities in the neural projections of sensory systems. To better understand the potential role of 5-HT in the development of auditory system projections, we examined 5-HT immunoreactivity (IR) in auditory brainstem nuclei of postnatal mice. We previously observed 5-HT-IR in the lateral superior olive (LSO) of wild type mice. In the current study, we used a genetic model (monoamine oxidase-A knockout mouse) in which brain 5-HT levels are abnormally high to improve detection of 5-HT. In the cochlear nucleus of this knockout, 5-HT-IR cell bodies were observed in the dorsal cochlear nucleus (DCN), a primary relay to the inferior colliculus (IC). In the superior olivary complex, 5-HT-IR somata were observed in the LSO, another relay to the IC. Labeled somata were also observed within the IC itself. The 5-HT immunostaining in all 3 regions was transient and was not observed beyond postnatal day 8. These results suggest that 5-HT may play a role in the branching and refinement of DCN and LSO axon collaterals within the IC, as well as IC axon collaterals within the medial geniculate body. The pattern of expression indicates that 5-HT has a developmental role in select populations of neurons of the ascending auditory pathway prior to any influences of sound-evoked activity.

  7. Is fetal brain monoamine oxidase inhibition the missing link between maternal smoking and conduct disorders?

    PubMed

    Baler, Ruben D; Volkow, Nora D; Fowler, Joanna S; Benveniste, Helene

    2008-05-01

    Smoking is the leading cause of preventable illness in the world today. Prenatal cigarette smoke exposure (PCSE) is a particularly insidious form because so many of its associated health effects befall the unborn child and produce behavioural outcomes that manifest themselves only years later. Among these are the associations between PCSE and conduct disorders, which have been mostly ascribed to the deleterious effects of nicotine on the fetal brain. Here we hypothesize that inhibition of brain monoamine oxidase (MAO) during fetal brain development, secondary to maternal cigarette smoking and in addition to nicotine, is a likely contributor to this association. MAOs play a central role in monoaminergic balance in the brain, and their inhibition during fetal development - but not during adult life - is known to result in an aggressive phenotype in laboratory animals. This paper provides theoretical and experimental support for the notion that cigarette smoke-induced inhibition of MAO in the fetal brain, particularly when it occurs in combination with polymorphisms in the MAOA gene that lead to lower enzyme concentration in the brain, may result in brain morphologic and functional changes that enhance the risk of irritability, poor self-control and aggression in the offspring. It also encourages research to evaluate whether the interaction of smoking exposure during fetal development and MAOA genotype increases the risk for conduct disorder over that incurred by mere fetal exposure to tobacco smoke.

  8. Monoamine oxidases are novel sources of cardiovascular oxidative stress in experimental diabetes.

    PubMed

    Sturza, Adrian; Duicu, Oana M; Vaduva, Adrian; Dănilă, Maria D; Noveanu, Lavinia; Varró, András; Muntean, Danina M

    2015-07-01

    Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease associated with increased cardiovascular morbidity and mortality. The generation of reactive oxygen species (ROS) is a major event causally linked to the development of cardiovascular complications throughout the evolution of DM. Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2 isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen peroxide (H2O2) production in the cardiovascular system via the oxidative deamination of biogenic amines and neurotransmitters. Whether MAOs are mediators of endothelial dysfunction in DM is unknown, and so we studied this in a streptozotocin-induced rat model of diabetes. MAO expression (mRNA and protein) was increased in both arterial samples and hearts isolated from the diabetic animals. Also, H2O2 production (ferrous oxidation - xylenol orange assay) in aortic samples was significantly increased, together with an impairment of endothelium-dependent relaxation (organ-bath studies). MAO inhibitors (clorgyline and selegiline) attenuated ROS production by 50% and partially normalized the endothelium-dependent relaxation in diseased vessels. In conclusion, MAOs, in particular the MAO-B isoform, are induced in aortas and hearts in the streptozotocin-induced diabetic rat model and contribute, via the generation of H2O2, to the endothelial dysfunction associated with experimental diabetes.

  9. Revisiting the Effectiveness of Standard Antidepressants in Bipolar Disorder: Are Monoamine Oxidase Inhibitors Superior?

    PubMed Central

    Mallinger, Alan G.; Frank, Ellen; Thase, Michael E.; Barwell, Michelle M.; DiazGranados, Nancy; Luckenbaugh, David A.; Kupfer, David J.

    2011-01-01

    Objective The role of antidepressants in bipolar disorder is controversial, and the comparative effectiveness of specific drugs is insufficiently studied. We report here a comparison of monoamine oxidase inhibitors (MAOI) with the serotonin reuptake inhibitor paroxetine (PAROX). Experimental Design We conducted a retrospective analysis of data from a larger study, using the first antidepressant trial administered either after entry (n = 46) or after a recurrent episode during study participation (n = 6). Twenty two patients were treated with PAROX and 30 with MAOI. Durable recovery was determined from Hamilton depression and Young mania scores, based on published criteria. Principal Observations PAROX treatment led to durable recovery in 27% of patients, a result very similar to the 24% recovery rate found in a recent STEP-BD trial. In contrast, patients treated with MAOI had a 53% durable recovery rate. Survival analysis showed a significantly faster recovery with MAOI (χ2 = 4.77, p = 0.029). Among subjects who were able to complete an adequate treatment trial of at least four weeks duration, durable recovery was attained in a significantly greater proportion of those treated with MAOI (16 of 23, 70%) as compared to PAROX (6 of 18, 33%)(Fisher's Exact Test, p = 0.023). Conclusions In these patients with bipolar depression, the antidepressant effectiveness of PAROX was unacceptably low, but rates of recovery with MAOI were significantly higher. PMID:19629023

  10. Genetic variation in the monoamine oxidase A and serotonin transporter genes in sudden infant death syndrome.

    PubMed

    Opdal, Siri H; Vege, Åshild; Rognum, Torleiv O

    2014-04-01

    The purpose of this study was to investigate common polymorphisms in the genes encoding monoamine oxidase A (MAOA) and serotonin transporter (5-HTT) in Norwegian cases of sudden infant death syndrome (SIDS). This was done to further elucidate the role of genetic variation in these genes and SIDS. A variable number of tandem repeat area in the promoter of the MAOA gene and rs25531 in the promoter region of the gene encoding 5-HTT were investigated in 193 SIDS cases and 335 controls. The methods used were polymerase chain reaction, restriction fragment analysis and gel electrophoresis. There were no differences between SIDS cases and controls for any of the investigated polymorphisms. This was also true when male and female SIDS cases were analysed separately. This article indicates that neither the VNTR in the promoter of the MAOA gene, nor rs25531 in the gene encoding 5-HTT, is involved in SIDS. However, as medullary serotonergic abnormalities most likely contribute to the death in at least some SIDS cases, it is important to investigate these genes, as well as other genes involved in the serotonergic network, in more detail. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  11. The separate and combined effects of monoamine oxidase A inhibition and nicotine on resting state EEG.

    PubMed

    Smith, Dylan M; Fisher, Derek; Blier, Pierre; Ilivitsky, Vadim; Knott, Verner

    2016-01-01

    While nicotine is often associated with the neuropsychological effects of tobacco smoke, the robust monoamine oxidase (MAO) inhibition observed in chronic smokers is also likely to play a role. Electroencephalographically-indexed alterations in baseline neural oscillations by nicotine have previously been reported in both smokers and non-smokers, however, little is known about the effects of MAO inhibition in combination with nicotine on resting state EEG. In a sample of 24 healthy non-smoking males, the effects of 6 mg nicotine gum, as well as MAO-A inhibition via 75 mg moclobemide, were investigated in separate and combined conditions over four separate test sessions. Drug effects were observed in the alpha2, beta2, and theta band frequencies. Nicotine increased alpha2 power, and moclobemide decreased beta2 power. Theta power was decreased most robustly by the combination of both drugs. Therefore, this study demonstrated that the nicotinic and MAO inhibiting properties of tobacco may differentially influence fast-wave oscillations (alpha2 and beta2), while acting in synergy to influence theta oscillations. © The Author(s) 2015.

