Octopamine: Presence in Single Neurons of Aplysia Suggests Neurotransmitter Function

DTIC Science & Technology

1974-10-01

responsive to octopamine than 2 any other phenylethylamine . All of these observations indicate that octopamine may function as a neurotransmitter...B., Landsberg, L. and Axelrod, J. An enzymatic assay for octop- amine and other g-hydroxylated phenylethylamines . J. Pharmacol. Exptl. Ther

Control of Biogenic Amines in Food—Existing and Emerging Approaches

PubMed Central

Naila, Aishath; Flint, Steve; Fletcher, Graham; Bremer, Phil; Meerdink, Gerrit

2010-01-01

Biogenic amines have been reported in a variety of foods, such as fish, meat, cheese, vegetables, and wines. They are described as low molecular weight organic bases with aliphatic, aromatic, and heterocyclic structures. The most common biogenic amines found in foods are histamine, tyramine, cadaverine, 2-phenylethylamine, spermine, spermidine, putrescine, tryptamine, and agmatine. In addition octopamine and dopamine have been found in meat and meat products and fish. The formation of biogenic amines in food by the microbial decarboxylation of amino acids can result in consumers suffering allergic reactions, characterized by difficulty in breathing, itching, rash, vomiting, fever, and hypertension. Traditionally, biogenic amine formation in food has been prevented, primarily by limiting microbial growth through chilling and freezing. However, for many fishing based subsistence populations, such measures are not practical. Therefore, secondary control measures to prevent biogenic amine formation in foods or to reduce their levels once formed need to be considered as alternatives. Such approaches to limit microbial growth may include hydrostatic pressures, irradiation, controlled atmosphere packaging, or the use of food additives. Histamine may potentially be degraded by the use of bacterial amine oxidase or amine-negative bacteria. Only some will be cost-effective and practical for use in subsistence populations. PMID:21535566

Biogenic amines in the nervous system of the cockroach, Periplaneta americana following envenomation by the jewel wasp, Ampulex compressa.

PubMed

Banks, Christopher N; Adams, Michael E

2012-02-01

The emerald jewel wasp, Ampulex compressa, exploits the American cockroach, Periplaneta americana, as a host for its progeny. The wasp subdues the host by stinging directly into the brain and subesophageal ganglion, inducing long-term hypokinesia. The hypokinesic host lacks normal escape behavior and motivation to walk, making it easy for subjugation by the wasp. The mechanism underlying hypokinesia induction is not known, but depletion of monoamines induces behavior resembling venom-induced hypokinesia. To test whether amine depletion occurs in stung animals, we used high-performance liquid chromatography with electrochemical detection (HPLC-ED) to measure quantitatively amine levels in the central nervous system. Our data show clearly that levels of dopamine, serotonin, octopamine and tyramine remain unchanged in stung animals, whereas animals treated with reserpine exhibited marked depletion of all amines sampled. Furthermore, stung animals treated with reserpine show depletion of amines, demonstrating that envenomation also does not interfere with amine release. These results show that hypokinesia induced by Ampulex venom does not result from amine depletion or inability to release monoamines in the central nervous system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Molecular, pharmacological, and signaling properties of octopamine receptors from honeybee (Apis mellifera) brain.

PubMed

Balfanz, Sabine; Jordan, Nadine; Langenstück, Teresa; Breuer, Johanna; Bergmeier, Vera; Baumann, Arnd

2014-04-01

G protein-coupled receptors are important regulators of cellular signaling processes. Within the large family of rhodopsin-like receptors, those binding to biogenic amines form a discrete subgroup. Activation of biogenic amine receptors leads to transient changes of intracellular Ca²⁺-([Ca²⁺](i)) or 3',5'-cyclic adenosine monophosphate ([cAMP](i)) concentrations. Both second messengers modulate cellular signaling processes and thereby contribute to long-lasting behavioral effects in an organism. In vivo pharmacology has helped to reveal the functional effects of different biogenic amines in honeybees. The phenolamine octopamine is an important modulator of behavior. Binding of octopamine to its receptors causes elevation of [Ca²⁺](i) or [cAMP](i). To date, only one honeybee octopamine receptor that induces Ca²⁺ signals has been molecularly and pharmacologically characterized. Here, we examined the pharmacological properties of four additional honeybee octopamine receptors. When heterologously expressed, all receptors induced cAMP production after binding to octopamine with EC₅₀(s) in the nanomolar range. Receptor activity was most efficiently blocked by mianserin, a substance with antidepressant activity in vertebrates. The rank order of inhibitory potency for potential receptor antagonists was very similar on all four honeybee receptors with mianserin > cyproheptadine > metoclopramide > chlorpromazine > phentolamine. The subroot of octopamine receptors activating adenylyl cyclases is the largest that has so far been characterized in arthropods, and it should now be possible to unravel the contribution of individual receptors to the physiology and behavior of honeybees. © 2013 International Society for Neurochemistry.

Consumption of tyrosine in royal jelly increases brain levels of dopamine and tyramine and promotes transition from normal to reproductive workers in queenless honey bee colonies.

PubMed

Matsuyama, Syuhei; Nagao, Takashi; Sasaki, Ken

2015-01-15

Dopamine (DA) and tyramine (TA) have neurohormonal roles in the production of reproductive workers in queenless colonies of honey bees, but the regulation of these biogenic amines in the brain are still largely unclear. Nutrition is an important factor in promoting reproduction and might be involved in the regulation of these biogenic amines in the brain. To test this hypothesis, we examined the effect of oral treatments of tyrosine (Tyr; a common precursor of DA, TA and octopamine, and a component of royal jelly) in queenless workers and quantified the resulting production of biogenic amines. Tyrosine treatments enhanced the levels of DA, TA and their metabolites in the brain. Workers fed royal jelly had significantly larger brain levels of Tyr, DA, TA and the metabolites in the brains compared with those bees fed honey or sucrose (control). Treatment with Tyr also inhibited the behavior of workers outside of the hive and promoted ovarian development. These results suggest that there is a link between nutrition and the regulation of DA and TA in the brain to promote the production of reproductive workers in queenless honey bee colonies. Copyright © 2014 Elsevier Inc. All rights reserved.

Radioenzymatic analysis of neurotransmitters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Philips, S.R.

Since the late 1960's, radioenzymatic assays have gradually come to replace the less sensitive and less specific spectrofluorometric and bioassay procedures previously used to determine many of the neurotransmitters. These assays provide the means to measure picogram quantities of most of these substances, and have enabled determinations to be made in very small volumes of body fluids, in brain perfusates and individual brain nuclei, and in large individual cells of some simple animals. This paper reviews briefly some of the radioenzymatic techniques presently available for assaying norepinephrine (NE), epinephrine (E), dopamine (DA), serotonin, and the trace amines octopamine (OA), phenylethanolaminemore » (PEOHA), phenylethylamine (PEA), tyramine (TA) and tryptamine (T).« less

Antagonistic Serotonergic and Octopaminergic Neural Circuits Mediate Food-Dependent Locomotory Behavior in Caenorhabditis elegans

PubMed Central

McCloskey, Richard J.; Peters, Emily

2017-01-01

Biogenic amines are conserved signaling molecules that link food cues to behavior and metabolism in a wide variety of organisms. In the nematode Caenorhabditis elegans, the biogenic amines serotonin (5-HT) and octopamine regulate a number of food-related behaviors. Using a novel method for long-term quantitative behavioral imaging, we show that 5-HT and octopamine jointly influence locomotor activity and quiescence in feeding and fasting hermaphrodites, and we define the neural circuits through which this modulation occurs. We show that 5-HT produced by the ADF neurons acts via the SER-5 receptor in muscles and neurons to suppress quiescent behavior and promote roaming in fasting worms, whereas 5-HT produced by the NSM neurons acts on the MOD-1 receptor in AIY neurons to promote low-amplitude locomotor behavior characteristic of well fed animals. Octopamine, produced by the RIC neurons, acts via SER-3 and SER-6 receptors in SIA neurons to promote roaming behaviors characteristic of fasting animals. We find that 5-HT signaling is required for animals to assume food-appropriate behavior, whereas octopamine signaling is required for animals to assume fasting-appropriate behavior. The requirement for both neurotransmitters in both the feeding and fasting states enables increased behavioral adaptability. Our results define the molecular and neural pathways through which parallel biogenic amine signaling tunes behavior appropriately to nutrient conditions. SIGNIFICANCE STATEMENT Animals adjust behavior in response to environmental changes, such as fluctuations in food abundance, to maximize survival and reproduction. Biogenic amines, such as like serotonin, are conserved neurotransmitters that regulate behavior and metabolism in relation to energy status. Disruptions of biogenic amine signaling contribute to human neurological diseases of mood, appetite, and movement. In this study, we investigated the roles of the biogenic amines serotonin and octopamine in regulating locomotion behaviors associated with feeding and fasting in the roundworm Caenorhabditis elegans. We identified neural circuits through which these signals work to govern behavior. Understanding the molecular pathways through which biogenic amines function in model organisms may improve our understanding of dysfunctions of appetite and behavior found in mammals, including humans. PMID:28698386

Serotonin-induced mate rejection in the female cabbage butterfly, Pieris rapae crucivora

NASA Astrophysics Data System (ADS)

Obara, Yoshiaki; Fukano, Yuya; Watanabe, Kenta; Ozawa, Gaku; Sasaki, Ken

2011-11-01

Virgin female cabbage butterflies, Pieris rapae crucivora, accept and mate with courting males, whereas mated females reject them and assume the "mate refusal posture". This study tested whether the biogenic amines, serotonin (5HT), dopamine (DA), and octopamine (OA), were responsible for this change in behavior. The results showed that 2-3-day-old virgin females fed with 5HT rejected courting males significantly more frequently compared with controls fed on sucrose. In contrast, the proportions of courting males rejected by virgin females fed with either DA or OA did not differ from sucrose-fed controls. Oral application of each amine resulted in significantly increased levels of the amine applied (or its metabolite) in the brain. The results strongly suggest that 5HT or a 5HT metabolite may be responsible for the post-mating change in behavioral response of 2-3-day-old virgin females to courting males. Similar effects of 5HT treatment were observed in 6-8-day-old virgin females, but in this case the results were only marginally different from the controls, suggesting that the effect may decline with increasing female age.

Roles of Octopamine and Dopamine Neurons for Mediating Appetitive and Aversive Signals in Pavlovian Conditioning in Crickets

PubMed Central

Mizunami, Makoto; Matsumoto, Yukihisa

2017-01-01

Revealing neural systems that mediate appetite and aversive signals in associative learning is critical for understanding the brain mechanisms controlling adaptive behavior in animals. In mammals, it has been shown that some classes of dopamine neurons in the midbrain mediate prediction error signals that govern the learning process, whereas other classes of dopamine neurons control execution of learned actions. In this review, based on the results of our studies on Pavlovian conditioning in the cricket Gryllus bimaculatus and by referring to the findings in honey bees and fruit-flies, we argue that comparable aminergic systems exist in the insect brain. We found that administrations of octopamine (the invertebrate counterpart of noradrenaline) and dopamine receptor antagonists impair conditioning to associate an olfactory or visual conditioned stimulus (CS) with water or sodium chloride solution (appetitive or aversive unconditioned stimulus, US), respectively, suggesting that specific octopamine and dopamine neurons mediate appetitive and aversive signals, respectively, in conditioning in crickets. These findings differ from findings in fruit-flies. In fruit-flies, appetitive and aversive signals are mediated by different dopamine neuron subsets, suggesting diversity in neurotransmitters mediating appetitive signals in insects. We also found evidences of “blocking” and “auto-blocking” phenomena, which suggested that the prediction error, the discrepancy between actual US and predicted US, governs the conditioning in crickets and that octopamine neurons mediate prediction error signals for appetitive US. Our studies also showed that activations of octopamine and dopamine neurons are needed for the execution of an appetitive conditioned response (CR) and an aversive CR, respectively, and we, thus, proposed that these neurons mediate US prediction signals that drive appetitive and aversive CRs. Our findings suggest that the basic principles of functioning of aminergic systems in associative learning, i.e., to transmit prediction error signals for conditioning and to convey US prediction signals for execution of CR, are conserved among insects and mammals, on account of the fact that the organization of the insect brain is much simpler than that of the mammalian brain. Further investigation of aminergic systems that govern associative learning in insects should lead to a better understanding of commonalities and diversities of computational rules underlying associative learning in animals. PMID:29311961

Roles of Octopamine and Dopamine Neurons for Mediating Appetitive and Aversive Signals in Pavlovian Conditioning in Crickets.

PubMed

Mizunami, Makoto; Matsumoto, Yukihisa

2017-01-01

Revealing neural systems that mediate appetite and aversive signals in associative learning is critical for understanding the brain mechanisms controlling adaptive behavior in animals. In mammals, it has been shown that some classes of dopamine neurons in the midbrain mediate prediction error signals that govern the learning process, whereas other classes of dopamine neurons control execution of learned actions. In this review, based on the results of our studies on Pavlovian conditioning in the cricket Gryllus bimaculatus and by referring to the findings in honey bees and fruit-flies, we argue that comparable aminergic systems exist in the insect brain. We found that administrations of octopamine (the invertebrate counterpart of noradrenaline) and dopamine receptor antagonists impair conditioning to associate an olfactory or visual conditioned stimulus (CS) with water or sodium chloride solution (appetitive or aversive unconditioned stimulus, US), respectively, suggesting that specific octopamine and dopamine neurons mediate appetitive and aversive signals, respectively, in conditioning in crickets. These findings differ from findings in fruit-flies. In fruit-flies, appetitive and aversive signals are mediated by different dopamine neuron subsets, suggesting diversity in neurotransmitters mediating appetitive signals in insects. We also found evidences of "blocking" and "auto-blocking" phenomena, which suggested that the prediction error, the discrepancy between actual US and predicted US, governs the conditioning in crickets and that octopamine neurons mediate prediction error signals for appetitive US. Our studies also showed that activations of octopamine and dopamine neurons are needed for the execution of an appetitive conditioned response (CR) and an aversive CR, respectively, and we, thus, proposed that these neurons mediate US prediction signals that drive appetitive and aversive CRs. Our findings suggest that the basic principles of functioning of aminergic systems in associative learning, i.e., to transmit prediction error signals for conditioning and to convey US prediction signals for execution of CR, are conserved among insects and mammals, on account of the fact that the organization of the insect brain is much simpler than that of the mammalian brain. Further investigation of aminergic systems that govern associative learning in insects should lead to a better understanding of commonalities and diversities of computational rules underlying associative learning in animals.

Octopamine modulates honey bee dance behavior.

PubMed

Barron, Andrew B; Maleszka, Ryszard; Vander Meer, Robert K; Robinson, Gene E

2007-01-30

Honey bees communicate the location and desirability of valuable forage sites to their nestmates through an elaborate, symbolic "dance language." The dance language is a uniquely complex communication system in invertebrates, and the neural mechanisms that generate dances are largely unknown. Here we show that treatments with controlled doses of the biogenic amine neuromodulator octopamine selectively increased the reporting of resource value in dances by forager bees. Oral and topical octopamine treatments modulated aspects of dances related to resource profitability in a dose-dependent manner. Dances for pollen and sucrose responded similarly to octopamine treatment, and these effects were eliminated by treatment with the octopamine antagonist mianserin. We propose that octopamine modulates the representation of floral rewards in dances by changing the processing of reward in the honey bee brain. Octopamine is known to modulate appetitive behavior in a range of solitary insects; the role of octopamine in dance provides an example of how neural substrates can be adapted for new behavioral innovations in the process of social evolution.

Octopamine modulates honey bee dance behavior

PubMed Central

Barron, Andrew B.; Maleszka, Ryszard; Vander Meer, Robert K.; Robinson, Gene E.

2007-01-01

Honey bees communicate the location and desirability of valuable forage sites to their nestmates through an elaborate, symbolic “dance language.” The dance language is a uniquely complex communication system in invertebrates, and the neural mechanisms that generate dances are largely unknown. Here we show that treatments with controlled doses of the biogenic amine neuromodulator octopamine selectively increased the reporting of resource value in dances by forager bees. Oral and topical octopamine treatments modulated aspects of dances related to resource profitability in a dose-dependent manner. Dances for pollen and sucrose responded similarly to octopamine treatment, and these effects were eliminated by treatment with the octopamine antagonist mianserin. We propose that octopamine modulates the representation of floral rewards in dances by changing the processing of reward in the honey bee brain. Octopamine is known to modulate appetitive behavior in a range of solitary insects; the role of octopamine in dance provides an example of how neural substrates can be adapted for new behavioral innovations in the process of social evolution. PMID:17237217

Cocaine affects foraging behaviour and biogenic amine modulated behavioural reflexes in honey bees.

PubMed

Søvik, Eirik; Even, Naïla; Radford, Catherine W; Barron, Andrew B

2014-01-01

In humans and other mammals, drugs of abuse alter the function of biogenic amine pathways in the brain leading to the subjective experience of reward and euphoria. Biogenic amine pathways are involved in reward processing across diverse animal phyla, however whether cocaine acts on these neurochemical pathways to cause similar rewarding behavioural effects in animal phyla other than mammals is unclear. Previously, it has been shown that bees are more likely to dance (a signal of perceived reward) when returning from a sucrose feeder after cocaine treatment. Here we examined more broadly whether cocaine altered reward-related behaviour, and biogenic amine modulated behavioural responses in bees. Bees developed a preference for locations at which they received cocaine, and when foraging at low quality sucrose feeders increase their foraging rate in response to cocaine treatment. Cocaine also increased reflexive proboscis extension to sucrose, and sting extension to electric shock. Both of these simple reflexes are modulated by biogenic amines. This shows that systemic cocaine treatment alters behavioural responses that are modulated by biogenic amines in insects. Since insect reward responses involve both octopamine and dopamine signalling, we conclude that cocaine treatment altered diverse reward-related aspects of behaviour in bees. We discuss the implications of these results for understanding the ecology of cocaine as a plant defence compound. Our findings further validate the honey bee as a model system for understanding the behavioural impacts of cocaine, and potentially other drugs of abuse.

Knockout crickets for the study of learning and memory: Dopamine receptor Dop1 mediates aversive but not appetitive reinforcement in crickets.

PubMed

Awata, Hiroko; Watanabe, Takahito; Hamanaka, Yoshitaka; Mito, Taro; Noji, Sumihare; Mizunami, Makoto

2015-11-02

Elucidation of reinforcement mechanisms in associative learning is an important subject in neuroscience. In mammals, dopamine neurons are thought to play critical roles in mediating both appetitive and aversive reinforcement. Our pharmacological studies suggested that octopamine and dopamine neurons mediate reward and punishment, respectively, in crickets, but recent studies in fruit-flies concluded that dopamine neurons mediates both reward and punishment, via the type 1 dopamine receptor Dop1. To resolve the discrepancy between studies in different insect species, we produced Dop1 knockout crickets using the CRISPR/Cas9 system and found that they are defective in aversive learning with sodium chloride punishment but not appetitive learning with water or sucrose reward. The results suggest that dopamine and octopamine neurons mediate aversive and appetitive reinforcement, respectively, in crickets. We suggest unexpected diversity in neurotransmitters mediating appetitive reinforcement between crickets and fruit-flies, although the neurotransmitter mediating aversive reinforcement is conserved. This study demonstrates usefulness of the CRISPR/Cas9 system for producing knockout animals for the study of learning and memory.

Tyraminergic modulation of agonistic outcomes in crayfish.

PubMed

Momohara, Yuto; Aonuma, Hitoshi; Nagayama, Toshiki

2018-05-01

Octopamine, a biogenic amine, modulates various behaviors, ranging from locomotion and aggression to learning and memory in invertebrates. Several studies recently demonstrated that tyramine, the biological precursor of octopamine, also affects behaviors independent of octopamine. Here we investigated the involvement of tyramine in agonistic interaction of the male crayfish Procambarus clarkii. When male crayfish fight, larger animals (3-7% difference in body length) are more likely to win. By contrast, direct injection of tyramine or octopamine counteracted the physical advantage of larger animals. Tyramine or octopamine-injected naive large animals were mostly beaten by untreated smaller naive animals. This pharmacological effect was similar to the loser effect in which subordinate larger animals are frequently beaten by smaller animals. Furthermore, loser effects were partly eliminated by either injection of epinastine, an octopamine blocker, or yohimbine, a tyramine blocker, and significantly diminished by injection of a mixture of both blockers. We also observed that tyramine levels in the subesophageal ganglion were remarkably increased in subordinate crayfish after losing a fight. These results suggest that tyramine modulates aggressive levels of crayfish and contributes to the loser effect in parallel with octopamine.

Octopamine connects nutrient cues to lipid metabolism upon nutrient deprivation.

PubMed

Tao, Jun; Ma, Yi-Cheng; Yang, Zhong-Shan; Zou, Cheng-Gang; Zhang, Ke-Qin

2016-05-01

Starvation is probably the most common stressful situation in nature. In vertebrates, elevation of the biogenic amine norepinephrine levels is common during starvation. However, the precise role of norepinephrine in nutrient deprivation remains largely unknown. We report that in the free-living nematode Caenorhabditis elegans, up-regulation of the biosynthesis of octopamine, the invertebrate counterpart of norepinephrine, serves as a mechanism to adapt to starvation. During nutrient deprivation, the nuclear receptor DAF-12, known to sense nutritional cues, up-regulates the expression of tbh-1 that encodes tyramine β-hydroxylase, a key enzyme for octopamine biosynthesis, in the RIC neurons. Octopamine induces the expression of the lipase gene lips-6 via its receptor SER-3 in the intestine. LIPS-6, in turn, elicits lipid mobilization. Our findings reveal that octopamine acts as an endocrine regulator linking nutrient cues to lipolysis to maintain energy homeostasis, and suggest that such a mechanism may be evolutionally conserved in diverse organisms.

Octopamine and Dopamine differentially modulate the nicotine-induced calcium response in Drosophila Mushroom Body Kenyon Cells.

PubMed

Leyton, V; Goles, N I; Fuenzalida-Uribe, N; Campusano, J M

2014-02-07

In Drosophila associative olfactory learning, an odor, the conditioned stimulus (CS), is paired to an unconditioned stimulus (US). The CS and US information arrive at the Mushroom Bodies (MB), a Drosophila brain region that processes the information to generate new memories. It has been shown that olfactory information is conveyed through cholinergic inputs that activate nicotinic acetylcholine receptors (nAChRs) in the MB, while the US is coded by biogenic amine (BA) systems that innervate the MB. In this regard, the MB acts as a coincidence detector. A better understanding of the properties of the responses gated by nicotinic and BA receptors is required to get insights on the cellular and molecular mechanisms responsible for memory formation. In recent years, information has become available on the properties of the responses induced by nAChR activation in Kenyon Cells (KCs), the main neuronal MB population. However, very little information exists on the responses induced by aminergic systems in fly MB. Here we have evaluated some of the properties of the calcium responses gated by Dopamine (DA) and Octopamine (Oct) in identified KCs in culture. We report that exposure to BAs induces a fast but rather modest increase in intracellular calcium levels in cultured KCs. The responses to Oct and DA are fully blocked by a VGCC blocker, while they are differentially modulated by cAMP. Moreover, co-application of BAs and nicotine has different effects on intracellular calcium levels: while DA and nicotine effects are additive, Oct and nicotine induce a synergistic increase in calcium levels. These results suggest that a differential modulation of nicotine-induced calcium increase by DA and Oct could contribute to the events leading to learning and memory in flies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Octopamine and tyramine influence the behavioral profile of locomotor activity in the honey bee (Apis mellifera).

PubMed

Fussnecker, Brendon L; Smith, Brian H; Mustard, Julie A

2006-10-01

The biogenic amines octopamine and tyramine are believed to play a number of important roles in the behavior of invertebrates including the regulation of motor function. To investigate the role of octopamine and tyramine in locomotor behavior in honey bees, subjects were injected with a range of concentrations of octopamine, tyramine, mianserin or yohimbine. Continuous observation of freely moving worker bees was used to examine the effects of these treatments on the amount of time honey bees spent engaged in different locomotor behaviors such as walking, grooming, fanning and flying. All treatments produced significant shifts in behavior. Decreases in time spent walking and increases in grooming or stopped behavior were observed for every drug. However, the pattern of the shift depended on drug, time after injection and concentration. Flying behavior was differentially affected with increases in flying seen in octopamine treated bees, whereas those receiving tyramine showed a decrease in flying. Taken together, these data provide evidence that octopamine and tyramine modulate motor function in the honey bee perhaps via interaction with central pattern generators or through effects on sensory perception.

Octopamine and tyramine influence the behavioral profile of locomotor activity in the honey bee (Apis mellifera)

PubMed Central

Fussnecker, Brendon L.; Smith, Brian H.; Mustard, Julie A.

2006-01-01

The biogenic amines octopamine and tyramine are believed to play a number of important roles in the behavior of invertebrates including the regulation of motor function. To investigate the role of octopamine and tyramine in locomotor behavior in honey bees, subjects were injected with a range of concentrations of octopamine, tyramine, mianserin or yohimbine. Continuous observation of freely moving worker bees was used to examine the effects of these treatments on the amount of time honey bees spent engaged in different locomotor behaviors such as walking, grooming, fanning and flying. All treatments produced significant shifts in behavior. Decreases in time spent walking and increases in grooming or stopped behavior were observed for every drug. However, the pattern of the shift depended on drug, time after injection and concentration. Flying behavior was differentially effected with increases in flying seen in octopamine treated bees, whereas those receiving tyramine showed a decrease in flying. Taken together, these data provide evidence that octopamine and tyramine modulate motor function in the honey bee perhaps via interaction with central pattern generators or through effects on sensory perception. PMID:17028016

Roles of octopaminergic and dopaminergic neurons in appetitive and aversive memory recall in an insect.

PubMed

Mizunami, Makoto; Unoki, Sae; Mori, Yasuhiro; Hirashima, Daisuke; Hatano, Ai; Matsumoto, Yukihisa

2009-08-04

In insect classical conditioning, octopamine (the invertebrate counterpart of noradrenaline) or dopamine has been suggested to mediate reinforcing properties of appetitive or aversive unconditioned stimulus, respectively. However, the roles of octopaminergic and dopaminergic neurons in memory recall have remained unclear. We studied the roles of octopaminergic and dopaminergic neurons in appetitive and aversive memory recall in olfactory and visual conditioning in crickets. We found that pharmacological blockade of octopamine and dopamine receptors impaired aversive memory recall and appetitive memory recall, respectively, thereby suggesting that activation of octopaminergic and dopaminergic neurons and the resulting release of octopamine and dopamine are needed for appetitive and aversive memory recall, respectively. On the basis of this finding, we propose a new model in which it is assumed that two types of synaptic connections are formed by conditioning and are activated during memory recall, one type being connections from neurons representing conditioned stimulus to neurons inducing conditioned response and the other being connections from neurons representing conditioned stimulus to octopaminergic or dopaminergic neurons representing appetitive or aversive unconditioned stimulus, respectively. The former is called 'stimulus-response connection' and the latter is called 'stimulus-stimulus connection' by theorists studying classical conditioning in higher vertebrates. Our model predicts that pharmacological blockade of octopamine or dopamine receptors during the first stage of second-order conditioning does not impair second-order conditioning, because it impairs the formation of the stimulus-response connection but not the stimulus-stimulus connection. The results of our study with a cross-modal second-order conditioning were in full accordance with this prediction. We suggest that insect classical conditioning involves the formation of two kinds of memory traces, which match to stimulus-stimulus connection and stimulus-response connection. This is the first study to suggest that classical conditioning in insects involves, as does classical conditioning in higher vertebrates, the formation of stimulus-stimulus connection and its activation for memory recall, which are often called cognitive processes.

Octopamine connects nutrient cues to lipid metabolism upon nutrient deprivation

PubMed Central

Tao, Jun; Ma, Yi-Cheng; Yang, Zhong-Shan; Zou, Cheng-Gang; Zhang, Ke-Qin

2016-01-01

Starvation is probably the most common stressful situation in nature. In vertebrates, elevation of the biogenic amine norepinephrine levels is common during starvation. However, the precise role of norepinephrine in nutrient deprivation remains largely unknown. We report that in the free-living nematode Caenorhabditis elegans, up-regulation of the biosynthesis of octopamine, the invertebrate counterpart of norepinephrine, serves as a mechanism to adapt to starvation. During nutrient deprivation, the nuclear receptor DAF-12, known to sense nutritional cues, up-regulates the expression of tbh-1 that encodes tyramine β-hydroxylase, a key enzyme for octopamine biosynthesis, in the RIC neurons. Octopamine induces the expression of the lipase gene lips-6 via its receptor SER-3 in the intestine. LIPS-6, in turn, elicits lipid mobilization. Our findings reveal that octopamine acts as an endocrine regulator linking nutrient cues to lipolysis to maintain energy homeostasis, and suggest that such a mechanism may be evolutionally conserved in diverse organisms. PMID:27386520

Octopamine partially restores walking in hypokinetic cockroaches stung by the parasitoid wasp Ampulex compressa.

PubMed

Rosenberg, Lior Ann; Glusman, Jose Gustavo; Libersat, Frederic

2007-12-01

When stung by the parasitoid wasp Ampulex compressa, cockroaches Periplaneta americana enter a hypokinetic state that is characterized by little, if any, spontaneous locomotor activity. In the present study we investigate the effect of an octopamine receptor agonist and an antagonist on the locomotor behavior of stung and control cockroaches. We show that in cockroaches stung by a wasp the octopamine receptor agonist chlordimeform induces a significant increase in spontaneous walking. In good agreement, in control individuals an octopamine receptor antagonist significantly reduces walking activity. Adipokinetic hormone I (AKH-I) promotes spontaneous walking in controls but does not do so in stung individuals, which suggests that the venom effect is most probably not mediated by AKH-I. Dopamine receptor agonists or antagonists had no significant effect on the spontaneous walking of stung or control cockroaches, respectively. The effect of the octopamine receptor agonist was maximal when injected into the brain, suggesting that the wasp venom interferes with octopaminergic modulation of walking initiation in central structures of the cockroach brain.

Lyme and Dopaminergic Function: Hypothesizing Reduced Reward Deficiency Symptomatology by Regulating Dopamine Transmission

PubMed Central

Blum, Kenneth; Modestino, Edward J; Febo, Marcelo; Steinberg, Bruce; McLaughlin, Thomas; Fried, Lyle; Baron, David; Siwicki, David; Badgaiyan, Rajendra D

2017-01-01

The principal vector of Lyme disease in the United States is Ixodes scapularis: black legged or deer ticks. There is increased evidence that those infected may be plagued by anxiety or depression as well. Researchers have identified transcripts coding for two putative cytosolic sulfotransferases in these ticks, which recognized phenolic monoamines as their substrates. It is hypothesized that protracted Lyme disease sequelae may be due to impairment of dopaminergic function of the brain reward circuitry. The subsequent recombinant proteins exhibited sulfotransferase function against two neurotransmitters: dopamine and octopamine. This, in itself, can reduce dopamine function leading to many Reward Deficiency Syndrome behaviors, including depression and possibly, anxiety. In fact, it was shown that activity of Ixosc Sult 1 and Sult 2 in the Ixodid tick salivary glands might contain inactivation of the salivation signal through sulfonation of either dopamine or octopamine. This infraction results in a number of clinically observed mood changes, such as anxiety and depression. In fact, there are common symptoms observed for both Parkinson and Lyme diseases. The importance of understanding the mechanistic and neurobiological effects of Lyme on the central nervous system (CNS) provides the basis for pro-dopamine regulation as a treatment. WC 195 PMID:28736624

Lyme and Dopaminergic Function: Hypothesizing Reduced Reward Deficiency Symptomatology by Regulating Dopamine Transmission.

PubMed

Blum, Kenneth; Modestino, Edward J; Febo, Marcelo; Steinberg, Bruce; McLaughlin, Thomas; Fried, Lyle; Baron, David; Siwicki, David; Badgaiyan, Rajendra D

2017-05-01

The principal vector of Lyme disease in the United States is Ixodes scapularis: black legged or deer ticks. There is increased evidence that those infected may be plagued by anxiety or depression as well. Researchers have identified transcripts coding for two putative cytosolic sulfotransferases in these ticks, which recognized phenolic monoamines as their substrates. It is hypothesized that protracted Lyme disease sequelae may be due to impairment of dopaminergic function of the brain reward circuitry. The subsequent recombinant proteins exhibited sulfotransferase function against two neurotransmitters: dopamine and octopamine. This, in itself, can reduce dopamine function leading to many Reward Deficiency Syndrome behaviors, including depression and possibly, anxiety. In fact, it was shown that activity of Ixosc Sult 1 and Sult 2 in the Ixodid tick salivary glands might contain inactivation of the salivation signal through sulfonation of either dopamine or octopamine. This infraction results in a number of clinically observed mood changes, such as anxiety and depression. In fact, there are common symptoms observed for both Parkinson and Lyme diseases. The importance of understanding the mechanistic and neurobiological effects of Lyme on the central nervous system (CNS) provides the basis for pro-dopamine regulation as a treatment. WC 195.

Catecholaminergic System of Invertebrates: Comparative and Evolutionary Aspects in Comparison With the Octopaminergic System.

PubMed

Gallo, Valentina P; Accordi, Fiorenza; Chimenti, Claudio; Civinini, Annalena; Crivellato, Enrico

2016-01-01

In this review we examined the catecholaminergic system of invertebrates, starting from protists and getting to chordates. Different techniques used by numerous researchers revealed, in most examined phyla, the presence of catecholamines dopamine, noradrenaline, and adrenaline or of the enzymes involved in their synthesis. The catecholamines are generally linked to the nervous system and they can act as neurotransmitters, neuromodulators, and hormones; moreover they play a very important role as regards the response to a large number of stress situations. Nevertheless, in some invertebrate phyla belonging to Protostoma, the monoamine octopamine is the main biogenic amine. The presence of catecholamines in some protists suggests a role as intracellular or interorganismal signaling molecules and an ancient origin of their synthetic pathways. The catecholamines appear also involved in the regulation of bioluminescence and in the control of larval development and metamorphosis in some marine invertebrate phyla. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of tyramine and octopamine in the regulation of reproduction in queenless worker honeybees

NASA Astrophysics Data System (ADS)

Salomon, Mor; Malka, Osnat; Meer, Robert K. Vander; Hefetz, Abraham

2012-02-01

In honeybees, workers under queenless condition compete for reproduction and establish reproductive dominance hierarchy. Ovary activation is generally accompanied by the expression of queen-like pheromones. Biogenic amines (BAs), in particular dopamine, are believed to be involved in this process by regulating ovarian development. However, the role of BAs in establishing reproductive dominance or their effect on queen-like pheromone production was not investigated. Here, we explored the effect of octopamine (OA) and tyramine (TA) oral treatments on the propensity of treated bees to become reproductively dominant and produce queen-like pheromones in Dufour's and mandibular glands. One bee in a pair was treated with either OA or TA while the other was fed sugar solution. TA was found to enhance ovary development and the production of esters in the Dufour's gland and 9HDA (queen component) in the mandibular glands, thus facilitating worker reproductive dominance. OA, on the other hand, did not enhance ovarian development or ester production, but increased the production of 10HDA (worker major component) in the mandibular glands of their sugar-paired mates. OA is known to induce foraging behavior by workers, while increased production of 10HDA characterizes nursing workers. Therefore, we suggest that TA induces reproductive division of labor, while OA treatment results in caste differentiation of workers to foragers and nurses.

Biogenic amines in the stable fly Stomoxys calcitrans L. (Diptera: Muscidae): tissue localization and roles in feeding and reproduction

USDA-ARS?s Scientific Manuscript database

Biogenic amines, such as serotonin (5-hdroxytryptamine [5-HT]) and octopamine (OA), play critical roles as neurotransmitters and neuromodulators that control or modulate many behaviors in insects, such as feeding and reproduction. Neurons immunoreactive (IR) to 5-HT and OA were detected in the centr...

Molecular characterization and localization of the first tyramine receptor of the American cockroach (Periplaneta americana).

PubMed

Rotte, C; Krach, C; Balfanz, S; Baumann, A; Walz, B; Blenau, W

2009-09-15

The phenolamines octopamine and tyramine control, regulate, and modulate many physiological and behavioral processes in invertebrates. Vertebrates possess only small amounts of both substances, and thus, octopamine and tyramine, together with other biogenic amines, are referred to as "trace amines." Biogenic amines evoke cellular responses by activating G-protein-coupled receptors. We have isolated a complementary DNA (cDNA) that encodes a biogenic amine receptor from the American cockroach Periplaneta americana, viz., Peatyr1, which shares high sequence similarity to members of the invertebrate tyramine-receptor family. The PeaTYR1 receptor was stably expressed in human embryonic kidney (HEK) 293 cells, and its ligand response has been examined. Receptor activation with tyramine reduces adenylyl cyclase activity in a dose-dependent manner (EC(50) approximately 350 nM). The inhibitory effect of tyramine is abolished by co-incubation with either yohimbine or chlorpromazine. Receptor expression has been investigated by reverse transcription polymerase chain reaction and immunocytochemistry. The mRNA is present in various tissues including brain, salivary glands, midgut, Malpighian tubules, and leg muscles. The effect of tyramine on salivary gland acinar cells has been investigated by intracellular recordings, which have revealed excitatory presynaptic actions of tyramine. This study marks the first comprehensive molecular, pharmacological, and functional characterization of a tyramine receptor in the cockroach.

A decision underlies phototaxis in an insect

PubMed Central

2016-01-01

Like a moth into the flame—phototaxis is an iconic example for innate preferences. Such preferences probably reflect evolutionary adaptations to predictable situations and have traditionally been conceptualized as hard-wired stimulus–response links. Perhaps for that reason, the century-old discovery of flexibility in Drosophila phototaxis has received little attention. Here, we report that across several different behavioural tests, light/dark preference tested in walking is dependent on various aspects of flight. If we temporarily compromise flying ability, walking photopreference reverses concomitantly. Neuronal activity in circuits expressing dopamine and octopamine, respectively, plays a differential role in photopreference, suggesting a potential involvement of these biogenic amines in this case of behavioural flexibility. We conclude that flies monitor their ability to fly, and that flying ability exerts a fundamental effect on action selection in Drosophila. This work suggests that even behaviours which appear simple and hard-wired comprise a value-driven decision-making stage, negotiating the external situation with the animal's internal state, before an action is selected. PMID:28003472

AmTAR2: Functional characterization of a honeybee tyramine receptor stimulating adenylyl cyclase activity.

PubMed

Reim, Tina; Balfanz, Sabine; Baumann, Arnd; Blenau, Wolfgang; Thamm, Markus; Scheiner, Ricarda

2017-01-01

The biogenic monoamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. Insects such as honeybees do not synthesize these neuroactive substances. Instead, they employ octopamine and tyramine for comparable physiological functions. These biogenic amines activate specific guanine nucleotide-binding (G) protein-coupled receptors (GPCRs). Based on pharmacological data obtained on heterologously expressed receptors, α- and β-adrenergic-like octopamine receptors are better activated by octopamine than by tyramine. Conversely, GPCRs forming the type 1 tyramine receptor clade (synonymous to octopamine/tyramine receptors) are better activated by tyramine than by octopamine. More recently, receptors were characterized which are almost exclusively activated by tyramine, thus forming an independent type 2 tyramine receptor clade. Functionally, type 1 tyramine receptors inhibit adenylyl cyclase activity, leading to a decrease in intracellular cAMP concentration ([cAMP] i ). Type 2 tyramine receptors can mediate Ca 2+ signals or both Ca 2+ signals and effects on [cAMP] i . We here provide evidence that the honeybee tyramine receptor 2 (AmTAR2), when heterologously expressed in flpTM cells, exclusively causes an increase in [cAMP] i . The receptor displays a pronounced preference for tyramine over octopamine. Its activity can be blocked by a series of established antagonists, of which mianserin and yohimbine are most efficient. The functional characterization of two tyramine receptors from the honeybee, AmTAR1 (previously named AmTYR1) and AmTAR2, which respond to tyramine by changing cAMP levels in opposite direction, is an important step towards understanding the actions of tyramine in honeybee behavior and physiology, particularly in comparison to the effects of octopamine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic distortion of the balance between punishment and relief learning in Drosophila.

PubMed

Yarali, Ayse; Krischke, Markus; Michels, Birgit; Saumweber, Timo; Mueller, Martin J; Gerber, Bertram

2009-01-01

An experience with electric shock can support two opposing kinds of behavioral effects: Stimuli that precede shock during training are subsequently avoided as predictors for punishment, whereas stimuli that follow shock during training are later on approached, as they predict relief. We show here, for the fruit fly Drosophila, that upon the loss of white-function, the balance between these two kinds of learning is distorted in favor of punishment learning: white1118 mutants show stronger punishment learning and weaker relief learning, as compared to wild type flies. Thus, white1118 mutants establish, overall, more "negative" memories for the shock experience. This only concerns the mnemonic effects of the shock; the immediate, reflexive responsiveness to shock remains unaltered. Also, learning about reward is apparently unaffected, both in adult and larval Drosophila. Prompted by the proposed function of the White protein as the transporter for biogenic amine precursors, we probed the brains of white1118 mutants for the amounts of biogenic amines (octopamine, tyramine, dopamine, and serotonin) by using high-pressure liquid chromatography coupled to mass spectrometry. Using this method, we found, however, no difference between white1118 and wild type files for any of the probed amines. In any event, analyses of how the white1118 mutation affects the balance between punishment and relief learning should provide a study case of how heritable distortions of such balance can come about. Finally, the effects of the white1118 mutation should be considered as a source of confound when using white as the "marker gene" in behavior-genetic analyses of any sort.

Octopamine and tyramine modulate the thermoregulatory fanning response in honey bees (Apis mellifera L.)

USDA-ARS?s Scientific Manuscript database

Biogenic amines regulate the proximate mechanisms underlying most behavior, including those that contribute to the overall success of complex societies. For honey bees one critical set of behaviors contributing to the welfare of a colony are involved with nest thermoregulation. Worker honey bees co...

Development of an ionic liquid-based ultrasonic-assisted liquid-liquid microextraction method for sensitive determination of biogenic amines: application to the analysis of octopamine, tyramine and phenethylamine in beer samples.

PubMed

Huang, Ke-Jing; Jin, Chun-Xue; Song, Shi-Lin; Wei, Cai-Yun; Liu, Yan-Ming; Li, Jing

2011-03-15

A simple and efficient method, ionic liquid-based ultrasound-assisted liquid-liquid microextraction, has been developed for the determination of three biogenic amines including octopamine (OCT), tyramine (TYR) and phenethylamine (PHE). Fluorescence probe 2,6-dimethyl-4-quinolinecarboxylic acid N-hydroxysuccinimide ester was applied for derivatization of biogenic amines and high-performance liquid chromatography coupled with fluorescence detection was used for the determination of the derivatives. The factors affecting the extraction efficiency, such as the type and volume of ionic liquid, ultrasonication time and centrifugation time have been investigated in detail. Under the optimum conditions, linearity of the method was observed in the range of 0.5-50 μgmL(-1) for OCT and TYR, and 0.025-2.5 μgmL(-1) for PHE, respectively, with correlation coefficients (γ)>0.996. The limits of detection ranged from 0.25-50 ngmL(-1) (S/N=3). The spiked recoveries of three target compounds in beer samples were in the range of 90.2-114%. As a result, this method has been successfully applied for the sensitive determination of OCT, TYR and PHE in beer samples. Copyright © 2011 Elsevier B.V. All rights reserved.