  12. Red emission fluorescent probes for visualization of monoamine oxidase in living cells

    PubMed Central

    Li, Ling-Ling; Li, Kun; Liu, Yan-Hong; Xu, Hao-Ran; Yu, Xiao-Qi

    2016-01-01

    Here we report two novel red emission fluorescent probes for the highly sensitive and selective detection of monoamine oxidase (MAO) with large Stokes shift (227 nm). Both of the probes possess solid state fluorescence and can accomplish the identification of MAO on test papers. The probe MAO-Red-1 exhibited a detection limit down to 1.2 μg mL−1 towards MAO-B. Moreover, the cleavage product was unequivocally conformedby HPLC and LCMS and the result was in accordance with the proposed oxidative deamination mechanism. The excellent photostability of MAO-Red-1 was proved both in vitro and in vivo through fluorescent kinetic experiment and laser exposure experiment of confocal microscopy, respectively. Intracellular experiments also confirmed the low cytotoxity and exceptional cell imaging abilities of MAO-Red-1. It was validated both in HeLa and HepG2 cells that MAO-Red-1 was capable of reporting MAO activity through the variation of fluorescence intensity. PMID:27499031

  13. Chemical analysis, antioxidant, antichemotactic and monoamine oxidase inhibition effects of some pteridophytes from Brazil

    PubMed Central

    Andrade, Juliana MM; Passos, Carolina dos S; Dresch, Roger R; Kieling-Rubio, Maria Angélica; Moreno, Paulo Roberto H; Henriques, Amélia T

    2014-01-01

    Background: Ferns are a group of plants that have been little explored from a chemical and biological perspective but that have interesting potential, occurring in various parts of the world. Objective: This work investigates the chemical profile and the biological effects of ferns from Brazil. Materials and Methods: Analyses were performed using rapid performance liquid chromatography (RP-LC) with a diode array detector (DAD). Extracts were tested for their in vitro antioxidant activity, by the total reactive antioxidant potential method and for their antichemotactic potential, by the Boyden chamber method. Cytotoxic effects were assessed by lactate dehydrogenase levels, while the monoamine oxidase (MAO) assay was carried out using a fluorescence-based method. Results: Different chemical compositions were found for the studied ferns, such as Asplenium gastonis, in which hesperidin was identified in its extract, while A. serra showed the presence of xanthone mangiferin. The most samples with highest antioxidant activity were the Asplenium serra, Lastreopsis amplissima and Cyathea dichromatolepis extracts, at 10 μg/mL. High antichemotactic activity was found for A. serra (94.06%) and Didymochlaena truncatula (93.41%), at 10 μg/mL. The extracts showed no cytotoxicity at the highest concentration. Against MAO-A, D. truncatula (82.61%), Alsophila setosa (82.21%), Cyathea phalerata (74.07%) and C. delgadii (70.32%) were the most active extracts (100 μg/mL). Conclusion: The hypothesis was considered that phenolics and triterpenes are responsible for these pronounced activities. PMID:24914288

  14. Psychological traits and platelet monoamine oxidase activity in eating disorder patients: their relationship and stability.

    PubMed

    Podar, Iris; Jaanisk, Maiken; Allik, Jüri; Harro, Jaanus

    2007-01-30

    Self-reported behavior and attitudes towards eating [Eating Disorder Inventory-2; Garner DM (1991). Eating Disorder Inventory-2: Professional Manual. Odessa, Fl.: Psychological Assessment Resources; Estonian version Podar I, Hannus A, Allik J (1999). Personality and Affectivity Characteristics Associated With Eating Disorders: a Comparison of Eating Disordered, Weight-Preoccupied, and Normal Samples. J Pers Assess; 73(1), 133-147] and the activity of platelet monoamine oxidase (MAO) was studied in 11 patients with anorexia nervosa (AN), 43 patients with bulimia nervosa (BN) and a healthy control group (n=138). Nineteen patients filled in the EDI-2 questionnaire and donated blood samples three times with three month intervals in order to determine platelet MAO activity. Eating disordered (ED) patients scored higher on all EDI-2 subscales and had lower MAO activity compared to the control group. They also scored higher than the control group on the Neuroticism domain but lower on the Extraversion, Openness, and Conscientiousness domains of the NEO-PI-R questionnaire. The average stability of MAO on different occasions (r=.56) was slightly smaller than the stability of the EDI-2 scores (r=.70). The lack of correlations between personality dispositions and MAO activity indicates that they have independent influence on eating disorders. A possible relationship between neurochemical mechanisms and psychological symptoms of eating disordered behavior is discussed.

  15. Monoamine oxidase A genotype is associated with gang membership and weapon use.

    PubMed

    Beaver, Kevin M; DeLisi, Matt; Vaughn, Michael G; Barnes, J C

    2010-01-01

    A functional polymorphism in the promoter region of the monoamine oxidase A (MAOA) gene has been found to be associated with a broad range of antisocial phenotypes, including physical violence. At the same time, it is well known that gang members represent some of the most serious violent offenders. Even so, no research has ever examined the association between MAOA and gang membership. The aim of this study is to examine the association between MAOA and gang membership and between MAOA and weapon use. We examined the effects of MAOA by using a molecular genetic association research design. A nonclinical sample was used in this study. Participants were drawn from the National Longitudinal Study of Adolescent Health (1155 females, 1041 males). The outcome measures of this study are gang membership and weapon use. The low MAOA activity alleles conferred an increased risk of joining a gang and using a weapon in a fight for males but not for females. Moreover, among male gang members, those who used weapons in a fight were more likely to have a low MAOA activity allele when compared with male gang members who do not use weapons in a fight. Male carriers of low MAOA activity alleles are at risk for becoming a gang member and, once a gang member, are at risk for using weapons in a fight. Copyright 2010 Elsevier Inc. All rights reserved.

  16. Interactions Between Monoamine Oxidase A and Punitive Discipline in African American and Caucasian Men's Antisocial Behavior.

    PubMed

    Choe, Daniel Ewon; Shaw, Daniel S; Hyde, Luke W; Forbes, Erika E

    2014-09-01

    Although previous studies have shown that interactions between monoamine oxidase A (MAOA) genotype and childhood maltreatment predict Caucasian boys' antisocial behavior, the generalizability of this gene-environment interaction to more diverse populations and more common parenting behaviors, such as punitive discipline in early childhood, is not clearly understood. Among 189 low-income men (44% African American, 56% Caucasian) who underwent rigorous assessments of family behavior and social context longitudinally across 20 years, those men with the low activity MAOA allele who experienced more punitive discipline at ages 1.5, 2, and 5 years showed more antisocial behavior from ages 15 through 20 years. Effects of punitive discipline on antisocial behavior differed by caregiver and age at which it occurred, suggesting sensitive periods throughout early childhood in which low MAOA activity elevated boys' vulnerability to harsh parenting and risk for antisocial behavior. This genetic vulnerability to punitive discipline-and not just extreme, maltreatment experiences-may generalize to other male populations at risk for antisocial behavior.

  17. In vitro evaluation of Bacopa monniera extract and individual constituents on human recombinant monoamine oxidase enzymes.

    PubMed

    Singh, Rajbir; Ramakrishna, Rachumallu; Bhateria, Manisha; Bhatta, Rabi Sankar

    2014-09-01

    Bacopa monniera is a traditional Ayurvedic medicinal plant that has been used worldwide for its nootropic action. Chemically standardized extract of B. monniera is now available as over the counter herbal remedy to enhance memory in children and adults. Considering the nootropic action of B. monniera, we evaluated the effect of clinically available B. monniera extract and six of B. monniera constituents (bacoside A3, bacopaside I, bacopaside II, bacosaponin C, bacosine, and bacoside A mixture) on recombinant human monoamine oxidase (MAO) enzymes. The effect of B. monniera extract and individual constituents on human recombinant MAO-A and MAO-B enzymes was evaluated using MAO-Glo(TM) assay kit (Promega Corporation, USA), following the instruction manual. IC50 and mode of inhibition were measured for MAO enzymes. Bacopaside I and bacoside A mixture inhibited the MAO-A and MAO-B enzymes. Bacopaside I exhibited mixed mode of inhibition with IC50 and Ki values of 17.08 ± 1.64 and 42.5 ± 3.53 µg/mL, respectively, for MAO-A enzyme. Bacopaside I is the major constituent of B. monniera, which inhibited the MAO-A enzyme selectively.

  18. Methadone, monoamine oxidase, and depression: opioid distribution and acute effects on enzyme activity

    SciTech Connect

    Kaufmann, C.A.; Kreek, M.J.; Raghunath, J.; Arns, P.

    1983-09-01

    Narcotic withdrawal is often accompanied by an atypical depression which responds to resumption of narcotics. It was hypothesized that methadone might exert its antidepressant effects through monoamine oxidase (MAO) inhibition. The current study examined /sub 3/H-methadone distribution in rat brain and effects on regional MAO activity with acute doses (2.5 mg/kg) which approximate those found during chronic methadone maintenance in man. Limbic areas (amygdala, basomedial hypothalamus, caudate-putamen, hippocampus, preoptic nucleus), as well as pituitary and liver were assayed for MAO activity and methadone concentration. MAO activities did not differ significantly in acute methadone or saline-treated cage-mates at 1 or 24 hr. The concentrations of methadone at 1 hr ranged between 17 and 223 ng/100 mg wet wt tissue in the preoptic nucleus and pituitary, respectively. No significant correlation was found between change in MAO activity (MAO methadone/MAO saline) and methadone concentration in any region at 1 or 24 hr. This study does not support the hypothesis that methadone acts as an antidepressant through MAO inhibition, at least not following acute administration of this exogenous opioid.

  19. Effect of PCB and DES on rat monoamine oxidase, acetylcholinesterase, testosterone, and estradiol ontogeny

    SciTech Connect

    Vincent, D.R.; Bradshaw, W.S.; Booth, G.M.; Seegmiller, R.E.; Allen, S.D.

    1992-06-01

    Diethylstilbestrol (DES) and polychlorinated biphenyl (PCB) have been documented as potentially hazardous environmental agents. In utero exposure to DES produces human vaginal adenocarcinoma, male reproductive tract lesions in mice, and has been correlated with personality changes in human males. PCB (Kanechlor) was found to be the major toxin in the {open_quotes}Yusho{close_quotes} rice oil poisoning in Japan in 1968. Other investigators have shown in rats that PCB (Arochlor) causes liver adenofibrosis, thyroid dysfunction, atypical mitochondria, and dilation of both smooth and rough endoplasmic reticulum. Matthews et al. (1978) also reported that 4, 4{prime} chlorinated biphenyl was the most potent inducer of monooxygenases, irrespective of chlorination at other sites. Although these compounds have been studied extensively in mammals, there is a paucity of data examining their effects when non-fetotoxic amounts are administered chronically and orally during gestation. The present study is part of a larger effort designed to establish a protocol for testing the developmental effects of xenobiotics such as DES and PCB. Levels of acetylcholinesterase (AChE) were measured as an indicator of the integrity of nerve transmission in the central nervous system. Monoamine oxidase (MAO) is a marker for the outer mitochondrial membrane and is an important amine metabolizing enzyme. Testosterone and estradiol are important sex steroids in mammals, and effects upon levels of the two hormones may signal anomalies in development of sex characteristics. 35 refs., 3 figs., 1 tab.

  20. Deviant peer affiliation and antisocial behavior: interaction with Monoamine Oxidase A (MAOA) genotype.

    PubMed

    Lee, Steve S

    2011-04-01

    Although genetic and environmental factors are separately implicated in the development of antisocial behavior (ASB), interactive models have emerged relatively recently, particularly those incorporating molecular genetic data. Using a large sample of male Caucasian adolescents and young adults from the National Longitudinal Study of Adolescent Health (Add Health), the association of deviant peer affiliation, the 30-base pair variable number tandem repeat polymorphism in promoter region of the monoamine oxidase-A (MAOA) gene, and their interaction, with antisocial behavior (ASB) was investigated. Weighted analyses accounting for over-sampling and clustering within schools as well as controlling for age and wave suggested that deviant peer affiliation and MAOA genotype were each significantly associated with levels of overt ASB across a 6-year period. Only deviant peer affiliation was significantly related to covert ASB, however. Additionally, there was evidence suggestive of a gene-environment interaction (G × E) where the influence of deviant peer affiliation on overt ASB was significantly stronger among individuals with the high-activity MAOA genotype than the low-activity genotype. MAOA was not significantly associated with deviant peer affiliation, thus strengthening the inference of G × E rather than gene-environment correlation (rGE). Different forms of gene-environment interplay and implications for future research on ASB are discussed.

  1. Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity.

    PubMed

    Williard, Robin L; Middaugh, Lawrence D; Zhu, Hao-Jie B; Patrick, Kennerly S

    2007-02-01

    Ethylphenidate is formed by metabolic transesterification of methylphenidate and ethanol. Study objectives were to (a) establish that ethylphenidate is formed in C57BL/6 (B6) mice; (b) compare the stimulatory effects of ethylphenidate and methylphenidate enantiomers; (c) determine methylphenidate and ethylphenidate plasma and brain distribution and (d) establish in-vitro effects of methylphenidate and ethylphenidate on monoamine transporter systems. Experimental results were that: (a) coadministration of ethanol with the separate methylphenidate isomers enantioselectively produced l-ethylphenidate; (b) d and dl-forms of methylphenidate and ethylphenidate produced dose-responsive increases in motor activity with stimulation being less for ethylphenidate; (c) plasma and whole-brain concentrations were greater for ethylphenidate than methylphenidate and (d) d and DL-methylphenidate and ethylphenidate exhibited comparably potent low inhibition of the dopamine transporter, whereas ethylphenidate was a less potent norepinephrine transporter inhibitor. These experiments establish the feasibility of the B6 mouse model for examining the interactive effects of ethanol and methylphenidate. As reported for humans, concurrent exposure of B6 mice to methylphenidate and ethanol more readily formed l-ethylphenidate than d-ethylphenidate, and the l-isomers of both methylphenidate and ethylphenidate were biologically inactive. The observed reduced stimulatory effect of d-ethylphenidate relative to d-methylphenidate appears not to be the result of brain dispositional factors, but rather may be related to its reduced inhibition of the norepinephrine transporter, perhaps altering the interaction of dopaminergic and noradrenergic neural systems.

  2. Release of (/sup 3/H)-monoamines from superfused rat striatal slices by methylenedioxymethamphetamine (MDMA)

    SciTech Connect

    Levin, J.A.; Schmidt, C.J.; Lovenberg, W.

    1986-03-05

    MDMA is a phenylisopropylamine which is reported to have unique behavioral effects in man. Because of its structural similarities to the amphetamines the authors have compared the effects of MDMA and two related amphetamines on the spontaneous release of tritiated dopamine (DA) and serotonin (5HT) from superfused rat striatal slices. At concentrations of 10/sup -7/ - 10/sup -5/M MDMA and the serotonergic neurotoxin, p-chloroamphetamine, were equipotent releasers of (/sup 3/H)5HT being approximately 10x more potent than methamphetamine. However, methamphetamine was the more potent releaser of (/sup 3/H)DA by a factor of approximately 10x. MDMA-induced release of both (/sup 5/H)5HT and (/sup 3/H)DA was Ca/sup 2 +/-independent and inhibited by selective monoamine uptake blockers suggesting a carrier-dependent release mechanism. Synaptosomal uptake experiments with (+)(/sup 3/H)MDMA indicated no specific uptake of the drug further suggesting the effect of uptake blockers may be to inhibit the carrier-mediated export of amines displaced by MDMA.