Flight and Walking in Locusts–Cholinergic Co-Activation, Temporal Coupling and Its Modulation by Biogenic Amines

PubMed Central

Rillich, Jan; Stevenson, Paul A.; Pflueger, Hans-Joachim

2013-01-01

Walking and flying in locusts are exemplary rhythmical behaviors generated by central pattern generators (CPG) that are tuned in intact animals by phasic sensory inputs. Although these two behaviors are mutually exclusive and controlled by independent CPGs, leg movements during flight can be coupled to the flight rhythm. To investigate potential central coupling between the underlying CPGs, we used the muscarinic agonist pilocarpine and the amines octopamine and tyramine to initiate fictive flight and walking in deafferented locust preparations. Our data illustrate that fictive walking is readily evoked by comparatively lower concentrations of pilocarpine, whereas higher concentrations are required to elicit fictive flight. Interestingly, fictive flight did not suppress fictive walking so that the two patterns were produced simultaneously. Frequently, leg motor units were temporally coupled to the flight rhythm, so that each spike in a step cycle volley occurred synchronously with wing motor units firing at flight rhythm frequency. Similarly, tyramine also induced fictive walking and flight, but mostly without any coupling between the two rhythms. Octopamine in contrast readily evoked fictive flight but generally failed to elicit fictive walking. Despite this, numerous leg motor units were recruited, whereby each was temporarily coupled to the flight rhythm. Our results support the notion that the CPGs for walking and flight are largely independent, but that coupling can be entrained by aminergic modulation. We speculate that octopamine biases the whole motor machinery of a locust to flight whereas tyramine primarily promotes walking. PMID:23671643

Trace Amine-Associated Receptor 1 – Family Archetype or Iconoclast?

PubMed Central

Grandy, David K.

2009-01-01

Interest has recently been rekindled in receptors that are activated by low molecular weight, non-catecholic, biogenic amines that are typically found as trace constituents of various vertebrate and invertebrate tissues and fluids. The timing of this resurgent focus on receptors activated by the ‘trace amines’ (TAs) β-phenylethylamine (PEA), tyramine (TYR), octopamine (OCT), synephrine (SYN), and tryptamine (TRYP) is the direct result of two publications that appeared in 2001 describing the cloning of a novel G protein-coupled receptor (GPCR) referred to by their discoverers as TA1 (Borowsky et al., 2001) and TAR1 (Bunzow et al., 2001). When heterologously expressed in Xenopus laevis oocytes and various eukaryotic cell lines recombinant rodent and human TA receptors dose-dependently couple to the stimulation of cAMP production. Structure-activity profiling based on this functional response has revealed that in addition to the TAs, other biologically active compounds containing a 2 carbon aliphatic side chain linking an amino group to at least one benzene ring are potent and efficacious TA receptor agonists with amphetamine, methamphetamine, 3-iodothyronamine, thyronamine, and dopamine among the most notable. Almost 100 years after the search for TA receptors began numerous TA1/TAR1-related sequences, now called Trace Amine-Associated Receptors (TAARs), have been identified in the genome of every species of vertebrate examined to date. Consequently, even though heterologously expressed TAAR1 fits the pharmacological criteria established for a bona fide TA receptor a major challenge for those working in the field is to discern the in vivo pharmacology and physiology of each purported member of this extended family of GPCRs. Only then will it be possible to establish whether TAAR1 is the family archetype or an iconoclast. PMID:17888514

Trace amine-associated receptor 1-Family archetype or iconoclast?

PubMed

Grandy, David K

2007-12-01

Interest has recently been rekindled in receptors that are activated by low molecular weight, noncatecholic, biogenic amines that are typically found as trace constituents of various vertebrate and invertebrate tissues and fluids. The timing of this resurgent focus on receptors activated by the "trace amines" (TA) beta-phenylethylamine (PEA), tyramine (TYR), octopamine (OCT), synephrine (SYN), and tryptamine (TRYP) is the direct result of 2 publications that appeared in 2001 describing the cloning of a novel G protein-coupled receptor (GPCR) referred to by their discoverers Borowsky et al. as TA1 and Bunzow et al. as TA receptor 1 (TAR1). When heterologously expressed in Xenopus laevis oocytes and various eukaryotic cell lines, recombinant rodent and human TAR dose-dependently couple to the stimulation of adenosine 3',5'-monophosphate (cAMP) production. Structure-activity profiling based on this functional response has revealed that in addition to the TA, other biologically active compounds containing a 2-carbon aliphatic side chain linking an amino group to at least 1 benzene ring are potent and efficacious TA receptor agonists with amphetamine (AMPH), methamphetamine, 3-iodothyronamine, thyronamine, and dopamine (DA) among the most notable. Almost 100 years after the search for TAR began, numerous TA1/TAR1-related sequences, now called TA-associated receptors (TAAR), have been identified in the genome of every species of vertebrate examined to date. Consequently, even though heterologously expressed TAAR1 fits the pharmacological criteria established for a bona fide TAR, a major challenge for those working in the field is to discern the in vivo pharmacology and physiology of each purported member of this extended family of GPCR. Only then will it be possible to establish whether TAAR1 is the family archetype or an iconoclast.

Visual discrimination transfer and modulation by biogenic amines in honeybees.

PubMed

Vieira, Amanda Rodrigues; Salles, Nayara; Borges, Marco; Mota, Theo

2018-05-10

For more than a century, visual learning and memory have been studied in the honeybee Apis mellifera using operant appetitive conditioning. Although honeybees show impressive visual learning capacities in this well-established protocol, operant training of free-flying animals cannot be combined with invasive protocols for studying the neurobiological basis of visual learning. In view of this, different attempts have been made to develop new classical conditioning protocols for studying visual learning in harnessed honeybees, though learning performance remains considerably poorer than that for free-flying animals. Here, we investigated the ability of honeybees to use visual information acquired during classical conditioning in a new operant context. We performed differential visual conditioning of the proboscis extension reflex (PER) followed by visual orientation tests in a Y-maze. Classical conditioning and Y-maze retention tests were performed using the same pair of perceptually isoluminant chromatic stimuli, to avoid the influence of phototaxis during free-flying orientation. Visual discrimination transfer was clearly observed, with pre-trained honeybees significantly orienting their flights towards the former positive conditioned stimulus (CS+), thus showing that visual memories acquired by honeybees are resistant to context changes between conditioning and the retention test. We combined this visual discrimination approach with selective pharmacological injections to evaluate the effect of dopamine and octopamine in appetitive visual learning. Both octopaminergic and dopaminergic antagonists impaired visual discrimination performance, suggesting that both these biogenic amines modulate appetitive visual learning in honeybees. Our study brings new insight into cognitive and neurobiological mechanisms underlying visual learning in honeybees. © 2018. Published by The Company of Biologists Ltd.

Venom of a parasitoid wasp induces prolonged grooming in the cockroach

PubMed

Weisel-Eichler; Haspel; Libersat

1999-04-01

The parasitoid wasp Ampulex compressa hunts cockroaches Periplaneta americana, stinging them first in the thorax and then in the head, the sting penetrating towards the subesophageal ganglion. After being stung the cockroach grooms almost continuously for approximately 30 min, performing all the normal components of grooming behavior. This excessive grooming is only seen after the head sting and cannot be attributed to stress, to contamination of the body surface or to systemic or peripheral effects. This suggests that the venom is activating a neural network for grooming. We suggest that the venom induces prolonged grooming by stimulating dopamine receptors in the cockroach, for the following reasons. (1) Reserpine, which causes massive release of monoamines, induces excessive grooming. (2) Dopamine injected into the hemocoel also induces excessive grooming and is significantly more effective than octopamine or serotonin. In addition, the dopamine agonist SKF 82958 induces excessive grooming when injected directly into the subesophageal ganglion. (3) Injection of the dopamine antagonist flupenthixol greatly reduces venom-induced grooming. (4) Dopamine, or a dopamine-like substance, is present in the venom.

Kinetics of intraventricularly injected trace amines and their deuterated isotopomers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Durden, D.A.; Nguyen, T.V.; Boulton, A.A.

Intraventricular injection into the rat brain of four trace amines and a catecholamine resulted in rapid exponential loss of the amines in the first 30 minutes after injection. The half-lives were: phenylethylamine 3.8 min, para-tyramine 5.1 min, meta-tyramine 7.4 min and dopamine 8.0 min. Tryptamine showed a biphasic loss with half-lives of 4.7 min (over the 5 to 10 min period) and 14.1 min (10 to 30 min). The half-lives were substantially increased by deuterium labeling at the alpha carbon position: phenylethylamine 4.8 min, para-tyramine 8.8 min, meta-tyramine 14.1 min, dopamine 13.0 min and tryptamine 6.0 min (5 to 10more » min period) and 28.7 min (10 to 20 min). The loss of the amines was reduced by monoamine oxidase inhibition by pargyline hydrochloride and the deuterium isotope effect was abolished. It is noteworthy that the half-life of dopamine was similar to those of the trace amines in this time period and that the trace amine half-lives after i.v. injection was longer than those obtained from measurements of increases of concentrations of endogenous amines after MAOI in vivo and that of dopamine shorter than values calculated from turnover measurements.« less

Aminergic neuromodulation of associative visual learning in harnessed honey bees.

PubMed

Mancini, Nino; Giurfa, Martin; Sandoz, Jean-Christophe; Avarguès-Weber, Aurore

2018-05-21

The honey bee Apis mellifera is a major insect model for studying visual cognition. Free-flying honey bees learn to associate different visual cues with a sucrose reward and may deploy sophisticated cognitive strategies to this end. Yet, the neural bases of these capacities cannot be studied in flying insects. Conversely, immobilized bees are accessible to neurobiological investigation but training them to respond appetitively to visual stimuli paired with sucrose reward is difficult. Here we succeeded in coupling visual conditioning in harnessed bees with pharmacological analyses on the role of octopamine (OA), dopamine (DA) and serotonin (5-HT) in visual learning. We also studied if and how these biogenic amines modulate sucrose responsiveness and phototaxis behaviour as intact reward and visual perception are essential prerequisites for appetitive visual learning. Our results suggest that both octopaminergic and dopaminergic signaling mediate either the appetitive sucrose signaling or the association between color and sucrose reward in the bee brain. Enhancing and inhibiting serotonergic signaling both compromised learning performances, probably via an impairment of visual perception. We thus provide a first analysis of the role of aminergic signaling in visual learning and retention in the honey bee and discuss further research trends necessary to understand the neural bases of visual cognition in this insect. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparative Exploration of the Structure-Activity Space of Cloned α-Like Octopamine Receptors from a Marine and a Terrestrial Arthropod.

PubMed

Dalwadi, Dhwanil A; Schetz, John A

2017-09-01

The α -like octopamine receptors (OctR) are believed to be the evolutionary precursor to the vertebrate α 2 -adrenergic receptors ( α 2 -ARs) based upon sequence similarity and the ability to interact with norepinephrine and a number of compounds that bind with high affinity to α 2 -ARs. Barnacles and fruit flies are two prominent model marine and terrestrial representatives of the Arthropoda phylum, and although α -like OctRs have been cloned from Balanus improvisus (BiOctR) and Drosophila melanogaster (DmOctR), little is known about the structure-activity space for these important species. A diverse panel of 22 probes spanning different structural classes were employed to interrogate the structure-activity of the BiOctR and DmOctR. While BiOctR and DmOctR exhibited similar functional profiles for mammalian biogenic amine G protein-coupled receptor agonists and antagonists, some ligands had dramatically different mechanisms of action. For instance, significant differences in the efficacy for some agonists were observed, including that vertebrate biogenic amines structurally related to octopamine acted as superagonists at the DmOctR but partial agonists at the BiOctR, and the two species diverged in their sensitivities to the α 2 -AR antagonist [ 3 H]rauwolscine. Furthermore, sodium enhanced [ 3 H]rauwolscine's interactions with the BiOctR, but not at a vertebrate α 2 -AR. Molecular mechanistic studies indicate that rauwolscine interacts with the BiOctR, DmOctR, and α 2C -adrenergic receptor at an allosteric site. In addition, compounds that acted as agonists at a cloned α -like BiOctR also induced a hyperactivity response in Balanus cyprids mediated by the α -like OctR, suggesting that the receptor may serve as a higher throughput proxy for discovering compounds with potential cyprid deterrent properties. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

A fighter's comeback: dopamine is necessary for recovery of aggression after social defeat in crickets.

PubMed

Rillich, Jan; Stevenson, Paul A

2014-09-01

Social defeat, i.e. losing an agonistic dispute with a conspecific, is followed by a period of suppressed aggressiveness in many animal species, and is generally regarded as a major stressor, which may play a role in psychiatric disorders such as depression and post-traumatic stress disorder. Despite numerous animal models, the mechanisms underlying loser depression and subsequent recovery are largely unknown. This study on crickets is the first to show that a neuromodulator, dopamine (DA), is necessary for recovery of aggression after social defeat. Crickets avoid any conspecific male just after defeat, but regain their aggressiveness over 3 h. This recovery was prohibited after depleting nervous stores of DA and octopamine (OA, the invertebrate analogue of noradrenaline) with α-methyl-tyrosine (AMT). Loser recovery was also prohibited by the insect DA-receptor (DAR) antagonist fluphenazine, but not the OA-receptor (OAR) blocker epinastine, or yohimbine, which blocks receptors for OA's precursor tyramine. Conversely, aggression was restored prematurely in both untreated and amine depleted losers given either chlordimeform (CDM), a tissue permeable OAR-agonist, or the DA-metabolite homovanillyl alcohol (HVA), a component of the honeybee queen mandibular pheromone. As in honeybees, HVA acts in crickets as a DAR-agonist since its aggression promoting effect on losers was selectively blocked by the DAR-antagonist, but not by the OAR-antagonist. Conversely, CDM's aggression promoting effect was selectively blocked by the OAR-antagonist, but not the DAR-antagonist. Hence, only DA is necessary for recovery of aggressiveness after social defeat, although OA can promote loser aggression independently to enable experience dependent adaptive responses. Copyright © 2014 Elsevier Inc. All rights reserved.

Are monoaminergic systems involved in the lethargy induced by a parasitoid wasp in the cockroach prey?

PubMed

Weisel-Eichler, A; Libersat, F

2002-05-01

The venom of the parasitoid wasp Ampulex compressa induces long-lasting hypokinesia in the cockroach prey. Previous work indicates that the venom acts in the subesophageal ganglion to indirectly affect modulation of thoracic circuits for locomotion. However, the target of the venom in the subesophageal ganglion, and the mechanism by which the venom achieves its effects are as yet unknown. While the stung cockroaches appear generally lethargic, not all behaviors were affected, indicating that the venom targets specific motor systems and not behavior in general. Stung cockroaches were observed "freezing" in abnormal positions. Reserpine, which depletes monoamines, mimics the behavioral effects of the venom. We treated cockroaches with antagonists to dopamine and octopamine receptors, and found that the dopamine system is required for normal escape response. Dopamine injection induces prolonged grooming in normal cockroaches, but not in stung, suggesting that the venom is affecting dopamine receptors, or targets downstream of these receptors, in the subesophageal ganglion. This dopamine blocking effect fades slowly over the course of several weeks, similar to the time course of recovery from hypokinesia. The similarity in the time courses suggests that the mechanism underlying the hypokinesia may be the block of the dopamine receptors.

Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor.

PubMed

Bunzow, J R; Sonders, M S; Arttamangkul, S; Harrison, L M; Zhang, G; Quigley, D I; Darland, T; Suchland, K L; Pasumamula, S; Kennedy, J L; Olson, S B; Magenis, R E; Amara, S G; Grandy, D K

2001-12-01

The trace amine para-tyramine is structurally and functionally related to the amphetamines and the biogenic amine neurotransmitters. It is currently thought that the biological activities elicited by trace amines such as p-tyramine and the psychostimulant amphetamines are manifestations of their ability to inhibit the clearance of extracellular transmitter and/or stimulate the efflux of transmitter from intracellular stores. Here we report the discovery and pharmacological characterization of a rat G protein-coupled receptor that stimulates the production of cAMP when exposed to the trace amines p-tyramine, beta-phenethylamine, tryptamine, and octopamine. An extensive pharmacological survey revealed that psychostimulant and hallucinogenic amphetamines, numerous ergoline derivatives, adrenergic ligands, and 3-methylated metabolites of the catecholamine neurotransmitters are also good agonists at the rat trace amine receptor 1 (rTAR1). These results suggest that the trace amines and catecholamine metabolites may serve as the endogenous ligands of a novel intercellular signaling system found widely throughout the vertebrate brain and periphery. Furthermore, the discovery that amphetamines, including 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"), are potent rTAR1 agonists suggests that the effects of these widely used drugs may be mediated in part by this receptor as well as their previously characterized targets, the neurotransmitter transporter proteins.

Titres of biogenic amines and ecdysteroids: effect of octopamine on the production of ecdysteroids in the silkworm Bombyx mori.

PubMed

Hirashima, A; Hirokado, S; Ohta, H; Suetsugu, E; Sakaguchi, M; Kuwano, E; Taniguchi, E; Eto, M

1999-09-01

At day two, a sharp peak of octopamine (OA) was observed in last instar female Bombyx mori larvae. This peak also appeared in male larvae a day later than in females at day three. An OA peak was also observed before the 3rd ecdysis. However, no OA peaks were observed in 4th instar larvae. At day eight and nine of the 5th instar, another OA peak was observed for male and female, respectively. A peak of tyramine (TA) was found at day one followed by a peak of OA at day two in 3rd instar larvae. At day two, a day before OA peak, a peak of TA was observed for male insects and before the 2nd peak of OA, TA titre was also high in 5th instar larvae. Immediately after 3rd ecdysis, a high titre of DL-beta-(3,4-dihydroxyphenyl)alanine (DOPA) was observed, followed by a peak of dopamine (DA) at day five. A peak of DOPA was found at day one followed by a peak of DA at day two in 3rd instar larvae. Similarly, a small peak of DOPA was observed at day two, followed by an increase of DA at days eight and nine after the 4th ecdysis. Ecdysteroid peaks were observed just before the 3rd and 4th ecdysis and an ecdysteroid titre increased after the start of spinning. The effects of OA and JH on production of ecdysteroids by prothoracic glands (PGs) were examined in order to identify neuromediators responsible for triggering pupation in B. mori larvae. Exogeneous OA (10-100 mM) reduced and 10 &mgr;M OA stimulated the production of ecdysteroids in the presence and absence of brain extracts by PGs in the final instar (day five) of B. mori in vitro. Meanwhile, exogeneous JHI (10 &mgr;g/ml) stimulated and at 5 &mgr;g/ml it reduced production of ecdysteroids in the presence of brain extracts. Gramine, an OA antagonist, delayed pupation when applied in the diet. Thus, OA may produce some biological effects on the programming of larval-pupal development.

Nitrogen-based drugs are not essential for blockade of monoamine transporters.

PubMed

Madras, B K; Pristupa, Z B; Niznik, H B; Liang, A Y; Blundell, P; Gonzalez, M D; Meltzer, P C

1996-12-01

In brain, monoamine transporters are principal targets of widely used therapeutic drugs including antidepressants, methylphenidate (Ritalin), and the addictive drug cocaine. Without exception, these transport blocking agents contain an amine nitrogen. A prevalent view and untested premise is that an amine nitrogen is needed to bind to the same counterion on the transporter as does the amine nitrogen of the monoamine neurotransmitter. We report that several compounds without nitrogen (8-oxa-bicyclo-3-aryl-[3.2.1] octanes, or aryloxatropanes) are active at monoamine transporters. One of these, tropoxane (0-914), bound with high affinity to the dopamine (IC50: 3.35 +/- 0.39 nM), serotonin (IC50: 6.52 +/- 2.05 nM), and norepinephrine (IC50: 20.0 +/- 0.3 nM) transporters in monkey brain, the human striatal dopamine transporter (IC50: 5.01 +/- 1.74 nM), and blocked dopamine transport (IC50: 7.2 +/- 3.0 nM) in COS-7 cells transfected with the human dopamine transporter. These unique compounds require a revision of current concepts of the drug binding domains on monoamine transporters, open avenues for discovery of a new generation of drugs and raise the issue of whether mammalian transporters and receptors may respond to, as yet, undiscovered non-amine bearing neurotransmitters or drugs.

Amtyr1: characterization of a gene from honeybee (Apis mellifera) brain encoding a functional tyramine receptor.

PubMed

Blenau, W; Balfanz, S; Baumann, A

2000-03-01

Biogenic amine receptors are involved in the regulation and modulation of various physiological and behavioral processes in both vertebrates and invertebrates. We have cloned a member of this gene family from the CNS of the honeybee, Apis mellifera. The deduced amino acid sequence is homologous to tyramine receptors cloned from Locusta migratoria and Drosophila melanogaster as well as to an octopamine receptor cloned from Heliothis virescens. Functional properties of the honeybee receptor were studied in stably transfected human embryonic kidney 293 cells. Tyramine reduced forskolin-induced cyclic AMP production in a dose-dependent manner with an EC50 of approximately 130 nM. A similar effect of tyramine was observed in membrane homogenates of honeybee brains. Octopamine also reduced cyclic AMP production in the transfected cell line but was both less potent (EC50 of approximately 3 microM) and less efficacious than tyramine. Receptor-encoding mRNA has a wide-spread distribution in the brain and subesophageal ganglion of the honeybee, suggesting that this tyramine receptor is involved in sensory signal processing as well as in higher-order brain functions.

Depression of brain dopamine and its metabolite after mating in European honeybee (Apis mellifera) queens

NASA Astrophysics Data System (ADS)

Harano, Ken-Ichi; Sasaki, Ken; Nagao, Takashi

2005-07-01

To explore neuro-endocrinal changes in the brain of European honeybee (Apis mellifera) queens before and after mating, we measured the amount of several biogenic amines, including dopamine and its metabolite in the brain of 6- and 12-day-old virgins and 12-day-old mated queens. Twelve-day-old mated queens showed significantly lower amounts of dopamine and its metabolite (N-acetyldopamine) than both 6- and 12-day-old virgin queens, whereas significant differences in the amounts of these amines were not detected between 6- and 12-day-old virgin queens. These results are explained by down-regulation of both synthesis and secretion of brain dopamine after mating. It is speculated that higher amounts of brain dopamine in virgin queens might be involved in activation of ovarian follicles arrested in previtellogenic stages, as well as regulation of their characteristic behaviors.

The vascular effects of trace amines and amphetamines.

PubMed

Broadley, Kenneth J

2010-03-01

Trace amines, including tyramine, beta-phenylethylamine (beta-PEA), tryptamine and octopamine, are biologically active amines mostly based on phenylethylamine, occurring in the body in trace amounts. They are a diverse group of naturally occurring and synthetic amines, which are also found in the diet and in herbal plants, such as ephedrine and cathinone. They include amphetamine and its analogues, such as MDMA ('ecstasy'), and synthetic proprietary sympathomimetic agents such as phenylpropanolamine and pseudoephedrine. On the vascular system they cause vasoconstriction and a rise in blood pressure. This effect is the basis of their use as nasal decongestants. For over 50 years, they have been assumed to be indirectly acting sympathomimetic amines, their responses being due to the release of noradrenaline from sympathetic neurones. There are, however, results that suggest that this is not their only mechanism of action and that they may also exert direct vascular effects independent of a noradrenergic mechanism. Recently, a group of novel trace amine-associated receptors (TAARs) have been cloned and identified in the brain and peripheral tissues including blood vessels. Trace amines bind to these cloned receptors and it is suggested that their vasoconstrictor effects can in part be attributed to this mechanism. This review describes the cardiovascular pharmacology of this diverse group of amines, their structures and uses and their endogenous synthesis and metabolism. The review also considers their clinical relevance as constituents of the diet, as therapeutic agents (ritodrine, phenylpropanolamine, and pseudoephedrine) and as drugs of abuse (amphetamine, 'ecstasy') and their mechanisms of action. 2009 Elsevier Inc. All rights reserved.

Phenethylamines in brain and liver of rats with experimentally induced phenylketonuria-like characteristics

PubMed Central

Edwards, David J.; Blau, Karl

1973-01-01

1. Phenethylamines were extracted from brain and liver of rats with phenylketonuria-like characteristics produced in vivo by inhibition of phenylalanine hydroxylase (EC 1.14.3.1) with p-chlorophenylalanine, with or without phenylalanine administration. To protect amines against oxidation by monoamine oxidase, pargyline was also administered. 2. β-Phenethylamine was the major compound found in brain and liver. β-Phenethanolamine and octopamine were also present, in lesser amounts, and the concentrations of these three amines paralleled blood phenylalanine concentrations. By comparison, tissues from control animals had only very low concentrations of these amines. 3. Small amounts of normetadrenaline, m-tyramine and 3-methoxytyramine were also found. 4. The inhibitors used, p-chlorophenylalanine and pargyline, gave rise to p-chlorophenethylamine and benzylamine respectively, the first via decarboxylation, the second probably by breakdown during extraction. 5. Distribution of phenethylamines in different brain regions and in subcellular fractions of rat brain cells was also investigated. The content of phenethylamine was highest in the striatum. 6. These findings are discussed in the light of changes occurring in human patients with uncontrolled phenylketonuria. PMID:4269184

Nosema ceranae parasitism impacts olfactory learning and memory and neurochemistry in honey bees (Apis mellifera).

PubMed

Gage, Stephanie L; Kramer, Catherine; Calle, Samantha; Carroll, Mark; Heien, Michael; DeGrandi-Hoffman, Gloria

2018-02-19

Nosema sp. is an internal parasite of the honey bee, Apis mellifera , and one of the leading contributors to colony losses worldwide. This parasite is found in the honey bee midgut and has profound consequences for the host's physiology. Nosema sp. impairs foraging performance in honey bees, yet, it is unclear whether this parasite affects the bee's neurobiology. In this study, we examined whether Nosema sp. affects odor learning and memory and whether the brains of parasitized bees show differences in amino acids and biogenic amines. We took newly emerged bees and fed them with Nosema ceranae At approximate nurse and forager ages, we employed an odor-associative conditioning assay using the proboscis extension reflex and two bioanalytical techniques to measure changes in brain chemistry. We found that nurse-aged bees infected with N. ceranae significantly outperformed controls in odor learning and memory, suggestive of precocious foraging, but by forager age, infected bees showed deficits in learning and memory. We also detected significant differences in amino acid concentrations, some of which were age specific, as well as altered serotonin, octopamine, dopamine and l-dopa concentrations in the brains of parasitized bees. These findings suggest that N. ceranae infection affects honey bee neurobiology and may compromise behavioral tasks. These results yield new insight into the host-parasite dynamic of honey bees and N. ceranae , as well as the neurochemistry of odor learning and memory under normal and parasitic conditions. © 2018. Published by The Company of Biologists Ltd.

Pyrylium Salts as Reactive Matrices for MALDI-MS Imaging of Biologically Active Primary Amines

NASA Astrophysics Data System (ADS)

Shariatgorji, Mohammadreza; Nilsson, Anna; Källback, Patrik; Karlsson, Oskar; Zhang, Xiaoqun; Svenningsson, Per; Andren, Per E.

2015-06-01

Many neuroactive substances, including endogenous biomolecules, environmental compounds, and pharmaceuticals possess primary amine functional groups. Among these are catecholamine neurotransmitters (e.g., dopamine), many substituted phenethylamines (e.g., amphetamine), as well as amino acids and neuropeptides. In most cases, mass spectrometric (ESI and MALDI) analyses of trace amounts of such compounds are challenging because of their poor ionization properties. We present a method for chemical derivatization of primary amines by reaction with pyrylium salts that facilitates their detection by MALDI-MS and enables the imaging of primary amines in brain tissue sections. A screen of pyrylium salts revealed that the 2,4-diphenyl-pyranylium ion efficiently derivatizes primary amines and can be used as a reactive MALDI-MS matrix that induces both derivatization and desorption. MALDI-MS imaging with such matrix was used to map the localization of dopamine and amphetamine in brain tissue sections and to quantitatively map the distribution of the neurotoxin β- N-methylamino-L-alanine.

Neurotransmitter and psychostimulant recognition by the dopamine transporter

PubMed Central

Wang, Kevin H.; Penmatsa, Aravind; Gouaux, Eric

2015-01-01

Na+/Cl−-coupled biogenic amine transporters are the primary targets of therapeutic and abused drugs, ranging from antidepressants to the psychostimulants cocaine and amphetamines, and to their cognate substrates. Here we determine x-ray crystal structures of the Drosophila melanogaster dopamine transporter (dDAT) bound to its substrate dopamine (DA), a substrate analogue 3,4-dichlorophenethylamine, the psychostimulants D-amphetamine, methamphetamine, or to cocaine and cocaine analogues. All ligands bind to the central binding site, located approximately halfway across the membrane bilayer, in close proximity to bound sodium and chloride ions. The central binding site recognizes three chemically distinct classes of ligands via conformational changes that accommodate varying sizes and shapes, thus illustrating molecular principles that distinguish substrates from inhibitors in biogenic amine transporters. PMID:25970245

Pharmacological characterization of a β-adrenergic-like octopamine receptor in Plutella xylostella.

PubMed

Huang, Qing-Ting; Ma, Hai-Hao; Deng, Xi-Le; Zhu, Hang; Liu, Jia; Zhou, Yong; Zhou, Xiao-Mao

2018-04-25

The β-adrenergic-like octopamine receptor (OA2B2) belongs to the class of G-protein coupled receptors. It regulates important physiological functions in insects, thus is potentially a good target for insecticides. In this study, the putative open reading frame sequence of the Pxoa2b2 gene in Plutella xylostella was cloned. Orthologous sequence alignment, phylogenetic tree analysis, and protein sequence analysis all showed that the cloned receptor belongs to the OA2B2 protein family. PxOA2B2 was transiently expressed in HEK-293 cells. It was found that PxOA2B2 could be activated by both octopamine and tyramine, resulting in increased intracellular cyclic AMP (cAMP) levels, whereas dopamine and serotonin were not effective in eliciting cAMP production. Further studies with series of PxOA2B2 agonists and antagonists showed that all four tested agonists (e.g., naphazoline, clonidine, 2-phenylethylamine, and amitraz) could activate the PxOA2B2 receptor, and two of tested antagonists (e.g., phentolamine and mianserin) had significant antagonistic effects. However, antagonist of yohimbine had no effects. Quantitative real-time polymerase chain reaction analysis showed that Pxoa2b2 gene was expressed in all developmental stages of P. xylostella and that the highest expression occurred in male adults. Further analysis with fourth-instar P. xylostella larvae showed that the Pxoa2b2 gene was mainly expressed in Malpighian tubule, epidermal, and head tissues. This study provides both a pharmacological characterization and the gene expression patterns of the OA2B2 in P. xylostella, facilitating further research for insecticides using PxOA2B2 as a target. © 2018 Wiley Periodicals, Inc.

Octopamine and tyramine regulate the activity of reproductive visceral muscles in the adult female blood-feeding bug, Rhodnius prolixus.

PubMed

Hana, Sam; Lange, Angela B

2017-05-15

The role of octopamine and tyramine in regulating spontaneous contractions of reproductive tissues was examined in the female Rhodnius prolixus Octopamine decreased the amplitude of spontaneous contractions of the oviducts and reduced RhoprFIRFa-induced contractions in a dose-dependent manner, whereas tyramine only reduced the RhoprFIRFa-induced contractions. Both octopamine and tyramine decreased the frequency of spontaneous bursal contractions and completely abolished the contractions at 5×10 -7  mol l -1 and above. Phentolamine, an octopamine receptor antagonist, attenuated the inhibition induced by octopamine on the oviducts and the bursa. Octopamine also increased the levels of cAMP in the oviducts, and this effect was blocked by phentolamine. Dibutyryl cyclic AMP mimicked the effects of octopamine by reducing the frequency of bursal contractions, suggesting that the octopamine receptor may act by an Octβ receptor. The tyramine receptor antagonist yohimbine failed to block the inhibition of contractions induced by tyramine on the bursa, suggesting that tyramine may be acting on the Octβ receptor in the bursa. © 2017. Published by The Company of Biologists Ltd.

Octopamine influences honey bee foraging preference.

PubMed

Giray, Tugrul; Galindo-Cardona, Alberto; Oskay, Devrim

2007-07-01

Colony condition and differences in individual preferences influence forage type collected by bees. Physiological bases for the changing preferences of individual foragers are just beginning to be examined. Recently, for honey bees octopamine is shown to influence age at onset of foraging and probability of dance for rewards. However, octopamine has not been causally linked with foraging preference in the field. We tested the hypothesis that changes in octopamine may alter forage type (preference hypothesis). We treated identified foragers orally with octopamine or its immediate precursor, tyramine, or sucrose syrup (control). Octopamine-treated foragers switched type of material collected; control bees did not. Tyramine group results were not different from the control group. In addition, sugar concentrations of nectar collected by foragers after octopamine treatment were lower than before treatment, indicating change in preference. In contrast, before and after nectar concentrations for bees in the control group were similar. These results, taken together, support the preference hypothesis.

Various Wolbachia genotypes differently influence host Drosophila dopamine metabolism and survival under heat stress conditions.

PubMed

Gruntenko, Nataly Е; Ilinsky, Yury Yu; Adonyeva, Natalya V; Burdina, Elena V; Bykov, Roman A; Menshanov, Petr N; Rauschenbach, Inga Yu

2017-12-28

One of the most widespread prokaryotic symbionts of invertebrates is the intracellular bacteria of Wolbachia genus which can be found in about 50% of insect species. Wolbachia causes both parasitic and mutualistic effects on its host that include manipulating the host reproductive systems in order to increase their transmission through the female germline, and increasing the host fitness. One of the mechanisms, promoting adaptation in biological organisms, is a non-specific neuroendocrine stress reaction. In insects, this reaction includes catecholamines, dopamine, serotonin and octopamine, which act as neurotransmitters, neuromodulators and neurohormones. The level of dopamine metabolism correlates with heat stress resistance in Drosophila adults. To examine Wolbachia effect on Drosophila survival under heat stress and dopamine metabolism we used five strains carrying the nuclear background of interbred Bi90 strain and cytoplasmic backgrounds with different genotype variants of Wolbachia (produced by 20 backcrosses of Bi90 males with appropriate source of Wolbachia). Non-infected Bi90 strain (treated with tetracycline for 3 generations) was used as a control group. We demonstrated that two of five investigated Wolbachia variants promote changes in Drosophila heat stress resistance and activity of enzymes that produce and degrade dopamine, alkaline phosphatase and dopamine-dependent arylalkylamine N-acetyltransferase. What is especially interesting, wMelCS genotype of Wolbachia increases stress resistance and the intensity of dopamine metabolism, whereas wMelPop strain decreases them. wMel, wMel2 and wMel4 genotypes of Wolbachia do not show any effect on the survival under heat stress or dopamine metabolism. L-DOPA treatment, known to increase the dopamine content in Drosophila, levels the difference in survival under heat stress between all studied groups. The genotype of symbiont determines the effect that the symbiont has on the stress resistance of the host insect.

Carbon nanopipette electrodes for dopamine detection in Drosophila.

PubMed

Rees, Hillary R; Anderson, Sean E; Privman, Eve; Bau, Haim H; Venton, B Jill

2015-04-07

Small, robust, sensitive electrodes are desired for in vivo neurotransmitter measurements. Carbon nanopipettes have been previously manufactured and used for single-cell drug delivery and electrophysiological measurements. Here, a modified fabrication procedure was developed to produce batches of solid carbon nanopipette electrodes (CNPEs) with ∼250 nm diameter tips, and controllable lengths of exposed carbon, ranging from 5 to 175 μm. The electrochemical properties of CNPEs were characterized with fast-scan cyclic voltammetry (FSCV) for the first time. CNPEs were used to detect the electroactive neurotransmitters dopamine, serotonin, and octopamine. CNPEs were significantly more sensitive for serotonin detection than traditional carbon-fiber microelectrodes (CFMEs). Similar to CFMEs, CNPEs have a linear response for dopamine concentrations ranging from 0.1 to 10 μM and a limit of detection of 25 ± 5 nM. Recordings with CNPEs were stable for over 3 h when the applied triangle waveform was scanned between -0.4 and +1.3 V vs Ag/AgCl/Cl(-) at 400 V/s. CNPEs were used to detect endogenous dopamine release in Drosophila larvae using optogenetics, which verified the utility of CNPEs for in vivo neuroscience studies. CNPEs are advantageous because they are 1 order of magnitude smaller in diameter than typical CFMEs and have a sharp, tunable geometry that facilitates penetration and implantation for localized measurements in distinct regions of small organisms, such as the Drosophila brain.

Carbon nanopipette electrodes for dopamine detection in Drosophila

PubMed Central

Rees, Hillary R.; Anderson, Sean E.; Privman, Eve; Bau, Haim H.; Venton, B. Jill

2015-01-01

Small, robust, sensitive electrodes are desired for in vivo neurotransmitter measurements. Carbon nanopipettes have been previously manufactured and used for single cell drug delivery and electrophysiological measurements. Here, a modified fabrication procedure was developed to produce batches of solid carbon nanopipette electrodes (CNPEs) with ~250 nm diameter tips, and controllable lengths of exposed carbon, ranging from 5 μm to 175 μm. The electrochemical properties of CNPEs were characterized with fast-scan cyclic voltammetry (FSCV) for the first time. CNPEs were used to detect the electroactive neurotransmitters dopamine, serotonin, and octopamine. CNPEs were significantly more sensitive for serotonin detection than traditional carbon fiber microelectrodes (CFMEs). Similar to CFMEs, CNPEs have a linear response for dopamine concentrations ranging from 0.1 to 10 μM and a LOD of 25 ± 5 nM. Recordings with CNPEs were stable for over 3 hours when the applied triangle waveform was scanned between −0.4 and 1.3 V vs. Ag/AgCl/Cl− at 400 V/s. CNPEs were used to detect endogenous dopamine release in Drosophila larvae using optogenetics, which verified the utility of CNPEs for in vivo neuroscience studies. CNPEs are advantageous because they are an order of magnitude smaller in diameter than typical CFMEs and have a sharp, tunable geometry that facilitates penetration and implantation for localized measurements in distinct regions of small organisms, such as the Drosophila brain. PMID:25711512

Non-amine-based dopamine transporter (reuptake) inhibitors retain properties of amine-based progenitors.

PubMed

Madras, Bertha K; Fahey, Michele A; Miller, Gregory M; De La Garza, Richard; Goulet, Martin; Spealman, Roger D; Meltzer, Peter C; George, Susan R; O'Dowd, Brian F; Bonab, Ali A; Livni, Eli; Fischman, Alan J

2003-10-31

Without exception, therapeutic and addictive drugs that produce their primary effects by blocking monoamine transporters in brain contain an amine nitrogen in their structure. This fundamental canon of drug design was based on a prevailing premise that an amine nitrogen is required to mimic the structures of monoamine neurotransmitters and other natural products. Non-amines, a novel class of compounds that contain no amine nitrogen, block monoamine transporters in the nM range and display markedly high selectivity for monoamine transporters, but not for receptors. Non-amines retain the spectrum of biochemical and pharmacological properties characteristic of amine-bearing counterparts. These novel drugs compel a revision of current concepts of drug-monoamine transporter complex formation and open avenues for discovery of a new generation of therapeutic drugs.

Morphology of salivary gland and distribution of dopamine and serotonin on red palm weevil (RPW), Rhynchophorus ferrugineus (Coleoptera: Curculionidae)

NASA Astrophysics Data System (ADS)

Hidayah, A. S. Nurul; Wahida, O. Nurul; Shafinaz, M. N. Norefrina; Idris, A. G.

2013-11-01

The Red Palm Weevil (RPW), Rhynchophorus ferrugineus (Olivier, 1790) is insect pest to plants of the family Palmaceae. No study has been reported on the digestive mechanism of Red Palm Weevil (RPW). Salivary glands are responsible in the feeding regulation of insect while serotonin and dopamine play a significant role in the regulation of this gland. It is great to see the morphology of the salivary gland and how dopamine and serotonin possibly play their role in this gland. Two variation of RPW, striped and spotted RPW were chosen. The morphology of the gland of both RPW variants examined by using light microscopy was found to be a tubular type. Immunohistochemical analysis conducted showed that serotonin and dopamine in both variations did not innervate the glands suggesting they are not act as neurotransmitter. However, it can be detected on few areas within the glands. This suggests that serotonin and dopamine may act as a hormone because there is no evidence on the nerve fibers. The role of these biogenic amines in the salivary gland of RPW needs further investigation. Hopefully the data would help in understanding the mechanism of salivary glands control by biogenic amines in RPW specifically and insects with sucking mouthpart generally.

Opposite Actions of Dopamine on Aversive and Appetitive Memories in the Crab

ERIC Educational Resources Information Center

Klappenbach, Martin; Maldonado, Hector; Locatelli, Fernando; Kaczer, Laura

2012-01-01

The understanding of how the reinforcement is represented in the central nervous system during memory formation is a current issue in neurobiology. Several studies in insects provide evidence of the instructive role of biogenic amines during the learning and memory process. In insects it was widely accepted that dopamine (DA) mediates aversive…

Central nervous system promotes thermotolerance via FoxO/DAF-16 activation through octopamine and acetylcholine signaling in Caenorhabditis elegans.

PubMed

Furuhashi, Tsubasa; Sakamoto, Kazuichi

2016-03-25

The autonomic nervous system (ANS) responds to many kinds of stressors to maintain homeostasis. Although the ANS is believed to regulate stress tolerance, the exact mechanism underlying this is not well understood. To understand this, we focused on longevity genes, which have functions such as lifespan extension and promotion of stress tolerance. To understand the relationship between ANS and longevity genes, we analyzed stress tolerance of Caenorhabditis elegans treated with octopamine, which has an affinity to noradrenaline in insects, and acetylcholine. Octopamine and acetylcholine did not show resistance against H2O2, but the neurotransmitters promoted thermotolerance via DAF-16. However, chronic treatment with octopamine and acetylcholine did not extend the lifespan, although DAF-16 plays an important role in longevity. In conclusion, our results show that octopamine and acetylcholine activate DAF-16 in response to stress, but chronic induction of octopamine and acetylcholine is not beneficial for increasing longevity. Copyright © 2016 Elsevier Inc. All rights reserved.

Altered dopamine levels induced by the parasite Profilicollis antarcticus on its intermediate host, the crab Hemigrapsus crenulatus.

PubMed

Rojas, José Miguel; Ojeda, F Patricio

2005-01-01

A serotonergic pathway is apparently involved in parasite-host interactions. Previous studies conducted in our laboratory showed increased rates in oxygen consumption and alterations in body posture in the crab Hemigrapsus crenulatus parasitized by the acanthocephalan, Profilicollis antarcticus. Such changes may be related to the functions described for biogenic amines in crustaceans. During the infective stage the acanthocephalans live freely in the hemocelomic cavity, suggesting that the possible alteration induced by biogenic amines may be related to their neurohormonal function in crustaceans. To test whether the presence of P. antarcticus produced neurohormonal changes in its intermediate host, H. crenulatus, we analyzed serotonin and dopamine levels in the host using HPLC with electrochemical detection. Two groups of 11 female crabs were studied; one group was artificially inoculated with two cystacanths while the other was used as the control. Our results show a dramatic increase in hemolymph dopamine, but not serotonin in H. crenulatus parasitized by the acanthocephalan P. antarcticus. Our results, along with those reported by Maynard (1996), suggest a parasite-specific strategy involved in the behavior alteration caused by the acanthocephalans on their intermediate host. The use of a biogenic amine as a mechanism of interaction by the parasites gives them an endless number of alternative potential actions on their intermediate hosts.

The sensory system: More than just a window to the external world.

PubMed

Gendron, Christi M; Chung, Brian Y; Pletcher, Scott D

2015-01-01

While the traditional importance of the sensory system lies in its ability to perceive external information about the world, emerging discoveries suggest that sensory perception has a greater impact on health and longevity than was previously appreciated. These effects are conserved across species. In this mini-review, we discuss the specific sensory cues that have been identified to significantly impact organismal physiology and lifespan. Ongoing work in the aging field has begun to identify the downstream molecules that mediate the broad effects of sensory signals. Candidates include FOXO, neuropeptide F (NPF), adipokinetic hormone (AKH), dopamine, serotonin, and octopamine. We then discuss the many implications that arise from our current understanding of the effects of sensory perception on health and longevity.