  3. Alterations of monoamine metabolites and neurobehavioral function in lead-exposed workers.

    PubMed

    Tang, H W; Liang, Y X; Hu, X H; Yang, H G

    1995-03-01

    Neurobehavioral and neurochemical effects of occupational lead exposure were investigated by WHO Neurobehavioral Core Test Battery (NCTB) testing and a series of monoamine neurotransmitters and their metabolites analyzing in workers from lead smeltery and storage-battery manufacturing factory and matched controls. Indicators of lead exposure, the blood lead (PbB) and zinc protophorphyrin (ZPP) levels were found significantly higher in the exposed group compared with that of the controls (70.55 micrograms/dL vs 3.67 micrograms/dL; and 294.92 micrograms/dL vs 38.32 micrograms/dL, respectively). Furthermore, elevated urinary homovanillic acid (HVA) and impairment of certain neurobehavioral performances were also found in the lead exposed workers; the latter included attention/response speed, manual dexterity, perceptual-motor speed, visual perception/memory, and motor speed/steadiness. Positive or negative correlations were observed between certain parameters. Thus, homovanillic acid (HVA) is positively correlated with PbB and ZPP; dopamine (DA) negatively correlated with Benton visual retention (BVR); and HVA negatively correlated with digit symbol (DSy), BVR, and pursuit aiming (PA). It is suggested that the alterations of dopamine and its metabolites HVA in urine associated with impairment of neurobehavioral function might be served as biomarkers of lead-induced neurotoxicity.

  4. Calcium disodium edetate enhances type A monoamine oxidase activity in monkey brain.

    PubMed

    Egashira, Toru; Sakai, Kumiko; Sakurai, Mami; Takayama, Fusako

    2003-09-01

    The effects of metal chelators on monoamine oxidase (MAO) isozymes, MAO-A and MAO-B, in monkey brain mitochondria were investigated in vitro. MAO-A activity increased to about 40% with 0.1 microM calcium disodium edetate (CaNa2EDTA) using serotonin as a substrate, and this activation was proportional to the concentration of CaNa2EDTA. On the other hand, MAO-A activities were decreased gradually with an increasing concentration of o-phenanthroline and diethyldithiocarbamic acid, but these metal chelators had no effect on MAO-B activity in monkey brain. The activation of MAO-A activity by CaNa2EDTA was reversible. CaNa2EDTA did not activate both MAO-A and MAO-B activities in rat brain mitochondria. Zn and Fe ions were found in the mitochondria of monkey brain. Zn ions potently inhibited MAO-A activity, but Fe ions did not inhibit either MAO-A or MAO-B activity in monkey brain mitochondria. These results indicate that the activating action of CaNa2EDTA on MAO-A was the result of the chelating of Zn ions contained in mitochondria by CaNa2EDTA. These results also indicate the possibility that Zn ions may regulate physiologically the level of serotonin and norepinephrine content in brain by inhibiting a MAO-A activity.

  5. Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug

    PubMed Central

    Sharpe, Martyn A.; Livingston, Andrew D.; Gist, Taylor L.; Ghosh, Pardip; Han, Junyan; Baskin, David S.

    2015-01-01

    The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P+-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models. PMID:26501110

  6. The role of monoamine oxidase A in aggression: current translational developments and future challenges

    PubMed Central

    Godar, Sean C; Fite, Paula J; McFarlin, Kenneth M; Bortolato, Marco

    2016-01-01

    Drawing upon the recent resurgence of biological criminology, several studies have highlighted a critical role for genetic factors in the ontogeny of antisocial and violent conduct. In particular, converging lines of evidence have documented that these maladaptive manifestations of aggression are influenced by monoamine oxidase A (MAOA), the enzyme that catalyzes the degradation of brain serotonin, norepinephrine and dopamine. The interest on the link between MAOA and aggression was originally sparked by Han Brunner’s discovery of a syndrome characterized by marked antisocial behaviors in male carriers of a nonsense mutation of this gene. Subsequent studies showed that MAOA allelic variants associated with low enzyme activity moderate the impact of early-life maltreatment on aggression propensity. In spite of overwhelming evidence pointing to the relationship between MAOA and aggression, the neurobiological substrates of this link remain surprisingly elusive; very little is also known about the interventions that may reduce the severity of pathological aggression in genetically predisposed subjects. Animal models offer a unique experimental tool to investigate these issues; in particular, several lines of transgenic mice harboring total or partial loss-of-function Maoa mutations have been shown to recapitulate numerous psychological and neurofunctional endophenotypes observed in humans. This review summarizes the current knowledge on the link between MAOA and aggression; in particular, we will emphasize how an integrated translational strategy coordinating clinical and preclinical research may prove critical to elucidate important aspects of the pathophysiology of aggression, and identify potential targets for its diagnosis, prevention and treatment. PMID:26776902

  7. Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease

    PubMed Central

    German, Christopher L.; Baladi, Michelle G.; McFadden, Lisa M.; Hanson, Glen R.

    2015-01-01

    Dopamine (DA) plays a well recognized role in a variety of physiologic functions such as movement, cognition, mood, and reward. Consequently, many human disorders are due, in part, to dysfunctional dopaminergic systems, including Parkinson’s disease, attention deficit hyperactivity disorder, and substance abuse. Drugs that modify the DA system are clinically effective in treating symptoms of these diseases or are involved in their manifestation, implicating DA in their etiology. DA signaling and distribution are primarily modulated by the DA transporter (DAT) and by vesicular monoamine transporter (VMAT)-2, which transport DA into presynaptic terminals and synaptic vesicles, respectively. These transporters are regulated by complex processes such as phosphorylation, protein–protein interactions, and changes in intracellular localization. This review provides an overview of 1) the current understanding of DAT and VMAT2 neurobiology, including discussion of studies ranging from those conducted in vitro to those involving human subjects; 2) the role of these transporters in disease and how these transporters are affected by disease; and 3) and how selected drugs alter the function and expression of these transporters. Understanding the regulatory processes and the pathologic consequences of DAT and VMAT2 dysfunction underlies the evolution of therapeutic development for the treatment of DA-related disorders. PMID:26408528

  8. Switch in treatment from tricyclic antidepressants to moclobemide: a new generation monoamine oxidase inhibitor.

    PubMed

    Dingemanse, J; Kneer, J; Fotteler, B; Groen, H; Peeters, P A; Jonkman, J H

    1995-02-01

    The combination of classic monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressant drugs (TCAs) has been associated with a variety of adverse events. A switch in treatment from TCAs to moclobemide, a reversible and selective inhibitor of MAO-A, was investigated in a double-blind, placebo-controlled study in healthy volunteers. Two groups of 12 subjects were treated with either amitriptyline (75 mg/day) or clomipramine (100 mg/day) until steady-state conditions had been attained (14 days). Treatment with the TCAs was discontinued abruptly and switched to either a therapeutic dose regimen of moclobemide (300 mg/day) or placebo. The tolerability and safety pattern did not reveal any clinically relevant differences between moclobemide and placebo recipients, nor was there any sign of a pharmacokinetic interaction between the TCAs and moclobemide. In conclusion, the findings of this study suggest that therapeutic doses of moclobemide up to 300 mg daily can be given 24 hours after the last dose of treatment with either amitriptyline or clomipramine without major risks.

  9. Simultaneous determination of cadaverine and putrescine using a disposable monoamine oxidase based biosensor.

    PubMed

    Henao-Escobar, Wilder; Domínguez-Renedo, Olga; Asunción Alonso-Lomillo, M; Julia Arcos-Martínez, M

    2013-12-15

    The selective and simultaneous amperometric determination of putrescine (Put) and cadaverine (Cad) has been carried out using a novel design of screen-printed carbon electrode (SPCE) with two working electrodes connected in array mode. A mixture of 3% of tetrathiafulvalene (TTF), as mediator, and carbon ink was used for the construction of the screen-printed working electrode. The employment of different amounts of monoamine oxidase (MAO) enzyme on these modified TTF/SPCEs and the use of gold nanoparticles (AuNPs) allowed performing the simultaneous determination of both analytes. The amperometric detection has been performed by measuring the oxidation current of the mediator at a potential of+250 mV vs. screen-printed Ag/AgCl reference electrode. A linear response in the Cad concentration range from 19.6 till 107.1 µM and from 9.9 till 74.1 μM for Put was obtained at the MAO/AuNPs/TTF/SPCE biosensor. This device showed a capability of detection of 9.9 and 19.9±0.9 µM (n=4 α=β=0.05) and a precision of 4.9% and 10.3% in terms of relative standard deviation for Put and Cad, respectively. The developed biosensor was successfully applied to the simultaneous determination of Put and Cad in octopus samples.

  10. Monoamine Oxidase Is Overactivated in Left and Right Ventricles from Ischemic Hearts: An Intriguing Therapeutic Target

    PubMed Central

    Manni, Maria Elena; Borchi, Elisabetta; Bargelli, Valentina

    2016-01-01

    Growing evidence indicates that reactive oxygen species (ROS) may play a key role in human heart failure (HF). Monoamine oxidase (MAO) is emerging as a major ROS source in several cardiomyopathies. However, little is known about MAO activity in human failing heart and its relationship with redox imbalance. Therefore, we measured MAO activity in the left (LV) and in the right (RV) ventricle of human nonfailing (NF) and in end-stage ischemic (IHD) and nonischemic failing hearts. We found that both MAO isoforms (MAO-A/B) significantly increased in terms of activity and expression levels only in IHD ventricles. Catalase and aldehyde dehydrogenase-2 activities (ALDH-2), both implicated in MAO-catalyzed catecholamine catabolism, were significantly elevated in the failing LV, whereas, in the RV, statistical significance was observed only for ALDH-2. Oxidative stress markers levels were significantly increased only in the failing RV. Actin oxidation was significantly elevated in both failing ventricles and related to MAO-A activity and to functional parameters. These data suggest a close association between MAO-A-dependent ROS generation, actin oxidation, and ventricular dysfunction. This latter finding points to a possible pathogenic role of MAO-A in human myocardial failure supporting the idea that MAO-A could be a new therapeutic target in HF. PMID:28044091

  11. Switching antipsychotics to aripiprazole or blonanserin and plasma monoamine metabolites levels in patients with schizophrenia.

    PubMed

    Miura, Itaru; Shiga, Tetsuya; Katsumi, Akihiko; Kanno-Nozaki, Keiko; Mashiko, Hirobumi; Niwa, Shin-Ichi; Yabe, Hirooki

    2014-03-01

    Blonanserin is a novel atypical antipsychotic drug that has efficacy equal to risperidone. We investigated the effects of aripiprazole and blonanserin on clinical symptoms and plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol in the switching strategy of schizophrenia. Twenty two Japanese patients with schizophrenia were enrolled into this open study. The antipsychotics of all patients were switched to aripiprazole or blonanserin for the improvement of clinical symptoms or side effects. Plasma monoamine metabolites levels were analyzed with high-performance liquid chromatography. There were no significant effects for time (p = 0.346) or time × group interaction (p = 0.27) on the changes of positive and negative syndrome scale (PANSS) total score, although blonanserin decreased PANSS scores. We observed negative correlation between pHVA at baseline and the change in PANSS total score (rs = -0.450, p = 0.046). We also found positive correlation between the changes in pHVA and the changes in PANSS total (rs = 0.536, p = 0.015) and positive (rs = 0.572, p = 0.008) scores. There were no differences between blonanserin and aripiprazole in the improvement of clinical symptoms. Our results suggest that pHVA may be useful indicator for the switching strategy to aripiprazole or blonanserin in schizophrenia. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Binding models of reversible inhibitors to type-B monoamine oxidase

    NASA Astrophysics Data System (ADS)

    Carrieri, Antonio; Carotti, Andrea; Barreca, M. Letizia; Altomare, Cosimo

    2002-11-01

    Interest in the inhibitors of type-B monoamine oxidase has grown in recent years, due to the evidence for multiple roles of one such agent (selegiline) in the pharmacological management of neurodegenerative disorders. A set of 130 reversible and selective inhibitors of MAO-B (including tetrazole, oxadiazolone, and oxadiazinone derivatives) were taken from the literature and subjected to a three-dimensional quantitative structure-activity relationship (3D-QSAR) study, using CoMFA and GOLPE procedures. The steric and lipophilic fields, alone and in combination, provided us with informative models and satisfactory predictions (q2=0.73). The validity of these models was checked against the 3D X-ray structure of human MAO-B. Flexible docking calculations, performed by using a new approach which took advantage from QXP and GRID computational tools, showed the diverse inhibitors to interact with MAO-B in a similar binding mode, irrespective of the heterocycle characterizing them. A significant trend of correlation was observed between estimated energies of the complexes and the experimental inhibition data.

  13. Platelet monoamine oxidase activity in underweight and weight-recovered females with anorexia nervosa.

    PubMed

    Ehrlich, S; Franke, L; Schott, R; Salbach-Andrae, H; Pfeiffer, E; Lehmkuhl, U; Uebelhack, R

    2008-11-01

    Central serotonergic pathways may play an important role in the etiology of anorexia nervosa (AN). Although platelet monoamine oxidase activity (MAO-B) has been proposed as an index of cerebral serotonin activity, studies in patients with AN are scarce. Platelet MAO-B activity was determined in 59 acutely underweight AN patients (acAN, aged 14-29 years, BMI=15.2+/-1.4), 35 weight-recovered AN patients (recAN, aged 15-29, BMI=20.8+/-2.2) and 59 healthy control women (HCW, aged 14-26, BMI=21.6+/-2.1). Plasma leptin served as an indicator of malnutrition. Results were compared by ANCOVA controlling for confounding variables. Platelet MAO-B activity in acAN patients (5.2+/-1.4 nmol/10 (9)pltx15 min) was similar to HCW (5.5+/-1.9) but significantly lower in recAN patients (4.4+/-1.5). BMI and leptin showed a significant negative correlation with MAO-B activity in AN patients, but not in HCW. Our results highlight the importance of malnutrition for the interpretation of abnormalities in neurotransmitter systems in AN. Whether low MAO-B activity in weight-recovered AN patients indicates a premorbid trait or a secondary change due to recovery remains to be elucidated.

  14. PACAP38 increases vesicular monoamine transporter 2 (VMAT2) expression and attenuates methamphetamine toxicity

    PubMed Central

    Guillot, TS; Richardson, JR; Wang, MZ; Li, YJ; Taylor, TN; Ciliax, BJ; Zachrisson, O; Mercer, A; Miller, GW

    2008-01-01

    Pituitary adenylyl cyclase activating polypeptide, 38 amino acids (PACAP38) is a brain-gut peptide with diverse physiological functions and is neuroprotective in several models of neurological disease. In this study, we show that systemic administration of PACAP38, which is transported across the blood-brain barrier, greatly reduces the neurotoxicity of methamphetamine (METH). Mice treated with PACAP38 exhibited an attenuation of striatal dopamine loss after METH exposure as well as greatly reduced markers of oxidative stress. PACAP38 treatment also prevented striatal neuroinflammation after METH administration as measured by overexpression of glial fibrillary acidic protein (GFAP), an indicator of astrogliosis, and glucose transporter 5 (GLUT5), a marker of microgliosis. In PACAP38 treated mice, the observed protective effects were not due to an altered thermal response to METH. Since the mice were not challenged with METH until 28 days after PACAP38 treatment, this suggests the neuroprotective effects are mediated by regulation of gene expression. At the time of METH administration, PACAP38 treated animals exhibited a preferential increase in the expression and function of the vesicular monoamine transporter (VMAT2). Genetic reduction of VMAT2 has been shown to increase the neurotoxicity of METH, thus we propose that the increased expression of VMAT2 may underlie the protective actions of PACAP38 against METH. The ability of PACAP38 to increase VMAT2 expression suggests that PACAP38 signaling pathways may constitute a novel therapeutic approach to treat and prevent disorders of dopamine storage. PMID:18533255

  15. Chromone, a privileged scaffold for the development of monoamine oxidase inhibitors.

    PubMed

    Gaspar, Alexandra; Silva, Tiago; Yáñez, Matilde; Vina, Dolores; Orallo, Franscisco; Ortuso, Francesco; Uriarte, Eugenio; Alcaro, Stefano; Borges, Fernanda

    2011-07-28

    Two series of novel chromone derivatives were synthesized and investigated for their ability to inhibit the activity of monoamine oxidase. The SAR data indicate that chromone derivatives with substituents in position 3 of γ-pyrone nucleus act preferably as MAO-B inhibitors, with IC(50) values in the nanomolar to micromolar range. Almost all chromone 3-carboxamides display selectivity toward MAO-B. Identical substitutions on position 2 of γ-pyrone nucleus result in complete loss of activity in both isoforms (chromones 2-12 except 3 and 5). Notably, chromone (19) exhibits an MAO-B IC(50) of 63 nM, greater than 1000-fold selectivity over MAO-A, and behaves as a quasi-reversible inhibitor. Docking experiments onto the MAO binding of the most active compound highlight different interaction patterns among the isoforms A and B. The differential analysis of the solvation effects among the chromone isomers gave additional insight about the superior outline of the 3-substituted chromone derivatives.