An Easily Fabricated Electrochemical Sensor Based on a Graphene-Modified Glassy Carbon Electrode for Determination of Octopamine and Tyramine

PubMed Central

Zhang, Yang; Zhang, Meiqin; Wei, Qianhui; Gao, Yongjie; Guo, Lijuan; Al-Ghanim, Khalid A.; Mahboob, Shahid; Zhang, Xueji

2016-01-01

A simple electrochemical sensor has been developed for highly sensitive detection of octopamine and tyramine by electrodepositing reduced graphene oxide (ERGO) nanosheets onto the surface of a glassy carbon electrode (GCE). The electrocatalytic oxidation of octopamine and tyramine is individually investigated at the surface of the ERGO modified glassy carbon electrode (ERGO/GCE) by using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Several essential factors including the deposition cycle of reduced graphene oxide nanosheets and the pH of the running buffer were investigated in order to determine the optimum conditions. Furthermore, the sensor was applied to the quantification of octopamine and tyramine by DPV in the concentration ranges from 0.5 to 40 μM and 0.1 to 25 μM, respectively. In addition, the limits of detection of octopamine and tyramine were calculated to be 0.1 μM and 0.03 μM (S/N = 3), respectively. The sensor showed good reproducibility, selectivity and stability. Finally, the sensor successfully detected octopamine and tyramine in commercially available beer with satisfactory recovery ranges which were 98.5%–104.7% and 102.2%–103.1%, respectively. These results indicate the ERGO/GCE based sensor is suitable for the detection of octopamine and tyramine. PMID:27089341

Octopamine increases the excitability of neurons in the snail feeding system by modulation of inward sodium current but not outward potassium currents.

PubMed

Vehovszky, Agnes; Szabó, Henriette; Elliott, Christopher J H

2005-12-06

Although octopamine has long been known to have major roles as both transmitter and modulator in arthropods, it has only recently been shown to be functionally important in molluscs, playing a role as a neurotransmitter in the feeding network of the snail Lymnaea stagnalis. The synaptic potentials cannot explain all the effects of octopamine-containing neurons on the feeding network, and here we test the hypothesis that octopamine is also a neuromodulator. The excitability of the B1 and B4 motoneurons in the buccal ganglia to depolarising current clamp pulses is significantly (P < < 0.05) increased by (10 microM) octopamine, whereas the B2 motoneuron becomes significantly less excitable. The ionic currents evoked by voltage steps were recorded using 2-electrode voltage clamp. The outward current of B1, B2 and B4 motoneurons had two components, a transient IA current and a sustained IK delayed-rectifier current, but neither was modulated by octopamine in any of these three buccal neurons. The fast inward current was eliminated in sodium-free saline and so is likely to be carried by sodium ions. 10 microM octopamine enhanced this current by 33 and 45% in the B1 and B4 motoneurons respectively (P < < 0.05), but a small reduction was seen in the B2 neuron. A Hodgkin-Huxley style simulation of the B1 motoneuron confirms that a 33% increase in the fast inward current by octopamine increases the excitability markedly. We conclude that octopamine is also a neuromodulator in snails, changing the excitability of the buccal neurons. This is supported by the close relationship from the voltage clamp data, through the quantitative simulation, to the action potential threshold, changing the properties of neurons in a rhythmic network. The increase in inward sodium current provides an explanation for the polycyclic modulation of the feeding system by the octopamine-containing interneurons, making feeding easier to initiate and making the feeding bursts more intense.

Dietary trace amine-dependent vasoconstriction in porcine coronary artery

PubMed Central

Herbert, A A; Kidd, E J; Broadley, K J

2008-01-01

Background and purpose: The dietary trace amines tyramine and β-phenylethylamine (β-PEA) can increase blood pressure. However, the mechanisms involved in the vascular effect of trace amines have not been fully established. The purpose of this study was to evaluate whether trace amine-dependent vasoconstriction was brought about by tyramine and β-PEA acting as indirect sympathomimetic agents, as previously assumed, or whether trace amine-dependent vasoconstriction could be mediated by recently discovered trace amine-associated (TAA) receptors. Experimental approach: The responses to p-tyramine and β-PEA were investigated in vitro in rings of the left anterior descending coronary arteries of pigs. Key results: p-Tyramine induced a concentration-dependent (0.1–3 mM) vasoconstriction. The maximum response and pD2 value for p-tyramine was unaffected by endothelium removal or pre-treatment with antagonists for adrenoceptors, histamine, dopamine or 5-HT receptors. β-PEA also produced a concentration-dependent (0.3–10 mM) vasoconstriction which was unaffected by endothelium removal, β-adrenoceptor or 5-HT receptor antagonists. A substantial, but reduced, response to β-PEA was obtained in the presence of prazosin (α1-adrenoceptor antagonist), haloperidol (D2/D3 dopamine receptor antagonist) or mepyramine (H1 histamine receptor antagonist). The pD2 value for β-PEA was unaffected by any of the antagonists tested. Conclusions and implications: Vasoconstriction induced by p-tyramine does not involve an indirect sympathomimetic effect, although vasoconstriction caused by β-PEA may occur, in part, by this mechanism. We therefore propose that trace amine-dependent vasoconstriction is mediated by phenylethylamine-specific receptors, which are closely related to or identical to TAA receptors. These receptors could provide a target for new antihypertensive therapies. PMID:18604230

Nanodiamonds on tetrahedral amorphous carbon significantly enhance dopamine detection and cell viability.

PubMed

Peltola, Emilia; Wester, Niklas; Holt, Katherine B; Johansson, Leena-Sisko; Koskinen, Jari; Myllymäki, Vesa; Laurila, Tomi

2017-02-15

We hypothesize that by using integrated carbon nanostructures on tetrahedral amorphous carbon (ta-C), it is possible to take the performance and characteristics of these bioelectrodes to a completely new level. The integrated carbon electrodes were realized by combining nanodiamonds (NDs) with ta-C thin films coated on Ti-coated Si-substrates. NDs were functionalized with mixture of carboxyl and amine groups ND andante or amine ND amine , carboxyl ND vox or hydroxyl groups ND H and drop-casted or spray-coated onto substrate. By utilizing these novel structures we show that (i) the detection limit for dopamine can be improved by two orders of magnitude [from 10µM to 50nM] in comparison to ta-C thin film electrodes and (ii) the coating method significantly affects electrochemical properties of NDs and (iii) the ND coatings selectively promote cell viability. ND andante and ND H showed most promising electrochemical properties. The viability of human mesenchymal stem cells and osteoblastic SaOS-2 cells was increased on all ND surfaces, whereas the viability of mouse neural stem cells and rat neuroblastic cells was improved on ND andante and ND H and reduced on ND amine and ND vox. The viability of C6 cells remained unchanged, indicating that these surfaces will not cause excess gliosis. In summary, we demonstrated here that by using functionalized NDs on ta-C thin films we can significantly improve sensitivity towards dopamine as well as selectively promote cell viability. Thus, these novel carbon nanostructures provide an interesting concept for development of various in vivo targeted sensor solutions. Copyright © 2016 Elsevier B.V. All rights reserved.

A sleep state in Drosophila larvae required for neural stem cell proliferation

PubMed Central

Szuperak, Milan; Churgin, Matthew A; Borja, Austin J; Raizen, David M; Fang-Yen, Christopher

2018-01-01

Sleep during development is involved in refining brain circuitry, but a role for sleep in the earliest periods of nervous system elaboration, when neurons are first being born, has not been explored. Here we identify a sleep state in Drosophila larvae that coincides with a major wave of neurogenesis. Mechanisms controlling larval sleep are partially distinct from adult sleep: octopamine, the Drosophila analog of mammalian norepinephrine, is the major arousal neuromodulator in larvae, but dopamine is not required. Using real-time behavioral monitoring in a closed-loop sleep deprivation system, we find that sleep loss in larvae impairs cell division of neural progenitors. This work establishes a system uniquely suited for studying sleep during nascent periods, and demonstrates that sleep in early life regulates neural stem cell proliferation. PMID:29424688

Contrary effects of octopamine receptor ligands on behavioral and neuronal changes in locomotion of lymnaea.

PubMed

Miyamae, Yurie; Komuro, Mami; Murata, Aya; Aono, Kanako; Nishikata, Kaori; Kanazawa, Akira; Fujito, Yutaka; Komatsu, Takumi; Ito, Daisuke; Abe, Takashi; Nagayama, Masafumi; Uchida, Tsutomu; Gohara, Kazutoshi; Murakami, Jun; Kawai, Ryo; Hatakeyama, Dai; Lukowiak, Ken; Ito, Etsuro

2010-02-01

The pond snail Lymnaea stagnalis moves along the sides and bottom of an aquarium, but it can also glide upside down on its back below the water's surface. We have termed these two forms of locomotion "standard locomotion" and "upside-down gliding," respectively. Previous studies showed that standard locomotion is produced by both cilia activity on the foot and peristaltic contraction of the foot muscles, whereas upside-down gliding is mainly caused by cilia activity. The pedal A neurons are thought to receive excitatory octopaminergic input, which ultimately results in increased cilia beating. However, the relationship between locomotory speed and the responses of these neurons to octopamine is not known. We thus examined the effects of both an agonist and an antagonist of octopamine receptors on locomotory speed and the firing rate of the pedal A neurons. We also examined, at the electron and light-microscopic levels, whether structural changes occur in cilia following the application of either an agonist or an antagonist of octopamine receptors to the central nervous system (CNS). We found that the application of an octopamine antagonist to the CNS increased the speed of both forms of locomotion, whereas application of octopamine increased only the firing rate of the pedal A neurons. Microscopic examination of the cilia proved that there were no changes in their morphology after application of octopamine ligands. These data suggest that there is an unidentified octopaminergic neuronal network in the CNS whose activation reduces cilia movement and thus locomotory speed.

Syntheses of conformationally defined analogues of tyramine and phenylethanolamine and their biological evaluations at central dopamine receptors and the active site of phenylethanolamine N-methyltransferase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ye, Q.

Tyramine analogues 31-33 and 37-39 were evaluated for dopaminergic activities on rat striatal tissues with radioligands ({sup 3}H)SCH23390 for D-1 receptor and ({sup 3}H)spiroperidol for D-2 receptor. The tertiary amines 37-39 were generally more potent than the primary amines 31-33. In the primary amines, 33 (2-OH) was more potent than 31 and 32, and in the tertiary amines, 37 (4-OH) was more potent than 38 and 39 at both D-1 and D-2 receptors. The reduced activity of 31-33 and 37-39 compared with corresponding hydroxyl-substituted 2ATs is consistent with a negative interaction from the extra ethano bridge in their binding tomore » the dopamine receptors. No selectivity was observed in both these conformationally defined tyramines (31-33 and 37-39) and conformationally restricted tyramines; a good correlation was observed between log IC{sub 5}O values at D-1 and D-2 receptors. The tyramines 31-33, the phenylethanolamines 45 and 46, and the phenylethylamine 44 (X, Y = H) were evaluated for activities as either substrates or inhibitors of phenylethanolamine N-methyltransferase (PNMT) by an in vitro radiochemical assay.« less

D2 dopaminergic and 5-HT1A serotonergic activity of 2-(1-naphthyl)ethyl- and 2-(2-naphthyl)ethyl amines.

PubMed

Šukalović, V; Roglić, G; Husinec, S; Kostić-Rajaćić, S; Andrić, D; Šoškić, Vukić

2003-11-01

Several tertiary 2-phenylethyl, 2-(1-naphthyl)ethyl and 2-(2-naphthyl)ethyl amines were synthesized and their binding affinities for dopamine D(1), D(2) and serotonin 5-HT(1A) receptors evaluated in radioligand binding assays. All compounds were inactive in D(1) dopamine radioligand binding assay. The 2-(1-naphthyl)ethyl analogues expressed a low but significant binding affinity for the D(2) and moderate one for the 5-HT(1A) receptor subtypes. Most of the remaining compounds expressed binding affinity at the 5-HT(1A) receptor subtype but were inactive in D(2) receptor binding assay. Based on these results and considering the chemical characteristics of the compounds synthesized and evaluated for dopaminergic and serotonergic activity throughout the present study it can be concluded that hydrophobic type of interaction (stacking or edge-to-face) plays a significant role in the formation of receptor-ligand complexes of 2-(1-naphthyl)ethyl amines. This structural motive can be applied to design and synthesize new, more potent dopaminergic/serotonergic ligands by slight chemical modifications.

Determination of biogenic amines in chocolate by ion chromatographic separation and pulsed integrated amperometric detection with implemented wave-form at Au disposable electrode.

PubMed

Pastore, Paolo; Favaro, Gabriella; Badocco, Denis; Tapparo, Andrea; Cavalli, Silvano; Saccani, Giovanna

2005-12-09

A rapid and selective cation exchange chromatographic method coupled to integrated pulsed amperometric detection (PAD) has been developed to quantify biogenic amines in chocolate. The method is based on gradient elution of aqueous methanesulfonic acid with post column addition of strong base to obtain suitable conditions for amperometric detection. A potential waveform able to keep long time performance of the Au disposable electrode was set up. Total analysis time is less than 20min. Concentration levels of dopamine, serotonin, tyramine, histamine and 2-phenylethylamine were measured, after extraction with perchloric acid from 2g samples previously defatted twice with petroleum ether. The method was used to determine the analytes in chocolate real matrices and their quantification was made with standard addition method. Only dopamine, histamine and serotonin were found in the analysed real samples. Repeatabilities of their signals, computed on their amounts in the real samples, were 5% for all of them. Repeatabilities of tyramine and phenethylamine were relative to standard additions to real samples (close to 1mg/l in the extract) and were 7 and 3%, respectively. Detection limits were computed with the 3s of the baseline noise combined with the calibration plot regression parameters. They were satisfactorily low for all amines: 3mg/kg for dopamine, 2mg/kg for tyramine, 1mg/kg for histamine, 2mg/kg for serotonin, 3mg/kg for 2-phenylethylamine.

N-Docosahexaenoyl Dopamine, an Endocannabinoid-like Conjugate of Dopamine and the n-3 Fatty Acid Docosahexaenoic Acid, Attenuates Lipopolysaccharide-Induced Activation of Microglia and Macrophages via COX-2.

PubMed

Wang, Ya; Plastina, Pierluigi; Vincken, Jean-Paul; Jansen, Renate; Balvers, Michiel; Ten Klooster, Jean Paul; Gruppen, Harry; Witkamp, Renger; Meijerink, Jocelijn

2017-03-15

Several studies indicate that the n-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) contributes to an attenuated inflammatory status in the development of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. To explain these effects, different mechanisms are being proposed, including those involving endocannabinoids and related signaling molecules. Many of these compounds belong to the fatty acid amides, conjugates of fatty acids with biogenic amines. Conjugates of DHA with ethanolamine or serotonin have previously been shown to possess anti-inflammatory and potentially neuroprotective properties. Here, we synthesized another amine conjugate of DHA, N-docosahexaenoyl dopamine (DHDA), and tested its immune-modulatory properties in both RAW 264.7 macrophages and BV-2 microglial cells. N-Docosahexaenoyl dopamine significantly suppressed the production of nitric oxide (NO), the cytokine interleukin-6 (IL-6), and the chemokines macrophage-inflammatory protein-3α (CCL20) and monocyte chemoattractant protein-1 (MCP-1), whereas its parent compounds, dopamine and DHA, were ineffective. Further exploration of potential effects of DHDA on key inflammatory mediators revealed that cyclooxygenase-2 (COX-2) mRNA level and production of prostaglandin E 2 (PGE 2 ) were concentration-dependently inhibited in macrophages. In activated BV-2 cells, PGE 2 production was also reduced, without changes in COX-2 mRNA levels. In addition, DHDA did not affect NF-kB activity in a reporter cell line. Finally, the immune-modulatory activities of DHDA were compared with those of N-arachidonoyl dopamine (NADA) and similar potencies were found in both cell types. Taken together, our data suggest that DHDA, a potentially endogenous endocannabinoid, may be an additional member of the group of immune-modulating n-3 fatty acid-derived lipid mediators.

Octopaminergic gene expression and flexible social behaviour in the subsocial burying beetle Nicrophorus vespilloides

PubMed Central

Cunningham, C B; Douthit, M K; Moore, A J

2014-01-01

Flexible behaviour allows organisms to respond appropriately to changing environmental and social conditions. In the subsocial beetle Nicrophorus vespilloides, females tolerate conspecifics when mating, become aggressive when defending resources, and return to social tolerance when transitioning to parenting. Given the association between octopamine and aggression in insects, we hypothesized that genes in the octopaminergic system would be differentially expressed across different social and reproductive contexts. To test this in N. vespilloides, we first obtained the sequences of orthologues of the synthetic enzymes and receptors of the octopaminergic system. We next compared relative gene expression from virgin females, mated females, mated females alone on a resource required for reproduction and mated females on a resource with a male. Expression varied for five receptor genes. The expression of octopamine β receptor 1 and octopamine β receptor 2 was relatively higher in mated females than in other social conditions. Octopamine β receptor 3 was influenced by the presence or absence of a resource and less by social environment. Octopamine α receptor and octopamine/tyramine receptor 1 gene expression was relatively lower in the mated females with a resource and a male. We suggest that in N. vespilloides the octopaminergic system is associated with the expression of resource defence, alternative mating tactics, social tolerance and indirect parental care. PMID:24646461

Effect of a single neonatal oxytocin treatment (hormonal imprinting) on the biogenic amine level of the adult rat brain: could oxytocin-induced labor cause pervasive developmental diseases?

PubMed

Hashemi, F; Tekes, Kornélia; Laufer, R; Szegi, P; Tóthfalusi, L; Csaba, G

2013-10-01

Perinatal single-hormone treatment causes hormonal imprinting with lifelong consequences in receptor-binding capacity, hormone production as well as in social and sexual behavior. In the present experiments, newborn rats were treated with a single dose of oxytocin, and the levels of biogenic amines and their metabolites were studied in 8 different brain regions and in the sera when the male and female animals were 4 months old. Both dopaminergic and serotonergic neurotransmission was found to be significantly influenced. The levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindole acetic acid metabolites decreased in the hypothalamus and striatum. Dopamine, serotonin, norepinephrine, and 5-hydroxytryptophol levels were hardly altered, and there was no difference in the epinephrine levels. The results show that dopamine and serotonin metabolism of hypothalamus and striatum are deeply and lifelong influenced by a single neonatal oxytocin treatment Oxytocin imprinting resulted in decreased dopamine turnover in the hypothalamus and decreased serotonin turnover in the hypothalamus, medulla oblongata, and striatum of females. As the disturbance of brain dopamine and serotonin system has an important role in the development of pervasive developmental diseases (eg, autism) and neuropsychiatric disorders (eg, schizophrenia), the growing number of oxytocin-induced labor as a causal factor, cannot be omitted.

Concentrations of biogenic amines in fundal layers in chickens with normal visual experience, deprivation, and after reserpine application.

PubMed

Ohngemach, S; Hagel, G; Schaeffel, F

1997-01-01

Previous experiments in chickens have shown that dopamine released from the retina may be one of the messengers controlling the growth of the underlying sclera. It is also possible, however, that the apparent relationship between dopamine and myopia is secondary and artifactual. We have done experiments to assess this hypothesis. Using High Pressure Liquid Chromatography with electrochemical detection (HPLC-ED), we have asked whether changes in dopamine metabolism are restricted to the local retinal regions in which myopia was locally induced. Furthermore, we have measured the concentrations of biogenic amines separately in different fundal layers (vitreous, retina, choroid, and sclera) to find out how changes induced by "deprivation" (= removal of high spatial frequencies from the retinal image by translucent eye occluders which produce "deprivation myopia") are transmitted through these layers. Finally, we have repeated the deprivation experiments after intravitreal application of the irreversible dopamine re-uptake blocker reserpine to see how suppression of dopaminergic transmission affects these changes. We found that (1) Alterations in retinal dopamine metabolism were indeed restricted to the retinal areas in which myopia was induced. (2) The retina was the major source of dopamine release with a steep gradient both to the vitreal and choroidal side. Vitreal content was about one-tenth, choroidal content about one-third, and scleral content about one-twentieth of that of the retina. (3) There was a drop by about 40% in vitreal dopamine, DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanilic acid) concentrations following deprivation which occurred already at a time where little changes could yet be seen in their total retinal contents. (4) Choroidal and scleral dopamine levels were not affected by deprivation, indicating that other messengers must relay the information to the sclera. (5) A single intravitreal injection of reserpine lowered dopamine and HVA levels in retina and vitreous for at least 10 days in a dose-dependent fashion and diminished or suppressed further effects of deprivation on these compounds. DOPAC levels continued to change upon deprivation even after reserpine injection (Fig. 3). Our results suggest that the release rates of dopamine from retinal amacrine cells can be estimated from vitreal dopamine concentrations; furthermore, they are in line with the hypothesis that there is an inverse relationship between dopamine release and axial eye growth rates. Although our experiments do not ultimately prove that dopamine has a functional role in the visual control of eye growth, they are in line with this notion.

Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase.

PubMed

Murphy, D L; Sims, K B; Karoum, F; Garrick, N A; de la Chapelle, A; Sankila, E M; Norio, R; Breakefield, X O

1991-01-01

Two individuals with an X-chromosomal deletion were recently found to lack the genes encoding monoamine oxidase type A (MAO-A) and MAO-B. This abnormality was associated with almost total (90%) reductions in the oxidatively deaminated urinary metabolites of the MAO-A substrate, norepinephrine, and with marked (100-fold) increases in an MAO-B substrate, phenylethylamine, confirming systemic functional consequences of the genetic enzyme deficiency. However, urinary concentrations of the deaminated metabolites of dopamine and serotonin (5-HT) were essentially normal. To investigate other deaminating systems besides MAO-A and MAO-B that might produce these metabolites of dopamine and 5-HT, we examined plasma amine oxidase (AO) activity in these two patients and two additional patients with the same X-chromosomal deletion. Normal plasma AO activity was found in all four Norrie disease-deletion patients, in four patients with classic Norrie disease without a chromosomal deletion, and in family members of patients from both groups. Marked plasma amine metabolite abnormalities and essentially absent platelet MAO-B activity were found in all four Norrie disease-deletion patients, but in none of the other subjects in the two comparison groups. These results indicate that plasma AO is encoded by gene(s) independent of those for MAO-A and MAO-B, and raise the possibility that plasma AO, and perhaps the closely related tissue AO, benzylamine oxidase, as well as other atypical AOs or MAOs encoded independently from MAO-A and MAO-B may contribute to the oxidative deamination of dopamine and 5-HT in humans.

Influence of He-Ne laser radiation on biogenic amines content and cytochemical parameters of polymorphonuclear leukocytes in short-term stress

NASA Astrophysics Data System (ADS)

Brill, Gregory E.; Dobrovolsky, Gennady A.; Romanova, Tatyana P.; Porozova, Svetlana G.; Brill, Alexander G.

1997-06-01

In experiments on white male rats short-term immobilization- sound stress was modelled. Decrease of glycogen content and myeloperoxidase activity, increase of lysosomal cationic proteins level and NBT-test parameters as well as fall of adrenaline, dopamine and 5-hydroxytryptamine amount in polymorphonuclear leukocytes were observed. Preliminary transcutaneous He-Ne laser irradiation modified metabolic reaction of leukocytes to stress and prevented stress- induced decrease of biogenic amines content in cells.

Synthesis of hybrid cellulose nanocomposite bonded with dopamine SiO2/TiO2 and its antimicrobial activity

NASA Astrophysics Data System (ADS)

Ramesh, Sivalingam; Kim, Gwang-Hoon; Kim, Jaehwan; Kim, Joo-Hyung

2015-04-01

Organic-inorganic hybrid material based cellulose was synthesized by the sol-gel approach. The explosion of activity in this area in the past decade has made tremendous progress in industry or academic both fundamental understanding of sol-gel process and applications of new functionalized hybrid materials. In this present research work, we focused on cellulose-dopamine functionalized SiO2/TiO2 hybrid nanocomposite by sol-gel process. The cellulose-dopamine hybrid nanocomposite was synthesized via γ-aminopropyltriethoxysilane (γ-APTES) coupling agent by in-situ sol-gel process. The chemical structure of cellulose-amine functionalized dopamine bonding to cellulose structure with covalent cross linking hybrids was confirmed by FTIR spectral analysis. The morphological analysis of cellulose-dopamine nanoSiO2/TiO2 hybrid nanocomposite materials was characterized by XRD, SEM and TEM. From this different analysis results indicate that the optical transparency, thermal stability, control morphology of cellulose-dopamine-SiO2/TiO2 hybrid nanocomposite. Furthermore cellulose-dopamine-SiO2/TiO2 hybrid nanocomposite was tested against pathogenic bacteria for antimicrobial activity.

Identified Serotonin-Releasing Neurons Induce Behavioral Quiescence and Suppress Mating in Drosophila.

PubMed

Pooryasin, Atefeh; Fiala, André

2015-09-16

Animals show different levels of activity that are reflected in sensory responsiveness and endogenously generated behaviors. Biogenic amines have been determined to be causal factors for these states of arousal. It is well established that, in Drosophila, dopamine and octopamine promote increased arousal. However, little is known about factors that regulate arousal negatively and induce states of quiescence. Moreover, it remains unclear whether global, diffuse modulatory systems comprehensively affecting brain activity determine general states of arousal. Alternatively, individual aminergic neurons might selectively modulate the animals' activity in a distinct behavioral context. Here, we show that artificially activating large populations of serotonin-releasing neurons induces behavioral quiescence and inhibits feeding and mating. We systematically narrowed down a role of serotonin in inhibiting endogenously generated locomotor activity to neurons located in the posterior medial protocerebrum. We identified neurons of this cell cluster that suppress mating, but not feeding behavior. These results suggest that serotonin does not uniformly act as global, negative modulator of general arousal. Rather, distinct serotoninergic neurons can act as inhibitory modulators of specific behaviors. An animal's responsiveness to external stimuli and its various types of endogenously generated, motivated behavior are highly dynamic and change between states of high activity and states of low activity. It remains unclear whether these states are mediated by unitary modulatory systems globally affecting brain activity, or whether distinct neurons modulate specific neuronal circuits underlying particular types of behavior. Using the model organism Drosophila melanogaster, we find that activating large proportions of serotonin-releasing neurons induces behavioral quiescence. Moreover, distinct serotonin-releasing neurons that we genetically isolated and identified negatively affect aspects of mating behavior, but not food uptake. This demonstrates that individual serotoninergic neurons can modulate distinct types of behavior selectively. Copyright © 2015 the authors 0270-6474/15/3512792-21$15.00/0.

Losing without Fighting - Simple Aversive Stimulation Induces Submissiveness Typical for Social Defeat via the Action of Nitric Oxide, but Only When Preceded by an Aggression Priming Stimulus

PubMed Central

Rillich, Jan; Stevenson, Paul A.

2017-01-01

Losing a fight (social defeat) induces submissiveness and behavioral depression in many animals, but the mechanisms are unclear. Here we investigate how the social defeat syndrome can be established as a result of experiencing aversive stimuli and the roles of neuromodulators in the process. While biogenic amines and nitric oxide (NO) are associated with reduced aggression in mammals and insects, their specific actions during conflict are unknown. Although the social defeat syndrome normally results from complex interactions, we could induce it in male crickets simply by applying aversive stimuli (AS) in an aggressive context. Aggressive crickets became immediately submissive and behaved like losers after experiencing two brief AS (light wind puffs to the cerci), but only when preceded by a priming stimulus (PS, stroking the antenna with another male antenna). Notably, submissiveness was not induced when the PS preceded the AS by more than 1 min, or when the PS followed the AS, or using a female antenna as the preceding stimulus. These findings suggest that any potentially detrimental stimulus can acquire the attribute of an aversive agonistic signal when experienced in an aggressive context. Crickets, it seems, need only to evaluate their net sensory impact rather than the qualities of a variety of complex agonistic signals. Selective drug treatments revealed that NO, but not serotonin, dopamine or octopamine, is necessary to establish the submissive status following pairing of the priming and aversive stimuli. Moreover, treatment with an NO donor also induced the social defeat syndrome, but only when combined with the PS. This confirms our hypothesis that aversive agonistic experiences accumulated by crickets during fighting invoke social defeat via the action of NO and illustrates that a relatively simple mechanism underlies the seemingly complex social decision to flee. The simple stimulus regime described here for inducing social defeat opens new avenues for investigating the cellular control of subordinate behavior and post-conflict depression. PMID:28381994

RELATIVE ACTIONS OF QUATERNARY METHYL DERIVATIVES OF TYRAMINE, DOPAMINE AND NORADRENALINE.

PubMed

CUTHBERT, M F

1964-08-01

Tyramine methiodide and dopamine methobromide have greater pressor effect (three- to five-times) in the spinal cat than the parent amines. Noradrenaline methochloride has little pressor effect. Dopamine methobromide is about four times as potent as nicotine; tyramine methiodide is about equiactive to nicotine; and noradrenaline methochloride has only one-tenth the potency of nicotine. Their pressor effects are usually abolished by hexamethonium but in some experiments the effect of noradrenaline methochloride persisted and was then abolished by tolazoline. Injected intravenously into the cat anaesthetized with chloralose, each of the three quaternary derivatives contracts the nictitating membrane; dopamine methobromide is again the most active, having more than six times the potency of nicotine. When the contractions of the nictitating membrane are induced by continuous stimulation of the preganglionic fibres of the cervical sympathetic nerve, intravenous injection of the quaternary derivatives of tyramine and dopamine has a biphasic effect; there is a block on which a contraction of the membrane appears to be superimposed. Noradrenaline methochloride produces only a further contraction of the membrane. On the isolated rectus abdominis muscle preparation of the frog, dopamine methobromide is the most active in contracting the muscle, being about twelve times as active as nicotine; noradrenaline methochloride is weakest, having only one-hundredth the activity of nicotine. These effects are antagonized by hexamethonium. On the isolated phrenic nerve-diaphragm preparation of the rat, the quaternary derivatives of tyramine and dopamine each have neuromuscular blocking properties, 0.7- and 3-times respectively that of nicotine. Noradrenaline methochloride has no effect. In the sciatic nerve-tibialis preparation of the cat, the quaternary derivatives of tyramine and dopamine are approximately equipotent in producing neuromuscular paralysis, having about three times the activity of nicotine and one-fifth that of suxamethonium. These effects are not antagonized either by neostigmine or by edrophonium. Noradrenaline methochloride has no neuromuscular blocking effect. The nicotine-like properties of these quaternized sympathomimetic amines are discussed. It is of interest that the presence of an hydroxyl group attached to the beta-carbon atom of the side-chain greatly reduces nicotine-like activity. By comparison, choline had about one forty-fifth the pressor activity of ethyltrimethylammonium.

Relative actions of quaternary methyl derivatives of tyramine, dopamine and noradrenaline

PubMed Central

Cuthbert, M. F.

1964-01-01

Tyramine methiodide and dopamine methobromide have greater pressor effect (three- to five-times) in the spinal cat than the parent amines. Noradrenaline methochloride has little pressor effect. Dopamine methobromide is about four times as potent as nicotine; tyramine methiodide is about equiactive to nicotine; and noradrenaline methochloride has only one-tenth the potency of nicotine. Their pressor effects are usually abolished by hexamethonium but in some experiments the effect of noradrenaline methochloride persisted and was then abolished by tolazoline. Injected intravenously into the cat anaesthetized with chloralose, each of the three quaternary derivatives contracts the nictitating membrane; dopamine methobromide is again the most active, having more than six times the potency of nicotine. When the contractions of the nictitating membrane are induced by continuous stimulation of the preganglionic fibres of the cervical sympathetic nerve, intravenous injection of the quaternary derivatives of tyramine and dopamine has a biphasic effect; there is a block on which a contraction of the membrane appears to be superimposed. Noradrenaline methochloride produces only a further contraction of the membrane. On the isolated rectus abdominis muscle preparation of the frog, dopamine methobromide is the most active in contracting the muscle, being about twelve times as active as nicotine; noradrenaline methochloride is weakest, having only one-hundredth the activity of nicotine. These effects are antagonized by hexamethonium. On the isolated phrenic nerve-diaphragm preparation of the rat, the quaternary derivatives of tyramine and dopamine each have neuromuscular blocking properties, 0.7- and 3-times respectively that of nicotine. Noradrenaline methochloride has no effect. In the sciatic nerve-tibialis preparation of the cat, the quaternary derivatives of tyramine and dopamine are approximately equipotent in producing neuromuscular paralysis, having about three times the activity of nicotine and one-fifth that of suxamethonium. These effects are not antagonized either by neostigmine or by edrophonium. Noradrenaline methochloride has no neuromuscular blocking effect. The nicotine-like properties of these quaternized sympathomimetic amines are discussed. It is of interest that the presence of an hydroxyl group attached to the β-carbon atom of the side-chain greatly reduces nicotine-like activity. By comparison, choline had about one forty-fifth the pressor activity of ethyltrimethylammonium. PMID:14206269

Neural control of salivary glands in ixodid ticks.

PubMed

Šimo, Ladislav; Zitňan, Dušan; Park, Yoonseong

2012-04-01

Studies of tick salivary glands (SGs) and their components have produced a number of interesting discoveries over the last four decades. However, the precise neural and physiological mechanisms controlling SG secretion remain enigmatic. Major studies of SG control have identified and characterized many pharmacological and biological compounds that activate salivary secretion, including dopamine (DA), octopamine, γ-aminobutyric acid (GABA), ergot alkaloids, pilocarpine (PC), and their pharmacological relatives. Specifically, DA has shown the most robust activities in various tick species, and its effect on downstream actions in the SGs has been extensively studied. Our recent work on a SG dopamine receptor has aided new interpretations of previous pharmacological studies and provided new concepts for SG control mechanisms. Furthermore, our recent studies have suggested that multiple neuropeptides are involved in SG control. Myoinhibitory peptide (MIP) and SIFamide have been identified in the neural projections reaching the basal cells of acini types II and III. Pigment-dispersing factor (PDF)-immunoreactive neural projections reach type II acini, and RFamide- and tachykinin-immunoreactive projections reach the SG ducts, but the chemical nature of the latter three immunoreactive substances are unidentified yet. Here, we briefly review previous pharmacological studies and provide a revised summary of SG control mechanisms in ticks. Copyright © 2011 Elsevier Ltd. All rights reserved.

Agonist-specific coupling of a cloned Drosophila octopamine/tyramine receptor to multiple second messenger systems.

PubMed Central

Robb, S; Cheek, T R; Hannan, F L; Hall, L M; Midgley, J M; Evans, P D

1994-01-01

A cloned seven transmembrane-spanning Drosophila octopamine/tyramine receptor, permanently expressed in a Chinese hamster ovary cell line, both inhibits adenylate cyclase activity and leads to the elevation of intracellular Ca2+ levels by separate G-protein-coupled pathways. Agonists of this receptor (octopamine and tyramine), differing by only a single hydroxyl group in their side chain, may be capable of differentially coupling it to different second messenger systems. Thus, a single receptor may have a different pharmacological profile depending on which second messenger system is used to assay its efficacy. PMID:8137817

Dopamine transporter-dependent and -independent actions of trace amine beta-phenylethylamine.

PubMed

Sotnikova, Tatyana D; Budygin, Evgeny A; Jones, Sara R; Dykstra, Linda A; Caron, Marc G; Gainetdinov, Raul R

2004-10-01

Beta-phenylethylamine (beta-PEA) is an endogenous amine that is found in trace amounts in the brain. It is believed that the locomotor-stimulating action of beta-PEA, much like amphetamine, depends on its ability to increase extracellular dopamine (DA) concentrations owing to reversal of the direction of dopamine transporter (DAT)-mediated DA transport. beta-PEA can also bind directly to the recently identified G protein-coupled receptors, but the physiological significance of this interaction is unclear. To assess the mechanism by which beta-PEA mediates its effects, we compared the neurochemical and behavioral effects of this amine in wild type (WT), heterozygous and 'null' DAT mutant mice. In microdialysis studies, beta-PEA, administered either systemically or locally via intrastriatal infusion, produced a pronounced outflow of striatal DA in WT mice whereas no increase was detected in mice lacking the DAT (DAT-KO mice). Similarly, in fast-scan voltammetry studies beta-PEA did not alter DA release and clearance rate in striatal slices from DAT-KO mice. In behavioral studies beta-PEA produced a robust but transient increase in locomotor activity in WT and heterozygous mice. In DAT-KO mice, whose locomotor activity and stereotypy are increased in a novel environment, beta-PEA (10-100 mg/kg) exerted a potent inhibitory action. At high doses, beta-PEA induced stereotypies in WT and heterozygous mice; some manifestations of stereotypy were also observed in the DAT-KO mice. These data demonstrate that the DAT is required for the striatal DA-releasing and hyperlocomotor actions of beta-PEA. The inhibitory action on hyperactivity and certain stereotypies induced by beta-PEA in DAT-KO mice indicate that targets other than the DAT are responsible for these effects.

Monoamine oxidase-B inhibitors in the treatment of Parkinson's disease: clinical-pharmacological aspects.

PubMed

Riederer, Peter; Müller, Thomas

2018-03-22

This invited narrative review emphasizes the role of MAO-B inhibition in the drug portfolio for dopamine substitution in patients with Parkinson's disease. Neuronal and glial MAO-B inhibition contributes to more stable levels of dopamine and other biogenic amines in the synaptic cleft. Accordingly, symptomatic effects of MAO-B inhibition for a limited amelioration of impaired motor behaviour and wearing-off phenomena in patients with Parkinson's disease are well proven, even when MAO-B inhibitors are only applied together with dopamine agonists. Delay of disease progression by MAO-B inhibition is under debate despite positive experimental findings. This discussion does not consider, that levodopa, respectively, dopamine agonists, are substrates, respectively, inhibitors of the ABCB1 (P-gp, MDR1, and CD243) transporter system. It supports toxin efflux over the blood-brain barrier. ABCB1 transporters have a limited capacity. MAO-B inhibitors do not weaken it. Treatment with MAO-B inhibitors is advantageous as it enables sparing of dopamine agonist and levodopa dosing.

Octopamine-signaling in the metazoan pathogen, Schistosoma mansoni: localization, small-molecule screening and opportunities for drug development.

PubMed

El-Sakkary, Nelly; Chen, Steven; Arkin, Michelle R; Caffrey, Conor R; Ribeiro, Paula

2018-06-20

Schistosomiasis is a tropical disease caused by a flatworm trematode parasite that infects over 240 million people worldwide. Treatment and control of the disease rely on just one drug, praziquantel. The possibility of drug resistance coupled with praziquantel's variable efficacy encourages the identification of new drugs and drug targets. Disruption of neuromuscular homeostasis in parasitic worms is a validated strategy for drug development. However, in schistosomes, much remains to be understood about the organization of the nervous system, its component neurotransmitters and potential for drug discovery. Using synapsin as a neuronal marker, we map the central and peripheral nervous systems in the Schistosoma mansoni adult and schistosomulum (post-infective larva). We discover the widespread presence of octopamine (OA), a tyrosine-derived and invertebrate-specific neurotransmitter involved in neuromuscular coordination. OA-labeling facilitated the discovery of two pairs of ganglia in the brain of the adult schistosome rather than the one pair thus far reported for this or other trematodes. In quantitative phenotypic assays, OA and structurally-related tyrosine-derived phenolamine and catecholamine neurotransmitters differentially modulated schistosomulum motility and length. Similarly, from a screen of 28 drug agonists and antagonists of tyrosine derivative-signaling, certain drugs that act on OA and dopamine receptors induced robust and sometimes complex concentration-dependent effects on schistosome motility and length, including at concentrations achievable in vivo The present data advance our knowledge of the organization of the nervous system in this globally important pathogen and identify a number of drugs that interfere with tyrosine-derived signaling, one or more of which may provide the basis for a new chemotherapeutic approach to treat schistosomiasis. © 2018. Published by The Company of Biologists Ltd.

A new Drosophila octopamine receptor responds to serotonin.

PubMed

Qi, Yi-Xiang; Xu, Gang; Gu, Gui-Xiang; Mao, Fen; Ye, Gong-Yin; Liu, Weiwei; Huang, Jia

2017-11-01

As the counterparts of the vertebrate adrenergic transmitters, octopamine and tyramine are important physiological regulators in invertebrates. They control and modulate many physiological and behavioral functions in insects. In this study, we reported the pharmacological properties of a new α2-adrenergic-like octopamine receptor (CG18208) from Drosophila melanogaster, named DmOctα2R. This new receptor gene encodes two transcripts by alternative splicing. The long isoform DmOctα2R-L differs from the short isoform DmOctα2R-S by the presence of an additional 29 amino acids within the third intracellular loop. When heterologously expressed in mammalian cell lines, both receptors were activated by octopamine, tyramine, epinephrine and norepinephrine, resulting in the inhibition of cAMP production in a dose-dependent manner. The long form is more sensitive to the above ligands than the short form. The adrenergic agonists naphazoline, tolazoline and clonidine can stimulate DmOctα2R as full agonists. Surprisingly, serotonin and serotoninergic agonists can also activate DmOctα2R. Several tested adrenergic antagonists and serotonin antagonists blocked the action of octopamine or serotonin on DmOctα2R. The data presented here reported an adrenergic-like G protein-coupled receptor activated by serotonin, suggesting that the neurotransmission and neuromodulation in the nervous system could be more complex than previously thought. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of beta-phenylethylamine on extracellular concentrations of dopamine in the nucleus accumbens and prefrontal cortex.

PubMed

Murata, Mikio; Katagiri, Nobuyuki; Ishida, Kota; Abe, Kenji; Ishikawa, Masago; Utsunomiya, Iku; Hoshi, Keiko; Miyamoto, Ken-ichi; Taguchi, Kyoji

2009-05-07

It is known that psychostimulants stimulate dopamine transmission in the nucleus accumbens. In the present study, we examined the effects of systemically administered beta-phenylethylamine (beta-PEA), a psychomotor-stimulating trace amine, on dopamine concentrations in the nucleus accumbens and prefrontal cortex in freely moving rats, using an in vivo microdialysis technique. Intraperitoneal administration of beta-PEA (12.5 and 25 mg/kg) significantly increased extracellular dopamine levels in the nucleus accumbens shell. The observed increase in the dopamine concentration in nucleus accumbens shell dialysate after intraperitoneal administration of 25 mg/kg beta-PEA was inhibited by pre-treatment with a dopamine uptake inhibitor, GBR12909 (10 mg/kg, i.p.). In contrast, beta-PEA (25 mg/kg, i.p.) did not affect dopamine release in the nucleus accumbens core. Although a high dose of beta-PEA (50 mg/kg) significantly increased dopamine levels in the nucleus accumbens core, the dopamine increasing effect of beta-PEA was more potent in the nucleus accumbens shell. Systemic administration of 12.5 and 25 mg/kg beta-PEA also increased extracellular dopamine levels in the prefrontal cortex of rats. However, systemic 25 mg/kg beta-PEA-induced increases in extracellular dopamine levels were not blocked by GBR12909 within the prefrontal cortex. These results suggest that beta-PEA has a greater effect in the shell than in the core and low-dose beta-PEA stimulates dopamine release in the nucleus accumbens shell through uptake by a dopamine transporter. Similarly, beta-PEA increased extracellular dopamine levels in the prefrontal cortex. Thus, beta-PEA may increase extracellular dopamine concentrations in the mesocorticolimbic pathway.

EXPERIMENTS ON PHOTOCHEMICAL AMINE FORMATION (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flemming, K.

It is shown that phenylalanine, tryptophan, and tyrosine in aqueous solutions are decarboxylized to phenylethylamine, tryptamine, and tyramine by uv- irradiation: therefore, production of dopamine in uv-irradiated dioxyphenylalanine solutions is considered probable. Therefore, not only vasodilating (histamine, serotonine) but also vasoconstrictor amines are produced by the photochemical amino acid decomposition. A substance in its effect similar to histamine is formed in addition to tyramine in uv-irradiated tyrosine solutions. Its chemical nature is unknown. The photochemical production of amines is increased by oxygen, reducing substances, and H/sub 2/O/sub 2/. It is assumed that it is caused not only directly by energymore » absorption but also indirectiy by the influence of OH- radicals. The radiobiological importance of the results is discussed. (auth)« less

Recent Advances in Methamphetamine Neurotoxicity Mechanisms and Its Molecular Pathophysiology

PubMed Central

Yu, Shaobin; Zhu, Ling; Shen, Qiang; Bai, Xue; Di, Xuhui

2015-01-01

Methamphetamine (METH) is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level. PMID:25861156

Transmitter-induced glycogenolysis and gluconeogenesis in leech segmental ganglia.