  16. Inhibition of monoamine oxidase by selected C6-substituted chromone derivatives.

    PubMed

    Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2012-03-01

    Chromone has been reported to be a useful scaffold for the design of monoamine oxidase (MAO) inhibitors. In an attempt to discover highly potent MAO inhibitors and to contribute to the known structure-activity relationships (SAR) of MAO inhibition by chromones, in the present study, we have synthesized a series of chromone derivatives substituted at C6 with a variety of alkyloxy substituents, and evaluated the resulting compounds as inhibitors of recombinant human MAO-A and -B. The results document that the C6-substituted chromones are potent reversible MAO-B inhibitors with IC(50) values in the low nM range (2-76 nM). The chromones were also found to bind reversibly to MAO-A, but with lower affinities compared to MAO-B. It may therefore be concluded that C6-substituted chromones are highly potent MAO-B selective inhibitors and promising lead compounds for the development of therapy for neurodegenerative disorders such as Parkinson's disease. The results of this study are discussed with reference to possible binding orientations of a selected C6-substituted chromone in the active site cavities of MAO-A and -B. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  17. Serotonin transporter (5-HTTLPR) and monoamine oxidase (MAOA) promoter polymorphisms in women with severe alcoholism.

    PubMed

    Gokturk, Camilla; Schultze, Stefan; Nilsson, Kent W; von Knorring, Lars; Oreland, Lars; Hallman, Jarmila

    2008-12-01

    The serotonin system is known to play a pivotal role for mood, behaviour and psychic illness as e.g. alcoholism. Alcoholism in both males and females has been associated with polymorphisms in genes encoding for proteins of importance for central serotonergic function. Genotyping of two functional polymorphisms in the promoter region of the serotonin transporter and monoamine oxidase-A, respectively, (5-HTT-LPR and MAOA-VNTR), was performed in a group of women with severe alcohol addiction. A large sample of adolescent females from a normal population was used as controls. A significantly higher frequency of the LL 5-HTT genotype (high activity) was found in female addicts without a known co-morbid psychiatric disorder than in the controls. Genotype of the MAOA-VNTR polymorphism did not differ significantly between addicts and controls. However, within the group of alcoholics, when the patients with known co-morbid psychiatric disorders were excluded, aggressive anti-social behaviour was significantly linked to the presence of the high activity MAOA allele. The pattern of associations between genotypes of 5-HTT-LPR and MAOA-VNTR in women with severe alcoholism differs from most corresponding studies on males.

  18. Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo

    PubMed Central

    Lohr, Kelly M.; Bernstein, Alison I.; Stout, Kristen A.; Dunn, Amy R.; Lazo, Carlos R.; Alter, Shawn P.; Wang, Minzheng; Li, Yingjie; Fan, Xueliang; Hess, Ellen J.; Yi, Hong; Vecchio, Laura M.; Goldstein, David S.; Guillot, Thomas S.; Salahpour, Ali; Miller, Gary W.

    2014-01-01

    Disruption of neurotransmitter vesicle dynamics (transport, capacity, release) has been implicated in a variety of neurodegenerative and neuropsychiatric conditions. Here, we report a novel mouse model of enhanced vesicular function via bacterial artificial chromosome (BAC)-mediated overexpression of the vesicular monoamine transporter 2 (VMAT2; Slc18a2). A twofold increase in vesicular transport enhances the vesicular capacity for dopamine (56%), dopamine vesicle volume (33%), and basal tissue dopamine levels (21%) in the mouse striatum. The elevated vesicular capacity leads to an increase in stimulated dopamine release (84%) and extracellular dopamine levels (44%). VMAT2-overexpressing mice show improved outcomes on anxiety and depressive-like behaviors and increased basal locomotor activity (41%). Finally, these mice exhibit significant protection from neurotoxic insult by the dopaminergic toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as measured by reduced dopamine terminal damage and substantia nigra pars compacta cell loss. The increased release of dopamine and neuroprotection from MPTP toxicity in the VMAT2-overexpressing mice suggest that interventions aimed at enhancing vesicular capacity may be of therapeutic benefit in Parkinson disease. PMID:24979780

  19. Prenatal exposure to ozone disrupts cerebellar monoamine contents in newborn rats.

    PubMed

    Gonzalez-Pina, Rigoberto; Escalante-Membrillo, Carmen; Alfaro-Rodriguez, Alfonso; Gonzalez-Maciel, Angelica

    2008-05-01

    Ozone (O3) is widely distributed in environments with high levels of air pollution. Since cerebellar morphologic disruptions have been reported with prenatal O3 exposure, O3 may have an effect on some neurotransmitter systems, such as monoamines. In order to test this hypothesis, we used 60 male rats taken from either, mothers exposed to 1 ppm of O3 during the entire pregnancy, or from mothers breathing filtered and clean air during pregnancy. The cerebellum was extracted at 0, 5, and 10 postnatal days. Tissues were processed in order to analyze by HPLC, dopamine (DA) levels, 3,4 dihydroxyphenilacetic acid (DOPAC) and homovanillic acid (HVA), norepinephrine (NA), serotonin, and 5-hydroxy-indole-acetic acid (5-HIAA) contents. Results showed a decrease of DA, NA, DOPAC and HVA mainly in 0 and 5 postnatal days. There were no changes in 5-HT levels, and 5-HIAA showed an increase after 10 postnatal days. DOPAC + HVA/DA ratio showed changes in 0 and 10 postnatal days, while 5-HIAA/5-HT ratio showed a slight decrease in 0 days. The data suggest that prenatal O3 exposure disrupts the cerebellar catecholamine system rather than the indole-amine system. Disruptions in cerebellar NA could lead to ataxic symptoms and also could limit recovery after cortical brain damage in adults. These finding are important given that recovery mechanisms observed in animals are also observed in humans.

  20. Biosensor based on inhibition of monoamine oxidases A and B for detection of β-carbolines.

    PubMed

    Radulescu, Maria-Cristina; Bucur, Madalina-Petruta; Bucur, Bogdan; Radu, Gabriel Lucian

    2015-05-01

    β-Carbolines are inhibitors of monoamine oxidases (MAO-A and MAO-B) and can be found in foods, hallucinogenic plant or various drugs. We have developed a fast analysis method for β-carbolines based on the inhibition of MAO. The enzymes were immobilized on screen-printed electrodes modified with a stabilized film of Prussian blue that contain also copper. We have used benzylamine as substrate for the enzymatic reaction and the hydrogen peroxide was measured amperometrically at -50 mV. The detection limits obtained were 5.0 µM for harmane and 2.5 µM for both harmaline and norharmane. The MAO-A is inhibited by all three tested β-carbolines (harmane, norharmane, and harmaline) while MAO-B is inhibited only by norharmane. The presence of norharmane in mixtures of β-carbolines can be identified based on the difference between the cumulative inhibition of MAO-A by all β-carbolines and MAO-B inhibition. The developed biosensors were used for food analysis.

  1. Indazole- and indole-5-carboxamides: selective and reversible monoamine oxidase B inhibitors with subnanomolar potency.

    PubMed

    Tzvetkov, Nikolay T; Hinz, Sonja; Küppers, Petra; Gastreich, Marcus; Müller, Christa E

    2014-08-14

    Indazole- and indole-carboxamides were discovered as highly potent, selective, competitive, and reversible inhibitors of monoamine oxidase B (MAO-B). The compounds are easily accessible by standard synthetic procedures with high overall yields. The most potent derivatives were N-(3,4-dichlorophenyl)-1-methyl-1H-indazole-5-carboxamide (38a, PSB-1491, IC50 human MAO-B 0.386 nM, >25000-fold selective versus MAO-A) and N-(3,4-dichlorophenyl)-1H-indole-5-carboxamide (53, PSB-1410, IC50 human MAO-B 0.227 nM, >5700-fold selective versus MAO-A). Replacement of the carboxamide linker with a methanimine spacer leading to (E)-N-(3,4-dichlorophenyl)-1-(1H-indazol-5-yl)methanimine (58) represents a further novel class of highly potent and selective MAO-B inhibitors (IC50 human MAO-B 0.612 nM, >16000-fold selective versus MAO-A). In N-(3,4-difluorophenyl-1H-indazole-5-carboxamide (30, PSB-1434, IC50 human MAO-B 1.59 nM, selectivity versus MAO-A>6000-fold), high potency and selectivity are optimally combined with superior physicochemical properties. Computational docking studies provided insights into the inhibitors' interaction with the enzyme binding site and a rationale for their high potency despite their small molecular size.

  2. Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug.

    PubMed

    Sharpe, Martyn A; Livingston, Andrew D; Gist, Taylor L; Ghosh, Pardip; Han, Junyan; Baskin, David S

    2015-09-01

    The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P(+)-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models.

  3. beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO).

    PubMed

    Herraiz, T; González, D; Ancín-Azpilicueta, C; Arán, V J; Guillén, H

    2010-03-01

    Peganum harmala L. is a multipurpose medicinal plant increasingly used for psychoactive recreational purposes (Ayahuasca analog). Harmaline, harmine, harmalol, harmol and tetrahydroharmine were identified and quantified as the main beta-carboline alkaloids in P. harmala extracts. Seeds and roots contained the highest levels of alkaloids with low levels in stems and leaves, and absence in flowers. Harmine and harmaline accumulated in dry seeds at 4.3% and 5.6% (w/w), respectively, harmalol at 0.6%, and tetrahydroharmine at 0.1% (w/w). Roots contained harmine and harmol with 2.0% and 1.4% (w/w), respectively. Seed extracts were potent reversible and competitive inhibitors of human monoamine oxidase (MAO-A) with an IC(50) of 27 microg/l whereas root extracts strongly inhibited MAO-A with an IC(50) of 159 microg/l. In contrast, they were poor inhibitors of MAO-B. Inhibition of MAO-A by seed extracts was quantitatively attributed to harmaline and harmine whereas inhibition by root extracts came from harmine with no additional interferences. Stems and leaves extracts were poor inhibitors of MAO. The potent inhibition of MAO-A by seed and root extracts of P. harmala containing beta-carbolines should contribute to the psychopharmacological and toxicological effects of this plant and could be the basis for its purported antidepressant actions.

  4. Inhibition of rat fat cell lipolysis by monoamine oxidase and semicarbazide-sensitive amine oxidase substrates.

    PubMed

    Visentin, Virgile; Prévot, Danielle; Marti, Luc; Carpéné, Christian

    2003-04-18

    It has been demonstrated that amine oxidase substrates stimulate glucose transport in cardiomyocytes and adipocytes, promote adipogenesis in pre-adipose cell lines and lower blood glucose in diabetic rats. These insulin-like effects are dependent on amine oxidation by semicarbazide-sensitive amine oxidase or by monoamine oxidase. The present study aimed to investigate whether amine oxidase substrates also exhibit another insulin-like property, the inhibition of lipolysis. We therefore tested the influence of tyramine and benzylamine on lipolytic activity in rat adipocytes. These amines did not modify basal lipolysis but dose-dependently counteracted the stimulation induced by lipolytic agents. The response to 10 nM isoprenaline was totally inhibited by tyramine 1 mM. The blockade produced by inhibition of amine oxidase activity or by 1 mM glutathione suggested that the generation of oxidative species, which occurs during amine oxidation, was involved in tyramine antilipolytic effect. Among the products resulting from amine oxidation, only hydrogen peroxide was antilipolytic in a manner that was potentiated by vanadate, as for tyramine or benzylamine. Antilipolytic responses to tyramine and to insulin were sensitive to wortmannin. These data suggest that inhibition of lipolysis is a novel insulin-like effect of amine oxidase substrates which is mediated by hydrogen peroxide generated during amine oxidation.

  5. Monoamine oxidase A genotype, childhood adversity, and criminal behavior in an incarcerated sample.

    PubMed

    Armstrong, Todd A; Boutwell, Brian B; Flores, Shahida; Symonds, Mary; Keller, Shawn; Gangitano, David A

    2014-08-01

    A number of studies have found a functional variable number tandem repeat polymorphism in the upstream regulatory region of the monoamine oxidase A gene (MAOA-uVNTR) interacts with childhood adversity to increase risk for antisocial behavior. Several studies have also reported null findings. Here, we examine the association between MAOA-uVNTR genotype, childhood adversity, and criminal activity in a sample of 99 male volunteers who were incarcerated in a large city jail in the Southern United States. MAOA-uVNTR genotypes were obtained from DNA extracted from buccal swabs. Criminal activity in the year before incarceration and childhood adversity were measured with self-report surveys. Violent arrest rates and property arrest rates were quantified with official records of arrest and accounted for periods of incarceration in local and state correctional facilities. The low expressing allele of the MAOA-uVNTR genotype (MAOAL) interacted with abuse to predict self-reports of less serious criminal and delinquent behavior and had a direct association with serious criminal activity. MAOAL genotype interacted with parental criminality to predict self-reports of serious criminal behavior, property arrest rates, and violent arrest rates. The findings suggest that crime prevention efforts may be improved through attention to the neurodevelopmental consequence of gene-by-environment interactions.

  6. Loss of striatal vesicular monoamine transporter protein (VMAT2) in human cocaine users.

    PubMed

    Little, Karley Y; Krolewski, David M; Zhang, Lian; Cassin, Bader J

    2003-01-01

    The hypothesis that human cocaine users lose vesicular monoamine transporter (VMAT2) protein was tested in striatal samples from cocaine users and age-, sex-, and postmortem interval-matched comparison subjects. Striatal samples were retrieved at autopsy; immunoblot assays were then performed by using a highly specific VMAT2 antibody. Striatal radioligand binding to VMAT2 was assessed with dihydrotetrabenazine ([(3)H]DTBZ) and dopamine levels employing high-performance liquid chromatography. Cocaine users displayed a marked reduction in VMAT2 immunoreactivity as well as reduced [(3)H]DTBZ binding and dopamine levels. It did not appear that the reduction in VMAT2 immunoreactivity was related to ethanol use, but dopamine levels were lower in subjects with only ethanol diagnoses. Subjects suffering from cocaine-induced mood disorders displayed a greater loss of VMAT2 immunoreactivity that approached significance. Human cocaine users lose VMAT2 protein, which might reflect damage to striatal dopamine fibers. These neuronal changes could play a role in causing disordered mood and motivational processes in more severely dependent patients.

  7. Platelet monoamine oxidase activity is related to MAOB intron 13 genotype.

    PubMed

    Garpenstrand, H; Ekblom, J; Forslund, K; Rylander, G; Oreland, L

    2000-01-01

    Monoamine oxidases (MAO) play a critical role in the degradation of endogenous and exogenous amines throughout the body. There are two distinct MAO isoforms, MAO-A and MAO-B, which both are encoded in genes on the X chromosome. Alterations in MAO-B activity have previously been connected with several neurological disorders. Platelet MAO (trbc-MAO) is exclusively of the B-type and the catalytic activity of this enzyme is under strong, yet unknown, genetic control. Specific trbc-MAO activity has been reported to be increased in certain neurodegenerative diseases and to correlate with personality traits such as sensation seeking and impulsiveness. In the present study, we investigated if trbc-MAO activity is associated with genotype at a variable region (A/G dimorphism) in intron 13 of the human gene encoding MAO-B. The MAOB intron 13 allele status and levels of trbc-MAO were determined for 55 Caucasian non-smoking males. Individuals with the "A-allele" displayed significantly lower enzyme activity than individuals with the "G-allele", i.e. 11.4 +/- 0.6 nmol/10(10) platelets/min compared with 13.5 +/- 0.6 (mean +/- SEM, p = 0.019). The present results suggest that the MAOB genotype may be involved in determining trbc-MAO activity.