PubMed

Pennington, A J; Pentreath, V W

1987-01-01

1. The utilization and control of glycogen stores were studied in the isolated segmental ganglia of the horse leech, Haemopis sanguisuga. The glycogen in the ganglia was extracted and assayed fluorimetrically and its cellular localization and turnover studied by autoradiography in conjunction with [3H] glucose. 2. The glycogen levels were measured after incubation with different neurotransmitters for 60 min at 28 degrees C. The results for each experimental ganglion were compared to a paired control ganglion, and the results analysed by paired t-tests. 3. Several transmitter substances (5-HT, octopamine, dopamine, noradrenaline, histamine) produced reductions in glycogen (glycogenolysis); other transmitters (glutamate, GABA) produced increases in glycogen (gluconeogenesis); others (adenosine, glycine) produced reductions or increases, depending on concentration. Acetylcholine had no effect on the glycogen levels. 4. Most of the glycogen in the ganglia is localized in the packet glial cells, which surround the neuron perikarya. Autoradiographic analysis demonstrated that the effects of histamine and dopamine were principally on the glycogen in the glial cells. 5. Adenylate cyclase was demonstrated by electron microscope histochemistry to be localized on the plasma membranes of the glial cells, and to a lesser extent on the neuronal membranes. 6. It is concluded that the changes in glycogen in the glial cells may be party controlled by transmitters via adenylate cyclase. This may provide a sensitive mechanism for coupling neuronal activity with energy metabolism.

Path Integral Simulation of the H/D Kinetic Isotope Effect in Monoamine Oxidase B Catalyzed Decomposition of Dopamine.

PubMed

Mavri, Janez; Matute, Ricardo A; Chu, Zhen T; Vianello, Robert

2016-04-14

Brain monoamines regulate many centrally mediated body functions, and can cause adverse symptoms when they are out of balance. A starting point to address challenges raised by the increasing burden of brain diseases is to understand, at atomistic level, the catalytic mechanism of an essential amine metabolic enzyme-monoamine oxidase B (MAO B). Recently, we demonstrated that the rate-limiting step of MAO B catalyzed conversion of amines into imines represents the hydride anion transfer from the substrate α-CH2 group to the N5 atom of the flavin cofactor moiety. In this article we simulated for MAO B catalyzed dopamine decomposition the effects of nuclear tunneling by the calculation of the H/D kinetic isotope effect. We applied path integral quantization of the nuclear motion for the methylene group and the N5 atom of the flavin moiety in conjunction with the QM/MM treatment on the empirical valence bond (EVB) level for the rest of the enzyme. The calculated H/D kinetic isotope effect of 12.8 ± 0.3 is in a reasonable agreement with the available experimental data for closely related biogenic amines, which gives strong support for the proposed hydride mechanism. The results are discussed in the context of tunneling in enzyme centers and advent of deuterated drugs into clinical practice.

Octopamine Neuromodulation Regulates Gr32a-Linked Aggression and Courtship Pathways in Drosophila Males

PubMed Central

Andrews, Jonathan C.; Fernández, María Paz; Yu, Qin; Leary, Greg P.; Leung, Adelaine K. W.; Kavanaugh, Michael P.; Kravitz, Edward A.; Certel, Sarah J.

2014-01-01

Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a neurons promote male aggression and form synaptic contacts with OA neurons. By restricting the monoamine neuron target population, we show that three previously identified OA-FruM neurons involved in behavioral choice are among the Gr32a-OA connections. Our findings demonstrate that octopaminergic neuromodulatory neurons function as early as a second-order step in this chemosensory-driven male social behavior pathway. PMID:24852170

Gold nanocages decorated biocompatible amine functionalized graphene as an efficient dopamine sensor platform.

PubMed

Daemi, Sahar; Ashkarran, Ali Akbar; Bahari, Ali; Ghasemi, Shahram

2017-05-15

Nanocomposite of gold nanocages and chemically modified graphene oxide (GNCs/CMG) was synthesized in N,N-dimethylformamide (DMF) for sensitive detection of dopamine (DA). DA is widely spread in central nervous system which can regulates essential body functions like movement and emotional behaviour. In this regard sensitive and fast detection of DA level in human body is still challenging considering its interference with other biomolecules in biological samples. CMG was synthesized through amine modification of graphene oxide (GO) with DMF at relatively high temperature followed by attachment of GNCs, fabricated using a galvanic replacement between silver nanocubes and HAuCl 4 solution in the DMF. X-ray diffraction (XRD) pattern of GNCs/CMG nanocomposite revealed high crystallization of GNCs attached to the graphene nanosheets and microscopic images revealed relatively uniform decoration of GNCs on the surface of CMG. Nanocomposite modified glassy carbon electrode (GNCs/CMG/GCE) was used to investigate the electrochemical behaviour of DA with cyclic voltammetry and amperometry techniques. The linear range for dopamine was between 0.1 and 80μM with a low detection limit of 0.02μM. Furthermore, GNCs/CMG/GCE exhibited satisfying reproducibility, long-term stability and high selectivity for DA detection in large amount of ascorbic acid with good results for determination in human serum samples. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacological characterization of a tyramine receptor from the southern cattle tick, Rhipicephalus (Boophilus) microplus.

PubMed

Gross, Aaron D; Temeyer, Kevin B; Day, Tim A; Pérez de León, Adalberto A; Kimber, Michael J; Coats, Joel R

2015-08-01

The southern cattle tick (Rhipicephalus (Boophilus) microplus) is a hematophagous external parasite that vectors the causative agents of bovine babesiosis or cattle tick fever, Babesia bovis and B. bigemina, and anaplasmosis, Anaplasma marginale. The southern cattle tick is a threat to the livestock industry in many locations throughout the world. Control methods include the use of chemical acaricides including amitraz, a formamidine insecticide, which is proposed to activate octopamine receptors. Previous studies have identified a putative octopamine receptor from the southern cattle tick in Australia and the Americas. Furthermore, this putative octopamine receptor could play a role in acaricide resistance to amitraz. Recently, sequence data indicated that this putative octopamine receptor is probably a type-1 tyramine receptor (TAR1). In this study, the putative TAR1 was heterologously expressed in Chinese hamster ovary (CHO-K1) cells, and the expressed receptor resulted in a 39-fold higher potency for tyramine compared to octopamine. Furthermore, the expressed receptor was strongly antagonized by yohimbine and cyproheptadine, and mildly antagonized by mianserin and phentolamine. Tolazoline and naphazoline had agonistic or modulatory activity against the expressed receptor, as did the amitraz metabolite, BTS-27271; however, this was only observed in the presence of tyramine. The southern cattle tick's tyramine receptor may serve as a target for the development of anti-parasitic compounds, in addition to being a likely target of formamidine insecticides. Copyright © 2015 Elsevier Ltd. All rights reserved.

A single amino acid residue controls Ca2+ signaling by an octopamine receptor from Drosophila melanogaster

PubMed Central

Hoff, Max; Balfanz, Sabine; Ehling, Petra; Gensch, Thomas; Baumann, Arnd

2011-01-01

Rhythmic activity of cells and cellular networks plays an important role in physiology. In the nervous system oscillations of electrical activity and/or second messenger concentrations are important to synchronize neuronal activity. At the molecular level, rhythmic activity can be initiated by different routes. We have recently shown that an octopamine-activated G-protein-coupled receptor (GPCR; DmOctα1Rb, CG3856) from Drosophila initiates Ca2+ oscillations. Here, we have unraveled the molecular basis of cellular Ca2+ signaling controlled by the DmOctα1Rb receptor using a combination of pharmacological intervention, site-directed mutagenesis, and functional cellular Ca2+ imaging on heterologously expressed receptors. Phosphorylation of a single amino acid residue in the third intracellular loop of the GPCR by PKC is necessary and sufficient to desensitize the receptor. From its desensitized state, DmOctα1Rb is resensitized by dephosphorylation, and a new Ca2+ signal occurs on octopamine stimulation. Our findings show that transient changes of the receptor's surface profile have a strong effect on its physiological signaling properties. We expect that the detailed knowledge of DmOctα1Rb-dependent signal transduction fosters the identification of specific drugs that can be used for GPCR-mediated pest control, since octopamine serves important physiological and behavioral functions in arthropods.—Hoff M., Balfanz, S., Ehling, P., Gensch, T., Baumann, A. A single amino acid residue controls Ca2+ signaling by an octopamine receptor from Drosophila melanogaster. PMID:21478261

Uptake of plant-derived specific alkaloids allows males of a butterfly to copulate.

PubMed

Honda, Keiichi; Matsumoto, Junya; Sasaki, Ken; Tsuruta, Yoshiaki; Honda, Yasuyuki

2018-04-03

Certain butterflies utilize plant-acquired alkaloids for their own chemical defense and/or for producing male sex pheromone; a trait known as pharmacophagy. Males of the danaine butterfly, Parantica sita, have been reported to ingest pyrrolizidine alkaloids (PAs) as adults to produce two PA-derived sex pheromone components, viz. danaidone (major) and 7R-hydroxydanaidal. We found, however, that not all PAs that can be precursors for the pheromone serve for mating success of males. Here we show that although the sex pheromone is regarded as a requisite for successful mating, uptake of specific PA(s) (lycopsamine-type PAs) is also imperative for the males to achieve copulation. The increase in the levels of two biogenic amines, octopamine and/or serotonin, in the brain and thoracic ganglia of males fed with specific PA(s) suggested that these alkaloids most likely enhance male mating activity. The results can present new evidence for the evolutionary provenance of pharmacophagous acquisition of PAs in PA-adapted insects.

Effects of Fluoxetine and Potential Antidepressant 8-Trifluoromethyl 1,2,3,4,5-Benzopentathiepin-6-Amine Hydrochloride (TC-2153) on Behavior of Danio rerio Fish in the Novel Tank Test and Brain Content of Biogenic Amines and Their Metabolites.

PubMed

Sinyakova, N A; Kulikova, E A; Englevskii, N A; Kulikov, A V

2018-03-01

We compared the effect of a new potential antidepressant 8-trifluoromethyl 1,2,3,4,5-benzopentathiepine-6-amine hydrochloride (TC-2153) and classical antidepressant fluoxetine in a dose of 0.25 mg/liter on the behavior of Danio rerio in the "novel tank" test and content of biogenic amines and their metabolites in the brain. Fluoxetine alone and TC-2153 alone significantly increased the time spent in the upper part of the tank and insignificantly reduced motor activity. Combined exposure of fishes in the solution containing potential and classical antidepressants potentiated their effects on both parameters. The compounds did not affect brain contents of serotonin, dopamine, and norepinephrine. At the same time, fluoxetine, but not TC-2153, reduced brain content of the main serotonin metabolite 5-hydroxyindole acetic acid.

The Power of Integrating Kinetic Isotope Effects into the Formalism of the Michaelis-Menten Equation

PubMed Central

Klinman, Judith P.

2014-01-01

The final arbiter of enzyme mechanism is the ability to establish and test a kinetic mechanism. Isotope effects play a major role in expanding the scope and insight derived from the Michaelis-Menten equation. The integration of isotope effects into the formalism of the Michaelis-Menten equation began in the 1970s and has continued to this day. This review discusses a family of eukaryotic copper proteins that includes dopamine β-monooxygenase, tyramine β-monooxygenase, and peptidylglycine α-amidating enzyme, responsible for the synthesis of the neuro-active compounds, norepinephrine, octopamine and C-terminally carboxamidated peptides, respectively. Highlighted are results that show how combining kinetic isotope effects with initial rate parameters permits an evaluation of: (i) the order of substrate binding to multi-substrate enzymes; (ii) the magnitude of individual rate constants in complex, multi-step reactions; (iii) the identification of chemical intermediates; and (iv) the role of non-classical (tunneling) behavior in C–H activation. PMID:23937475

Ergopeptines bromocriptine and ergovaline and the dopamine type-2 receptor inhibitor domperidone inhibit bovine equilibrative nucleoside transporter 1-like activity

USDA-ARS?s Scientific Manuscript database

Forages infected with Neotyphodium coenophialum produce ergot alkaloids that alter the systemic physiology of cattle such that reproduction, lactation, and growth are decreased. Ergopeptines are one predominant class of ergot alkaloids. However, aside from their interactions with biogenic amine rece...

Acute Exposure to Worst-Case Concentrations of Amitraz Does Not Affect Honey Bee Learning, Short-Term Memory, or Hemolymph Octopamine Levels.

PubMed

Rix, Rachel R; Christopher Cutler, G

2017-02-01

Amitraz, an acaricide used to treat Varroa destructor Anderson & Trueman, is one of the most commonly detected pesticides in honey bee (Apis mellifera L.) hives. Acaricides sometimes negatively impact honey bee cognition, but potential effects of amitraz on honey bee learning have been rarely studied. We topically exposed foragers to 95th percentile field-relevant levels of amitraz and, 24 h later, tested the ability of bees to associate a sucrose reward with a conditioned odor (learning response) using the proboscis extension response (PER). We then tested the ability of the bees to retain this memory 1 h and 2 h post-conditioning. Because amitraz is thought to affect octopamine metabolism in honey bees, and because octopamine is directly related to honey bee learning and memory, we also examined effects of exposure to amitraz on octopamine levels in honey bee hemolymph. We found that acute exposure to 95th percentile doses of amitraz had no impact on honey bee learning or short-term memory as measured by PER. Concentrations of octopamine in hemolymph from our low amitraz treatment were 1.4-fold higher than control levels, but other treatments had no effect. Our results from worst-case acute exposure experiments with worker bees in the laboratory suggest that typical field-relevant (within hive) exposures to amitraz probably have little effect on honey bee learning and memory. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dopamine D1 and D2 dopamine receptors regulate immobilization stress-induced activation of the hypothalamus-pituitary-adrenal axis.

PubMed

Belda, Xavier; Armario, Antonio

2009-10-01

Whereas the role of most biogenic amines in the control of the hypothalamus-pituitary-adrenal (HPA) response to stress has been extensively studied, the role of dopamine has not. We studied the effect of different dopamine receptor antagonists on HPA response to a severe stressor (immobilization, IMO) in adult male Sprague-Dawley rats. Haloperidol administration reduced adrenocorticotropin hormone and corticosterone responses to acute IMO, particularly during the post-IMO period. This effect cannot be explained by a role of dopamine to maintain a sustained activation of the HPA axis as haloperidol did not modify the response to prolonged (up to 6 h) IMO. Administration of more selective D1 and D2 receptor antagonists (SCH23390 and eticlopride, respectively) also resulted in lower and/or shorter lasting HPA response to IMO. Dopamine, acting through both D1 and D2 receptors, exerts a stimulatory role on the activation of the HPA axis in response to a severe stressor. The finding that dopamine is involved in the maintenance of post-stress activation of the HPA axis is potentially important because the actual pathological impact of HPA activation is likely to be related to the area under the curve of plasma glucocorticoid levels, which is critically dependent on how long after stress high levels of glucocorticoid are maintained.

Dopamine is a key regulator in the signalling pathway underlying predator-induced defences in Daphnia

PubMed Central

Weiss, Linda C.; Leese, Florian; Laforsch, Christian; Tollrian, Ralph

2015-01-01

The waterflea Daphnia is a model to investigate the genetic basis of phenotypic plasticity resulting from one differentially expressed genome. Daphnia develops adaptive phenotypes (e.g. morphological defences) thwarting predators, based on chemical predator cue perception. To understand the genomic basis of phenotypic plasticity, the description of the precedent cellular and neuronal mechanisms is fundamental. However, key regulators remain unknown. All neuronal and endocrine stimulants were able to modulate but not induce defences, indicating a pathway of interlinked steps. A candidate able to link neuronal with endocrine responses is the multi-functional amine dopamine. We here tested its involvement in trait formation in Daphnia pulex and Daphnia longicephala using an induction assay composed of predator cues combined with dopaminergic and cholinergic stimulants. The mere application of both stimulants was sufficient to induce morphological defences. We determined dopamine localization in cells found in close association with the defensive trait. These cells serve as centres controlling divergent morphologies. As a mitogen and sclerotization agent, we anticipate that dopamine is involved in proliferation and structural formation of morphological defences. Furthermore, dopamine pathways appear to be interconnected with endocrine pathways, and control juvenile hormone and ecdysone levels. In conclusion, dopamine is suggested as a key regulator of phenotypic plasticity. PMID:26423840

Assessment of renal dopaminergic system activity during cyclosporine A administration in the rat.

PubMed Central

Pestana, M.; Vieira-Coelho, M. A.; Pinto-do-O, P. C.; Fernandes, M. H.; Soares-da-Silva, P.

1995-01-01

1. Administration of cyclosporine A (CsA; 50 mg kg-1 day-1, s.c.) for 14 days produced an increase in both systolic (SBP) and diastolic (DBP) blood pressure by 60 and 25 mmHg, respectively. The urinary excretion of dopamine, DOPAC and HVA was reduced from day 5-6 of CsA administration onwards (dopamine from 19 to 46%, DOPAC from 16 to 48%; HVA from 18 to 42%). In vehicle-treated rats, the urinary excretion of dopamine and DOPAC increased (from 7 to 60%) from day 5 onwards; by contrast, the urinary excretion of HVA was reduced (from 27 to 60%) during the second week. 2. No significant difference was observed between the Vmax and Km values of renal aromatic L-amino acid decarboxylase (AAAD) in rats treated with CsA for 7 and 14 days or with vehicle. 3. Km and Vmax of monoamine oxidase types A and B did not differ significantly between rats treated with CsA for 7 and 14 days or with vehicle. 4. Maximal catechol-O-methyltransferase activity (Vmax) in homogenates of renal tissues obtained from rats treated with CsA for 7 or 14 days was significantly higher than that in vehicle-treated rats; Km (22.3 +/- 1.5 microM) values for COMT did not differ between the three groups of rats. 5. The accumulation of newly-formed dopamine and DOPAC in cortical tissues of rats treated with CsA for 14 days was three to four times higher than in controls. The outflow of both dopamine and DOPAC declined progressively with time and reflected the amine and amine metabolite tissue contents. No significant difference was observed between the DOPAC/dopamine ratios in the perifusate of renal tissues obtained from CsA- and vehicle-treated rats. In addition, no significant differences were observed in k values or in the slope of decline of both DA and DOPAC between experiments performed with CsA and vehicle-treated animals. 6. The Vmax for the saturable component of L-3,4-dihydroxyphenylalanine (L-DOPA) uptake in renal tubules from rats treated with CsA was twice that of vehicle-treated animals. Km in CsA- and vehicle-treated rats did not differ. 7. The decrease in the urinary excretion of sodium and an increase in blood pressure during CsA treatment was accompanied by a reduction in daily urinary excretion of dopamine. This appears to result from a reduction in the amount of L-DOPA made available to the kidney and does not involve changes in tubular AAAD, the availability of dopamine to leave the renal cells and dopamine metabolism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8564191

Ontogenesis of uptake and deamination of 5-hydroxytryptamine, dopamine and beta-phenylethylamine in isolated perfused lung and lung homogenates from rats.

PubMed Central

Ben-Harari, R. R.; Youdim, M. B.

1981-01-01

1. Uptake of 5-hydroxytryptamine (5-HT) and beta-phenylethylamine (PEA) was studied in perfused lung from male rats between 10 and 70 days old. 2. Monoamine oxidase (MAO) activity towards 5-HT, PEA and dopamine was studied in homogenate preparations of lung from rats aged between 5 and 80 days. 3. Uptake of 5-HT (10 microM) decreased throughout the age range studied but uptake of PEA (50 microM) increased for the first 30 days and beyond this age it decreased. Metabolites formed for both amines reflected the changes in uptake. 4. MAO activity deaminating 5-HT is well developed by day 10 and reaches its maximum by day 40. For dopamine and PEA, MAO activity remained low until day 20, and the developed rapidly, reaching a maximum by day 40 for dopamine; activity towards PEA did not reach a maximum by day 80. 5. These results show that uptake and MAO activity changes with age and thus the lung responds like other tissues. 6. These results also demonstrate the independent development of uptake and MAO activity towards 5-HT, PEA and dopamine. PMID:7284689

Arylalkylamine N-acetyltransferase 1 gene (TcAANAT1) is required for cuticle morphology and pigmentation of the adult red flour beetle, Tribolium castaneum.

PubMed

Noh, Mi Young; Koo, Bonwoo; Kramer, Karl J; Muthukrishnan, Subbaratnam; Arakane, Yasuyuki

2016-12-01

In the insect cuticle tanning pathway (sclerotization and pigmentation), the enzyme arylalkylamine N-acetyltransferase (AANAT) catalyzes the acetylation of dopamine to form N-acetyldopamine (NADA), which is one of the major precursors for quinone-mediated tanning. In this study we characterized and investigated the function of TcAANAT1 in cuticle pigmentation of the red flour beetle, Tribolium castaneum. We isolated a full length TcAANAT1 cDNA that encodes a protein of 256 amino acid residues with a predicted GCN5-related acetyltransferase domain containing an acetyl-CoA binding motif. TcAANAT1 transcripts were detected at all stages of development with lowest expressions at the embryonic and pharate pupal stages. We expressed and purified the encoded recombinant TcAANAT1 protein (rTcAANAT1) that exhibited highest activity at slightly basic pH values (for example, pH 7.5 to 8.5 using dopamine as the substrate). In addition, rTcAANAT1 acts on a wide range of substrates including tryptamine, octopamine and norepinephrine with similar substrate affinities with K m values in the range of 0.05-0.11 mM except for tyramine (K m  = 0.56 mM). Loss of function of TcAANAT1 caused by RNAi had no effect on larval and pupal development. The tanning of pupal setae, gin traps and urogomphi proceeded normally. However, the resulting adults (∼70%) exhibited a roughened exoskeletal surface, separated elytra and improperly folded hindwings. The body wall, elytra and veins of the hindwing of the mature adults were significantly darker than those of control insects probably due to the accumulation of dopamine melanin. A dark pigmentation surrounding the bristles located on the inter-veins of the elytron was evident primarily because of the underlying darkly pigmented trabeculae that partition the dorsal and ventral layers of the elytron. These results support the hypothesis that TcAANAT1 acetylates dopamine and plays a role in development of the morphology and pigmentation of T. castaneum adult cuticle. Copyright © 2016 Elsevier Ltd. All rights reserved.

N-propargylbenzylamine, a major metabolite of pargyline, is a potent inhibitor of monoamine oxidase type B in rats in vivo: a comparison with deprenyl.

PubMed Central

Karoum, F.

1987-01-01

In an effort to explore the contribution of the metabolites of pargyline towards the in vivo inhibition of monoamine oxidase (MAO), the effects of pargyline and its major metabolites on the production and metabolism of a number of biogenic amines were studied in rats. The administration of pargyline gave rise to three major ethyl acetate extractable metabolites: benzylamine, N-methylbenzylamine and N-propargylbenzylamine (NPB). Only NPB demonstrated in vivo monoamine oxidase inhibitory properties at an acute dose of 30 mg kg-1. The acute effects of pargyline, NPB, and deprenyl on urine and brain concentrations of a number of biogenic amines (phenylethylamine (PEA), m- and p-tyramine, noradrenaline (NA), dopamine, and 5-hydroxytryptamine (5-HT) and their metabolites were evaluated. Increased urine and brain concentrations of PEA were considered to represent in vivo inhibition of type B MAO while decreased concentrations of NA and 5-HT metabolites were regarded as indicators of an in vivo inhibition of MAO type A. NPB, like deprenyl and pargyline, significantly increased urine and brain PEA while only pargyline reduced 5-HT metabolism, suggesting that the metabolism of pargyline to NPB may contribute towards the MAO type B inhibitory effects of pargyline in vivo. Since the therapeutic benefits of MAO inhibitors in clinical practice usually require some period of chronic treatment, the chronic effects of repeated 14 daily doses of the above MAO inhibitors on central and peripheral biogenic amines were evaluated at the following times: during treatment, one day and five days after termination of treatment. The biochemical changes observed during the course of chronic NPB, pargyline and deprenyl treatments generally follow the expected in vitro characteristics of these drugs, but the detailed changes observed suggest clear differences. For example, the in vivo effect of pargyline on urine 5-hydroxyindoleacetic acid excretion was considerably weaker than its effect on the excretion of NA and dopamine metabolites. These changes are opposite to the in vitro effects of pargyline on 5-HT, dopamine and NA oxidative deamination. Inhibitions of the metabolism of all the amines studied were clearly observed during chronic MAOI treatments, but these effects were less evident five days after the end of treatment, suggesting an almost normal metabolism of biogenic amines. It is concluded that while MAO inhibitors may be the primary compound responsible for MAO inhibition, the effects of their metabolites in some cases may also play equally important roles in the regulation of monoamines both in the periphery and the brain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3103805

From the Cover: Harmane-Induced Selective Dopaminergic Neurotoxicity in Caenorhabditis elegans.

PubMed

Sammi, Shreesh Raj; Agim, Zeynep Sena; Cannon, Jason R

2018-02-01

Parkinson's disease (PD) is a debilitating neurodegenerative disease. Although numerous exposures have been linked to PD etiology, causative factors for most cases remain largely unknown. Emerging data on the neurotoxicity of heterocyclic amines suggest that this class of compounds should be examined for relevance to PD. Here, using Caenorhabditis elegans as a model system, we tested whether harmane exposure produced selective toxicity to dopamine neurons that is potentially relevant to PD. Harmane is a known tremorigenic β-carboline (a type of heterocyclic amine) found in cooked meat, roasted coffee beans, and tobacco. Thus, this compound represents a potentially important exposure. In the nematode model, we observed dopaminergic neurons to be selectively vulnerable, showing significant loss in terms of structure and function at lower doses than other neuronal populations. In examining mechanisms of toxicity, we observed significant harmane-induced decreases in mitochondrial viability and increased reactive oxygen species levels. Blocking transport through the dopamine transporter (DAT) was not neuroprotective, suggesting that harmane is unlikely to enter the cell through DAT. However, a mitochondrial complex I activator did partially ameliorate neurodegeneration. Further, mitochondrial complex I activator treatment reduced harmane-induced dopamine depletion, measured by the 1-nonanol assay. In summary, we have shown that harmane exposure in C. elegans produces selective dopaminergic neurotoxicity that may bear relevance to PD, and that neurotoxicity may be mediated through mitochondrial mechanisms. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Neuromodulation of Nestmate Recognition Decisions by Pavement Ants.

PubMed

Bubak, Andrew N; Yaeger, Jazmine D W; Renner, Kenneth J; Swallow, John G; Greene, Michael J

2016-01-01

Ant colonies are distributed systems that are regulated in a non-hierarchical manner. Without a central authority, individuals inform their decisions by comparing information in local cues to a set of inherent behavioral rules. Individual behavioral decisions collectively change colony behavior and lead to self-organization capable of solving complex problems such as the decision to engage in aggressive societal conflicts with neighbors. Despite the relevance to colony fitness, the mechanisms that drive individual decisions leading to cooperative behavior are not well understood. Here we show how sensory information, both tactile and chemical, and social context-isolation, nestmate interaction, or fighting non-nestmates-affects brain monoamine levels in pavement ants (Tetramorium caespitum). Our results provide evidence that changes in octopamine and serotonin in the brains of individuals are sufficient to alter the decision by pavement ants to be aggressive towards non-nestmate ants whereas increased brain levels of dopamine correlate to physical fighting. We propose a model in which the changes in brain states of many workers collectively lead to the self-organization of societal aggression between neighboring colonies of pavement ants.

Neuromodulation of Nestmate Recognition Decisions by Pavement Ants

PubMed Central

Bubak, Andrew N.; Yaeger, Jazmine D. W.; Renner, Kenneth J.; Swallow, John G.; Greene, Michael J.

2016-01-01

Ant colonies are distributed systems that are regulated in a non-hierarchical manner. Without a central authority, individuals inform their decisions by comparing information in local cues to a set of inherent behavioral rules. Individual behavioral decisions collectively change colony behavior and lead to self-organization capable of solving complex problems such as the decision to engage in aggressive societal conflicts with neighbors. Despite the relevance to colony fitness, the mechanisms that drive individual decisions leading to cooperative behavior are not well understood. Here we show how sensory information, both tactile and chemical, and social context—isolation, nestmate interaction, or fighting non-nestmates—affects brain monoamine levels in pavement ants (Tetramorium caespitum). Our results provide evidence that changes in octopamine and serotonin in the brains of individuals are sufficient to alter the decision by pavement ants to be aggressive towards non-nestmate ants whereas increased brain levels of dopamine correlate to physical fighting. We propose a model in which the changes in brain states of many workers collectively lead to the self-organization of societal aggression between neighboring colonies of pavement ants. PMID:27846261

A single amino acid residue controls Ca2+ signaling by an octopamine receptor from Drosophila melanogaster.

PubMed

Hoff, Max; Balfanz, Sabine; Ehling, Petra; Gensch, Thomas; Baumann, Arnd

2011-07-01

Rhythmic activity of cells and cellular networks plays an important role in physiology. In the nervous system oscillations of electrical activity and/or second messenger concentrations are important to synchronize neuronal activity. At the molecular level, rhythmic activity can be initiated by different routes. We have recently shown that an octopamine-activated G-protein-coupled receptor (GPCR; DmOctα1Rb, CG3856) from Drosophila initiates Ca(2+) oscillations. Here, we have unraveled the molecular basis of cellular Ca(2+) signaling controlled by the DmOctα1Rb receptor using a combination of pharmacological intervention, site-directed mutagenesis, and functional cellular Ca(2+) imaging on heterologously expressed receptors. Phosphorylation of a single amino acid residue in the third intracellular loop of the GPCR by PKC is necessary and sufficient to desensitize the receptor. From its desensitized state, DmOctα1Rb is resensitized by dephosphorylation, and a new Ca(2+) signal occurs on octopamine stimulation. Our findings show that transient changes of the receptor's surface profile have a strong effect on its physiological signaling properties. We expect that the detailed knowledge of DmOctα1Rb-dependent signal transduction fosters the identification of specific drugs that can be used for GPCR-mediated pest control, since octopamine serves important physiological and behavioral functions in arthropods.

Functional Fast Scan Cyclic Voltammetry Assay to Characterize Dopamine D2 and D3 Autoreceptors in the Mouse Striatum

PubMed Central

2010-01-01

Dopamine D2 and D3 autoreceptors are located on presynaptic terminals and are known to control the release and synthesis of dopamine. Dopamine D3 receptors have a fairly restricted pattern of expression in the mammalian brain. Their localization in the nucleus accumbens core and shell is of particular interest because of their association with the rewarding properties of drugs of abuse. Using background subtracted fast scan cyclic voltammetry, we investigated the effects of dopamine D2 and D3 agonists on electrically stimulated dopamine release and uptake rates in the mouse caudate putamen and nucleus accumbens core and shell. The dopamine D2 agonists (−)-quinpirole hydrochloride and 5,6,7,8-tetrahydro-6-(2-propen-1-yl)-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride (B-HT 920) had the same dopamine release inhibition effects on caudate putamen and nucleus accumbens (core and shell) on the basis of their EC50 values and efficacies. This suggests that the dopamine D2 autoreceptor functionality is comparable in all three striatal regions investigated. The dopamine D3 agonists (4aR,10bR)-3,4a,4,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride ((+)-PD 128907) and (±)-7-Hydroxy-2-dipropylaminotetralin hydrobromide (7-OH-DPAT) had a significantly greater effect on dopamine release inhibition in the nucleus accumbens shell than in the caudate putamen. This study confirms that, the dopamine D3 autoreceptor functionality is greater in the nucleus accumbens shell followed by the nucleus accumbens core, with the caudate putamen having the least. Neither dopamine D2 nor D3 agonists affected the uptake rates in nucleus accumbens but concentrations greater than 0.1 μM lowered the uptake rate in caudate putamen. To validate our method of evaluating dopamine D2 and D3 autoreceptors, sulpiride (D2 antagonist) and nafadotride (D3 antagonist) were used to reverse the effects of the dopamine agonists to approximately 100% of the preagonist dopamine release concentration. Finally, these results demonstrate a functional voltammetric assay that characterizes dopamine D2-like agonists as either D2- or D3-preferring agonists by taking advantage of the unique receptor density within the striatum. PMID:20567609

Growth Stimulation by Catecholamines in Plant Tissue/Organ Cultures 1

PubMed Central

Protacio, Calixto M.; Dai, Yao-ren; Lewis, Eldrin F.; Flores, Hector E.

1992-01-01

Addition of catecholamines at micromolar concentrations caused a dramatic stimulation of growth of tobacco (Nicotiana tabacum) thin cell layers (TCLs) and Acmella oppositifolia “hairy” root cultures. A threefold increase in the rate of ethylene evolution was observed in the catecholamine-treated explants. Aminooxyacetic acid and silver thiosulfate, inhibitors of ethylene biosynthesis and action, respectively, reduced the growth-promoting effect of dopamine. However, these compounds alone could also inhibit the growth of the TCL explants. When ethylene in the culture vessel was depleted by trapping with mercuric perchlorate, dopamine-stimulated growth was still obtained, suggesting that ethylene does not mediate the dopamine effect. Dopamine potentiated the growth of TCLs grown in Murashige and Skoog medium supplemented with indoleacetic acid (IAA) and kinetin. When IAA was replaced by 2,4-dichlorophenoxyacetic acid, dopamine addition showed no growth-promoting effect. Instead, 2,4-dichlorophenoxyacetic acid stimulated the growth of TCL explants to the same extent as that obtained with IAA plus dopamine. Because synthetic auxins do not appear to be substrates for IAA oxidizing enzymes, we hypothesized that catecholamines exert their effect by preventing IAA oxidation. Consistent with this explanation, dopamine (25 micromolar) inhibited IAA oxidase activity by 60 to 100% in crude enzyme extracts from tobacco roots and etiolated corn coleoptiles, but had no effect on peroxidase activity in the same extracts. Furthermore, addition of dopamine to TCL cultures resulted in a fourfold reduction in the oxidative degradation of [1-14C]IAA fed to the explants. Because the growth enhancement by catecholamines is observed in both IAA-requiring and IAA-independent cultures, we suggest that these aromatic amines may have a role in the regulation of IAA levels in vivo. ImagesFigure 2 PMID:16668653

Carbonic anhydrase activators: Activation of the β-carbonic anhydrase from Malassezia globosa with amines and amino acids.

PubMed

Vullo, Daniela; Del Prete, Sonia; Capasso, Clemente; Supuran, Claudiu T

2016-03-01

The β-carbonic anhydrase (CA, EC 4.2.1.1) from the dandruff producing fungus Malassezia globosa, MgCA, was investigated for its activation with amines and amino acids. MgCA was weakly activated by amino acids such as L-/D-His, L-Phe, D-DOPA, D-Trp, L-/D-Tyr and by the amine serotonin (KAs of 12.5-29.3μM) but more effectively activated by d-Phe, l-DOPA, l-Trp, histamine, dopamine, pyridyl-alkylamines, and 4-(2-aminoethyl)-morpholine, with KAs of 5.82-10.9μM. The best activators were l-adrenaline and 1-(2-aminoethyl)piperazine, with activation constants of 0.72-0.81μM. This study may help a better understanding of the activation mechanisms of β-CAs from pathogenic fungi as well as the design of tighter binding ligands for this enzyme which is a drug target for novel types of anti-dandruff agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Return of D4 Dopamine Receptor Antagonists in Drug Discovery.

PubMed

Lindsley, Craig W; Hopkins, Corey R

2017-09-14

The dopamine D 4 receptor garnered a great deal of interest in the early 1990s when studies showed the atypical antipsychotic clozapine possessed higher affinity for D 4 , relative to other dopamine receptor subtypes, and that this activity might underlie the unique clinical efficacy of clozapine. Unfortunately, D 4 antagonists that were developed for schizophrenia failed in the clinic. Thus, D 4 fell out of favor as a therapeutic target, and work in this area was silent for decades. Recently, D 4 ligands with improved selectivity for D 4 against not only D 1-3,5 but also other biogenic amine targets have emerged, and D 4 is once again in the spotlight as a novel target for both addiction and Parkinson's disease (PD), as well as other emerging diseases. This report will review the historical data for D 4 , review the known D 4 ligands, and then highlight new data supporting a role for D 4 inhibition in addiction, PD, and cancer.

Monitoring of biogenic amines and drugs of various therapeutic groups in urine samples with use of HPLC.

PubMed

Baranowska, Irena; Płonka, Joanna

2016-04-01

A high-performance liquid chromatography method for simultaneous separation and determination of biogenic amines [dopamine, epinephrine, serotonin and its six metabolites (normetanephrine, metanephrine, 3,4-dihydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenylglycol, homovanilic acid and 5-hydroxyindoloacetic acid)] with drugs from different therapeutically groups [analgesics (paracetamol, metamizol), diuretics (furosemide) and antibiotics (cefazolin, fluconazole)] was developed. A chromatographic column with pre-column with octadecylsilane phase (C18e ) and two detectors - diode array serial connected and fluorescence - was used. Gradient elution of mixture of acetate buffer (pH 4.66) and methanol as a mobile phase was applied. The limit of detection (LOD) of 8-10 ng/mL and limit of quantitation (LOQ) of 24-30 ng/mL for biogenic amines, as well as the LOD of 50-100 ng/mL and the LOQ of 150-300 ng/mL for drugs, were determined. The applied sample preparation method allowed recoveries of 93% for the biogenic amines and 92% for the drugs to be achieved. The developed procedure has been applied to simultaneous determination of the examined compounds in urine samples and could be used in clinical analysis. Copyright © 2015 John Wiley & Sons, Ltd.

Synergy between growth factors and transmitters required for catecholamine differentiation in brain neurons.

PubMed

Du, X; Iacovitti, L

1995-07-01

The phenotypically plastic neurons of the embryonic mouse striatum were used to explore mechanisms of catecholamine differentiation in culture. De novo transcription and translation of the CA biosynthetic enzyme, tyrosine hydroxylase (TH), was induced in striatal neurons exposed, simultaneously or sequentially, to the growth factor, acidic fibroblast growth factor (aFGF) and a catecholamine. Although dopamine was the most potent aFGF partner (ED50 = 4 microM), a number of substances, including dopamine (D1) receptor agonists, beta-adrenoceptor agonists, and dopamine uptake inhibitors also trigger TH induction when accompanied by aFGF. However, since none of the receptor antagonists nor transport blockers tested could inhibit dopamine's action, the mechanism remains obscure. Structure-activity analysis suggests that effective aFGF partners all contain an amine group separated from a catechol nucleus by two carbons. Thus, TH expression can be novelly induced by the synergistic interaction of aFGF, and to a lesser extent basic FGF, and a variety of CA-containing partner molecules. We speculate that a similar association between growth factor and transmitter may be required in development for the differentiation of a CA phenotype in brain neurons.

Trace amines depress D2-autoreceptor-mediated responses on midbrain dopaminergic cells

PubMed Central

Ledonne, Ada; Federici, Mauro; Giustizieri, Michela; Pessia, Mauro; Imbrici, Paola; Millan, Mark J; Bernardi, Giorgio; Mercuri, Nicola B

2010-01-01

Background and purpose: Although trace amines (TAs) are historically considered ‘false neurotransmitters’ on the basis of their ability to induce catecholamine release, there is evidence that they directly affect neuronal activity via TA receptors, ligand-gated receptor channels and/or σ receptors. Here, we have investigated the effects of two TAs, tyramine (TYR) and β-phenylethylamine (β-PEA), on electrophysiological responses of substantia nigra pars compacta (SNpc) dopaminergic cells to the D2 receptor agonist, quinpirole. Experimental approach: Electrophysiological recordings of D2 receptor-activated G-protein-gated inward rectifier K+ channel (GIRK) currents were performed on dopaminergic cells from midbrain slices of mice and on Xenopus oocytes expressing D2 receptors and GIRK channels. Key results: TYR and β-PEA reversibly reduced D2 receptor-activated GIRK currents in a concentration-dependent manner on SNpc neurones. The inhibitory effect of TAs was still present in transgenic mice with genetically deleted TA1 receptors and they could not be reproduced by the selective TA1 agonist, o-phenyl-3-iodotyramine (O-PIT). Pretreatment with antagonists of σ1 and σ2 receptors did not block TA-induced effects. In GTPγS-loaded neurones, the irreversibly-activated GIRK-current was still reversibly reduced by β-PEA. Moreover, β-PEA did not affect basal or dopamine-evoked GIRK-currents in Xenopus oocytes. Conclusions and implications: TAs reduced dopamine-induced responses on SNpc neurones by acting at sites different from TA1, σ-receptors, D2 receptors or GIRK channels. Although their precise mechanism of action remains to be identified, TAs, by antagonizing the inhibitory effects of dopamine, may render dopaminergic neurones less sensitive to autoreceptor feedback inhibition and hence enhance their sensitivity to stimulation. PMID:20590640

Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages

PubMed Central

Gratz, Michael J; Stavrou, Stavroula; Kuhn, Christina; Hofmann, Simone; Hermelink, Kerstin; Heidegger, Helene; Hutter, Stefan; Mayr, Doris; Mahner, Sven; Jeschke, Udo; Vattai, Aurelia

2018-01-01

Objectives l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D2-dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. Methods Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancies (n = 15) (pregnancy weeks 7–13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T0AM and T1AM in vitro. Results Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T1AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. Conclusions Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side. PMID:29686031

Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages.

PubMed

Gratz, Michael J; Stavrou, Stavroula; Kuhn, Christina; Hofmann, Simone; Hermelink, Kerstin; Heidegger, Helene; Hutter, Stefan; Mayr, Doris; Mahner, Sven; Jeschke, Udo; Vattai, Aurelia

2018-05-01

l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D 2 -dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancies (n = 15) (pregnancy weeks 7-13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T 0 AM and T 1 AM in vitro . Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T 1 AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side. © 2018 The authors.

Radiosynthesis and in vitro evaluation of 2-(N-alkyl-N-1'-11C-propyl)amino-5-hydroxytetralin analogs as high affinity agonists for dopamine D-2 receptors.

PubMed

Shi, B; Narayanan, T K; Yang, Z Y; Christian, B T; Mukherjee, J

1999-10-01

We have developed radiotracers based on agonists that may potentially allow the in vivo assessment of the high affinity (HA) state of the dopamine D-2 receptors. The population of HA state, which is likely the functional state of the receptor, may be altered in certain diseases. We carried out radiosyntheses and evaluated the binding affinities, lipophilicity, and in vitro autoradiographic binding characteristics of three dopamine D-2 receptor agonists: (+/-)-2-(N,N-dipropyl)amino-5-hydroxytetralin (5-OH-DPAT), (+/-)-2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin (PPHT), and (+/-)-2-(N-cyclohexylethyl-N-propyl)amino-5-hydroxytetralin (ZYY-339). In 3H-spiperone assays using rat striata, ZYY-339 exhibited subnanomolar affinity for D-2 receptor sites (IC50 = 0.010 nM), PPHT was somewhat weaker (IC50 = 0.65 nM), and 5-OH-DPAT exhibited the weakest affinity (IC50 = 2.5 nM) of the three compounds. Radiosynthesis of these derivatives, 2-(N-propyl-N-1'-11C-propyl)amino-5-hydroxytetralin (11C-5-OH-DPAT), 2-(N-phenethyl-N-1'-11C-propyl)amino-5-hydroxytetralin (11C-PPHT), and 2-(N-cyclohexylethyl-N-1'-11C-propyl)amino-5-hydroxytetralin (11C-ZYY-339) was achieved by first synthesizing 11C-1-propionyl chloride and subsequent coupling with the appropriate secondary amine precursor to form the respective amide, which was then reduced to provide the desired tertiary amine products. The final products were obtained by reverse-phase high performance liquid chromatography (HPLC) purification in radiochemical yields of 5-10% after 60-75 min from the end of 11CO2 trapping and with specific activities in the range of 250-1,000 Ci/mmol. In vitro autoradiographs in rat brain slices with 11C-5-OH-DPAT, 11C-PPHT, and 11C-ZYY-339 revealed selective binding of the three radiotracers to the dopamine D-2 receptors in the striata.

[Quantitative determination of biogenic amine from Biomphalaria glabrata nervous system by UPLC MS/MS].

PubMed

Tao, Huang; Yun-Hai, Guo; He-Xiang, Liu; Yi, Zhang

2018-04-19

To establish a method for the quantitative determination of serotonin and dopamine in the nervous system of Biomphalaria glabrata by using ultra high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC MS/MS) . The B. glabrata nervous system was broken in the pure methanol solution after obtaining it by dissecting with microscope. Then, the supernatant containing the target substance after twice high speed centrifugation was got. The extraction was separated on an ACQUITY UPLC BEH Amide column with Waters TQ-XS series mass spectrometry detector, with ESI source and positive electrospray ionization mode when the machine testing. The detection limit of serotonin was 0.03 ng/ml and the limit of quantification was 0.1 ng/ml. The detection limit of dopamine was 0.05 ng/ml and the limit of quantification was 0.15 ng/ml. The recoveries of serotonin ranged from 90.68% to 94.72% over the range of 1 to 40 ng/ml. The recoveries of dopamine ranged from 91.68% to 96.12% over the range of 1.0 ng/ml to 40 ng/ml. The established UPLC MS/MS method is simple, stable and reproducible. It can be used for the quantitative analysis of serotonin and dopamine in the nervous system of B. glabrata snails.