  8. Amphetamine and LSD as discriminative stimuli: alterations following neonatal monoamine reductions.

    PubMed

    Minnema, D J; Rosecrans, J A

    1984-01-01

    Male adult Sprague-Dawley rats (70 days of age), neonatally depleted of either 5-hydroxytryptamine (5HT) via 5,7-dihydroxytryptamine (5,7-DHT; ICS) + desmethylimipramine (DMI; IP) at 3 days of age or dopamine (DA) via 6-hydroxydopamine (6-OHDA; ICS) + DMI at 14 days of age, were trained to discriminate either d-LSD-tartrate (80 micrograms/kg; IP) or d-amphetamine (d-AMPH) sulfate (0.90 mg/kg; IP) from saline utilizing a two lever drug discrimination paradigm. A neurochemical analysis at the termination of these studies revealed the following in terms of %DA or %5HT (presented in that order) depleted with respect to the appropriate vehicle control group: telencephalon; 96 and 96%, diencephalon; 51 and 31%, and brain stem; 76 and 80%. Rats learned to discriminate either d-AMPH or LSD regardless of amine depleted. In addition, the depletion of 5HT had little effects on dose or drug generalizations, or the ability of known antagonists to antagonize the discrimination stimulus (DS) effects of either LSD or d-AMPH. The effect of DA depletion, on the other hand, was to increase the sensitivity of the LSD DS at low doses, while decreasing the sensitivity of the d-amphetamine DS. DA depletion also had the effect of reducing the effectiveness of the LSD-antagonists, pizotifen maleate (BC105), while the opposite was observed for the d-AMPH antagonist, trifluoperazine HCI. These data suggest that: (1) LSD and d-amphetamine discrimination stimuli are not mediated and/or influenced via the compromised aspects of the 5HT systems (other central mechanisms may have compromised for these 5HT deficits); (2) the LSD DS is mediated or influenced both by serotonergic and dopaminergic mechanisms; and (3) the d-amphetamine DS is mediated by certain aspects of the dopaminergic system with little evidence for the involvement of 5HT systems.

  9. A worldwide view of groundwater depletion

    NASA Astrophysics Data System (ADS)

    van Beek, L. P.; Wada, Y.; van Kempen, C.; Reckman, J. W.; Vasak, S.; Bierkens, M. F.

    2010-12-01

    During the last decades, global water demand has increased two-fold due to increasing population, expanding irrigated area and economic development. Globally such demand can be met by surface water availability (i.e., water in rivers, lakes and reservoirs) but regional variations are large and the absence of sufficient rainfall and run-off increasingly encourages the use of groundwater resources, particularly in the (semi-)arid regions of the world. Excessive abstraction for irrigation frequently leads to overexploitation, i.e. if groundwater abstraction exceeds the natural groundwater recharge over extensive areas and prolonged times, persistent groundwater depletion may occur. Observations and various regional studies have revealed that groundwater depletion is a substantial issue in regions such as Northwest India, Northeast Pakistan, Central USA, Northeast China and Iran. Here we provide a global overview of groundwater depletion from the year 1960 to 2000 at a spatial resolution of 0.5 degree by assessing groundwater recharge with the global hydrological model PCR-GLOBWB and subtracting estimates of groundwater abstraction obtained from IGRAC-GGIS database. PCR-GLOBWB was forced by the CRU climate dataset downscaled to daily time steps using ERA40 re-analysis data. PCR-GLOBWB simulates daily global groundwater recharge (0.5 degree) while considering sub-grid variability of each grid cell (e.g., short and tall vegetation, different soil types, fraction of saturated soil). Country statistics of groundwater abstraction were downscaled to 0.5 degree by using water demand (i.e., agriculture, industry and domestic) as a proxy. To limit problems related to increased capture of discharge and increased recharge due to groundwater pumping, we restricted our analysis to sub-humid to arid areas. The uncertainty in the resulting estimates was assessed by a Monte Carlo analysis of 100 realizations of groundwater recharge and 100 realizations of groundwater abstraction

  10. Iron isotope composition of depleted MORB

    NASA Astrophysics Data System (ADS)

    Labidi, J.; Sio, C. K. I.; Shahar, A.

    2015-12-01

    In terrestrial basalts, iron isotope ratios are observed to weakly fractionate as a function of olivine and pyroxene crystallization. However, a ~0.1‰ difference between chondrites and MORB had been reported (Dauphas et al. 2009, Teng et al. 2013 and ref. therein). This observation could illustrate an isotope fractionation occurring during partial melting, as a function of the Fe valence in melt versus crystals. Here, we present high-precision Fe isotopic data measured by MC-ICP-MS on well-characterized samples from the Pacific-Antarctic Ridge (PAR, n=9) and from the Garrett Transform Fault (n=8). These samples allow exploring the Fe isotope fractionation between melt and magnetite, and the role of partial melting on Fe isotope fractionation. Our average δ56Fe value is +0.095±0.013‰ (95% confidence, n=17), indistinguishable from a previous estimate of +0.105±0.006‰ (95% confidence, n=43, see ref. 2). Our δ56Fe values correlate weakly with MgO contents, and correlate positively with K/Ti ratios. PAC1 DR10 shows the largest Ti and Fe depletion after titanomagnetite fractionation, with a δ56Fe value of +0.076±0.036‰. This is ~0.05‰ below other samples at a given MgO. This may illustrate a significant Fe isotope fractionation between the melt and titanomagnetite, in agreement with experimental determination (Shahar et al. 2008). GN09-02, the most incompatible-element depleted sample, has a δ56Fe value of 0.037±0.020‰. This is the lowest high-precision δ56Fe value recorded for a MORB worldwide. This basalt displays an incompatible-element depletion consistent with re-melting beneath the transform fault of mantle source that was depleted during a first melting event, beneath the ridge axis (Wendt et al. 1999). The Fe isotope observation could indicate that its mantle source underwent 56Fe depletion after a first melting event. It could alternatively indicate a lower Fe isotope fractionation during re-melting, if the source was depleted of its Fe3

  11. Copenhagen delegates advance phaseout of ozone depleters

    SciTech Connect

    Kirschner, E.

    1992-12-09

    As expected, delegates at the United Nations Ozone Layer Conference in Copenhagen sped up ozone depleter phaseouts from the 1987 Montreal Protocol and the 1990 London amendments. The changes bring the worldwide production phaseout of chlorofluorocarbons (CFCs) and other ozone depleters in developed countries in line with U.S. and European plans announced earlier this year. Adjustments to the protocol, which are binding on the signatories, change the phaseout for CFC, carbon tetrachloride, and methyl chloroform production and consumption to January 1, 1996 from 2000. The 75% reduction of 1986 levels from CFCs by January 1, 1994 is a compromise between European pressure for an 85% cut and the US goal of 70%. Halon production is to end January 1, 1994, as anticipated. Developing countries continue to have a 10-year grace period. Friends of the Earth ozone campaign director Liz Cook counters that the phaseout dates were scheduled with concern for the chemical industry, not for the ozone layer.

  12. Replacements For Ozone-Depleting Foaming Agents

    NASA Technical Reports Server (NTRS)

    Blevins, Elana; Sharpe, Jon B.

    1995-01-01

    Fluorinated ethers used in place of chlorofluorocarbons and hydrochlorofluorocarbons. Replacement necessary because CFC's and HCFC's found to contribute to depletion of ozone from upper atmosphere, and manufacture and use of them by law phased out in near future. Two fluorinated ethers do not have ozone-depletion potential and used in existing foam-producing equipment, designed to handle liquid blowing agents soluble in chemical ingredients that mixed to make foam. Any polyurethane-based foams and several cellular plastics blown with these fluori