Beyond the central pattern generator: amine modulation of decision-making neural pathways descending from the brain of the medicinal leech.

PubMed

Crisp, Kevin M; Mesce, Karen A

2006-05-01

The biological mechanisms of behavioral selection, as it relates to locomotion, are far from understood, even in relatively simple invertebrate animals. In the medicinal leech, Hirudo medicinalis, the decision to swim is distributed across populations of swim-activating and swim-inactivating neurons descending from the subesophageal ganglion of the compound cephalic ganglion, i.e. the brain. In the present study, we demonstrate that the serotonergic LL and Retzius cells in the brain are excited by swim-initiating stimuli and during spontaneous swim episodes. This activity likely influences or resets the neuromodulatory state of neural circuits involved in the activation or subsequent termination of locomotion. When serotonin (5-HT) was perfused over the brain, multi-unit recordings from descending brain neurons revealed rapid and substantial alterations. Subsequent intracellular recordings from identified command-like brain interneurons demonstrated that 5-HT, especially in combination with octopamine, inhibited swim-triggering neuron Tr1, as well as swim-inactivating neurons Tr2 and SIN1. Although 5-HT inhibited elements of the swim-inactivation pathway, rather than promoting them, the indirect and net effect of the amine was a reliable and sustained reduction in the firing of the segmental swim-gating neuron 204. This modulation caused cell 204 to relinquish its excitatory drive to the swim central pattern generator. The activation pattern of serotonergic brain neurons that we observed during swimming and the 5-HT-immunoreactive staining pattern obtained, suggest that within the head brain 5-HT secretion is massive. Over time, 5-HT secretion may provide a homeostatic feedback mechanism to limit swimming activity at the level of the head brain.

Transgenerational hormonal imprinting caused by vitamin A and vitamin D treatment of newborn rats. Alterations in the biogenic amine contents of the adult brain.

PubMed

Tekes, Kornélia; Gyenge, Melinda; Hantos, Mónika; Csaba, György

2009-10-01

Biogenic amines (norepinephrine, dopamine, homovanillic acid, serotonin and 5-hyroxyindole acetic acid) were measured by HPLC method in adult F1 generation rats' brain regions (brainstem, hypothalamus, hippocampus, striatum and frontal cortex), whose mothers (P generation) were treated with vitamin A or vitamin D neonatally (hormonal imprinting). Many significant differences were found, related to the maternally untreated controls. In the earlier studied P generation females, vitamin A consistently influenced the serotonerg system (5HIAA), while vitamin D the dopaminerg system (DA or HVA). Vitamin A imprinting always resulted in reduced, while that by vitamin D always in increased tissue levels. In the present case (directly untreated F1 generation) the transgenerational effect was not unidirectional, however biogenic amine tissue levels were strongly disturbed and brain-area dependent. The results call attention to the transgenerational effect of hormonal imprinting in the case of receptor level acting vitamins which are frequently used in the most imprinting-sensitive period (perinatally) of human life and suggests that caution is warranted.

TAAR1 in Addiction: Looking Beyond the Tip of the Iceberg

PubMed Central

Liu, Jian-Feng; Li, Jun-Xu

2018-01-01

Trace-amine associated receptor 1 (TAAR1) is the best-characterized member of the family of TAARs. TAAR1 is broadly expressed in the brain, especially within the monoaminergic systems. Evidence from electrophysiological and neurochemical studies evaluating the effects of genetic and pharmacological interventions on TAAR1 revealed that TAAR1 modulates transmission of monoamines, especially dopamine. TAAR1 agonists dampened drugs of abuse-induced dopamine accumulation. In general, TAAR1 agonists specifically inhibited the rewarding and reinforcing effects of drugs of abuse and drug-abuse related behaviors. Details of the mechanism of TAAR1 remain elusive; however, it is thought to be regulated by its interactions with D2 receptors. In addition, the alternative cellular mechanism such as an interaction between TAAR1 and D3 may also participate in the action of TAAR1 agonists. Further studies are required to investigate the role of TAAR1 in other drugs of abuse-related behaviors and the underlying neural mechanisms. Collectively, TAAR1 negatively modulates dopaminergic systems and dopamine-related behaviors and TAAR1 agonists are promising pharmacotherapy to treat drug addiction and relapse. PMID:29636691

[Biogenic amines in the epiphysis and hypothalamus under normal conditions and following ovariectomy].

PubMed

Grishchenko, V I; Koliada, L D; Demidenko, D I

1977-01-01

Melatonin content in the epiphysis, serotonin, noradrenaline, dopamine-in the hypothalamus, gonadotropins--in the hypophysis of rats was studied under normal conditions and following ovariectomy; regularly of the estral cycle phases was studied as well. Two series of experiments were conducted on 120 rats with regular estral cycles. The animals were divided into groups according to the estral cycle phase. Melatonin concentration in the epiphysis, serotonin, noradrenaline, dopamine--in the hypothalamus was subject to variations coinciding with the estral cycle phases. Serotonin, noradrenaline, and dopamine content decreased in the hypophysis of ovariectomized rats in comparison with control; melatonin content rose in the epiphysis. There was no complete extinction of the estral cycle in the course of investigation (20 days). The action of castration on the sexual cycle depended on the phase at which the rats were subjected to ovariectomy. A reverse relationship existed between the melatonin content in the epiphysis and serotonin content in the hypothalamus, this serving as one of the important factors in the regulation of the sexual function.

Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

PubMed

Tutton, P J; Barkla, D H

1987-01-01

The role of extracellular amines such as noradrenaline and serotonin and their interaction with cyclic nucleotides and intracellular polyamines in the regulation of intestinal epithelial cell proliferation is reviewed with particular reference to the differences between normal and neoplastic cells. In respect to the normal epithelium of the small intestine there is a strong case to support the notion that cell proliferation is controlled by, amongst other things, sympathetic nerves. In colonic carcinomas, antagonists for certain serotonin receptors, for histamine H2 receptors and for dopamine D2 receptors inhibit both cell division and tumour growth. Because of the reproducible variations between tumour lines in the response to these antagonists, this inhibition appears to be due to a direct effect on the tumour cells rather than an indirect effect via the tumour host or stroma. This conclusion is supported by the cytocidal effects of toxic congeners of serotonin on the tumour cells. The most salient difference between the amine responses of normal and neoplastic cells relates to the issue of amine uptake. Proliferation of crypt cells is promoted by amine uptake inhibitors, presumably because they block amine re-uptake by the amine secreting cells--sympathetic neurones and enteroendocrine cells. However, tumour cell proliferation is strongly inhibited by amine uptake inhibitors, suggesting that neoplastic cells can, and need to take up the amine before being stimulated by it. Recent revelations in the field of oncogenes also support an important association between amines, cyclic nucleotides and cell division. The ras oncogenes code for a protein that is a member of a family of molecules which relay information from extracellular regulators, such as biogenic amines, to the intracellular regulators, including cyclic nucleotides. Evidence is presented suggesting that enteroendocrine cells, enterocytes, carcinoid tumour cells and adenocarcinoma cells all have the same embryonic origin and that cells exhibiting an admixture of endocrine and proliferative properties exist in colonic tumours, but not in the normal intestinal epithelium. Thus, it appears that in the normal intestine a clear structural and functional distinction exists between the regulating cells (i.e. the sympathetic neurones and enteroendocrine cells) and the regulated cells (i.e. the undifferentiated crypt cells): cells that have acquired a regulating role are no longer able to divide and cells which are able to divide do not take up or store amines.(ABSTRACT TRUNCATED AT 400 WORDS)

Limited distal organelles and synaptic function in extensive monoaminergic innervation.

PubMed

Tao, Juan; Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

2017-08-01

Organelles such as neuropeptide-containing dense-core vesicles (DCVs) and mitochondria travel down axons to supply synaptic boutons. DCV distribution among en passant boutons in small axonal arbors is mediated by circulation with bidirectional capture. However, it is not known how organelles are distributed in extensive arbors associated with mammalian dopamine neuron vulnerability, and with volume transmission and neuromodulation by monoamines and neuropeptides. Therefore, we studied presynaptic organelle distribution in Drosophila octopamine neurons that innervate ∼20 muscles with ∼1500 boutons. Unlike in smaller arbors, distal boutons in these arbors contain fewer DCVs and mitochondria, although active zones are present. Absence of vesicle circulation is evident by proximal nascent DCV delivery, limited impact of retrograde transport and older distal DCVs. Traffic studies show that DCV axonal transport and synaptic capture are not scaled for extensive innervation, thus limiting distal delivery. Activity-induced synaptic endocytosis and synaptic neuropeptide release are also reduced distally. We propose that limits in organelle transport and synaptic capture compromise distal synapse maintenance and function in extensive axonal arbors, thereby affecting development, plasticity and vulnerability to neurodegenerative disease. © 2017. Published by The Company of Biologists Ltd.

Organization of descending neurons in Drosophila melanogaster

PubMed Central

Hsu, Cynthia T.; Bhandawat, Vikas

2016-01-01

Neural processing in the brain controls behavior through descending neurons (DNs) - neurons which carry signals from the brain to the spinal cord (or thoracic ganglia in insects). Because DNs arise from multiple circuits in the brain, the numerical simplicity and availability of genetic tools make Drosophila a tractable model for understanding descending motor control. As a first step towards a comprehensive study of descending motor control, here we estimate the number and distribution of DNs in the Drosophila brain. We labeled DNs by backfilling them with dextran dye applied to the neck connective and estimated that there are ~1100 DNs distributed in 6 clusters in Drosophila. To assess the distribution of DNs by neurotransmitters, we labeled DNs in flies in which neurons expressing the major neurotransmitters were also labeled. We found DNs belonging to every neurotransmitter class we tested: acetylcholine, GABA, glutamate, serotonin, dopamine and octopamine. Both the major excitatory neurotransmitter (acetylcholine) and the major inhibitory neurotransmitter (GABA) are employed equally; this stands in contrast to vertebrate DNs which are predominantly excitatory. By comparing the distribution of DNs in Drosophila to those reported previously in other insects, we conclude that the organization of DNs in insects is highly conserved. PMID:26837716

Organization of descending neurons in Drosophila melanogaster.

PubMed

Hsu, Cynthia T; Bhandawat, Vikas

2016-02-03

Neural processing in the brain controls behavior through descending neurons (DNs) - neurons which carry signals from the brain to the spinal cord (or thoracic ganglia in insects). Because DNs arise from multiple circuits in the brain, the numerical simplicity and availability of genetic tools make Drosophila a tractable model for understanding descending motor control. As a first step towards a comprehensive study of descending motor control, here we estimate the number and distribution of DNs in the Drosophila brain. We labeled DNs by backfilling them with dextran dye applied to the neck connective and estimated that there are ~1100 DNs distributed in 6 clusters in Drosophila. To assess the distribution of DNs by neurotransmitters, we labeled DNs in flies in which neurons expressing the major neurotransmitters were also labeled. We found DNs belonging to every neurotransmitter class we tested: acetylcholine, GABA, glutamate, serotonin, dopamine and octopamine. Both the major excitatory neurotransmitter (acetylcholine) and the major inhibitory neurotransmitter (GABA) are employed equally; this stands in contrast to vertebrate DNs which are predominantly excitatory. By comparing the distribution of DNs in Drosophila to those reported previously in other insects, we conclude that the organization of DNs in insects is highly conserved.

Actions of certain amines on cerebral cortical neurones

PubMed Central

Krnjević, K.; Phillis, J. W.

1963-01-01

A number of derivatives of tryptamine and phenethylamine, and certain other compounds, were tested on neurones in the cerebral cortex of cats by iontophoretic release from micro-pipettes. The characteristic action of many of these compounds was a depression of the neuronal discharge initiated by synaptic activity or by the application of L-glutamate; imidazolylacetic acid, dopamine, ephedrine and ergometrine were particularly effective. Catechol amines, hydroxytryptamines and imidazolylacetic acid had a relatively quick and rapidly reversible action, not unlike that of γ-aminobutyric acid, whereas ephedrine and derivatives of lysergic acid diethylamide caused a slower and more prolonged depression of the amplitude of spikes, rather like atropine. Several compounds, including 5-hydroxytryptamine, adrenaline and ergometrine, could also excite the same neurone when larger amounts were applied. A few substances, such as dopa and methylergometrine, had a predominantly excitant action. PMID:14035890

Effect of scopoletin on monoamine oxidases and brain amines.

PubMed

Basu, Mahua; Mayana, Kamlesh; Xavier, S; Balachandran, S; Mishra, Nibha

2016-02-01

Naturally, occurring compounds with MAO inhibitory property may provide promising lead molecules against neurodegenerative disorders. We report MAO inhibitory activity of a naturally occurring coumarin (validated chemical scaffold as MAO inhibitors), scopoletin. It selectively (and reversibly) inhibits human (Ki = 20.7 μM) and mouse (Ki = 22 μM) MAO-B, ∼3.5 times more selective towards MAO-B than MAO-A. Docking studies revealed its molecular recognition and explained the selectivity mechanism towards MAO isoforms. Scopoletin occupied the hydrophobic aromatic pockets showing favorable interactions for MAO-B; experimental Ki agreed with the predicted Ki. In vivo, scopoletin (80 mg/kg, i.p.) treatment significantly increases dopamine level and decreases its metabolite DOPAC in striatum. Overall, scopoletin is a partially selective MAO-B inhibitor that increases brain dopamine level. Copyright © 2016. Published by Elsevier Ltd.

The Function of Emulsions on the Biogenic Amine Formation and their Indices of Sea Bass Fillets (Dicentrarchus Labrax) Stored in Vacuum Packaging.

PubMed

Ozogul, Yesim; Durmus, Mustafa; Kuley Boga, Esmeray; Uçar, Yılmaz; Ozogul, Fatih

2018-02-01

The impacts of emulsions based on commercial oils on the biogenic amine formation and their indices of vacuumed packed sea bass fillets were investigated. The results showed that among biogenic amines, cadaverine, putrescine, spermidine, spermine, serotonin, dopamine, and agmatine were predominant amines in sea bass fillets stored under vacuum packaging. Significant differences (P < 0.05) in biogenic amines concentrations of vacuumed packed sea bass treated with emulsions were observed. All groups contained histamine lower than 5.0 mg/100 g, regarded as the allowable limit by the U.S. Food and Drug Administration. Polyamine levels were not affected by application of emulsion. Quality index (QI) showed an increase and after 14 d of storage it decreased in all groups. The control generally seemed to higher QI value than those of treatment groups except at 14 and 18 days while soybean and corn gave lower QI among treatment groups. Only biogenic amine index correlated with sensory acceptability of vacuumed packed sea bass, indicating that this index can be used for determination of the degree of spoilage of vacuumed packed sea bass. Emulsions extended the shelf-life (approximately 2 to 4 d) of vacuumed packed sea bass fillets by inhibiting microbial growth compared to the control. Emulsions have become popular since they are regarded as ideal carrier for the delivery of lipophilic substances due to the ease of preparation, small particle size, their enhanced bioavailability, and long term kinetic stability. They have been proven to be self-preserving antimicrobials due to bound water in their structure and thus no available water to microorganisms. Antimicrobial emulsions have potential applications in many fields because they are inexpensive, stable, and nontoxic agents. © 2018 Institute of Food Technologists®.

[Medullary layer activity of the rat adrenals after a flight on the Kosmos-1129 biosatellite].

PubMed

Kvetnanský, R; Blazicek, P; Tigranian, R A

1982-01-01

After a 18.5-day space flight on Cosmos-1129 rat adrenals were investigated for the concentration of catecholamines and activity of enzymes involved in their synthesis, i.e. tyrosine hydroxylase, dopamine-beta-hydroxylase, and phenyl ethanol amine-N-methyl transferase. It was found that inflight the sympatho-adreno-medullary system of rats was not exposed to a prolonged or strong stressogenic effect. Postflight the rats showed an increased reactivity to the immobilization stress.

Adrenergic ligands that block oviposition in the cattle tick Rhipicephalus microplus affect ovary contraction

PubMed Central

Cossío-Bayúgar, Raquel; Miranda-Miranda, Estefan; Fernández-Rubalcaba, Manuel; Narváez Padilla, Verónica; Reynaud, Enrique

2015-01-01

The tyraminergic/octopaminergic system is central for the control of arthropod oviposition. Previous works demonstrated that the pharmacological perturbation of this system inhibits oviposition in the cattle tick Rhipicephalus microplus. In this work, we describe a physiologically active whole-mount preparation of the contractile tick ovary that allows the quantitative videometrical analysis of ovary contraction in response to different compounds. Eight adrenergic ligands known to inhibit oviposition, including octopamine and tyramine were tested. These compounds exhibited antagonistic effects; octopamine relaxes the ovary preparation while tyramine induces a very strong contraction. The other adrenergic compounds tested were classified as able to contract or relax ovary muscle tissue. Isoprotenerol has a stronger relaxative effect than octopamine. Tyramine induces the biggest contraction observed of all the compounds tested, followed, in descending amount of contraction, by salbutamol, prazosin, epinastine, clonidine and the acaricide amitraz. The effect of these adrenergic ligands on the ovary preparation, explains why these molecules inhibit tick oviposition and suggest a regulatory mechanism for ovary contraction and relaxation during oviposition. Our results also provide a physiological explanation of the egg-laying inhibition effect of amitraz when used on the cattle tick. PMID:26456007

Adrenergic ligands that block oviposition in the cattle tick Rhipicephalus microplus affect ovary contraction.

PubMed

Cossío-Bayúgar, Raquel; Miranda-Miranda, Estefan; Fernández-Rubalcaba, Manuel; Narváez Padilla, Verónica; Reynaud, Enrique

2015-10-12

The tyraminergic/octopaminergic system is central for the control of arthropod oviposition. Previous works demonstrated that the pharmacological perturbation of this system inhibits oviposition in the cattle tick Rhipicephalus microplus. In this work, we describe a physiologically active whole-mount preparation of the contractile tick ovary that allows the quantitative videometrical analysis of ovary contraction in response to different compounds. Eight adrenergic ligands known to inhibit oviposition, including octopamine and tyramine were tested. These compounds exhibited antagonistic effects; octopamine relaxes the ovary preparation while tyramine induces a very strong contraction. The other adrenergic compounds tested were classified as able to contract or relax ovary muscle tissue. Isoprotenerol has a stronger relaxative effect than octopamine. Tyramine induces the biggest contraction observed of all the compounds tested, followed, in descending amount of contraction, by salbutamol, prazosin, epinastine, clonidine and the acaricide amitraz. The effect of these adrenergic ligands on the ovary preparation, explains why these molecules inhibit tick oviposition and suggest a regulatory mechanism for ovary contraction and relaxation during oviposition. Our results also provide a physiological explanation of the egg-laying inhibition effect of amitraz when used on the cattle tick.

Facile Synthesis of Molecularly Imprinted Graphene Quantum Dots for the Determination of Dopamine with Affinity-Adjustable.

PubMed

Zhou, Xi; Wang, Anqi; Yu, Chenfei; Wu, Shishan; Shen, Jian

2015-06-10

A facilely prepared fluorescence sensor was developed for dopamine (DA) determination based on polyindole/graphene quantum dots molecularly imprinted polymers (PIn/GQDs@MIPs). The proposed sensor exhibits a high sensitivity with a linear range of 5 × 10(-10) to 1.2 × 10(-6) M and the limit of detection as low as 1 × 10(-10) M in the determination of DA, which is probably due to the tailor-made imprinted cavities for binding DA thought hydrogen bonds between amine groups of DA and oxygen-containing groups of the novel composite. Furthermore, the prepared sensor can rebind DA in dual-type: a low affinity type (noncovalent interaction is off) and a high affinity type (noncovalent interaction is on), and the rebinding interaction can be adjusted by tuning the pH, which shows a unique potential for adjusting the binding interaction while keeping the specificity, allowing for wider applications.

Iron oxide magnetic nanoparticles with versatile surface functions based on dopamine anchors

NASA Astrophysics Data System (ADS)

Mazur, Mykola; Barras, Alexandre; Kuncser, Victor; Galatanu, Andrei; Zaitzev, Vladimir; Turcheniuk, Kostiantyn V.; Woisel, Patrice; Lyskawa, Joel; Laure, William; Siriwardena, Aloysius; Boukherroub, Rabah; Szunerits, Sabine

2013-03-01

The synthesis of multifunctional magnetic nanoparticles (MF-MPs) is one of the most active research areas in advanced materials as their multifunctional surfaces allow conjugation of biological and chemical molecules, thus making it possible to achieve target-specific diagnostic in parallel to therapeutics. We report here a simple strategy to integrate in a one-step reaction several reactive sites onto the particles. The preparation of MF-MPs is based on their simultaneous modification with differently functionalized dopamine derivatives using simple solution chemistry. The formed MF-MPs show comparable magnetic properties to those of naked nanoparticles with almost unaltered particle size of around 25 nm. The different termini, amine, azide and maleimide functions, enable further functionalization of MF-MPs by the grafting-on approach. Michael addition, Cu(i) catalyzed « click » chemistry and amidation reactions are performed on the MF-MPs integrating subsequently 6-(ferrocenyl)-hexanethiol, horseradish peroxidase (HRP) and mannose.

Amphetamine Potentiates the Effects of β-Phenylethylamine through Activation of an Amine-Gated Chloride Channel

PubMed Central

Safratowich, Bryan D.; Hossain, Murad; Bianchi, Laura

2014-01-01

β-Phenylethylamine (βPEA) is a trace amine present in the CNS of all animals tested to date. However, its function is still not fully understood. βPEA has been suggested to function as a neurotransmitter and/or to mimic the effect of amphetamine (Amph). In support of the latter is the observation that βPEA and Amph produce similar but not identical behaviors. Here, we show that βPEA, like Amph, activates the dopamine transporter and the amine-gated chloride channel LGC-55 to generate behaviors in Caenorhabditis elegans. However, although Amph-induced behaviors occurred gradually during 10 min of treatment, βPEA induced maximal effects within 1 min. In vitro data demonstrate that βPEA activates the LGC-55 more efficiently than Amph (Km = 9 and 152 μm, respectively) and generates saturating currents that are 10 times larger than those produced by Amph. These results suggest that activation of LGC-55 mostly accounts for the behavioral effects reached after 1 min of treatment with βPEA. Importantly, our in vitro and in vivo data show that Amph increases the effects induced by βPEA on the LGC-55, indicating that Amph potentiates the effects generated by the biogenic amine βPEA. Together, our data not only identify a new target for βPEA, but also offer a novel mechanism of action of Amph. In addition, our results highlight C. elegans as a powerful genetic model for studying the effects of biogenic and synthetic amines both at the molecular and behavioral levels. PMID:24672014

Amphetamine potentiates the effects of β-phenylethylamine through activation of an amine-gated chloride channel.

PubMed

Safratowich, Bryan D; Hossain, Murad; Bianchi, Laura; Carvelli, Lucia

2014-03-26

β-Phenylethylamine (βPEA) is a trace amine present in the CNS of all animals tested to date. However, its function is still not fully understood. βPEA has been suggested to function as a neurotransmitter and/or to mimic the effect of amphetamine (Amph). In support of the latter is the observation that βPEA and Amph produce similar but not identical behaviors. Here, we show that βPEA, like Amph, activates the dopamine transporter and the amine-gated chloride channel LGC-55 to generate behaviors in Caenorhabditis elegans. However, although Amph-induced behaviors occurred gradually during 10 min of treatment, βPEA induced maximal effects within 1 min. In vitro data demonstrate that βPEA activates the LGC-55 more efficiently than Amph (Km = 9 and 152 μm, respectively) and generates saturating currents that are 10 times larger than those produced by Amph. These results suggest that activation of LGC-55 mostly accounts for the behavioral effects reached after 1 min of treatment with βPEA. Importantly, our in vitro and in vivo data show that Amph increases the effects induced by βPEA on the LGC-55, indicating that Amph potentiates the effects generated by the biogenic amine βPEA. Together, our data not only identify a new target for βPEA, but also offer a novel mechanism of action of Amph. In addition, our results highlight C. elegans as a powerful genetic model for studying the effects of biogenic and synthetic amines both at the molecular and behavioral levels.

The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia.

PubMed

Wolinsky, T D; Swanson, C J; Smith, K E; Zhong, H; Borowsky, B; Seeman, P; Branchek, T; Gerald, C P

2007-10-01

Trace amines have been implicated in a number of neuropsychiatric disorders including depression and schizophrenia. Although long known to modulate neurotransmission indirectly through the release of catecholamines, the identification of the Trace Amine 1 receptor (TA1) offers a mechanism by which trace amines can influence synaptic activity directly. TA1 binds and is activated by trace amines such as beta-phenylethylamine and tyramine. Our pharmacological characterization of mouse TA1 showed that, as in rat and primate, amphetamine is an agonist at this receptor but with surprisingly high potency. Without selective ligands for TA1 that do not also possess catecholamine-releasing properties, however, it has not been possible to study its physiological role in the central nervous system. To that end, a line of mice lacking the TA1 receptor was generated to characterize its contribution to the regulation of behavior. Compared with wild-type littermates, TA1 knockout (KO) mice displayed a deficit in prepulse inhibition. Knockout animals, in which the TA1-agonist influence of amphetamine was absent, showed enhanced sensitivity to the psychomotor-stimulating effect of this drug, which was temporally correlated with significantly larger increases in the release of both dopamine and norepinephrine in the dorsal striatum and associated with a 262% increase in the proportion of striatal high-affinity D2 receptors. TA1 therefore appears to play a modulatory role in catecholaminergic function and represents a potentially novel mechanism for the treatment of neuropsychiatric disorders. Furthermore, the TA1 KO mouse may provide a useful model for the development of treatments for some positive symptoms of schizophrenia.

Effect of salinity on regulation mechanism of neuroendocrine-immunoregulatory network in Litopenaeus vannamei.

PubMed

Zhao, Qun; Pan, Luqing; Ren, Qin; Wang, Lin; Miao, Jingjing

2016-02-01

The effects of low salinity (transferred from 31‰ to 26‰, 21‰, and 16‰) on the regulation pathways of neuroendocrine-immunoregulatory network were investigated in Litopenaeus vannamei. The results showed that the hormones (corticotrophin-releasing hormone, adrenocorticotropic hormone) and biogenic amines (dopamine, noradrenaline, 5-hydroxytryptamine) concentrations in lower salinity groups increased significantly within 12 h. The gene expression of biogenic amine receptors showed that dopamine receptor D4 and α2 adrenergic receptor in lower salinity groups decreased significantly within 12 h, whereas the 5-HT7 receptor significantly increased within 1d. The second messenger synthetases (adenylyl cyclase, phospholipase C) and the second messengers (cyclic adenosine monophosphate, cyclic guanosine monophosphate) of lower salinity groups shared a similar trend in which adenylyl cyclase and cyclic adenosine monophosphate reached the maximum at 12 h, whereas phospholipase C and cyclic guanosine monophosphate reached the minimum. The immune parameters (total hemocyte count, phenoloxidase activity, phagocytic activity, crustin expression, antibacterial activity, C-type lectin expression, hemagglutinating activity) in lower salinity groups decreased significantly within 12 h. Except for the total hemocyte count, all the parameters recovered to the control levels afterwards. Therefore, it may be concluded that the neuroendocrine-immunoregulatory network plays a principal role in adapting to salinity changes as the main center for sensing the stress and causes immune response in L. vannamei. Copyright © 2016 Elsevier Ltd. All rights reserved.

Frank Beach Award Winner: Steroids as Neuromodulators of Brain Circuits and Behavior

PubMed Central

Remage-Healey, Luke

2014-01-01

Neurons communicate primarily via action potentials that transmit information on the timescale of milliseconds. Neurons also integrate information via alterations in gene transcription and protein translation that are sustained for hours to days after initiation. Positioned between these two signaling timescales are the minute-by-minute actions of neuromodulators. Over the course of minutes, the classical neuromodulators (such as serotonin, dopamine, octopamine, and norepinephrine) can alter and/or stabilize neural circuit patterning as well as behavioral states. Neuromodulators allow many flexible outputs from neural circuits and can encode information content into the firing state of neural networks. The idea that steroid molecules can operate as genuine behavioral neuromodulators - synthesized by and acting within brain circuits on a minute-by-minute timescale - has gained traction in recent years. Evidence for brain steroid synthesis at synaptic terminals has converged with evidence for the rapid actions of brain-derived steroids on neural circuits and behavior. The general principle emerging from this work is that the production of steroid hormones within brain circuits can alter their functional connectivity and shift sensory representations by enhancing their information coding. Steroids produced in the brain can therefore change the information content of neuronal networks to rapidly modulate sensory experience and sensorimotor functions. PMID:25110187

Amine dependence of proliferative activity in two transplantable lines of mouse colonic carcinoma.

PubMed

Tutton, P J; Barkla, D H

1987-01-01

Serotonin, histamine and their antagonists have previously been shown to influence both the cell proliferation rate and the volumetric growth rate of colonic tumours. Of these earlier studies, those on cell proliferation could not distinguish between direct effects on tumour cells and indirect effects on the host, whereas those on the volumetric growth rate of tumours, whilst suggesting an outcome related to the individual properties of the tumour rather than the host, could not distinguish between influences on cell gain, cell loss or stromal changes. In an attempt to distinguish between these possibilities the current experiments on the mitotic rate in two lines of transplantable mouse colonic carcinoma were undertaken. One line of tumour proved to be sensitive to inhibition by a histamine H2 receptor antagonist and a dopamine D2 antagonist but resistant to serotonin antagonists; the inhibition by histamine antagonists was surmountable by co-administration of histamine. The other line proved to be highly sensitive to the inhibitory effects of serotonin antagonist and less so to antagonists of the other two amines and in this case the effect of serotonin antagonists was surmountable by serotonin. These results suggest that the variations between different colonic tumours in the response to amine antagonists is due to differences in the extent of inhibition of cell proliferation rather than differences in cell loss or stromal effects. Thus it appears likely that amine antagonists are able to directly interfere with the proliferation of some colonic tumour cells.

β-Phenylethylamine requires the dopamine transporter to increase extracellular dopamine in Caenorhabditis elegans dopaminergic neurons.

PubMed

Hossain, Murad; Wickramasekara, Rochelle N; Carvelli, Lucia

2014-07-01

β-Phenylethylamine (βPEA) is an endogenous amine that has been shown to increase the synaptic levels of dopamine (DA). A number of in vitro and behavioral studies suggest the dopamine transporter (DAT) plays a role in the effects generated by βPEA, however the mechanism through which βPEA affects DAT has not yet been elucidated. Here, we used Caenorhabditis (C.) elegans DAT (DAT-1) expressing LLC-pk1 cells and neuronal cultures to investigate whether the βPEA-induced increase of extracellular DA required DAT-1. Our data show that βPEA increases extracellular dopamine both in DAT-1 transfected cells and cultures of differentiated neurons. RTI-55, a cocaine homologue and DAT inhibitor, completely blocked the βPEA-induced effect in transfected cells. However in neuronal cultures, RTI-55 only partly inhibited the increase of extracellular DA generated by βPEA. These results suggest that βPEA requires DAT-1 and other, not yet identified proteins, to increase extracellular DA when tested in a native system. Furthermore, our results suggest that βPEA-induced increase of extracellular DA does not require functional monoamine vesicles as genetic ablation of the C. elegans homologue vesicular monoamine transporter, cat-1, did not compromise the ability of βPEA to increase extracellular DA. Finally, our electrophysiology data show that βPEA caused fast-rising and self-inactivating amperometric currents in a subset of wild-type DA neurons but not in neurons isolated from dat-1 knockout animals. Taken together, these data demonstrate that in both DA neurons and heterogeneous cultures of differentiated C. elegans neurons, βPEA releases cytoplasmic DA through DAT-1 to ultimately increase the extracellular concentration of DA. Copyright © 2013 Elsevier Ltd. All rights reserved.

β-phenylethylamine Requires the Dopamine Transporter to Increase Extracellular Dopamine in C. elegans Dopaminergic Neurons

PubMed Central

Hossain, Murad; Wickramasekara, Rochelle N.; Carvelli, Lucia

2013-01-01

β-phenylethylamine (βPEA) is an endogenous amine that has been shown to increase the synaptic levels of dopamine (DA). A number of in vitro and behavioral studies suggest the dopamine transporter (DAT) plays a role in the effects generated by βPEA, however the mechanism through which βPEA affects DAT has not yet been elucidated. Here, we used Caenorhabditis (C.) elegans DAT (DAT-1) expressing LLC-pk1 cells and neuronal cultures to investigate whether the βPEA-induced increase of extracellular DA required DAT-1. Our data show that βPEA increases extracellular dopamine both in DAT-1 transfected cells and cultures of differentiated neurons. RTI-55, a cocaine homologue and DAT inhibitor, completely blocked the βPEA-induced effect in transfected cells. However in neuronal cultures, RTI-55 only partly inhibited the increase of extracellular DA generated by βPEA. These results suggest that βPEA requires DAT-1 and other, not yet identified proteins, to increase extracellular DA when tested in a native system. Furthermore, our results suggest that βPEA-induced increase of extracellular DA does not require functional monoamine vesicles as genetic ablation of the C. elegans homologue vesicular monoamine transporter, cat-1, did not compromise the ability of βPEA to increase extracellular DA. Finally, our electrophysiology data show that βPEA caused fast-rising and self-inactivating amperometric currents in a subset of wild-type DA neurons but not in neurons isolated from dat-1 knockout animals. Taken together, these data demonstrate that in both DA neurons and heterogeneous cultures of differentiated C. elegans neurons, βPEA releases cytoplasmic DA through DAT-1 to ultimately increase the extracellular concentration of DA. PMID:24161617

Effect of genetic polymorphism on the inhibition of dopamine formation from p-tyramine catalyzed by brain cytochrome P450 2D6.

PubMed

Niwa, Toshiro; Shizuku, Marina; Yamano, Kaori

2017-04-15

The inhibitory effects of steroid hormones, including glucocorticoids such as cortisol, and related compounds on dopamine formation from p-tyramine, catalyzed by cytochrome P450 (CYP) 2D6.2 (Arg296Cys, Ser486Thr) and CYP2D6.10 (Pro34Ser, Ser486Thr) were compared with the effects of those catalyzed by CYP2D6.1 (wild type), to investigate the effect of a CYP2D6 polymorphism on neuroactive amine metabolism in the brain. Inhibition constants (K i ) or 50% inhibitory concentrations of six steroid hormones (cortisol, cortisone, corticosterone, dehydroepiandrosterone, progesterone, and pregnenolone) and quinidine and quinine-typical potent inhibitors of the human CYP2D6 and rat CYP2D subfamily, respectively-toward dopamine formation catalyzed by CYP2D6.1, CYP2D6.2, and CYP2D6.10 expressed in recombinant Escherichia coli were compared. Although most steroid hormones had no or minor inhibitory effects on the dopamine formation by all CYP2D6 variants, progesterone inhibited the metabolism and K i value against CYP2D6.10 was approximately twice that for CYP2D6.1 and CYP2D6.2. Quinidine exhibited stronger inhibition than quinine; however, these two compounds inhibited the CYP2D6.10-mediated reaction more weakly than the CYP2D6.1 and CYP2D6.2 reactions. These results suggest that CYP2D6 polymorphism would affect drug interaction through dopamine formation in the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Association of MAOA gene functional promoter polymorphism with CSF dopamine turnover and atypical depression.

PubMed

Aklillu, Eleni; Karlsson, Sara; Zachrisson, Olof O; Ozdemir, Vural; Agren, Hans

2009-04-01

Monoamine oxidase-A (MAO-A) is a key mitochondrial enzyme that metabolizes biogenic amine neurotransmitters such as dopamine and serotonin. Individuals with atypical depression (AD) are particularly responsive to treatment with MAO inhibitors (MAOIs). Biomarker tests are essential for prompt diagnosis of AD, and to identify those with an altered brain neurotransmitter metabolism who may selectively respond to MAOI therapy. In a sample of 118 Scandinavian patients with treatment-resistant depression who are naive to MAOI therapy, we investigated the associations between a common MAOA functional promoter polymorphism (MAOA-uVNTR), cerebrospinal fluid (CSF) neurotransmitter metabolites, and AD susceptibility. The metabolites for dopamine (homovanillic acid, HVA), serotonin (5-hydroxyindoleacetic acid) and noradrenaline (3-methoxy-4-hydroxyphenylglycol) were measured in the CSF. AD was associated with the female sex and a higher HVA in CSF (P=0.008). The carriers of the MAOA-uVNTR short allele were significantly overrepresented among women with AD (P=0.005; odds ratio=4.76; 95% confidence interval=1.5-13.1; statistical power=80.0%). Moreover, the MAOA-uVNTR genotype significantly influenced the HVA concentration (P=0.01) and showed a strong trend in relation to 5-hydroxyindoleacetic acid concentration (P=0.057) in women. The mediational statistical analyses showed the CSF-HVA concentration as a key driver of the relationship between MAOA-uVNTR genotype and AD. The association of the MAOA-uVNTR with both susceptibility to AD and dopamine metabolite (HVA) concentration lends further biological plausibility for high MAO-A enzyme activity as a mechanistic factor for genetic predisposition to AD through altered dopamine turnover. Our observations provide new evidence on the in-vivo functional significance of the MAOA-uVNTR short allele as a high activity variant.

Linking Inflammation and Parkinson Disease: Hypochlorous Acid Generates Parkinsonian Poisons

PubMed Central

Jeitner, Thomas M.; Kalogiannis, Mike; Krasnikov, Boris F.; Gomlin, Irving; Peltier, Morgan R.; Moran, Graham R.

2016-01-01

Inflammation is a common feature of Parkinson Disease and other neurodegenerative disorders. Hypochlorous acid (HOCl) is a reactive oxygen species formed by neutrophils and other myeloperoxidase-containing cells during inflammation. HOCl chlorinates the amine and catechol moieties of dopamine to produce chlorinated derivatives collectively termed chlorodopamine. Here, we report that chlorodopamine is toxic to dopaminergic neurons both in vivo and in vitro. Intrastriatal administration of 90 nmol chlorodopamine to mice resulted in loss of dopaminergic neurons from the substantia nigra and decreased ambulation-results that were comparable to those produced by the same dose of the parkinsonian poison, 1-methyl-4-phenylpyridinium (MPP+). Chlorodopamine was also more toxic to differentiated SH SY5Y cells than HOCl. The basis of this selective toxicity is likely mediated by chlorodopamine uptake through the dopamine transporter, as expression of this transporter in COS-7 cells conferred sensitivity to chlorodopamine toxicity. Pharmacological blockade of the dopamine transporter also mitigated the deleterious effects of chlorodopamine in vivo. The cellular actions of chlorodopamine included inactivation of the α-ketoglutarate dehydrogenase complex, as well as inhibition of mitochondrial respiration. The latter effect is consistent with inhibition of cytochrome c oxidase. Illumination at 670 nm, which stimulates cytochrome c oxidase, reversed the effects of chlorodopamine. The observed changes in mitochondrial biochemistry were also accompanied by the swelling of these organelles. Overall, our findings suggest that chlorination of dopamine by HOCl generates toxins that selectively kill dopaminergic neurons in the substantia nigra in a manner comparable to MPP+. PMID:27026709

Novel multi-target azinesulfonamides of cyclic amine derivatives as potential antipsychotics with pro-social and pro-cognitive effects.

PubMed

Zajdel, Paweł; Kos, Tomasz; Marciniec, Krzysztof; Satała, Grzegorz; Canale, Vittorio; Kamiński, Krzysztof; Hołuj, Małgorzata; Lenda, Tomasz; Koralewski, Robert; Bednarski, Marek; Nowiński, Leszek; Wójcikowski, Jacek; Daniel, Władysława A; Nikiforuk, Agnieszka; Nalepa, Irena; Chmielarz, Piotr; Kuśmierczyk, Justyna; Bojarski, Andrzej J; Popik, Piotr

2018-02-10

Currently used antipsychotics are characterized by multireceptor mode of action. While antagonism of dopamine D 2 receptors is responsible for the alleviation of "positive" symptoms of schizophrenia and the effects at other, particularly serotonergic receptors are necessary for their additional therapeutic effects, there is no consensus regarding an "ideal" target engagement. Here, a detailed SAR analysis in a series of 45 novel azinesulfonamides of cyclic amine derivatives, involving the aryl-piperazine/piperidine pharmacophore, central alicyclic amine and azinesulfonamide groups has led to the selection of (S)-4-((2-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)sulfonyl)isoquinoline (62). The polypharmacology profile of 62, characterized by partial 5-HT 1A R agonism, 5-HT 2A /5-HT 7 /D 2 /D 3 R antagonism, and blockade of SERT, reduced the "positive"-like, and "negative"-like symptoms of psychoses. Compound 62 produced no catalepsy, demonstrated a low hyperprolactinemia liability and displayed pro-cognitive effects in the novel object recognition task and attentional set-shifting test. While association of in vitro features with the promising in vivo profile of 62 is still not fully established, its clinical efficacy should be verified in further stages of development. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Oleic Acid Protects Against Oxidative Stress Exacerbated by Cytarabine and Doxorubicin in Rat Brain.

PubMed

Guzmán, David Calderón; Brizuela, Norma Osnaya; Herrera, Maribel Ortíz; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; Mejía, Gerardo Barragán

2016-01-01

The objective of this study was to analyze the effect of doxorubicin and cytarabine on biogenic amines and oxidative biomarkers in the brain of rats treated with oleic acid. Thirty-six Wistar rats distributed in 6 groups, were treated as follows: group 1 (control), NaCl 0.9%; group 2 doxorubicin (1mg/kg); group 3 cytarabine (70mg /kg); group 4 oleic acid (1500μl/kg); group 5 doxorubicin + oleic acid; group 6 cytarabine + oleic acid. All compounds were administered intraperitoneally for 5 days. The Rats were sacrificed after receiving the last administration and their brains were dissected in cortex, hemispheres, and cerebellum/medulla oblongata. Blood samples were obtained on sacrifice to assess the levels of glucose and triglycerides. In each brain region, lipoperoxidation (TBARS), H2O2, Na+, K+ ATPase, glutathione (GSH), serotonin metabolites (5-HIAA) and dopamine were measured using validated methods. Cytarabine decreased the levels of dopamine, TBARS, GSH, H2O2 and ATPase in all regions. Doxorubicin combined with oleic acid increased the levels of GSH in cortex, and decreased ATPase in cerebellum/medulla oblongata. These results suggest that the reduction of dopamine and oxidant effect during cytarabine treatment could result in brain injury but could be prevented by oleic acid supplementation.

SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and Internalization.

PubMed

Luqman, Arif; Nega, Mulugeta; Nguyen, Minh-Thu; Ebner, Patrick; Götz, Friedrich

2018-01-09

A subgroup of biogenic amines, the so-called trace amines (TAs), are produced by mammals and bacteria and can act as neuromodulators. In the genus Staphylococcus, certain species are capable of producing TAs through the activity of staphylococcal aromatic amino acid decarboxylase (SadA). SadA decarboxylates aromatic amino acids to produce TAs, as well as dihydroxy phenylalanine and 5-hydroxytryptophan to thus produce the neurotransmitters dopamine and serotonin. SadA-expressing staphylococci were prevalent in the gut of most probands, where they are part of the human intestinal microflora. Furthermore, sadA-expressing staphylococci showed increased adherence to HT-29 cells and 2- to 3-fold increased internalization. Internalization and adherence was also increased in a sadA mutant in the presence of tryptamine. The α2-adrenergic receptor is required for enhanced adherence and internalization. Thus, staphylococci in the gut might contribute to gut activity and intestinal colonization. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Measuring levels of biogenic amines and their metabolites in rat brain tissue using high-performance liquid chromatography with photodiode array detection.

PubMed

Gu, Min-Jung; Jeon, Ji-Hyun; Oh, Myung Sook; Hong, Seon-Pyo

2016-01-01

We developed a method to detect biogenic amines and their metabolites in rat brain tissue using simultaneous high-performance liquid chromatography and a photodiode array detection. Measurements were made using a Hypersil Gold C-18 column (250 × 2.1 mm, 5 µm). The mobile phase was 5 mM perchloric acid containing 5 % acetonitrile. The correlation coefficient was 0.9995-0.9999. LODs (S/N = 3) and LOQs (S/N = 10) were as follows: dopamine 0.4 and 1.3 pg, 3, 4-dihydroxyphenylacetic acid 8.4 and 28.0 pg, serotonin 0.4 and 1.3 pg, 5-hydroxyindolacetic acid 3.4 and 11.3 pg, and homovanillic acid 8.4 and 28.0 pg. This method does not require derivatization steps, and is more sensitive than the widely used HPLC-UV method.

Safinamide for symptoms of Parkinson's disease.

PubMed

Müller, T

2015-11-01

Chronic and slow progression of neuronal death in Parkinson's disease is responsible for an altered neurotransmission of various biogenic amines, such as dopamine. Therefore, an individually different pronounced heterogeneity of motor and nonmotor symptoms characterizes each Parkinson's disease patient. Ideal candidates for the balance of these neurotransmitter deficits are compounds like safinamide with broad mechanisms of action such as reversible monoamine oxidase type B inhibition, blockage of voltage-dependent sodium channels, modulation of calcium channels and of glutamate release. Safinamide is administered one time daily with oral doses ranging from 50 to 100 mg. Safinamide was well tolerated and safe, ameliorated motor symptoms when combined with dopamine agonist only or additional levodopa in clinical trials. Safinamide is a novel instrument for the drug therapy of Parkinson's disease with better safety and tolerability particularly concerning diarrhea than inhibitors of catechol-O-methyltransferase, like entacapone, according to an indirect comparison within a meta-analysis with entacapone. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Hemocompatibility improvement of poly(ethylene terephthalate) via self-polymerization of dopamine and covalent graft of zwitterions.

PubMed

Cai, Xianmei; Yuan, Jiang; Chen, Shuangchun; Li, Pengfei; Li, Li; Shen, Jian

2014-03-01

Poly (ethylene terephthalate) (PET) has been widely adopted as a scaffold biomaterial, but further hemocompatibility improvement is still needed for wide biomedical applications. Inspired by the composition of adhesive proteins in mussels, we propose to use self-polymerized dopamine to form a surface-adherent polydopamine layer onto PET sheet, followed by Michael addition with N,N-dimethylethylenediamine (DMDA) to build tertiary amine, and final zwitterions(sulfobetaine and carboxybetaine) construction through ring-opening reaction. Physicochemical properties of substrates were demonstrated by water contact angle measurement, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The hemocompatibility was evaluated by platelet adhesion, hemolytic, and protein adsorption. The results showed that the zwitterions immobilized PET endowed with improved resistance to nonspecific protein adsorption and platelet adhesion as well as nonhemolytic. The zwitterions with desirable hemocompatibility can be readily tailored to catheter for various biomedical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Mussel-inspired hyperbranched poly(amino ester) polymer as strong wet tissue adhesive.

PubMed

Zhang, Hong; Bré, Lígia P; Zhao, Tianyu; Zheng, Yu; Newland, Ben; Wang, Wenxin

2014-01-01

Current medical adhesives based on cyanoacrylates typically exhibit cellular toxicity. In contrast, fibrin adhesives are non-toxic but have poor adhesive properties. To overcome these drawbacks we designed a simple and scalable adhesive precursor inspired by marine mussel adhesion that functioned with strong adhesion in wet conditions and with low cytotoxicity. Dopamine, an-amine derivative of an amino acid abundantly present in mussel adhesive proteins, was co-polymerised with a tri-functional vinyl monomer, to form a hyperbranched poly(β-amino ester) polymer termed poly(dopamine-co-acrylate) (PDA). A variety of molecular weights and crosslinking methods were analysed using an ex vivo porcine skin model and an almost 4 fold increase in wet adhesion strength was observed compared to TISSEEL(®) fibrin sealant. With a fast curing time, degradable properties and low cytotoxicity, PDA is highly attractive for medical purposes and could have a broad impact on surgeries where surgical tissue adhesives, sealants, and haemostatic agents are used. Copyright © 2013 Elsevier Ltd. All rights reserved.

Accelerated molecular dynamics simulations of the octopamine receptor using GPUs: discovery of an alternate agonist-binding position.

PubMed

Kastner, Kevin W; Izaguirre, Jesús A

2016-10-01

Octopamine receptors (OARs) perform key biological functions in invertebrates, making this class of G-protein coupled receptors (GPCRs) worth considering for insecticide development. However, no crystal structures and very little research exists for OARs. Furthermore, GPCRs are large proteins, are suspended in a lipid bilayer, and are activated on the millisecond timescale, all of which make conventional molecular dynamics (MD) simulations infeasible, even if run on large supercomputers. However, accelerated Molecular Dynamics (aMD) simulations can reduce this timescale to even hundreds of nanoseconds, while running the simulations on graphics processing units (GPUs) would enable even small clusters of GPUs to have processing power equivalent to hundreds of CPUs. Our results show that aMD simulations run on GPUs can successfully obtain the active and inactive state conformations of a GPCR on this reduced timescale. Furthermore, we discovered a potential alternate active-state agonist-binding position in the octopamine receptor which has yet to be observed and may be a novel GPCR agonist-binding position. These results demonstrate that a complex biological system with an activation process on the millisecond timescale can be successfully simulated on the nanosecond timescale using a simple computing system consisting of a small number of GPUs. Proteins 2016; 84:1480-1489. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

PeaTAR1B: Characterization of a Second Type 1 Tyramine Receptor of the American Cockroach, Periplaneta americana

PubMed Central

Balfanz, Sabine

2017-01-01

The catecholamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. In insects; these neuroactive substances are functionally replaced by the phenolamines octopamine and tyramine. Phenolamines activate specific guanine nucleotide-binding (G) protein-coupled receptors (GPCRs). Type 1 tyramine receptors are better activated by tyramine than by octopamine. In contrast; type 2 tyramine receptors are almost exclusively activated by tyramine. Functionally; activation of type 1 tyramine receptors leads to a decrease in the intracellular concentration of cAMP ([cAMP]i) whereas type 2 tyramine receptors can mediate Ca2+ signals or both Ca2+ signals and effects on [cAMP]i. Here; we report that the American cockroach (Periplaneta americana) expresses a second type 1 tyramine receptor (PeaTAR1B) in addition to PeaTAR1A (previously called PeaTYR1). When heterologously expressed in flpTM cells; activation of PeaTAR1B by tyramine leads to a concentration-dependent decrease in [cAMP]i. Its activity can be blocked by a series of established antagonists. The functional characterization of two type 1 tyramine receptors from P. americana; PeaTAR1A and PeaTAR1B; which respond to tyramine by changing cAMP levels; is a major step towards understanding the actions of tyramine in cockroach physiology and behavior; particularly in comparison to the effects of octopamine. PMID:29084141

PeaTAR1B: Characterization of a Second Type 1 Tyramine Receptor of the American Cockroach, Periplaneta americana.

PubMed

Blenau, Wolfgang; Balfanz, Sabine; Baumann, Arnd

2017-10-30

The catecholamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. In insects; these neuroactive substances are functionally replaced by the phenolamines octopamine and tyramine. Phenolamines activate specific guanine nucleotide-binding (G) protein-coupled receptors (GPCRs). Type 1 tyramine receptors are better activated by tyramine than by octopamine. In contrast; type 2 tyramine receptors are almost exclusively activated by tyramine. Functionally; activation of type 1 tyramine receptors leads to a decrease in the intracellular concentration of cAMP ([cAMP] i ) whereas type 2 tyramine receptors can mediate Ca 2+ signals or both Ca 2+ signals and effects on [cAMP] i . Here; we report that the American cockroach ( Periplaneta americana ) expresses a second type 1 tyramine receptor (PeaTAR1B) in addition to PeaTAR1A (previously called PeaTYR1). When heterologously expressed in flpTM cells; activation of PeaTAR1B by tyramine leads to a concentration-dependent decrease in [cAMP] i . Its activity can be blocked by a series of established antagonists. The functional characterization of two type 1 tyramine receptors from P. americana ; PeaTAR1A and PeaTAR1B; which respond to tyramine by changing cAMP levels; is a major step towards understanding the actions of tyramine in cockroach physiology and behavior; particularly in comparison to the effects of octopamine.

Fabrication of Amine-Modified Magnetite-Electrochemically Reduced Graphene Oxide Nanocomposite Modified Glassy Carbon Electrode for Sensitive Dopamine Determination

PubMed Central

He, Quanguo; Liu, Jun; Liu, Xiaopeng; Li, Guangli; Chen, Dongchu; Deng, Peihong; Liang, Jing

2018-01-01

Amine-modified magnetite (NH2–Fe3O4)/reduced graphene oxide nanocomposite modified glassy carbon electrodes (NH2–Fe3O4/RGO/GCEs) were developed for the sensitive detection of dopamine (DA). The NH2-Fe3O4/RGO/GCEs were fabricated using a drop-casting method followed by an electrochemical reduction process. The surface morphologies, microstructure and chemical compositions of the NH2–Fe3O4 nanoparticles (NPs), reduced graphene oxide (RGO) sheets and NH2–Fe3O4/RGO nanocomposites were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-Ray diffraction (XRD) and Fourier-transform infrared (FTIR) spectroscopy. The electrochemical behaviors of DA on the bare and modified GCEs were investigated in phosphate buffer solution (PBS) by cyclic voltammetry (CV). Compared with bare electrode and RGO/GCE, the oxidation peak current (ipa) on the NH2–Fe3O4/RGO/GCE increase significantly, owing to the synergistic effect between NH2–Fe3O4 NPs and RGO sheets. The oxidation peak currents (ipa) increase linearly with the concentrations of DA in the range of 1 × 10−8 mol/L – 1 × 10−7 mol/L, 1 × 10−7 mol/L – 1 × 10−6 mol/L and 1 × 10−6 mol/L – 1 × 10−5 mol/L. The detection limit is (4.0 ± 0.36) ×10−9 mol/L (S/N = 3). Moreover, the response peak currents of DA were hardly interfered with the coexistence of ascorbic acid (AA) and uric acid (UA). The proposed NH2–Fe3O4/RGO/GCE is successfully applied to the detection of dopamine hydrochloride injections with satisfactory results. Together with low cost, facile operation, good selectivity and high sensitivity, the NH2–Fe3O4/RGO/GCEs have tremendous prospects for the detection of DA in various real samples. PMID:29584682

Neuromuscular transmission in a primitive insect: modulation by octopamine, and catch-like tension.

PubMed

Hoyle, G

1984-01-01

The third pair of legs of the primitive New Zealand orthopteran insect, the " weta ", has and innervation and muscle cell distribution exactly similar to that of locusts, but wetas do not jump. Neuromuscular transmission to the slow excitatory axon ( SETi ) is potentiated more than 10-fold by the natural modulator octopamine (OCT). A brief burst of SETi impulses following infusion of as little as 10(-8) M OCT is followed by a very long-lasting plateau of catch-like tension (CT). The plateau is abruptly relaxed by a single inhibitory impulse, or even by a single SETi impulse if this arrives no sooner than about 30 sec following excitation. CT is used by wetas in a defense posture. Locusts and grasshoppers have a different type of modulation by OCT.

Elicitation and abrupt termination of behaviorally significant catchlike tension in a primitive insect.

PubMed

Hoyle, G; Field, L H

1983-07-01

Sustained steady contractural or catchlike tension (CT) occurs in the metathoracic extensor tibiae muscle of the primitive insect the weta (Orthoptera: Stenopelmatidae) during its characteristic leg-extension defense behavior or following leg-position conditioning. Similar action occurs occasionally in semi-intact preparations and is abruptly turned off by a single peripheral inhibitory impulse. These phenomena were reproduced routinely by first infusing saline containing 10(-8) M (or stronger) octopamine into the muscle for 12 min, and then stimulating the slow excitatory motor neuron SETi with a brief burst. Direct stimulation of the dorsal unpaired median neuron, innervating the extensor tibiae (DUMETi) prior to SETi stimulation, also led to CT. Both octopamine and DUMETi markedly enhanced the tension developed in response to a burst of impulses in SETi.

Studies on the role of the retinal dopamine/melatonin system in experimental refractive errors in chickens.

PubMed

Schaeffel, F; Bartmann, M; Hagel, G; Zrenner, E

1995-05-01

We have found that development of both deprivation-induced and lens-induced refractive errors in chickens implicates changes of the diurnal growth rhythms in the eye (Fig. 1). Because the major diurnal oscillator in the eye is expressed by the retinal dopamine/melatonin system, effects of drugs were studied that change retinal dopamine and/or serotonin levels. Vehicle-injected and drug-injected eyes treated with either translucent occluders or lenses were compared to focus on visual growth mechanisms. Retinal biogenic amine levels were measured at the end of each experiment by HPLC with electrochemical detection. For reserpine (which was most extensively studied) electroretinograms were recorded to test retinal function [Fig. 3 (C)] and catecholaminergic and serotonergic retinal neurons were observed by immunohistochemical labelling [Fig. 3(D)]. Deprivation myopia was readily altered by a single intravitreal injection of drugs that affected retinal dopamine or serotonin levels; reserpine which depleted both serotonin and dopamine stores blocked deprivation myopia very efficiently [Fig. 3(A)], whereas 5,7-dihydroxy-tryptamine (5,7-DHT), sulpiride, melatonin and Sch23390 could enhance deprivation myopia (Table 1, Fig. 5). In contrast to other procedures that were previously employed to block deprivation myopia (6-OHDA injections or continuous light) and which had no significant effect on lens-induced refractive errors, reserpine also affected lens-induced changes in eye growth. At lower doses, the effect was selective for negative lenses (Fig. 4). We found that the individual retinal dopamine levels were very variable among individuals but were correlated in both eyes of an animal; a similar variability was previously found with regard to deprivation myopia. To test a hypothesis raised by Li, Schaeffel, Kohler and Zrenner [(1992) Visual Neuroscience, 9, 483-492] that individual dopamine levels might determine the susceptibility to deprivation myopia, refractive errors were correlated with dopamine levels in occluded and untreated eyes of monocularly deprived chickens (Fig. 6). The hypothesis was rejected. Although it has been previously found that the static retinal tissue levels of dopamine are not altered by lens treatment, subtle changes in the ratio of DOPAC to dopamine were detected in the present study. The result indicates that retinal dopamine might be implicated also in lens-induced growth changes. Surprisingly, the changes were in the opposite direction for deprivation and negative lenses although both produce myopia. Currently, there is evidence that deprivation-induced and lens-induced refractive errors in chicks are produced by different mechanisms. However, findings (1), (3) and (5) suggest that there may also be common features. Although it has not yet been resolved how both mechanisms merge to produce the appropriate axial eye growth rates, we propose a scheme (Fig. 7).

The effect of lysergic acid diethylamide, 5-hydroxytryptamine, and related compounds on the liver fluke, fasciola hepatica

PubMed Central

Mansour, T. E.

1957-01-01

The rhythmical activity of the liver fluke, Fasciola hepatica, was stimulated by 5-hydroxytryptamine and by lysergic acid diethylamide at very low concentrations. The effect was peripheral and was not mediated through the central ganglion. Other amines also stimulated rhythmical activity, the most potent being the indolamines. Bromolysergic acid diethylamide, and other analogues such as yohimbine, harmine, and dopamine depressed rhythmical movement and antagonized the stimulant action of 5-hydroxytryptamine and lysergic acid diethylamide. Evidence which suggests the presence of tryptamine receptors in the trematode is discussed. PMID:13489165

Assay for optical determination of biogenic amines using microtiterplates

NASA Astrophysics Data System (ADS)

Nedeljko, Polona; Turel, Matejka; Lobnik, Aleksandra

2013-05-01

Direct determination of catecholamine noradreanaline (NOR) is presented using o-phthaldialdehyde (OPA) as an indicator reagent. The fluorescent assay in which OPA forms with NOR a fluorescent complex (OPA-NOR) can be monitored at neutral, physiological conditions (pH 7) and performed in microtiterplates. The determination of NOR is optimal in the concentration range from 4.0×10-7 to 1.0×10-5 M and limit of detection is 4.0×10-7 M. The OPA-NOR complex maximum intensity is reached within 5 minutes. Dopamine and adrenaline could not be determined using the same approach.

Vasoactive amines modulate actin cables (stress fibers) and surface area in cultured bovine endothelium.

PubMed

Welles, S L; Shepro, D; Hechtman, H B

1985-06-01

Cultured bovine aortic endothelial cells were fixed and stained with NBD-phallicidin and quantitated with a digital image analyzer for changes in actin cables and surface area. Serotonin (5-HT), norepinephrine (NE), dopamine and histamine (all at 10(-4)M concentrations) were tested for their ability to induce cytoskeletal changes. Only 5-HT and NE increased actin cables significantly (p less than 0.01), 80.7% and 97.9%, respectively. Dopamine and histamine treated cells showed a 67.4% and 80.8% decrease in actin cables respectively (p less than 0.01). Stimulated increases of actin cables by 5-HT were inhibited by Ketanserin, and propranolol inhibited NE stimulation of actin cables. Treatment of cells with these blockers alone also decreased actin cables below control values (p less than 0.01). Pretreatment of cells with diphenhydramine, but not cimetidine, inhibited histamine-induced decreases in actin cables. Stimulation of surface area by 5-HT and NE was also observed, with 40.8% and 80.7% increases respectively, when compared with controls (p less than 0.01). The increases in actin cables were associated with a lack of ruffled edges that are indicative of motile cells. In contrast, induced decreases in actin cables resulted in cells with ruffled edges. Exogenous 5-HT and NE have been shown to prevent the increased permeability visible as extravasation of red blood cells from postcapillary venules in thrombocytopenic animals. The present data suggest that 5-HT and NE may be involved in maintaining the endothelial barrier function by a receptor-mediated stimulation of actin cables. Also, histamine-induced decreases in actin cables may be correlated with the amine's action in vivo as a mediator of increased inflammatory permeability.

Effects of drugs affecting endogenous amines or cyclic nucleotides on ethanol withdrawal head twitches in mice.

PubMed Central

Collier, H O; Hammond, M D; Schneider, C

1976-01-01

1 Twenty-four hours after ethanol withdrawal, dependent mice exhibited frequent head twitching. Naive mice exhibited similar twitching 15 min after treatment with 5-hydroxytryptophan (5-HTP) or 6 h after alpha-methyl-p-tyrosine (AMPT). Ethanol lessened the incidence of head twitches induced by any of these treatments. 5-HTP and AMPT each increased the incidence of head twitches induced by withdrawal of ethanol from dependent mice. 2 Drugs that affect the amount or activity of endogenous amines or cyclic nucleotides modified the incidence of head twitches. Nearly all drugs acted in the same direction on twitching elicited by any of these three treatments. 3 The incidence was lessened by: (a) methysergide, methergoline, MA 1420, p-chlorophenylalanine and p-chloroamphetamine; (b) dopamine, noradrenaline, L-DOPA, amphetamine and apomorphine; (c) hyoscine and nicotine; and (d) adenosine triphosphate, dibutyryl cyclic adenosine-3',5'-monophosphate (db cyclic AMP) and prostaglandins E1 and E2. 4 The incidence was increased by: (a) acetylcholine, carbachol and physostigmine; and (b) guanosine triphosphate, dibutyryl cyclic guanosine monophosphate (db cyclic GMP), theophylline and 3-isobutyl-1-methyl-xanthine. 5 These findings suggest that head twitching induced by these three treatments arises from a common biochemical mechanism, which may ultimately be a change in favour of cyclic GMP of the balance between this nucleotide and cyclic AMP within appropriate neurones. This imbalance appears to be elicited or increased by 5-hydroxytryptamine and acetylcholine and to be decreased by dopamine, noradrenaline and E prostaglandins. 6 Neither actinomycin D nor cycloheximide, given during the induction of ethanol dependence, altered the incidence of head twitches after ethanol withdrawal. PMID:987821

Effect of neonatal nociceptin or nocistatin imprinting on the brain concentration of biogenic amines and their metabolites.

PubMed

Tekes, Kornélia; Gyenge, Melinda; Sótonyi, Péter; Csaba, György

2009-04-01

Noradrenaline (NA), dopamine (DA), homovanillic acid (HA), serotonin (5HT) and 5-hydroxyindole acetic acid (5HIAA) content of five brain regions (hypothalamus, hippocampus, brainstem, striatum and frontal cortex) and the cerebrospinal fluid (CSF) was measured in adult (three months old) male and female rats treated neonatally with a single dose of 10 microg nociceptin (NC) or 10 microg nocistatin (NS) for hormonal imprinting. The biogenic amine and metabolite content of cerebrospinal fluid was also determined. In NC treated animals the serotonergic, dopaminergic as well as noradrenergic systems were influenced by the imprinting. The 5HT level increased in hypothalamus, the 5HIAA tissue levels were found increased in hypothalamus. Hippocampus and striatum and the HVA levels increased highly significantly in brainstem. Dopamine level decreased significantly in striatum, however in frontal cortex both noradrenalin and 5HIAA level decreased. Nevertheless, in NS-treated rats decreased NA tissue levels were found in hypothalamus, brainstem and frontal cortex. Decreased DA levels were found in the hypothalamus, brainstem and striatum. NS imprinting resulted in decreased HVA level, but increased one in the brainstem. The 5HT levels decreased in the hypothalamus, brainstem, striatum and frontal cortex, while 5HIAA content of CSF, and frontal cortex decreased, and that of hypothalamus, hippocampus and striatum increased. There was no significant difference between genders except in the 5HT tissue levels of NC treated rats. Data presented show that neonatal imprinting both by NC and NS have long-lasting and brain area specific effects. In earlier experiments endorphin imprinting also influenced the serotonergic system suggesting that during labour release of pain-related substances may durably affect the serotonergic (dopaminergic, adrenergic) system which can impress the animals' later behavior.

Regulation of tyramine oxidase synthesis in Klebsiella aerogenes.

PubMed Central

Okamura, H; Murooka, Y; Harada, T

1976-01-01

Tyramine oxidase in Klebsiella aerogenes is highly specific for tyramine, dopamine, octopamine, and norepinephrine, and its synthesis is induced specifically by these compounds. The enzyme is present in a membrane-bound form. The Km value for tyramine is 9 X 10(-4) M. Tyramine oxidase synthesis was subjected to catabolite repression by glucose in the presence of ammonium salts. Addition of cyclic adenosine 3',5'-monophosphate (cAMP) overcame the catabolite repression. A mutant strain, K711, which can produce a high level of beta-galactosidase in the presence of glucose and ammonium chloride, can also synthesize tyramine oxidase and histidase in the presence of inducer in glucose ammonium medium. Catabolite repression of tyramine oxidase synthesis was relieved when the cells were grown under conditions of nitrogen limitation, whereas beta-galactosidase was strongly repressed under these conditions. A cAMP-requiring mutant, MK54, synthesized tyramine oxidase rapidly when tyramine was used as the sole source of nitrogen in the absence of cAMP. However, a glutamine synthetase-constitutive mutant, MK94, failed to synthesize tyramine oxidase in the presence of glucose and ammonium chloride, although it synthesized histidase rapidly under these conditions. These results suggest that catabolite repression of tyramine oxidase synthesis in K. aerogenes is regulated by the intracellular level of cAMP and an unknown cytoplasmic factor that acts independently of cAMP and is formed under conditions of nitrogen limitation. PMID:179974

Calmodulin as a downstream gene of octopamine-OAR α1 signalling mediates olfactory attraction in gregarious locusts.

PubMed

Xu, L; Li, L; Yang, P; Ma, Z

2017-02-01

The migratory locust (Locusta migratoria) shows aggregative traits in nymph marching bands and swarm formations through mutual olfactory attraction of conspecifics. However, olfactory preference in different nymph stages in gregarious locusts is not sufficiently explored. In this study, we found that the nymph olfactory preference for gregarious volatiles exhibited obvious variations at different developmental stages. The gregarious locusts show attractive response to conspecific volatiles from the third stadium. Transcriptome comparison between third- and fourth-stadium nymphs showed that the G protein-coupled receptor (GPCR) pathways are significantly enriched. Amongst the genes present in GPCR pathways, the expression level of calmodulin in locust brains significantly increased from the third- to the fourth-stadium nymphs. Amongst the four octopamine receptors (OARs) belonging to the GPCR family, only OAR α1 showed similar expression patterns to those of calmodulin, and knockdown of OAR α1 reduced the expression level of calmodulin. RNA interference of calmodulin decreased locomotion and induced the loss of olfactory attraction in gregarious locusts. Moreover, the activation of OAR α1 in calmodulin-knockdown locusts did not induce olfactory attraction of the nymphs to gregarious volatiles. Thus, calmodulin as a downstream gene of octopamine-OAR α1 (OA-OAR α1) signalling mediates olfactory attraction in gregarious locusts. Overall, this study provides novel insights into the mechanism of OA-OAR α1 signalling involved in olfactory attraction of gregarious locusts. © 2016 The Royal Entomological Society.

Emerging approaches in Parkinson’s disease – adjunctive role of safinamide

PubMed Central

Müller, Thomas

2016-01-01

Ongoing neuronal death in Parkinson’s disease (PD) causes an altered neurotransmission of various biogenic amines, particularly dopamine. As these changes do not follow a distinct pattern, they vary individually, and are differently pronounced. As a result, a heterogeneous onset of motor and nonmotor features occurs in each patient with PD during the whole course of the disease. PD actually describes a set of distinct diseases that manifest themselves in clinical syndromes with certain similarities but also great differences. This clinical picture responds to drugs with a broad spectrum of modes of actions better than to compounds with an exclusive focus on specific receptor subtypes. Therefore, safinamide is an ideal candidate for treatment of patients with PD, since its pharmacological profile includes reversible monoamine oxidase-B inhibition, blockade of voltage-dependent sodium channels, modulation of calcium channels, and inhibition of glutamate release. Safinamide is applied only once daily. Its oral dose ranges from 50 to 100 mg. Safinamide was well tolerated and safe in the clinical development program that demonstrated the amelioration of motor symptoms and OFF phenomena by safinamide when combined with dopamine agonists or levodopa. In the real world of maintenance of patients with PD, effects of safinamide application resemble therapy with classical monoamine oxidase inhibitors or amantadine in combination with other dopamine-substituting drugs. Safinamide is becoming increasingly available in the EU despite complex approval and pricing scenarios. PMID:27536120

Emerging approaches in Parkinson's disease - adjunctive role of safinamide.

PubMed

Müller, Thomas

2016-01-01

Ongoing neuronal death in Parkinson's disease (PD) causes an altered neurotransmission of various biogenic amines, particularly dopamine. As these changes do not follow a distinct pattern, they vary individually, and are differently pronounced. As a result, a heterogeneous onset of motor and nonmotor features occurs in each patient with PD during the whole course of the disease. PD actually describes a set of distinct diseases that manifest themselves in clinical syndromes with certain similarities but also great differences. This clinical picture responds to drugs with a broad spectrum of modes of actions better than to compounds with an exclusive focus on specific receptor subtypes. Therefore, safinamide is an ideal candidate for treatment of patients with PD, since its pharmacological profile includes reversible monoamine oxidase-B inhibition, blockade of voltage-dependent sodium channels, modulation of calcium channels, and inhibition of glutamate release. Safinamide is applied only once daily. Its oral dose ranges from 50 to 100 mg. Safinamide was well tolerated and safe in the clinical development program that demonstrated the amelioration of motor symptoms and OFF phenomena by safinamide when combined with dopamine agonists or levodopa. In the real world of maintenance of patients with PD, effects of safinamide application resemble therapy with classical monoamine oxidase inhibitors or amantadine in combination with other dopamine-substituting drugs. Safinamide is becoming increasingly available in the EU despite complex approval and pricing scenarios.

Carvacrol: from ancient flavoring to neuromodulatory agent.

PubMed

Zotti, Margherita; Colaianna, Marilena; Morgese, Maria Grazia; Tucci, Paolo; Schiavone, Stefania; Avato, Pinarosa; Trabace, Luigia

2013-05-24

Oregano and thyme essential oils are used for therapeutic, aromatic and gastronomic purposes due to their richness in active substances, like carvacrol; however, the effects of the latter on the central nervous system have been poorly investigated. The aim of our study was to define the effects of carvacrol on brain neurochemistry and behavioural outcome in rats. Biogenic amine content in the prefrontal cortex and hippocampus after chronic or acute oral carvacrol administration was measured. Animals were assessed by a forced swimming test. Carvacrol, administered for seven consecutive days (12.5 mg/kg p.o.), was able to increase dopamine and serotonin levels in the prefrontal cortex and hippocampus. When single doses were used (150 and 450 mg/kg p.o.), dopamine content was increased in the prefrontal cortex at both dose levels. On the contrary, a significant dopamine reduction in hippocampus of animals treated with 450 mg/kg of carvacrol was found. Acute carvacrol administration only significantly reduced serotonin content in either the prefrontal cortex or in the hippocampus at the highest dose. Moreover, acute carvacrol was ineffective in producing changes in the forced swimming test. Our data suggest that carvacrol is a brain-active molecule that clearly influences neuronal activity through modulation of neurotransmitters. If regularly ingested in low concentrations, it might determine feelings of well-being and could possibly have positive reinforcer effects.

Linking Inflammation and Parkinson Disease: Hypochlorous Acid Generates Parkinsonian Poisons.

PubMed

Jeitner, Thomas M; Kalogiannis, Mike; Krasnikov, Boris F; Gomolin, Irving; Peltier, Morgan R; Moran, Graham R

2016-06-01

Inflammation is a common feature of Parkinson Disease and other neurodegenerative disorders. Hypochlorous acid (HOCl) is a reactive oxygen species formed by neutrophils and other myeloperoxidase-containing cells during inflammation. HOCl chlorinates the amine and catechol moieties of dopamine to produce chlorinated derivatives collectively termed chlorodopamine. Here, we report that chlorodopamine is toxic to dopaminergic neurons both in vivo and in vitro Intrastriatal administration of 90 nmol chlorodopamine to mice resulted in loss of dopaminergic neurons from the substantia nigra and decreased ambulation-results that were comparable to those produced by the same dose of the parkinsonian poison, 1-methyl-4-phenylpyridinium (MPP+). Chlorodopamine was also more toxic to differentiated SH SY5Y cells than HOCl. The basis of this selective toxicity is likely mediated by chlorodopamine uptake through the dopamine transporter, as expression of this transporter in COS-7 cells conferred sensitivity to chlorodopamine toxicity. Pharmacological blockade of the dopamine transporter also mitigated the deleterious effects of chlorodopamine in vivo The cellular actions of chlorodopamine included inactivation of the α-ketoglutarate dehydrogenase complex, as well as inhibition of mitochondrial respiration. The latter effect is consistent with inhibition of cytochrome c oxidase. Illumination at 670 nm, which stimulates cytochrome c oxidase, reversed the effects of chlorodopamine. The observed changes in mitochondrial biochemistry were also accompanied by the swelling of these organelles. Overall, our findings suggest that chlorination of dopamine by HOCl generates toxins that selectively kill dopaminergic neurons in the substantia nigra in a manner comparable to MPP+. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Ergopeptines bromocriptine and ergovaline and the dopamine type-2 receptor inhibitor domperidone inhibit bovine equilibrative nucleoside transporter 1-like activity.

PubMed

Miles, Edwena D; Xue, Yan; Strickland, James R; Boling, James A; Matthews, James C

2011-09-14

Neotyphodium coenophialum-infected tall fescue contains ergopeptines. Except for interactions with biogenic amine receptors (e.g., dopamine type-2 receptor, D2R), little is known about how ergopeptines affect animal metabolism. The effect of ergopeptines on bovine nucleoside transporters (NT) was evaluated using Madin-Darby bovine kidney (MDBK) cells. Equilibrative NT1 (ENT1)-like activity accounted for 94% of total NT activity. Inhibitory competition (IC(50)) experiments found that this activity was inhibited by both bromocriptine (a synthetic model ergopeptine and D2R agonist) and ergovaline (a predominant ergopeptine of tall fescue). Kinetic inhibition analysis indicated that bromocriptine inhibited ENT1-like activity through a competitive and noncompetitive mechanism. Domperidone (a D2R antagonist) inhibited ENT1 activity more in the presence than in the absence of bromocriptine and displayed an IC(50) value lower than that of bromocriptine or ergovaline, suggesting that inhibition was not through D2R-mediated events. These novel mechanistic findings imply that cattle consuming endophyte-infected tall fescue have reduced ENT1 activity and, thus, impaired nucleoside metabolism.

Simultaneous determination of primary and secondary phenethylamines in biological samples by high-performance liquid chromatographic method with fluorescence detection.

PubMed

Guo, Xiao-Feng; Wang, Jie-Yu; Wang, Hong; Zhang, Hua-Shan

2014-09-15

Phenylalanine is an essential amino acid and its metabolites relate to various physiological and immune functions of living organisms. To monitor the alteration of concentration of primary and secondary phenethylamines including N-methyltyramine, octopamine, tyramine, tyrosine and phenylalanine in the metabolic pathway of phenylalanine, a sensitive and selective reversed-phase high-performance liquid chromatographic method has been developed in this study. The identification and quantification of phenethylamines were performed by fluorescent detection after pre-column derivatization with 1,3,5,7-tetramethyl-8-(N-hydroxysuccinimidyl butyric ester)difluoroboradiaza-s-indacene, an excellent fluorescent probe which could react with both primary and secondary amino groups simultaneously. The derivatization was carried out at 25 °C for 25 min, and the separation was performed on a C18 column within 20 min. The linear ranges were from 2.0 to 100 nM for phenylalanine and tyramine to 5.0 to 250 for tyrosine and octopamine, with the detection limits of 0.1 nM for octopamine, tyramine, tyrosine and phenylalanine and 0.2 nM for N-methyltyramine (signal-to-noise ratio=3), which allowed for the sure determination of phenethylamines at trace levels in the real samples without complex pretreatment or enrichment during multitudinous samples analysis. The proposed method has been validated by the analysis of the five target compounds in biological samples with spiked recoveries of 96.4-104.4% and the relative standard deviation of 1.0 and 4.4%. Copyright © 2014 Elsevier B.V. All rights reserved.

Neuro-transmitters in the central nervous system & their implication in learning and memory processes.

PubMed

Reis, Helton J; Guatimosim, Cristina; Paquet, Maryse; Santos, Magda; Ribeiro, Fabíola M; Kummer, Arthur; Schenatto, Grace; Salgado, João V; Vieira, Luciene B; Teixeira, Antônio L; Palotás, András

2009-01-01

This review article gives an overview of a number of central neuro-transmitters, which are essential for integrating many functions in the central nervous system (CNS), such as learning, memory, sleep cycle, body movement, hormone regulation and many others. Neurons use neuro-transmitters to communicate, and a great variety of molecules are known to fit the criteria to be classified as such. A process shared by all neuro-transmitters is their release by excocytosis, and we give an outline of the molecular events and protein complexes involved in this mechanism. Synthesis, transport, inactivation, and cellular signaling can be very diverse when different neuro-transmitters are compared, and these processes are described separately for each neuro-transmitter system. Here we focus on the most well known neuro-transmitters: acetyl-choline, catechol-amines (dopamine and nor-adrenalin), indole-amine (serotonin), glutamate, and gamma-amino-butyric acid (GABA). Glutamate is the major excitatory neuro-transmitter in the brain and its actions are counter-balanced by GABA, which is the major inhibitory substance in the CNS. A balance of neuronal transmission between these two neuro-transmitters is essential to normal brain function. Acetyl-choline, serotonin and catechol-amines have a more modulatory function in the brain, being involved in many neuronal circuits. Apart from summarizing the current knowledge about the synthesis, release and receptor signaling of these transmitters, some disease states due to alteration of their normal neuro-transmission are also described.

Tyramine Actions on Drosophila Flight Behavior Are Affected by a Glial Dehydrogenase/Reductase.

PubMed

Ryglewski, Stefanie; Duch, Carsten; Altenhein, Benjamin

2017-01-01

The biogenic amines octopamine (OA) and tyramine (TA) modulate insect motor behavior in an antagonistic manner. OA generally enhances locomotor behaviors such as Drosophila larval crawling and flight, whereas TA decreases locomotor activity. However, the mechanisms and cellular targets of TA modulation of locomotor activity are incompletely understood. This study combines immunocytochemistry, genetics and flight behavioral assays in the Drosophila model system to test the role of a candidate enzyme for TA catabolism, named Nazgul (Naz), in flight motor behavioral control. We hypothesize that the dehydrogenase/reductase Naz represents a critical step in TA catabolism. Immunocytochemistry reveals that Naz is localized to a subset of Repo positive glial cells with cell bodies along the motor neuropil borders and numerous positive Naz arborizations extending into the synaptic flight motor neuropil. RNAi knock down of Naz in Repo positive glial cells reduces Naz protein level below detection level by Western blotting. The resulting consequence is a reduction in flight durations, thus mimicking known motor behavioral phenotypes as resulting from increased TA levels. In accord with the interpretation that reduced TA degradation by Naz results in increased TA levels in the flight motor neuropil, the motor behavioral phenotype can be rescued by blocking TA receptors. Our findings indicate that TA modulates flight motor behavior by acting on central circuitry and that TA is normally taken up from the central motor neuropil by Repo-positive glial cells, desaminated and further degraded by Naz.

Tyramine Actions on Drosophila Flight Behavior Are Affected by a Glial Dehydrogenase/Reductase

PubMed Central

Ryglewski, Stefanie; Duch, Carsten; Altenhein, Benjamin

2017-01-01

The biogenic amines octopamine (OA) and tyramine (TA) modulate insect motor behavior in an antagonistic manner. OA generally enhances locomotor behaviors such as Drosophila larval crawling and flight, whereas TA decreases locomotor activity. However, the mechanisms and cellular targets of TA modulation of locomotor activity are incompletely understood. This study combines immunocytochemistry, genetics and flight behavioral assays in the Drosophila model system to test the role of a candidate enzyme for TA catabolism, named Nazgul (Naz), in flight motor behavioral control. We hypothesize that the dehydrogenase/reductase Naz represents a critical step in TA catabolism. Immunocytochemistry reveals that Naz is localized to a subset of Repo positive glial cells with cell bodies along the motor neuropil borders and numerous positive Naz arborizations extending into the synaptic flight motor neuropil. RNAi knock down of Naz in Repo positive glial cells reduces Naz protein level below detection level by Western blotting. The resulting consequence is a reduction in flight durations, thus mimicking known motor behavioral phenotypes as resulting from increased TA levels. In accord with the interpretation that reduced TA degradation by Naz results in increased TA levels in the flight motor neuropil, the motor behavioral phenotype can be rescued by blocking TA receptors. Our findings indicate that TA modulates flight motor behavior by acting on central circuitry and that TA is normally taken up from the central motor neuropil by Repo-positive glial cells, desaminated and further degraded by Naz. PMID:29021745

Differential receptor activation by cockroach adipokinetic hormones produces differential effects on ion currents, neuronal activity, and locomotion.

PubMed

Wicher, Dieter; Agricola, Hans-Jürgen; Söhler, Sandra; Gundel, Matthias; Heinemann, Stefan H; Wollweber, Leo; Stengl, Monika; Derst, Christian

2006-04-01

Adipokinetic hormone (AKH) peptides in insects serve the endocrine control of energy supply. They also produce, however, neuronal, vegetative, and motor effects, suggesting that AKHs orchestrate adaptive behavior by multiple actions. We have cloned, for Periplaneta americana, the AKH receptor to determine its localization and, based on current measurements in neurons and heterologous expression systems, the mechanisms of AKH actions. Apart from fat body, various neurons express the AKH receptor, among them abdominal dorsal unpaired median (DUM) neurons, which release the biogenic amine octopamine. They are part of the arousal system and are involved in the control of circulation and respiration. Both the two Periplaneta AKHs activate the Gs pathway, and AKH I also potently activates Gq. AKH I and--with much less efficacy--AKH II accelerate spiking of DUM neurons through an increase of the pacemaking Ca2+ current. Because the AKHs are released from the corpora cardiaca into the hemolymph, they must penetrate the blood-brain barrier for acting on neurons. That this happens was shown electrophysiologically by applying AKH I to an intact ganglion. Systemically injected AKH I stimulates locomotion potently in striking contrast to AKH II. This behavioral difference can be traced back conclusively to the different effectiveness of the AKHs on the level of G proteins. Our findings also show that AKHs act through the same basic mechanisms on neuronal and nonneuronal cells, and they support an integration of metabolic and neuronal effects in homoeostatic mechanisms.

The Gastric Ganglion of Octopus vulgaris: Preliminary Characterization of Gene- and Putative Neurochemical-Complexity, and the Effect of Aggregata octopiana Digestive Tract Infection on Gene Expression

PubMed Central

Baldascino, Elena; Di Cristina, Giulia; Tedesco, Perla; Hobbs, Carl; Shaw, Tanya J.; Ponte, Giovanna; Andrews, Paul L. R.

2017-01-01

The gastric ganglion is the largest visceral ganglion in cephalopods. It is connected to the brain and is implicated in regulation of digestive tract functions. Here we have investigated the neurochemical complexity (through in silico gene expression analysis and immunohistochemistry) of the gastric ganglion in Octopus vulgaris and tested whether the expression of a selected number of genes was influenced by the magnitude of digestive tract parasitic infection by Aggregata octopiana. Novel evidence was obtained for putative peptide and non-peptide neurotransmitters in the gastric ganglion: cephalotocin, corticotrophin releasing factor, FMRFamide, gamma amino butyric acid, 5-hydroxytryptamine, molluscan insulin-related peptide 3, peptide PRQFV-amide, and tachykinin–related peptide. Receptors for cholecystokininA and cholecystokininB, and orexin2 were also identified in this context for the first time. We report evidence for acetylcholine, dopamine, noradrenaline, octopamine, small cardioactive peptide related peptide, and receptors for cephalotocin and octopressin, confirming previous publications. The effects of Aggregata observed here extend those previously described by showing effects on the gastric ganglion; in animals with a higher level of infection, genes implicated in inflammation (NFκB, fascin, serpinB10 and the toll-like 3 receptor) increased their relative expression, but TNF-α gene expression was lower as was expression of other genes implicated in oxidative stress (i.e., superoxide dismutase, peroxiredoxin 6, and glutathione peroxidase). Elevated Aggregata levels in the octopuses corresponded to an increase in the expression of the cholecystokininA receptor and the small cardioactive peptide-related peptide. In contrast, we observed decreased relative expression of cephalotocin, dopamine β-hydroxylase, peptide PRQFV-amide, and tachykinin-related peptide genes. A discussion is provided on (i) potential roles of the various molecules in food intake regulation and digestive tract motility control and (ii) the difference in relative gene expression in the gastric ganglion in octopus with relatively high and low parasitic loads and the similarities to changes in the enteric innervation of mammals with digestive tract parasites. Our results provide additional data to the described neurochemical complexity of O. vulgaris gastric ganglion. PMID:29326594

Drugs, Biogenic Amine Targets and the Developing Brain

PubMed Central

Frederick, Aliya L.; Stanwood, Gregg D.

2009-01-01

Defects in the development of the brain have profound impacts on mature brain functions and underlie psychopathology. Classical neurotransmitters and neuromodulators, such as dopamine, serotonin, norepinephrine, acetycholine, glutamate and GABA, have pleiotropic effects during brain development. In other words, these molecules produce multiple, diverse effects to serve as regulators of distinct cellular functions at different times in neurodevelopment. These systems are impacted upon by a variety of illicit drugs of abuse, neurotherapeutics, and environmental contaminants. In this review, we describe the impact of drugs and chemicals on brain formation and function in animal models and in human populations, highlighting sensitive periods and effects that may not emerge until later in life. PMID:19372683

The adsorption of rare earth ions using carbonized polydopamine nano shells

DOE PAGES

Sun, Xiaoqi; Luo, Huimin; Mahurin, Shannon Mark; ...

2016-01-07

Herein we report the structure effects of nano carbon shells prepared by carbonized polydopamine for rare earth elements (REEs) adsorption for the first time. The solid carbon sphere, 60 nm carbon shell and 500 nm carbon shell were prepared and investigated for adsorption and desorption of REEs. The adsorption of carbon shells for REEs was found to be better than the solid carbon sphere. The effect of acidities on the adsorption and desorption properties was discussed in this study. The good adsorption performance of carbon shells can be attributed to their porous structure, large specific surface area, amine group andmore » carbonyl group of dopamine.« less

A Mobile Device App to Reduce Time to Drug Delivery and Medication Errors During Simulated Pediatric Cardiopulmonary Resuscitation: A Randomized Controlled Trial.

PubMed

Siebert, Johan N; Ehrler, Frederic; Combescure, Christophe; Lacroix, Laurence; Haddad, Kevin; Sanchez, Oliver; Gervaix, Alain; Lovis, Christian; Manzano, Sergio

2017-02-01

During pediatric cardiopulmonary resuscitation (CPR), vasoactive drug preparation for continuous infusion is both complex and time-consuming, placing children at higher risk than adults for medication errors. Following an evidence-based ergonomic-driven approach, we developed a mobile device app called Pediatric Accurate Medication in Emergency Situations (PedAMINES), intended to guide caregivers step-by-step from preparation to delivery of drugs requiring continuous infusion. The aim of our study was to determine whether the use of PedAMINES reduces drug preparation time (TDP) and time to delivery (TDD; primary outcome), as well as medication errors (secondary outcomes) when compared with conventional preparation methods. The study was a randomized controlled crossover trial with 2 parallel groups comparing PedAMINES with a conventional and internationally used drugs infusion rate table in the preparation of continuous drug infusion. We used a simulation-based pediatric CPR cardiac arrest scenario with a high-fidelity manikin in the shock room of a tertiary care pediatric emergency department. After epinephrine-induced return of spontaneous circulation, pediatric emergency nurses were first asked to prepare a continuous infusion of dopamine, using either PedAMINES (intervention group) or the infusion table (control group), and second, a continuous infusion of norepinephrine by crossing the procedure. The primary outcome was the elapsed time in seconds, in each allocation group, from the oral prescription by the physician to TDD by the nurse. TDD included TDP. The secondary outcome was the medication dosage error rate during the sequence from drug preparation to drug injection. A total of 20 nurses were randomized into 2 groups. During the first study period, mean TDP while using PedAMINES and conventional preparation methods was 128.1 s (95% CI 102-154) and 308.1 s (95% CI 216-400), respectively (180 s reduction, P=.002). Mean TDD was 214 s (95% CI 171-256) and 391 s (95% CI 298-483), respectively (177.3 s reduction, P=.002). Medication errors were reduced from 70% to 0% (P<.001) by using PedAMINES when compared with conventional methods. In this simulation-based study, PedAMINES dramatically reduced TDP, to delivery and the rate of medication errors. ©Johan N Siebert, Frederic Ehrler, Christophe Combescure, Laurence Lacroix, Kevin Haddad, Oliver Sanchez, Alain Gervaix, Christian Lovis, Sergio Manzano. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 01.02.2017.

Monoamine oxidase: Radiotracer chemistry and human studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

β-phenylethylamine, a small molecule with a large impact.

PubMed

Irsfeld, Meredith; Spadafore, Matthew; Prüß, Birgit M

2013-09-30

During a screen of bacterial nutrients as inhibitors of Escherichia coli O157:H7 biofilm, the Prüß research team made an intriguing observation: among 95 carbon and 95 nitrogen sources tested, β-phenylethylamine (PEA) performed best at reducing bacterial cell counts and biofilm amounts, when supplemented to liquid beef broth medium. This review article summarizes what is known about PEA. After some starting information on the chemistry of the molecule, we focus on PEA as a neurotransmitter and then move on to its role in food processing. PEA is a trace amine whose molecular mechanism of action differs from biogenic amines, such as serotonin or dopamine. Especially low or high concentrations of PEA may be associated with specific psychological disorders. For those disorders that are characterized by low PEA levels ( e.g. attention deficit hyperactivity disorder), PEA has been suggested as a 'safe' alternative to drugs, such as amphetamine or methylphenidate, which are accompanied by many undesirable side effects. On the food processing end, PEA can be detected in food either as a result of microbial metabolism or thermal processing. PEA's presence in food can be used as an indicator of bacterial contamination.

Focus On: Neurotransmitter Systems

PubMed Central

Valenzuela, C. Fernando; Puglia, Michael P.; Zucca, Stefano

2011-01-01

Neurotransmitter systems have been long recognized as important targets of the developmental actions of alcohol (i.e., ethanol). Short- and long-term effects of ethanol on amino acid (e.g., γ-aminobutyric acid and glutamate) and biogenic amine (e.g., serotonin and dopamine) neurotransmitters have been demonstrated in animal models of fetal alcohol spectrum disorders (FASD). Researchers have detected ethanol effects after exposure during developmental periods equivalent to the first, second, and third trimesters of human pregnancy. Results support the recommendation that pregnant women should abstain from drinking—even small quantities—as effects of ethanol on neurotransmitter systems have been detected at low levels of exposure. Recent studies have elucidated new mechanisms and/or consequences of the actions of ethanol on amino acid and biogenic amine neurotransmitter systems. Alterations in these neurotransmitter systems could, in part, be responsible for many of the conditions associated with FASD, including (1) learning, memory, and attention deficits; (2) motor coordination impairments; (3) abnormal responsiveness to stress; and (4) increased susceptibility to neuropsychiatric disorders, such as substance abuse and depression, and also neurological disorders, such as epilepsy and sudden infant death syndrome. However, future research is needed to conclusively establish a causal relationship between these conditions and developmental dysfunctions in neurotransmitter systems. PMID:23580048

Cuticle Integrity and Biogenic Amine Synthesis in Caenorhabditis elegans Require the Cofactor Tetrahydrobiopterin (BH4)

PubMed Central

Loer, Curtis M.; Calvo, Ana C.; Watschinger, Katrin; Werner-Felmayer, Gabriele; O’Rourke, Delia; Stroud, Dave; Tong, Amy; Gotenstein, Jennifer R.; Chisholm, Andrew D.; Hodgkin, Jonathan; Werner, Ernst R.; Martinez, Aurora

2015-01-01

Tetrahydrobiopterin (BH4) is the natural cofactor of several enzymes widely distributed among eukaryotes, including aromatic amino acid hydroxylases (AAAHs), nitric oxide synthases (NOSs), and alkylglycerol monooxygenase (AGMO). We show here that the nematode Caenorhabditis elegans, which has three AAAH genes and one AGMO gene, contains BH4 and has genes that function in BH4 synthesis and regeneration. Knockout mutants for putative BH4 synthetic enzyme genes lack the predicted enzymatic activities, synthesize no BH4, and have indistinguishable behavioral and neurotransmitter phenotypes, including serotonin and dopamine deficiency. The BH4 regeneration enzymes are not required for steady-state levels of biogenic amines, but become rate limiting in conditions of reduced BH4 synthesis. BH4-deficient mutants also have a fragile cuticle and are generally hypersensitive to exogenous agents, a phenotype that is not due to AAAH deficiency, but rather to dysfunction in the lipid metabolic enzyme AGMO, which is expressed in the epidermis. Loss of AGMO or BH4 synthesis also specifically alters the sensitivity of C. elegans to bacterial pathogens, revealing a cuticular function for AGMO-dependent lipid metabolism in host–pathogen interactions. PMID:25808955

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

β-phenylethylamine, a small molecule with a large impact

PubMed Central

Irsfeld, Meredith; Spadafore, Matthew; Prüß, Birgit M.

2013-01-01

During a screen of bacterial nutrients as inhibitors of Escherichia coli O157:H7 biofilm, the Prüß research team made an intriguing observation: among 95 carbon and 95 nitrogen sources tested, β-phenylethylamine (PEA) performed best at reducing bacterial cell counts and biofilm amounts, when supplemented to liquid beef broth medium. This review article summarizes what is known about PEA. After some starting information on the chemistry of the molecule, we focus on PEA as a neurotransmitter and then move on to its role in food processing. PEA is a trace amine whose molecular mechanism of action differs from biogenic amines, such as serotonin or dopamine. Especially low or high concentrations of PEA may be associated with specific psychological disorders. For those disorders that are characterized by low PEA levels (e.g. attention deficit hyperactivity disorder), PEA has been suggested as a ‘safe’ alternative to drugs, such as amphetamine or methylphenidate, which are accompanied by many undesirable side effects. On the food processing end, PEA can be detected in food either as a result of microbial metabolism or thermal processing. PEA's presence in food can be used as an indicator of bacterial contamination. PMID:24482732

Dietary Neurotransmitters: A Narrative Review on Current Knowledge

PubMed Central

Dell’Osso, Bernardo; Malgaroli, Antonio; Banfi, Giuseppe; Zanaboni Dina, Carlotta; Galentino, Roberta; Porta, Mauro

2018-01-01

Foods are natural sources of substances that may exert crucial effects on the nervous system in humans. Some of these substances are the neurotransmitters (NTs) acetylcholine (ACh), the modified amino acids glutamate and γ-aminobutyric acid (GABA), and the biogenic amines dopamine, serotonin (5-HT), and histamine. In neuropsychiatry, progressive integration of dietary approaches in clinical routine made it necessary to discern the more about some of these dietary NTs. Relevant books and literature from PubMed and Scopus databases were searched for data on food sources of Ach, glutamate, GABA, dopamine, 5-HT, and histamine. Different animal foods, fruits, edible plants, roots, and botanicals were reported to contain NTs. These substances can either be naturally present, as part of essential metabolic processes and ecological interactions, or derive from controlled/uncontrolled food technology processes. Ripening time, methods of preservation and cooking, and microbial activity further contributes to NTs. Moreover, gut microbiota are considerable sources of NTs. However, the significance of dietary NTs intake needs to be further investigated as there are no significant data on their bioavailability, neuronal/non neuronal effects, or clinical implications. Evidence-based interventions studies should be encouraged. PMID:29748506

Assessment of Mexican Arnica (Heterotheca inuloides Cass) and Rosemary (Rosmarinus officinalis) Extracts on Dopamine and Selected Biomarkers of Oxidative Stress in Stomach and Brain of Salmonella typhimurium Infected rats.

PubMed

Guzmàn, David Calderón; Herrera, Maribel Ortiz; Brizuela, Norma Osnaya; Mejía, Gerardo Barragàn; García, Ernestina Hernàndez; Olguín, Hugo Juàrez; Peraza, Armando Valenzuela; Ruíz, Norma Labra; Del Angel, Daniel Santamaría

2017-01-01

The effects of some natural products on dopamine (DA) and 5-hydroxyindole acetic acid (5-HIAA) in brain of infected models are still unclear. The purpose of this study was to measure the effect of Mexican arnica/rosemary (MAR) water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Female Wistar rats (weight 80 g) in the presence of MAR or absence (no-MAR) were treated as follows: group 1, buffer solution (controls); oseltamivir (100 mg/kg), group 2; culture of Salmonella typhimurium ( S.Typh ) (1 × 10 6 colony-forming units/rat) group 3; oseltamivir (100 mg/kg) + S.Typh (same dose) group 4. Drug and extracts were administered intraperitoneally every 24 h for 5 days, and S.Typh was given orally on days 1 and 3. On the fifth day, blood was collected to measure glucose and hemoglobin. The brains and stomachs were obtained to measure levels of DA, 5-HIAA, glutathione (GSH), TBARS, H 2 O 2 , and total ATPase activity using validated methods. DA levels increased in MAR group treated with oseltamivir alone but decreased in no-MAR group treated with oseltamivir plus S.Typh . 5-HIAA, GSH, and H 2 O 2 decreased in this last group, and ATPase activity increased in MAR group treated with oseltamivir plus S.Typh . TBARS (lipid peroxidation) increased in MAR group that received oseltamivir alone. Most of the biomarkers were not altered significantly in the stomach. MAR extract alters DA and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. The purpose of this study was to measure the effect of Mexican arnica/rosemary water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Results: Mexican arnica and rosemary extract alter dopamine and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. Abbreviations used: AS: Automated system, ATP: Adenosine triphosphate, CNS: Central nervous system, CFU: Colony-forming unit, DA: Dopamine EDTA: Ethylenediaminetetraacetic acid, 5-HIAA: Äcido 5-hidroxindolacético (serotonina), GABA: γ-aminobutyric acid, GSH: Glutathione, H2O2: Hidrogen peroxide, HCLO4: Perchloric acid, iNOS: Inducible nitric oxide synthase, LPS: Lipopolysaccharides, MAR: Arnica/Rosemary, NaCl: Sodium Chloride, NOGSH: nitrosoglutathione, NOS: Nitric oxide, OPT: Ortho-phtaldialdehyde, Pbs: Phosphate buffered saline, pH: potential of Hydrogen, Pi: Inorganic phosphate, ROS: Reactive oxygen species, RNSs: Reactive nitrogen species Tba: Thiobarbaturic acid, TBARS: Thiobarbituric aid reactive, Tca: Trichloroacetic, Tris-HCL: Tris hydrochloride, TSA: Trypticasein Soya Agar.

Assessment of Mexican Arnica (Heterotheca inuloides Cass) and Rosemary (Rosmarinus officinalis) Extracts on Dopamine and Selected Biomarkers of Oxidative Stress in Stomach and Brain of Salmonella typhimurium Infected rats

PubMed Central

Guzmàn, David Calderón; Herrera, Maribel Ortiz; Brizuela, Norma Osnaya; Mejía, Gerardo Barragàn; García, Ernestina Hernàndez; Olguín, Hugo Juàrez; Peraza, Armando Valenzuela; Ruíz, Norma Labra; Del Angel, Daniel Santamaría

2017-01-01

Background: The effects of some natural products on dopamine (DA) and 5-hydroxyindole acetic acid (5-HIAA) in brain of infected models are still unclear. Objective: The purpose of this study was to measure the effect of Mexican arnica/rosemary (MAR) water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Methods: Female Wistar rats (weight 80 g) in the presence of MAR or absence (no-MAR) were treated as follows: group 1, buffer solution (controls); oseltamivir (100 mg/kg), group 2; culture of Salmonella typhimurium (S.Typh) (1 × 106 colony-forming units/rat) group 3; oseltamivir (100 mg/kg) + S.Typh (same dose) group 4. Drug and extracts were administered intraperitoneally every 24 h for 5 days, and S.Typh was given orally on days 1 and 3. On the fifth day, blood was collected to measure glucose and hemoglobin. The brains and stomachs were obtained to measure levels of DA, 5-HIAA, glutathione (GSH), TBARS, H2O2, and total ATPase activity using validated methods. Results: DA levels increased in MAR group treated with oseltamivir alone but decreased in no-MAR group treated with oseltamivir plus S.Typh. 5-HIAA, GSH, and H2O2 decreased in this last group, and ATPase activity increased in MAR group treated with oseltamivir plus S.Typh. TBARS (lipid peroxidation) increased in MAR group that received oseltamivir alone. Most of the biomarkers were not altered significantly in the stomach. Conclusion: MAR extract alters DA and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. SUMMARY The purpose of this study was to measure the effect of Mexican arnica/rosemary water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Results: Mexican arnica and rosemary extract alter dopamine and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. Abbreviations used: AS: Automated system, ATP: Adenosine triphosphate, CNS: Central nervous system, CFU: Colony-forming unit, DA: Dopamine EDTA: Ethylenediaminetetraacetic acid, 5-HIAA: Äcido 5-hidroxindolacético (serotonina), GABA: γ-aminobutyric acid, GSH: Glutathione, H2O2: Hidrogen peroxide, HCLO4: Perchloric acid, iNOS: Inducible nitric oxide synthase, LPS: Lipopolysaccharides, MAR: Arnica/Rosemary, NaCl: Sodium Chloride, NOGSH: nitrosoglutathione, NOS: Nitric oxide, OPT: Ortho-phtaldialdehyde, Pbs: Phosphate buffered saline, pH: potential of Hydrogen, Pi: Inorganic phosphate, ROS: Reactive oxygen species, RNSs: Reactive nitrogen species Tba: Thiobarbaturic acid, TBARS: Thiobarbituric aid reactive, Tca: Trichloroacetic, Tris-HCL: Tris hydrochloride, TSA: Trypticasein Soya Agar PMID:28539708

Determination of free amino compounds in betalainic fruits and vegetables by gas chromatography with flame ionization and mass spectrometric detection.

PubMed

Kugler, Florian; Graneis, Stephan; Schreiter, Pat P-Y; Stintzing, Florian C; Carle, Reinhold

2006-06-14

Amino acids and amines are the precursors of betalains. Therefore, the profiles of free amino compounds in juices obtained from cactus pears [Opuntia ficus-indica (L.) Mill. cv. Bianca, cv. Gialla, and cv. Rossa], pitaya fruits [Selenicereus megalanthus (K. Schumann ex Vaupel) Moran, Hylocereus polyrhizus (Weber) Britton & Rose, and Hylocereus undatus (Haworth) Britton & Rose], and in extracts from differently colored Swiss chard [Beta vulgaris L. ssp. cicla (L.) Alef. cv. Bright Lights] petioles and red and yellow beets (B. vulgaris L. ssp. vulgaris var. conditiva Alef. cv. Burpee's Golden) were investigated for the first time. Amino compounds were derivatized with propyl chloroformate. While gas chromatography (GC) with mass spectrometry was used for peak assignment, GC flame ionization detection was applied for quantification of individual compounds. Whereas proline was the major free amino compound of cactus pear and pitaya fruit juices, glutamine dominated in Swiss chard stems and beets, respectively. Interestingly, extremely high concentrations of dopamine were detected in Swiss chard stems and beets. Furthermore, the cleavage of betaxanthins caused by derivatization in alkaline reaction solutions is demonstrated for the first time. Amino acids and amines thus released might increase the actual free amino compound contents of the respective sample. To evaluate the contribution of betaxanthin cleavage to total amino acid and amine concentration, isolated betaxanthins were derivatized according to the "EZ:faast" method prior to quantification of the respective amino compounds released. On a molar basis, betaxanthin contribution to overall amino compound contents was always below 6.4%.

Monoamine oxidase-A polymorphisms might modify the association between the dopamine D2 receptor gene and alcohol dependence.

PubMed

Huang, San-Yuan; Lin, Wei-Wen; Wan, Fang-Jung; Chang, Ai-Ju; Ko, Huei-Chen; Wang, Tso-Jen; Wu, Pei-Lin; Lu, Ru-Band

2007-05-01

Low monoamine oxidase (MAO) activity and the neurotransmitter dopamine are 2 important factors in the development of alcohol dependence. MAO is an important enzyme associated with the metabolism of biogenic amines. Therefore, the present study investigates whether the association between the dopamine D2 receptor (DRD2) gene and alcoholism is affected by different polymorphisms of the MAO type A (MAOA) gene. A total of 427 Han Chinese men in Taiwan (201 control subjects and 226 with alcoholism) were recruited for the study. Of the subjects with alcoholism, 108 had pure alcohol dependence (ALC) and 118 had both alcohol dependence and anxiety, depression or both (ANX/DEP ALC). All subjects were assessed with the Chinese Version of the Modified Schedule of Affective Disorders and Schizophrenia-Lifetime. Alcohol dependence, anxiety and major depressive disorders were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria. The genetic variant of the DRD2 gene was only associated with the ANX/DEP ALC phenotype, and the genetic variant of the MAOA gene was associated with pure ALC. Subjects carrying the MAOA 3-repeat allele and genotype A1/A1 of the DRD2 were 3.48 times (95% confidence interval = 1.47-8.25) more likely to be ANX/DEP ALC than the subjects carrying the MAOA 3-repeat allele and DRD2 A2/A2 genotype. The MAOA gene may modify the association between the DRD2 gene and ANX/DEP ALC phenotype.

Molecular cloning and functional characterization of the dopamine transporter from Eloria noyesi, a caterpillar pest of cocaine-rich coca plants.

PubMed

Chen, Rong; Wu, Xiaohong; Wei, Hua; Han, Dawn D; Gu, Howard H

2006-01-17

Cocaine is produced by coca plants as a chemical defense to deter feeding by insects. It has been shown that cocaine sprayed on tomato leaves reduces insect feeding, causes abnormal behaviors at low doses and kills feeding insects at doses equivalent to that in coca leaves [Nathanson, J.A., Hunnicutt, E.J., Kantham, L., Scavone, C., 1993. Cocaine as a naturally occurring insecticide. Proc. Natl. Acad. Sci. U. S. A. 90, 9645-9648.]. Most insects avoid coca leaves except the larvae of Eloria noyesi, a caterpillar pest of coca plants, which feeds preferentially on coca leaves. In the current study, we cloned and characterized the dopamine transporters (DATs) from caterpillars of E. noyesi (enDAT) and the silkworm, Bombyx mori (B. mori, bmDAT). The two insect DATs shared 88% amino acid sequence homology and functional similarity. Although enDAT and bmDAT showed the highest affinity for dopamine among endogenous amines, they were more sensitive to mammalian NET-selective inhibitors than to mammalian DAT-selective inhibitors. Despite a high cocaine content in the food source for E. noyesi, cocaine sensitivity of enDAT was similar to that of bmDAT, suggesting that mechanisms other than DAT insensitivity to cocaine, such as cocaine sequestration, might be responsible for cocaine resistance in this species. Given the significant differences in pharmacological profile from mammalian DATs, invertebrate DATs provide excellent tools for identifying regions and residues in the transporters that contribute to high-affinity binding of psychostimulants and antidepressants.

Receptor recruitment: A mechanism for interactions between G protein-coupled receptors

PubMed Central

Holtbäck, Ulla; Brismar, Hjalmar; DiBona, Gerald F.; Fu, Michael; Greengard, Paul; Aperia, Anita

1999-01-01

There is a great deal of evidence for synergistic interactions between G protein-coupled signal transduction pathways in various tissues. As two specific examples, the potent effects of the biogenic amines norepinephrine and dopamine on sodium transporters and natriuresis can be modulated by neuropeptide Y and atrial natriuretic peptide, respectively. Here, we report, using a renal epithelial cell line, that both types of modulation involve recruitment of receptors from the interior of the cell to the plasma membrane. The results indicate that recruitment of G protein-coupled receptors may be a ubiquitous mechanism for receptor sensitization and may play a role in the modulation of signal transduction comparable to that of the well established phenomenon of receptor endocytosis and desensitization. PMID:10377404

Metabolic regulation and behavior: how hunger produces arousal - an insect study.

PubMed

Wicher, Dieter

2007-12-01

The metabolic state affects the level of general activity of an organism. Satiety is related to relaxation while hunger is coupled to elevated activity which supports the chance to balance the energy deficiency. The unrestricted food availability in modern industrial nations along with no required locomotor activity are risk factors to develop disorders such as obesity. One of the strategies to find new targets for future treatment of metabolic disorders in men is to gain detailed knowledge of molecular and cellular mechanisms involved in the regulation of metabolic homeostasis in less complex, i.e. invertebrate systems. This review reports recent molecular studies in insects about how hunger signals may be linked to global activation. Adipokinetic peptide hormones (AKHs) are the insect counterpart to the mammalian glucagon. They are released upon lack of energy and mobilize internal fuel reserves. In addition, AKHs stimulate the locomotor activity which involves their activity within the central nervous system. In the cockroach Periplaneta americana various neurons express the AKH receptor. Some of these, the dorsal unpaired median (DUM) neurons belonging to a general arousal system, release the biogenic amine octopamine, the insect counterpart to mammalian adrenergic hormones. The two Periplaneta AKHs activate Gs proteins, and AKH I also potently activates Gq proteins. AKH I and - less effectively - AKH II accelerate spiking of DUM neurons via an increase of a pacemaking Ca2+ current. Systemically injected AKH I stimulates locomotion in contrast to AKH II. This behavioral difference corresponds to the different effectiveness of the AKHs on the level of G-proteins.

Mating regulates neuromodulator ensembles at nerve termini innervating the Drosophila reproductive tract.

PubMed

Heifetz, Yael; Lindner, Moshe; Garini, Yuval; Wolfner, Mariana F

2014-03-31

Upon mating, regions of the female reproductive tract mature and alter their function [1-3], for example to facilitate storage of sperm or control the release of eggs [4-6]. The female's nervous system and neuromodulators play important roles in her responses to mating [7-13]. However, it is difficult to reconcile the reproductive tract's many changing but coordinated events with the small set of neuromodulators present [14-18]. We hypothesized that each part of the reproductive tract contains a characteristic combination of neuromodulators that confer unique identities on each region and that postmating changes in these combinations coordinate subsequent actions. We examined the presence, locations, and levels of neuromodulators and related molecules ("signaling molecules") in the reproductive tract of Drosophila melanogaster females before and after mating: the biogenic amine octopamine, which regulates ovulation rate in Drosophila and locusts [7, 14-20]; serotonin, which regulates muscle contraction in locust oviducts [21]; and the FMRF amide dromyosuppressin, which regulates contraction of Drosophila heart muscle [22] and may regulate muscle contractions in the reproductive tract, if it is expressed there. We find that separate aspects of mating (sperm, seminal proteins, and physical effects) independently modulate the release of signaling molecules. Each reproductive tract subregion displays a characteristic combination of signaling molecule release, resulting in a unique functional identity. These patterns, and thus functions, change reproducibly after mating. Thus, one event (mating) promotes new combinations of signaling molecules that endow different parts of the reproductive tract with unique temporal and spatial identities that facilitate many aspects of fertilization. Copyright © 2014 Elsevier Ltd. All rights reserved.

The organization of societal conflicts by pavement ants Tetramorium caespitum: an agent-based model of amine-mediated decision making

PubMed Central

Hoover, Kevin M.; Bubak, Andrew N.; Law, Isaac J.; Yaeger, Jazmine D. W.; Renner, Kenneth J.; Swallow, John G.; Greene, Michael J.

2016-01-01

Abstract Ant colonies self-organize to solve complex problems despite the simplicity of an individual ant’s brain. Pavement ant Tetramorium caespitum colonies must solve the problem of defending the territory that they patrol in search of energetically rich forage. When members of 2 colonies randomly interact at the territory boundary a decision to fight occurs when: 1) there is a mismatch in nestmate recognition cues and 2) each ant has a recent history of high interaction rates with nestmate ants. Instead of fighting, some ants will decide to recruit more workers from the nest to the fighting location, and in this way a positive feedback mediates the development of colony wide wars. In ants, the monoamines serotonin (5-HT) and octopamine (OA) modulate many behaviors associated with colony organization and in particular behaviors associated with nestmate recognition and aggression. In this article, we develop and explore an agent-based model that conceptualizes how individual changes in brain concentrations of 5-HT and OA, paired with a simple threshold-based decision rule, can lead to the development of colony wide warfare. Model simulations do lead to the development of warfare with 91% of ants fighting at the end of 1 h. When conducting a sensitivity analysis, we determined that uncertainty in monoamine concentration signal decay influences the behavior of the model more than uncertainty in the decision-making rule or density. We conclude that pavement ant behavior is consistent with the detection of interaction rate through a single timed interval rather than integration of multiple interactions. PMID:29491915

The Biogenic Amine Tyramine and its Receptor (AmTyr1) in Olfactory Neuropils in the Honey Bee (Apis mellifera) Brain

PubMed Central

Sinakevitch, Irina T.; Daskalova, Sasha M.; Smith, Brian H.

2017-01-01

This article describes the cellular sources for tyramine and the cellular targets of tyramine via the Tyramine Receptor 1 (AmTyr1) in the olfactory learning and memory neuropils of the honey bee brain. Clusters of approximately 160 tyramine immunoreactive neurons are the source of tyraminergic fibers with small varicosities in the optic lobes, antennal lobes, lateral protocerebrum, mushroom body (calyces and gamma lobes), tritocerebrum and subesophageal ganglion (SEG). Our tyramine mapping study shows that the primary sources of tyramine in the antennal lobe and calyx of the mushroom body are from at least two Ventral Unpaired Median neurons (VUMmd and VUMmx) with cell bodies in the SEG. To reveal AmTyr1 receptors in the brain, we used newly characterized anti-AmTyr1 antibodies. Immunolocalization studies in the antennal lobe with anti-AmTyr1 antibodies showed that the AmTyr1 expression pattern is mostly in the presynaptic sites of olfactory receptor neurons (ORNs). In the mushroom body calyx, anti-AmTyr1 mapped the presynaptic sites of uniglomerular Projection Neurons (PNs) located primarily in the microglomeruli of the lip and basal ring calyx area. Release of tyramine/octopamine from VUM (md and mx) neurons in the antennal lobe and mushroom body calyx would target AmTyr1 expressed on ORN and uniglomerular PN presynaptic terminals. The presynaptic location of AmTyr1, its structural similarity with vertebrate alpha-2 adrenergic receptors, and previous pharmacological evidence suggests that it has an important role in the presynaptic inhibitory control of neurotransmitter release. PMID:29114209

The organization of societal conflicts by pavement ants Tetramorium caespitum: an agent-based model of amine-mediated decision making.

PubMed

Hoover, Kevin M; Bubak, Andrew N; Law, Isaac J; Yaeger, Jazmine D W; Renner, Kenneth J; Swallow, John G; Greene, Michael J

2016-06-01

Ant colonies self-organize to solve complex problems despite the simplicity of an individual ant's brain. Pavement ant Tetramorium caespitum colonies must solve the problem of defending the territory that they patrol in search of energetically rich forage. When members of 2 colonies randomly interact at the territory boundary a decision to fight occurs when: 1) there is a mismatch in nestmate recognition cues and 2) each ant has a recent history of high interaction rates with nestmate ants. Instead of fighting, some ants will decide to recruit more workers from the nest to the fighting location, and in this way a positive feedback mediates the development of colony wide wars. In ants, the monoamines serotonin (5-HT) and octopamine (OA) modulate many behaviors associated with colony organization and in particular behaviors associated with nestmate recognition and aggression. In this article, we develop and explore an agent-based model that conceptualizes how individual changes in brain concentrations of 5-HT and OA, paired with a simple threshold-based decision rule, can lead to the development of colony wide warfare. Model simulations do lead to the development of warfare with 91% of ants fighting at the end of 1 h. When conducting a sensitivity analysis, we determined that uncertainty in monoamine concentration signal decay influences the behavior of the model more than uncertainty in the decision-making rule or density. We conclude that pavement ant behavior is consistent with the detection of interaction rate through a single timed interval rather than integration of multiple interactions.

5-HT stimulation of heart rate in Drosophila does not act through cAMP as revealed by pharmacogenetics.

PubMed

Majeed, Zana R; Nichols, Charles D; Cooper, Robin L

2013-12-01

The fruit fly, Drosophila melanogaster, is a good experimental organism to study the underlying mechanism of heart rate (HR) regulation. It is already known that many neuromodulators (serotonin, dopamine, octopamine, acetylcholine) change the HR in Drosophila melanogaster larvae. In this study, we investigated the role of cAMP-PKA signaling pathway in HR regulation and 5-HT positive chronotropic action. In order to obtain insight into the 5-HT mechanism of action in larvae cardiomyocytes, genetic and pharmacological approaches were used. We used transgenic flies that expressed the hM4Di receptor [designer receptors exclusively activated by designer drugs (DREADDs)] as one tool. Our previous results showed that activation of hM4Di receptors (modified muscarinic acetylcholine receptors) decreases or arrests the heart from beating. In this study, it was hypothesized that the positive chronotropic effect of serotonin [5-hydroxytryptamine (5-HT)] are mediated by serotonin receptors coupled to the adenylyl cyclase pathway and downstream cAMP and PKA activity. Activation of hM4Di by clozapine-N-oxide (CNO) was predicted to block the effects of serotonin by inhibiting adenylyl cyclase activity through Gαi pathway activation. Interestingly, we found here that manipulation of adenylyl cyclase activity and cAMP levels had no significant effect on HR. The ability of hM4Di receptor activation to slow or stop the heart is therefore likely mediated by activation of GIRK channels to produce hyperpolarization of cardiomyocytes, and not through inhibition of adenylyl cyclase.

Lessons from sleeping flies: insights from Drosophila melanogaster on the neuronal circuitry and importance of sleep.

PubMed

Potdar, Sheetal; Sheeba, Vasu

2013-06-01

Sleep is a highly conserved behavior whose role is as yet unknown, although it is widely acknowledged as being important. Here we provide an overview of many vital questions regarding this behavior, that have been addressed in recent years using the genetically tractable model organism Drosophila melanogaster in several laboratories around the world. Rest in D. melanogaster has been compared to mammalian sleep and its homeostatic and circadian regulation have been shown to be controlled by intricate neuronal circuitry involving circadian clock neurons, mushroom bodies, and pars intercerebralis, although their exact roles are not entirely clear. We draw attention to the yet unanswered questions and contradictions regarding the nature of the interactions between the brain regions implicated in the control of sleep. Dopamine, octopamine, γ-aminobutyric acid (GABA), and serotonin are the chief neurotransmitters identified as functioning in different limbs of this circuit, either promoting arousal or sleep by modulating membrane excitability of underlying neurons. Some studies have suggested that certain brain areas may contribute towards both sleep and arousal depending on activation of specific subsets of neurons. Signaling pathways implicated in the sleep circuit include cyclic adenosine monophosphate (cAMP) and epidermal growth factor receptor-extracellular signal-regulated kinase (EGFR-ERK) signaling pathways that operate on different neural substrates. Thus, this field of research appears to be on the cusp of many new and exciting findings that may eventually help in understanding how this complex physiological phenomenon is modulated by various neuronal circuits in the brain. Finally, some efforts to approach the "Holy Grail" of why we sleep have been summarized.

The behavioural effects of predator-induced stress responses in the cricket (Gryllus texensis): the upside of the stress response.

PubMed

Adamo, Shelley A; Kovalko, Ilya; Mosher, Brianna

2013-12-15

Predator-induced stress responses are thought to reduce an animal's risk of being eaten. Therefore, these stress responses should enhance anti-predator behaviour. We found that individual insects (the cricket Gryllus texensis) show reliable behavioural responses (i.e. behavioural types) in a plus-shaped maze. An individual's behaviour in the plus maze remained consistent for at least 1/2 of its adult life. However, after exposure to a model predator, both male and female crickets showed a reduced period of immobility and an increased amount of time spent under shelter compared with controls. These changes could be mimicked by injections of the insect stress neurohormone octopamine. These behavioural changes probably aid crickets in evading predators. Exposure to a model predator increased the ability of crickets to escape a live predator (a bearded dragon, Pogona vitticeps). An injection of octopamine had the same effect, showing that stress hormones can reduce predation. Using crickets to study the fitness consequences of predator-induced stress responses will help integrate ecological and biomedical concepts of 'stress'.

Autocrine regulation of ecdysone synthesis by β3-octopamine receptor in the prothoracic gland is essential for Drosophila metamorphosis.

PubMed

Ohhara, Yuya; Shimada-Niwa, Yuko; Niwa, Ryusuke; Kayashima, Yasunari; Hayashi, Yoshiki; Akagi, Kazutaka; Ueda, Hitoshi; Yamakawa-Kobayashi, Kimiko; Kobayashi, Satoru

2015-02-03

In Drosophila, pulsed production of the steroid hormone ecdysone plays a pivotal role in developmental transitions such as metamorphosis. Ecdysone production is regulated in the prothoracic gland (PG) by prothoracicotropic hormone (PTTH) and insulin-like peptides (Ilps). Here, we show that monoaminergic autocrine regulation of ecdysone biosynthesis in the PG is essential for metamorphosis. PG-specific knockdown of a monoamine G protein-coupled receptor, β3-octopamine receptor (Octβ3R), resulted in arrested metamorphosis due to lack of ecdysone. Knockdown of tyramine biosynthesis genes expressed in the PG caused similar defects in ecdysone production and metamorphosis. Moreover, PTTH and Ilps signaling were impaired by Octβ3R knockdown in the PG, and activation of these signaling pathways rescued the defect in metamorphosis. Thus, monoaminergic autocrine signaling in the PG regulates ecdysone biogenesis in a coordinated fashion on activation by PTTH and Ilps. We propose that monoaminergic autocrine signaling acts downstream of a body size checkpoint that allows metamorphosis to occur when nutrients are sufficiently abundant.

A putative octopamine/tyramine receptor mediating appetite in a hungry fly

NASA Astrophysics Data System (ADS)

Ishida, Yuko; Ozaki, Mamiko

2011-07-01

In the blowfly Phormia regina, experience of simultaneous feeding with d-limonene exposure inhibits proboscis extension reflex (PER) due to decreased tyramine (TA) titer in the brain. To elucidate the molecular mechanism of TA signaling pathway related to the associated feeding behavior, we cloned cDNA encoding the octopamine/TA receptor (PregOAR/TAR). The deduced protein is composed of 607 amino acid residues and has 7 predicted transmembrane domains. Based on homology and phylogenetic analyses, this protein belongs to the OAR/TAR family. The PregOAR/TAR was mainly expressed in head, with low levels of expression in other tissues at adult stages. Gene expression profile is in agreement with a plethora of functions ascribed to TA in various insect tissues. The immunolabeled cell bodies and processes were localized in the medial protocerebrum, outer layer of lobula, antennal lobe, and subesophageal ganglion. These results suggest that decrease of TA level in the brain likely affects neurons expressing PregOAR/TAR, causing mediation of the sensitivity in the sensillum and/or output of motor neurons for PER.

Inhibitors of calling behavior of Plodia interpunctella.

PubMed

Hirashima, Akinori; Shigeta, Yoko; Eiraku, Tomohiko; Kuwano, Eiichi

2003-01-01

Some octopamine agonists were found to suppress the calling behavior of the stored product Indian meal moth, Plodia interpunctella. Compounds were screened using a calling behavior bioassay using female P. interpunctella. Four active derivatives, with inhibitory activity at the nanomolar range, were identified in order of decreasing activity: 2-(1-phenylethylamino)-2-oxazoline > 2-(2-ethyl,6-methylanilino)oxazolidine > 2-(2-methyl benzylamino)-2-thiazoline > 2-(2,6-diethylanilino)thiazolidine. Three-dimensional pharmacophore hypotheses were built from a set of 15 compounds. Among the ten common-featured models generated by the program Catalyst/HipHop, a hypothesis including a hydrogen-bond acceptor lipid, a hydrophobic aromatic and two hydrophobic aliphatic features was considered to be essential for inhibitory activity in the calling behavior. Active compounds mapped well onto all the hydrogen-bond acceptor lipid, hydrophobic aromatic and hydrophobic aliphatic features of the hypothesis. On the other hand, less active compounds were shown not to achieve the energetically favorable conformation that is found in the active molecules in order to fit the 3D common-feature pharmacophore models. The present studies demonstrate that inhibition of calling behavior is via an octopamine receptor.

Octopamine mediated relaxation of maintained and catch tension in locust skeletal muscle.

PubMed

Evans, P D; Siegler, M V

1982-03-01

1. The modulatory actions of an identified octopaminergic neurone (DUMETi) that projects to the extensor-tibiae muscle of the locust hind leg depend upon the frequency of stimulation of the slow motoneurone (SETi) to this muscle. 2. At low frequencies of SETi stimulation (1Hz and below) the predominant modulatory effects are increases in the amplitude and relaxation rate of twitch tension. At higher frequencies, where twitches summate but tetanus is incomplete (up to 20 Hz), the reduction of maintained tension becomes considerably more important. 3. Both octopamine application and DUMETi stimulation reduce the amount of catch tension displayed by the extensor muscle when SETi is fired in a variety of different stimulus patterns. The extensor-tibiae muscle is itself 'pattern sensitive' since is shows a 'positive spacing effect' when SETi is stimulated at an average frequency of 1 Hz. 4. It is suggested that a primary function of DUMETi is to change the response of the muscle from one that favours maintenance of posture to one that favours rapid changes in joint position or force, such as might occur during locomotion.

Octopamine mediated relaxation of maintained and catch tension in locust skeletal muscle.

PubMed Central

Evans, P D; Siegler, M V

1982-01-01

1. The modulatory actions of an identified octopaminergic neurone (DUMETi) that projects to the extensor-tibiae muscle of the locust hind leg depend upon the frequency of stimulation of the slow motoneurone (SETi) to this muscle. 2. At low frequencies of SETi stimulation (1Hz and below) the predominant modulatory effects are increases in the amplitude and relaxation rate of twitch tension. At higher frequencies, where twitches summate but tetanus is incomplete (up to 20 Hz), the reduction of maintained tension becomes considerably more important. 3. Both octopamine application and DUMETi stimulation reduce the amount of catch tension displayed by the extensor muscle when SETi is fired in a variety of different stimulus patterns. The extensor-tibiae muscle is itself 'pattern sensitive' since is shows a 'positive spacing effect' when SETi is stimulated at an average frequency of 1 Hz. 4. It is suggested that a primary function of DUMETi is to change the response of the muscle from one that favours maintenance of posture to one that favours rapid changes in joint position or force, such as might occur during locomotion. PMID:6808122

Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo.

PubMed

Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

2016-08-01

The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [(18)F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment.

Trace Amine-Associated Receptor 1 Modulates the Locomotor and Sensitization Effects of Nicotine

PubMed Central

Sukhanov, Ilya; Dorofeikova, Mariia; Dolgorukova, Antonina; Dorotenko, Artem; Gainetdinov, Raul R.

2018-01-01

Trace amine-associated receptor 1 (TAAR1) has emerged as a promising target for addiction treatments because it affects dopamine transmission in the mesolimbic pathway. TAAR1 is involved in the effects of addictive drugs, such as amphetamines, cocaine and ethanol, but the impact of TAAR1 on the effects of nicotine, the psychoactive drug responsible for the development and maintenance of tobacco smoking, has not yet been studied. This study was performed to investigate the possible modulatory action of TAAR1 on the effects of nicotine on locomotor behaviors in rats and mice. Pretreatment with the TAAR1 agonist RO5263397 dose-dependently decreased nicotine-induced hyperlocomotion in rats habituated to locomotor boxes, prevented the development of nicotine sensitization and blocked hypermotility in nicotine-sensitized rats at the highest tested dose (10 mg/kg). The lack of TAAR1 failed to affect the effects of nicotine on the locomotion of mutant mice. Based on the results of the present study, TAAR1 activation attenuates the locomotion-stimulating effects of nicotine on rats. These results further support the previously proposed hypothesis that TAAR1 is a promising target for the prevention and treatment of drug addiction. Further studies aimed at analyzing the effects of TAAR1 agonists on animal models of nicotine addiction are warranted. PMID:29681856

Monoamine oxidase inactivation: from pathophysiology to therapeutics.

PubMed

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, beta-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.

Methods of biological fluids sample preparation - biogenic amines, methylxanthines, water-soluble vitamins.

PubMed

Płonka, Joanna

2015-01-01

In recent years demands on the amount of information that can be obtained from the analysis of a single sample have increased. For time and economic reasons it is necessary to examine at the same time larger number of compounds, and compounds from different groups. This can best be seen in such areas as clinical analysis. In many diseases, the best results for patients are obtained when treatment fits the individual characteristics of the patient. Dosage monitoring is important at the beginning of therapy and in the full process of treatment. In the treatment of many diseases biogenic amines (dopamine, serotonin) and methylxanthines (theophylline, theobromine, caffeine) play an important role. They are used as drugs separately or in combination with others to support and strengthen the action of other drugs - for example, the combination of caffeine and paracetamol. Vitamin supplementation may be also an integral part of the treatment process. Specification of complete sample preparation parameters for extraction of the above compounds from biological matrices has been reviewed. Particular attention was given to the preparation stage and extraction methods. This review provides universal guidance on establishing a common procedures across laboratories to facilitate the preparation and analysis of all discussed compounds. Copyright © 2014 John Wiley & Sons, Ltd.

Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure

PubMed Central

Xu, Jianchao; Li, Guoyong; Wang, Peili; Velazquez, Heino; Yao, Xiaoqiang; Li, Yanyan; Wu, Yanling; Peixoto, Aldo; Crowley, Susan; Desir, Gary V.

2005-01-01

The kidney not only regulates fluid and electrolyte balance but also functions as an endocrine organ. For instance, it is the major source of circulating erythropoietin and renin. Despite currently available therapies, there is a marked increase in cardiovascular morbidity and mortality among patients suffering from end-stage renal disease. We hypothesized that the current understanding of the endocrine function of the kidney was incomplete and that the organ might secrete additional proteins with important biological roles. Here we report the identification of a novel flavin adenine dinucleotide–dependent amine oxidase (renalase) that is secreted into the blood by the kidney and metabolizes catecholamines in vitro (renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine). In humans, renalase gene expression is highest in the kidney but is also detectable in the heart, skeletal muscle, and the small intestine. The plasma concentration of renalase is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects. Renalase infusion in rats caused a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify renalase as what we believe to be a novel amine oxidase that is secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure. PMID:15841207

Safinamide: an add-on treatment for managing Parkinson’s disease

PubMed Central

Müller, Thomas

2018-01-01

Heterogeneous expression of neurotransmitter deficits results from onset and progression of Parkinson’s disease. Intervals, characterized by reappearance of motor and associated certain nonmotor symptoms, determine the end of good tolerability and efficacy of oral levodopa therapy. These “OFF” states result from levodopa pharmacokinetics and disease progression-related deterioration of the central buffering capacity for fluctuations of dopamine levels. This review discusses safinamide as an add-on therapeutic agent in orally levodopa-treated patients with “OFF” phenomena. Safinamide provided beneficial effects on “OFF” symptoms in pivotal trials with doses of 50 or 100 mg once daily. Safinamide reversibly inhibits mono-amine oxidase B and declines abnormal glutamate release by modulation of potassium- and sodium ion channels. An ideal candidate for combination with safinamide is opicapone. This inhibitor of peripheral catechol-O-methyltransferase supports continuous brain delivery of levodopa and, thus, the continuous dopaminergic stimulation concept. Both compounds with their once-daily application and good tolerability may complement each other by reduction of necessary oral levodopa intakes and “OFF” times. Thus, a promising, future option will be combination of safinamide and opicapone in one formulation. It will reduce adherence issues and may complement levodopa treatment. It will probably cause less nausea and edema than a dopamine agonist/levodopa regimen. PMID:29670409

Safinamide: an add-on treatment for managing Parkinson's disease.

PubMed

Müller, Thomas

2018-01-01

Heterogeneous expression of neurotransmitter deficits results from onset and progression of Parkinson's disease. Intervals, characterized by reappearance of motor and associated certain nonmotor symptoms, determine the end of good tolerability and efficacy of oral levodopa therapy. These "OFF" states result from levodopa pharmacokinetics and disease progression-related deterioration of the central buffering capacity for fluctuations of dopamine levels. This review discusses safinamide as an add-on therapeutic agent in orally levodopa-treated patients with "OFF" phenomena. Safinamide provided beneficial effects on "OFF" symptoms in pivotal trials with doses of 50 or 100 mg once daily. Safinamide reversibly inhibits mono-amine oxidase B and declines abnormal glutamate release by modulation of potassium- and sodium ion channels. An ideal candidate for combination with safinamide is opicapone. This inhibitor of peripheral catechol-O-methyltransferase supports continuous brain delivery of levodopa and, thus, the continuous dopaminergic stimulation concept. Both compounds with their once-daily application and good tolerability may complement each other by reduction of necessary oral levodopa intakes and "OFF" times. Thus, a promising, future option will be combination of safinamide and opicapone in one formulation. It will reduce adherence issues and may complement levodopa treatment. It will probably cause less nausea and edema than a dopamine agonist/levodopa regimen.

Characterizations of the Formation of Polydopamine-Coated Halloysite Nanotubes in Various pH Environments.

PubMed

Feng, Junran; Fan, Hailong; Zha, Dao-An; Wang, Le; Jin, Zhaoxia

2016-10-11

Recent studies demonstrated that polydopamine (PDA) coating is universal to nearly all substrates, and it endows substrates with biocompatibility, postfunctionality, and other useful properties. Surface chemistry of PDA coating is important for its postmodifications and applications. However, there is less understanding of the formation mechanism and surface functional groups of PDA layers generated in different conditions. Halloysite is a kind of clay mineral with tubular nanostructure. Water-swellable halloysite has unique reactivity. In this study, we have investigated the reaction of dopamine in the presence of water-swellable halloysite. We have tracked the reaction progresses in different pH environments by using UV-vis spectroscopy and surface-enhanced Raman spectroscopy (SERS). The surface properties of PDA on halloysite were clarified by X-ray photoelectron spectroscopy (XPS), SERS, Fourier transform infrared (FTIR) characterizations, zeta potential, surface wettability, and morphological characterizations. We noticed that the interaction between halloysite surface and dopamine strongly influences the surface functionality of coated PDA. In addition, pH condition further modulates surface functional groups, resulting in less content of secondary/aromatic amine in PDA generated in weak acidic environment. This study demonstrates that the formation mechanism of polydopamine becomes complex in the presence of inorganic nanomaterials. Substrate property and reaction condition dominate the functionality of obtained PDA together.

Human Arylamine N-Acetyltransferase 1 Is Inhibited by the Dithiocarbamate Pesticide Thiram.

PubMed

Xu, Ximing; Mathieu, Cécile; Berthelet, Jérémy; Duval, Romain; Bui, Linh Chi; Busi, Florent; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2017-09-01

Thiram (tetramethylthiuram disulfide) is a representative dithiocarbamate (DTC) pesticide used in both the field and as a seed protectant. The widespread use of Thiram and other DTC pesticides has raised concerns for health, because these compounds can exert neuropathic, endocrine disruptive, and carcinogenic effects. These toxic effects are thought to rely, at least in part, on the reaction of Thiram (and certain of its metabolites) with cellular protein thiols with subsequent loss of protein function. So far, a limited number of molecular targets of Thiram have been reported, including few enzymes such as dopamine β -hydroxylase, 11 β -hydroxysteroid dehydrogenase, and brain glycogen phosphorylase. We provide evidence that Thiram is an inhibitor ( K I = 23 μ M; k inact = 0.085 second -1 ; k inact / K I = 3691 M -1 ⋅s -1 ) of human arylamine N -acetyltransferase 1 (NAT1), a phase II xenobiotic-metabolizing enzyme that plays a key role in the biotransformation of aromatic amine xenobiotics. Thiram was found to act as an irreversible inhibitor through the modification of NAT1 catalytic cysteine residue as also reported for other enzymes targeted by this pesticide. We also showed using purified NAT1 and human keratinocytes that Thiram impaired the N -acetylation of 3,4-dichloroaniline (3,4-DCA), a major toxic metabolite of aromatic amine pesticides (such as Diuron or Propanil). As coexposure to different classes of pesticides is common, our data suggest that pharmacokinetic drug-drug interactions between DTC pesticides such as Thiram and aromatic amine pesticides may occur through alteration of NAT1 enzymes functions. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

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.

Effects of the new psychoactive substances diclofensine, diphenidine, and methoxphenidine on monoaminergic systems.

PubMed

Luethi, Dino; Hoener, Marius C; Liechti, Matthias E

2018-01-15

Diclofensine, diphenidine, and methoxphenidine are new psychoactive substances (NPSs) that recently appeared on the illicit drug market. Pharmacological profiling of such newly emerged drugs is crucial for a better understanding of their psychotropic effects and toxicity. We therefore investigated the potential of these NPSs to inhibit the norepinephrine, dopamine, and serotonin transporters in human embryonic kidney cells stably transfected with the respective transporters. In addition, we determined monoamine transporter and receptor affinities for the substances. Diclofensine potently bound to the monoamine transporters in the submicromolar range and had similar inhibition potential for all three transporters in the range of 2.5-4.8μM. Moreover, diclofensine bound to adrenergic, dopamine, serotonin, and trace amine-associated receptors. Diphenidine was an equipotent inhibitor of the norepinephrine and dopamine transporters in the low micromolar range and a very weak inhibitor of the serotonin transporter. Besides binding to transporters, diphenidine bound to adrenergic α 1A and α 2A receptors and serotonin 5-hydroxytryptamine 1A (5-HT 1A ) and 5-HT 2A receptors in the range of 4-11μM. Methoxphenidine bound to all transporters, but considerable inhibition (IC 50 < 10μM) was observed only for the norepinephrine transporter. Moreover, methoxphenidine bound to adrenergic α 2A and serotonin 5-HT 2A and 5-HT 2C receptors in the range of 2.5-8.2μM. None of the test drugs mediated substrate-type efflux of monoamines. These data demonstrate that the monoamine transporter inhibition and receptor interactions most likely mediate the psychoactive effects of diclofensine and possibly play a contributory role for diphenidine and methoxphenidine. Copyright © 2017 Elsevier B.V. All rights reserved.

Deletion of MAOA and MAOB in a male patient causes severe developmental delay, intermittent hypotonia and stereotypical hand movements

PubMed Central

Whibley, Annabel; Urquhart, Jill; Dore, Jonathan; Willatt, Lionel; Parkin, Georgina; Gaunt, Lorraine; Black, Graeme; Donnai, Dian; Raymond, F Lucy

2010-01-01

Monoamine oxidases (MAO-A and MAO-B) have a key role in the degradation of amine neurotransmitters, such as dopamine, norepinephrine and serotonin. We identified an inherited 240 kb deletion on Xp11.3–p11.4, which encompasses both monoamine oxidase genes but, unlike other published reports, does not affect the adjacent Norrie disease gene (NDP). The brothers who inherited the deletion, and thus have no monoamine oxidase function, presented with severe developmental delay, intermittent hypotonia and stereotypical hand movements. The clinical features accord with published reports of larger microdeletions and selective MAO-A and MAO-B deficiencies in humans and mouse models and suggest considerable functional compensation between MAO-A and MAO-B under normal conditions. PMID:20485326

Asenapine Effects on Cognitive and Monoamine Dysfunction Elicited by Subchronic Phencyclidine Administration

PubMed Central

Elsworth, John D.; Groman, Stephanie; Jentsch, J. David; Valles, Rodrigo; Shahid, Mohammed; Wong, Erik; Marston, Hugh; Roth, Robert H.

2013-01-01

Purpose Repeated, intermittent administration of the psychotropic NMDA antagonist phencyclidine (PCP) to laboratory animals causes impairment in cognitive and executive functions, modeling important sequelae of schizophrenia; these effects are thought to be due to a dysregulation of neurotransmission within the prefrontal cortex. Atypical antipsychotic drugs have been reported to have measurable, if incomplete, effects on cognitive dysfunction in this model, and these effects may be due to their ability to normalize a subset of the physiological deficits occurring within the prefrontal cortex. Asenapine is an atypical antipsychotic approved in the US for the treatment of schizophrenia and for the treatment, as monotherapy or adjunctive therapy to lithium or valproate, of acute manic or mixed episodes associated bipolar I disorder. To understand its cognitive and neurochemical actions more fully, we explored the effects of short- and long-term dosing with asenapine on measures of cognitive and motor function in normal monkeys and in those previously exposed for 2 weeks to PCP; we further studied the impact of treatment with asenapine on dopamine and serotonin turnover in discrete brain regions from the same cohort. Methods Monkeys were trained to perform reversal learning and object retrieval procedures before twice-daily administration of PCP (0.3 mg/kg intramuscular) or saline for 14 days. Tests confirmed cognitive deficits in PCP-exposed animals before beginning twice-daily administration of saline (control) or asenapine (50, 100, or 150 μg/kg, intramuscular). Dopamine and serotonin turnover were assessed in 15 specific brain regions by high-pressure liquid chromatography measures of the ratio of parent amine to its major metabolite. Results On average, PCP-treated monkeys made twice as many errors in the reversal task as did control monkeys. Asenapine facilitated reversal learning performance in PCP-exposed monkeys, with improvements at trend level after 1 week of administration and reaching significance after 2–4 weeks of dosing. In week 4, the improvement with asenapine 150 μg/kg (p=0.01) rendered the performance of PCP-exposed monkeys indistinguishable from that of normal monkeys without compromising fine motor function. Asenapine administration (150 μg/kg twice daily) produced an increase in dopamine and serotonin turnover in most brain regions of control monkeys and asenapine (50–150 μg/kg) increased dopamine and serotonin turnover in several brain regions of subchronic PCP-treated monkeys. No significant changes in the steady-state levels of dopamine or serotonin were observed in any brain region except for the central amygdala, in which a significant depletion of dopamine was observed in PCP-treated control monkeys; asenapine treatment reversed this dopamine depletion. A significant decrease in serotonin utilization was observed in the orbitofrontal cortex and nucleus accumbens in PCP monkeys, which may underlie poor reversal learning. In the same brain regions, dopamine utilization was not affected. Asenapine ameliorated this serotonin deficit in a dose-related manner that matched its efficacy for reversing the cognitive deficit. Conclusions In this model of cognitive dysfunction, asenapine produced substantial gains in executive functions that were maintained with long-term administration. The cognition-enhancing effects of asenapine and the neurochemical changes in serotonin and dopamine turnover seen in this study are hypothesized to be primarily related to its potent serotonergic and noradrenergic receptor binding properties, and support the potential for asenapine to reduce cognitive dysfunction in patients with schizophrenia and bipolar disorder. PMID:21875607

Effects of dietary hexachlorobenzene exposure on regional brain biogenic amine concentrations in mink and European ferrets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bleavins, M.R.; Bursian, S.J.; Brewster, J.S.

1984-01-01

In the initial trial, adult mink and ferrets were administered hexachlorobenzene (HCB) via the feed at concentrations of 1, 5, or 25 ppm for 47 wk. Animals receiving 125 and 625 ppm HCB in the diet died before termination of the experiment, with female ferrets at the 125 ppm level displaying abnormal aggressiveness and hyperexcitability just prior to death. Hypothalamic serotonin (5-HT) was significantly elevated at all dose levels in mink, and cerebellar 5-HT was significantly elevated at 1 ppm in the ferret. Regional brain biogenic amine concentrations were also determined in the offspring of the female mink that weremore » administered 1 and 5 ppm HCB. Hypothalamic dopamine (DA) concentrations were significantly depressed by 1 and 5 ppm in these kits. In a second study, adult male and female ferrets were administered 250 or 500 ppm HCB via the diet for 7 wk. Two animals at the 250-ppm level and 3 animals at the 500-ppm level died before termination of the experiment without showing behavioral changes. Of the remaining animals, 3 ferrets at 250 ppm and 1 ferret at 500 ppm showed slight aggressiveness and hyperexcitability during the last week of the experiment. Concentrations of 5-HT were significantly elevated at 500 ppm in the cerebral hemispheres and at 250 ppm in the midbrain of male ferrets, while in the females, 5-HT was elevated in the cerebral hemispheres at 250 ppm and in the hypothalamus at both 250 and 500 ppm. Norepinephrine (NE) concentrations were significantly elevated in the cerebellum of males exposed to 250 and 500 ppm, as were NE concentrations in the midbrain. HCB at 500 ppm caused a significant increase in medullary NE, while 250 ppm caused an increase in hypothalamic NE in males. The only change in regional brain dopamine (DA) concentrations occurred at 500 ppm HCB in the midbrain of males, where there was a significant elevation of this neurotransmitter. 34 references, 7 tables.« less

Effects of neck and circumoesophageal connective lesions on posture and locomotion in the cockroach.

PubMed

Ridgel, Angela L; Ritzmann, Roy E

2005-06-01

Few studies in arthropods have documented to what extent local control centers in the thorax can support locomotion in absence of inputs from head ganglia. Posture, walking, and leg motor activity was examined in cockroaches with lesions of neck or circumoesophageal connectives. Early in recovery, cockroaches with neck lesions had hyper-extended postures and did not walk. After recovery, posture was less hyper-extended and animals initiated slow leg movements for multiple cycles. Neck lesioned individuals showed an increase in walking after injection of either octopamine or pilocarpine. The phase of leg movement between segments was reduced in neck lesioned cockroaches from that seen in intact animals, while phases in the same segment remained constant. Neither octopamine nor pilocarpine initiated changes in coordination between segments in neck lesioned individuals. Animals with lesions of the circumoesophageal connectives had postures similar to intact individuals but walked in a tripod gait for extended periods of time. Changes in activity of slow tibial extensor and coxal depressor motor neurons and concomitant changes in leg joint angles were present after the lesions. This suggests that thoracic circuits are sufficient to produce leg movements but coordinated walking with normal motor patterns requires descending input from head ganglia.

Synergistic action of octopamine receptor agonists on the activity of selected novel insecticides for control of dengue vector Aedes aegypti (Diptera: Culicidae) mosquito.

PubMed

Ahmed, Mohamed Ahmed Ibrahim; Vogel, Christoph Franz Adam

2015-05-01

Studying insecticide resistance in mosquitoes has attracted the attention of many scientists to elucidate the pathways of resistance development and to design novel strategies in order to prevent or minimize the spread and evolution of resistance. Here, we tested the synergistic action of piperonyl butoxide (PBO) and two octopamine receptor (OR) agonists, amitraz (AMZ) and chlordimeform (CDM) on selected novel insecticides to increase their lethal action on the fourth instar larvae of Aedes aegypti L. However, chlorfenapyr was the most toxic insecticide (LC50 = 193, 102, and 48 ng/ml, after 24, 48, and 72 h exposure, respectively) tested. Further, PBO synergized all insecticides and the most toxic combinatorial insecticide was nitenpyram even after 48 and 72 h exposure. In addition, OR agonists significantly synergized most of the selected insecticides especially after 48 and 72 h exposure. The results imply that the synergistic effects of amitraz are a promising approach in increasing the potency of certain insecticides in controlling the dengue vector Ae. aegypti mosquito. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of novel inhibitors of calling and in vitro [14C]acetate incorporation by pheromone glands of Plodia interpunctella.

PubMed

Hirashima, A; Eiraku, T; Watanabe, Y; Kuwano, E; Taniguchi, E; Eto, M

2001-08-01

Some octopamine agonists were found to suppress in vitro biosynthesis of the calling pheromone of the Indian meal moth, Plodia interpunctella. Isolated pheromone-gland preparations incorporated sodium [14C]acetate at a linear rate for 3 h when incubated with the pheromone biosynthesis activating neuropeptide (PBAN). This incorporation was dependent on the dose of PBAN (up to 0.5 microM). Thin-layer chromatography of a pheromone-gland extract revealed quantitative incorporation of radioactivity into a product exhibiting the same mobility as (Z,E)-9,12-tetradecadienyl acetate, the main component of the calling pheromone of P interpunctella. Twenty-seven octopamine agonists were initially screened using a calling behaviour bioassay of female P interpunctella. Four derivatives with activity in the nanomolar range were identified which were, in order of decreasing pheromonostatic activity: 2-(2,6-diethylphenylimino)thiazolidine > 2-(2,6-diethylphenylimino)oxazolidine > 2-(2,6-dimethylphenylimino)thiazolidine > 2-(2-ethylphenylimino)oxazolidine. These compounds also showed in vitro inhibitory activity in intracellular de novo pheromone biosynthesis. The results of the present study indicate that these derivatives could provide useful information in the characterization and differentiation of octopaminergic receptor types and subtypes.

Molecular cloning and pharmacological characterisation of a tyramine receptor from the rice stem borer, Chilo suppressalis (Walker).

PubMed

Wu, Shun-Fan; Huang, Jia; Ye, Gong-Yin

2013-01-01

Tyramine (TA) and octopamine (OA) are considered to be the invertebrate counterparts of the vertebrate adrenergic transmitters. Because these two phenolamines are the only biogenic amines whose physiological significance is presumably restricted to invertebrates, the attention of pharmacologists has been focused on the corresponding receptors, which are believed to represent promising targets for novel insecticides. For example, the formamidine pesticides, such as chlordimeform and amitraz, have been shown to activate OA receptors. A full-length cDNA (designated CsTyR1) from the rice stem borer, Chilo suppressalis (Walker), has been obtained through homology cloning in combination with rapid amplification of cDNA ends/polymerase chain reaction (RACE-PCR). The mRNA of CsTyR1 is present in various tissues, including hemocytes, fat body, midgut, Malpighian tubules, nerve cord and epidermis, and it is found predominantly in the larval nerve cord with 16-80-fold enrichment compared with other tissues. The authors generated a HEK 293 cell line stably expressing CsTyR1 in order to examine functional and pharmacological properties of this receptor. Both TA and OA at 0.01-100 µM can reduce forskolin-stimulated intracellular cAMP levels in a dose-dependent manner (TA, EC(50) = 369 nM; OA, EC(50) = 978 nM). In agonist assays, activation of CsTyR1 by clonidine and amitraz but not by naphazoline and chlordimeform can also significantly inhibit forskolin-stimulated cAMP production. The inhibitory effect of TA at 10 µM is eliminated by coincubation with yohimbine, phentolamine or chlorpromazine (each 10 µM). This study represents a comprehensive molecular and pharmacological characterisation of a tyramine receptor in the rice stem borer. Copyright © 2012 Society of Chemical Industry.

Independent origins of neurons and synapses: insights from ctenophores

PubMed Central

Moroz, Leonid L.; Kohn, Andrea B.

2016-01-01

There is more than one way to develop neuronal complexity, and animals frequently use different molecular toolkits to achieve similar functional outcomes. Genomics and metabolomics data from basal metazoans suggest that neural signalling evolved independently in ctenophores and cnidarians/bilaterians. This polygenesis hypothesis explains the lack of pan-neuronal and pan-synaptic genes across metazoans, including remarkable examples of lineage-specific evolution of neurogenic and signalling molecules as well as synaptic components. Sponges and placozoans are two lineages without neural and muscular systems. The possibility of secondary loss of neurons and synapses in the Porifera/Placozoa clades is a highly unlikely and less parsimonious scenario. We conclude that acetylcholine, serotonin, histamine, dopamine, octopamine and gamma-aminobutyric acid (GABA) were recruited as transmitters in the neural systems in cnidarian and bilaterian lineages. By contrast, ctenophores independently evolved numerous secretory peptides, indicating extensive adaptations within the clade and suggesting that early neural systems might be peptidergic. Comparative analysis of glutamate signalling also shows numerous lineage-specific innovations, implying the extensive use of this ubiquitous metabolite and intercellular messenger over the course of convergent and parallel evolution of mechanisms of intercellular communication. Therefore: (i) we view a neuron as a functional character but not a genetic character, and (ii) any given neural system cannot be considered as a single character because it is composed of different cell lineages with distinct genealogies, origins and evolutionary histories. Thus, when reconstructing the evolution of nervous systems, we ought to start with the identification of particular cell lineages by establishing distant neural homologies or examples of convergent evolution. In a corollary of the hypothesis of the independent origins of neurons, our analyses suggest that both electrical and chemical synapses evolved more than once. PMID:26598724

Neuromechanism Study of Insect–Machine Interface: Flight Control by Neural Electrical Stimulation

PubMed Central

Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A.; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

2014-01-01

The insect–machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee–machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control. PMID:25409523

Neuromechanism study of insect-machine interface: flight control by neural electrical stimulation.

PubMed

Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

2014-01-01

The insect-machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee-machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control.

Co-segregation of Norrie disease and idiopathic pulmonary hypertension in a family with a microdeletion of the NDP region at Xp11.3-p11.4.

PubMed

Staropoli, John F; Xin, Winnie; Sims, Katherine B

2010-11-01

Norrie disease is a rare X-linked congenital retinal vasculopathy that may be accompanied by sensorineural deafness, mental retardation, and other neurological deficits. Here we present a family in which Norrie disease co-segregated with either early-onset idiopathic pulmonary hypertension or sudden death preceded by a period of progressive dyspnea. Neither Norrie disease, nor its atypical variants described to date, have been associated with this extended clinical phenotype. Molecular analysis of the Norrie disease gene (NDP) and adjacent loci was performed by multiplex ligation-dependent probe amplification and comparative genomic hybridisation. Affected males in this family showed an inherited hemizygous deletion restricted to NDP and two immediately telomeric genes, monoamine oxidase-B (MAO-B) and monoamine oxidase-A (MAO-A), which encode closely related enzymes that metabolize biogenic amines including serotonin, dopamine, and norepinephrine. Sequencing of the deletion junction showed an unusual pattern in which a region of microhomology flanked intervening genomic sequence. Because abnormalities of biogenic amines, particularly serotonin, have been implicated in the pathophysiology of pulmonary hypertension, we propose that presumed MAO deficiency in these patients may represent a novel risk factor for pulmonary hypertension, particularly forms with very early onset. Fine-mapping of other microdeletions at this locus may provide insights into additional mechanisms for nonrecurrent genomic rearrangements at this and other chromosomal loci.

Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo

PubMed Central

Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

2016-01-01

The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [18F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment. PMID:26924680

Neuroprotective effect of curcumin in arsenic-induced neurotoxicity in rats.

PubMed

Yadav, Rajesh S; Shukla, Rajendra K; Sankhwar, Madhu Lata; Patel, Devendra K; Ansari, Reyaz W; Pant, Aditya B; Islam, Fakhrul; Khanna, Vinay K

2010-09-01

Our recent studies have shown that arsenic-induced neurobehavioral toxicity is protected by curcumin by modulating oxidative stress and dopaminergic functions in rats. In addition, the neuroprotective effect of curcumin has been investigated on arsenic-induced alterations in biogenic amines, their metabolites and nitric oxide (NO), which play an important role in neurotransmission process. Decrease in the levels of dopamine (DA, 28%), norepinephrine (NE, 54%), epinephrine (EPN, 46%), serotonin (5-HT, 44%), 3,4-dihydroxyphenylacetic acid (DOPAC, 20%) and homovanillic acid (HVA, 31%) in corpus striatum; DA (51%), NE (22%), EPN (47%), 5-HT (25%), DOPAC (34%) and HVA (41%) in frontal cortex and DA (35%), NE (35%), EPN (29%), 5-HT (54%), DOPAC (37%) and HVA (46%) in hippocampus, observed in arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) treated rats exhibited a trend of recovery in rats simultaneously treated with arsenic and curcumin (100 mg/kg body weight, p.o., 28 days). Increased levels of NO in corpus striatum (2.4-fold), frontal cortex (6.1-fold) and hippocampus (6.2-fold) in arsenic-treated rats were found decreased in rats simultaneously treated with arsenic and curcumin. It is evident that curcumin modulates levels of brain biogenic amines and NO in arsenic-exposed rats and these results further strengthen its neuroprotective efficacy. Copyright © 2010 Elsevier Inc. All rights reserved.

Urinary sampling for 5HIAA and metanephrines determination: revisiting the recommendations

PubMed Central

Chardon, Laurence; El Hajji Ridah, Ines; Brossaud, Julie

2017-01-01

Context Biogenic amines such as 5-hydroxy-indole acetic acid (5HIAA) the main metabolite of serotonin or metanephrines (catecholamines metabolites) are used as biomarkers of neuroendocrine tumours. Objective To re-evaluate the recommendations for urinary sampling (preservatives, diet, drugs, etc.) as many of the reported analytical interferences supporting these recommendations are related to obsolete assays. Methods Bibliographic analysis of old and modern assays concerning preservation, extraction, assay and interferences. Results 5HIAA may degrade as soon as urine is excreted. Thus, acids as preservatives (hydrochloric or acetic acid) have to be immediately added. Care should be taken not to decrease the pH under 2. Urine preservative for metanephrine assays is not mandatory. Diets including serotonin-, tryptophan- and dopamine-rich foods have to be avoided depending on the biomarkers investigated (bananas, plantain, nuts, etc.). Tryptophan-rich over-the-counter formulas have to be prohibited when 5HIAA has to be assayed. Acetaminophen may interfere with electrochemical detection depending on high-pressure liquid chromatography (HPLC) parameters. No interference is known with mass spectrometric assays but with the one described for metanephrines determination. Some drugs interfere however with serotonin and catecholamines secretion and/or metabolism (monoamine oxidase inhibitors, serotonin or dopamine recapture inhibitors, etc.). Conclusion Revisited recommendations are provided for the diet, the drugs and the preservatives before HPLC coupled with electrochemical and mass spectrometry assays. PMID:28566493

Urinary sampling for 5HIAA and metanephrines determination: revisiting the recommendations.

PubMed

Corcuff, Jean-Benoît; Chardon, Laurence; El Hajji Ridah, Ines; Brossaud, Julie

2017-08-01

Biogenic amines such as 5-hydroxy-indole acetic acid (5HIAA) the main metabolite of serotonin or metanephrines (catecholamines metabolites) are used as biomarkers of neuroendocrine tumours. To re-evaluate the recommendations for urinary sampling (preservatives, diet, drugs, etc.) as many of the reported analytical interferences supporting these recommendations are related to obsolete assays. Bibliographic analysis of old and modern assays concerning preservation, extraction, assay and interferences. 5HIAA may degrade as soon as urine is excreted. Thus, acids as preservatives (hydrochloric or acetic acid) have to be immediately added. Care should be taken not to decrease the pH under 2. Urine preservative for metanephrine assays is not mandatory. Diets including serotonin-, tryptophan- and dopamine-rich foods have to be avoided depending on the biomarkers investigated (bananas, plantain, nuts, etc.). Tryptophan-rich over-the-counter formulas have to be prohibited when 5HIAA has to be assayed. Acetaminophen may interfere with electrochemical detection depending on high-pressure liquid chromatography (HPLC) parameters. No interference is known with mass spectrometric assays but with the one described for metanephrines determination. Some drugs interfere however with serotonin and catecholamines secretion and/or metabolism (monoamine oxidase inhibitors, serotonin or dopamine recapture inhibitors, etc.). Revisited recommendations are provided for the diet, the drugs and the preservatives before HPLC coupled with electrochemical and mass spectrometry assays. © 2017 The authors.

Current pharmacotherapy of attention deficit hyperactivity disorder.

PubMed

Reddy, D S

2013-10-01

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder in children and adults characterized by a persistent pattern of impulsiveness, inattention and hyperactivity. It affects about 3-10% of children and 2-5% of adolescents and adults and occurs about four times more commonly in boys than girls. The cause of ADHD is unknown, but it has strong genetic and environment components. The first-line treatment options for ADHD include behavioral therapy, pharmacotherapy with stimulants or both. Methylphenidate and amphetamine salts are the stimulant drugs of choice for ADHD treatment. Amphetamines act by increasing presynaptic release of dopamine and other biogenic amines in the brain. Methylphenidate inhibits the reuptake of dopamine and norepinephrine and therefore its pharmacology is identical to that of amphetamines. Lisdex-amfetamine is a prodrug of dextroamphetamine with low feasibility for abuse. Atomoxetine, a selective norepinephrine reuptake inhibitor, is an alternative, non-stimulant drug for ADHD but it is less efficacious than stimulants. Stimulants are generally safe but are associated with adverse effects including headache, insomnia, anorexia and weight loss. There is increased awareness about serious cardiovascular and psychiatric adverse events with ADHD drugs including concern for growth suppression in children. Stimulants have a high potential for abuse and dependence, and should be handled safely to prevent misuse and abuse. Copyright 2013 Prous Science, S.A.U. or its licensors. All rights reserved.

Dopamine D3/D2 Receptor Antagonist PF-4363467 Attenuates Opioid Drug-Seeking Behavior without Concomitant D2 Side Effects.

PubMed

Wager, Travis T; Chappie, Thomas; Horton, David; Chandrasekaran, Ramalakshmi Y; Samas, Brian; Dunn-Sims, Elizabeth R; Hsu, Cathleen; Nawreen, Nawshaba; Vanase-Frawley, Michelle A; O'Connor, Rebecca E; Schmidt, Christopher J; Dlugolenski, Keith; Stratman, Nancy C; Majchrzak, Mark J; Kormos, Bethany L; Nguyen, David P; Sawant-Basak, Aarti; Mead, Andy N

2017-01-18

Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file, we identified a structurally unique D3 receptor (D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PF-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (≥4/6). In addition to good physicochemical properties, 3 exhibited low nanomolar affinity for the D3R (D3 K i = 3.1 nM), good subtype selectivity over D2R (D2 K i = 692 nM), and high selectivity for D3R versus other biogenic amine receptors. In vivo, 3 dose-dependently attenuated opioid self-administration and opioid drug-seeking behavior in a rat operant reinstatement model using animals trained to self-administer fentanyl. Further, traditional extrapyramidal symptoms (EPS), adverse side effects arising from D2R antagonism, were not observed despite high D2 receptor occupancy (RO) in rodents, suggesting that compound 3 has a unique in vivo profile. Collectively, our data support further investigation of dual D3R and D2R antagonists for the treatment of drug addiction.

Quantitative SERS Detection of Dopamine in Cerebrospinal Fluid by Dual-Recognition-Induced Hot Spot Generation.

PubMed

Zhang, Kun; Liu, Yu; Wang, Yuning; Zhang, Ren; Liu, Jiangang; Wei, Jia; Qian, Hufei; Qian, Kun; Chen, Ruoping; Liu, Baohong

2018-05-09

Reliable profiling of the extracellular dopamine (DA) concentration in the central nervous system is essential for a deep understanding of its biological and pathological functions. However, quantitative determination of this neurotransmitter remains a challenge because of the extremely low concentration of DA in the cerebrospinal fluid (CSF) of patients. Herein, on the basis of the specific recognition of boronate toward diol and N-hydroxysuccinimide ester toward the amine group, a simple and highly sensitive strategy was presented for DA detection by using surface-enhanced Raman scattering (SERS) spectroscopy as a signal readout. This was realized by first immobilizing 3,3'-dithiodipropionic acid di( N-hydroxysuccinimide ester) on gold thin film surfaces to capture DA, followed by introducing 3-mercaptophenylboronic acid (3-MPBA)-functionalized silver nanoparticles to generate numerous plasmonic "hot spots" with the nanoparticle-on-mirror geometry. Such a dual-recognition mechanism not only avoids complicated bioelement-based manipulations but also efficiently decreases the background signal. With the direct use of the recognition probe 3-MPBA as a Raman reporter, the "signal-on" SERS method was employed to quantify the concentration of DA from 1 pM to 1 μM with a detection limit of 0.3 pM. Moreover, our dual-recognition-directed SERS assay exhibited a high resistance to cerebral interference and was successfully applied to monitoring of DA in CSF samples of patients.

Inhibitors of calling behavior of Plodia interpunctella

PubMed Central

Hirashima, Akinori; Shigeta, Yoko; Eiraku, Tomohiko; Kuwano, Eiichi

2003-01-01

Some octopamine agonists were found to suppress the calling behavior of the stored product Indian meal moth, Plodia interpunctella. Compounds were screened using a calling behavior bioassay using female P. interpunctella. Four active derivatives, with inhibitory activity at the nanomolar range, were identified in order of decreasing activity: 2-(1-phenylethylamino)-2-oxazoline > 2-(2-ethyl,6-methylanilino)oxazolidine > 2-(2-methyl benzylamino)-2-thiazoline > 2-(2,6-diethylanilino)thiazolidine. Three-dimensional pharmacophore hypotheses were built from a set of 15 compounds. Among the ten common-featured models generated by the program Catalyst/HipHop, a hypothesis including a hydrogen-bond acceptor lipid, a hydrophobic aromatic and two hydrophobic aliphatic features was considered to be essential for inhibitory activity in the calling behavior. Active compounds mapped well onto all the hydrogen-bond acceptor lipid, hydrophobic aromatic and hydrophobic aliphatic features of the hypothesis. On the other hand, less active compounds were shown not to achieve the energetically favorable conformation that is found in the active molecules in order to fit the 3D common-feature pharmacophore models. The present studies demonstrate that inhibition of calling behavior is via an octopamine receptor. Abbreviation: AII 2-(arylimino)imidazolidine AIO 2-(arylimino)oxazolidine AIT 2-(arylimino)thiazolidine CBO 2-(4-chlorobenzylamino)-2-(4-phenyl)oxazoline CDM chlordimeform Confs number of conformers DIP 2-(2,6-diethylphenylimino)piperidine Features/Confs total number of features divided by the number of conformers (summed over the entire family of conformers) HBA hydrogen-bond acceptor HBAl hydrogen-bond acceptor lipid HBD hydrogen-bond donor Hp hydrophobic HpAl hydrophobic aliphatic HpAr hydrophobic aromatic mp melting point MTO 2-(3-methyl benzylthio)-2-oxazoline NI negative ionizable NIO 2-(1-naphthylimino)oxazolidine OA octopamine ODA 2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazine ODO 2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazine-5(6H)-one PBAN pheromone biosynthesis activating neuropeptide PEO 2-(1-phenylethylamino)-2-oxazoline PI positive ionizable PIT 1-(2,6-dimethylphenyl)imidazolidine-2-thione RA ring aromatic SBO 2-(substituted benzylamino)-2-oxazoline SBT 2-(substituted benzylamino)-2-thiazoline STO 2-(substituted benzylthio)-2-oxazoline ZETA (Z,E)-9,12-tetradecadienyl acetate PMID:15841221

Monoaminylation of Fibrinogen and Glia-Derived Proteins: Indication for Similar Mechanisms in Posttranslational Protein Modification in Blood and Brain.

PubMed

Hummerich, René; Costina, Victor; Findeisen, Peter; Schloss, Patrick

2015-07-15

Distinct proteins have been demonstrated to be posttranslationally modified by covalent transamidation of serotonin (5-hydropxytryptamin) to glutamine residues of the target proteins. This process is mediated by transglutaminase (TGase) and has been termed "serotonylation." It has also been shown that other biogenic amines, including the neurotransmitters dopamine and norepinephrine, can substitute for serotonin, implying a more general mechanism of "monoaminylation" for this kind of protein modification. Here we transamidated the autofluorescent monoamine monodansylcadaverine (MDC) to purified plasma fibrinogen and to proteins from a primary glia cell culture. Electrophoretic separation of MDC-conjugated proteins followed by mass spectrometry identified three fibrinogen subunits (Aα, Bβ, γ), a homomeric Aα2 dimer, and adducts of >250 kDa molecular weight, as well as several glial proteins. TGase-mediated MDC incorporation was strongly reduced by serotonin, underlining the general mechanism of monoaminylation.

The sympathetic nervous system and the physiologic consequences of spaceflight: a hypothesis

NASA Technical Reports Server (NTRS)

Robertson, D.; Convertino, V. A.; Vernikos, J.

1994-01-01

Many of the physiologic consequences of weightlessness and the cardiovascular abnormalities on return from space could be due, at least in part, to alterations in the regulation of the autonomic nervous system. In this article, the authors review the rationale and evidence for an autonomic mediation of diverse changes that occur with spaceflight, including the anemia and hypovolemia of weightlessness and the tachycardia and orthostatic intolerance on return from space. This hypothesis is supported by studies of two groups of persons known to have low catecholamine levels: persons subjected to prolonged bedrest and persons with syndromes characterized by low circulating catecholamines (Bradbury-Eggleston syndrome and dopamine beta-hydroxylase deficiency). Both groups exhibit the symptoms mentioned. The increasing evidence that autonomic mechanisms underlie many of the physiologic consequences of weightlessness suggests that new pharmacologic approaches (such as administration of beta-blockers and/or sympathomimetic amines) based on these findings may attenuate these unwanted effects.

Neuropharmacological and neurochemical properties of N-(2-cyanoethyl)-2-phenylethylamine, a prodrug of 2-phenylethylamine.

PubMed Central

Baker, G. B.; Coutts, R. T.; Rao, T. S.

1987-01-01

1 N-(2-cyanoethyl)-2-phenylethylamine (CEPEA) was examined as a possible prodrug of 2-phenylethylamine (PEA). 2 Pharmacokinetics of PEA and CEPEA were investigated in rat brain, blood and liver by gas chromatography with electron-capture detection (GC-ECD). Interactions of PEA and CEPEA with putative neurotransmitter amines were investigated by use of high performance liquid chromatography with electrochemical detection (h.p.l.c.-e.c.). 3 Administration of PEA caused transient increases in PEA concentrations which decreased rapidly in brain and blood and at a slower rate in liver. Administration of CEPEA caused sustained elevations of PEA concentrations and elimination of PEA was markedly decreased in these tissues relative to the situation after administration of PEA itself. 4 Administration of CEPEA caused more prolonged decreases in brain noradrenaline, dopamine and 5-hydroxytryptamine concentrations than those observed after PEA administration, although values increased to control levels eventually. PMID:2890391

Biophotons, microtubules and CNS, is our brain a "holographic computer"?

PubMed

Grass, F; Klima, H; Kasper, S

2004-01-01

Several experiments show that there is a cell to cell communication by light in different cell types. This article describes theoretical mechanisms and subcellular structures that could be involved in this phenomenon. Special consideration is given to the nervous system, since it would have excellent conditions for such mechanisms. Neurons are large colourless cells with wide arborisations, have an active metabolism generating photons, contain little pigment, and have a prominent cytoskeleton consisting of hollow microtubules. As brain and spinal cord are protected from environmental light by bone and connective tissue, the signal to noise ratio should be high for photons as signal. Fluorescent and absorbing substances should interfere with such a communication system. Of all biogenic amines nature has chosen the ones with the strongest fluorescence as neurotransmitters for mood reactions: serotonin, dopamine and norepinephrine. If these mechanisms are of relevance our brain would have to be looked upon as a "holographic computer".

Effect of temperature stress on circulating biogenic amines in bovine.

PubMed

Davis, T P; Johnson, H D; Gehrke, C W

1984-01-01

A sensitive, simple and selective chromatographic method using high performance liquid chromatography was developed to measure circulating levels of histamine (HI), norepinephrine (NE), dopamine (DA) and serotonin (5-HT) as indicators of response to thermal stress in two breeds of cattle. Duplicate exposures for 8 hr to 13 degrees C resulted in significantly elevated plasma NE and DA in longhorns but not in Herefords and suggest a relatively greater sensitivity to the cold (13 degrees C) in the longhorn. Environmental temperatures of 32 and 42 degrees C significantly increased rectal temperatures of both breeds with much higher rectal temperatures in Herefords. The 32 and 42 degrees C effects on circulating NE and DA of Herefords were highly significant but not in the longhorn. However, heat stress significantly elevated HI and 5-HT in the longhorn which may account for their relatively greater heat tolerance based on their lower rectal temperatures.

Eis, a novel family of arylalkylamine N-acetyltransferase (EC 2.3.1.87).

PubMed

Pan, Qian; Zhao, Feng-Lan; Ye, Bang-Ce

2018-02-05

Enhanced intracellular survival (Eis) proteins were found to enhance the intracellular survival of mycobacteria in macrophages by acetylating aminoglycoside antibiotics to confer resistance to these antibiotics and by acetylating DUSP16/MPK-7 to suppress host innate immune defenses. Eis homologs composing of two GCN5 N-acetyltransferase regions and a sterol carrier protein fold are found widely in gram-positive bacteria. In this study, we found that Eis proteins have an unprecedented ability to acetylate many arylalkylamines, are a novel type of arylalkylamine N-acetyltransferase AANAT (EC 2.3.1.87). Sequence alignment and phyletic distribution analysis confirmed Eis belongs to a new aaNAT-like cluster. Among the cluster, we studied three typical Eis proteins: Eis_Mtb from Mycobacterium tuberculosis, Eis_Msm from Mycobacterium smegmatis, and Eis_Sen from Saccharopolyspora erythraea. Eis_Mtb prefers to acetylate histamine and octopamine, while Eis_Msm uses tyramine and octopamine as substrates. Unlike them, Eis_Sen exihibits good catalytic efficiencies for most tested arylalkylamines. Considering arylalkylamines such as histamine plays a fundamental role in immune reactions, future work linking of AANAT activity of Eis proteins to their physiological function will broaden our understanding of gram-positive pathogen-host interactions. These findings shed insights into the molecular mechanism of Eis, and reveal potential clinical implications for many gram-positive pathogens.

Boron-based nanostructures: Synthesis, functionalization, and characterization

NASA Astrophysics Data System (ADS)

Bedasso, Eyrusalam Kifyalew

Boron-based nanostructures have not been explored in detail; however, these structures have the potential to revolutionize many fields including electronics and biomedicine. The research discussed in this dissertation focuses on synthesis, functionalization, and characterization of boron-based zero-dimensional nanostructures (core/shell and nanoparticles) and one-dimensional nanostructures (nanorods). The first project investigates the synthesis and functionalization of boron-based core/shell nanoparticles. Two boron-containing core/shell nanoparticles, namely boron/iron oxide and boron/silica, were synthesized. Initially, boron nanoparticles with a diameter between 10-100 nm were prepared by decomposition of nido-decaborane (B10H14) followed by formation of a core/shell structure. The core/shell structures were prepared using the appropriate precursor, iron source and silica source, for the shell in the presence of boron nanoparticles. The formation of core/shell nanostructures was confirmed using high resolution TEM. Then, the core/shell nanoparticles underwent a surface modification. Boron/iron oxide core/shell nanoparticles were functionalized with oleic acid, citric acid, amine-terminated polyethylene glycol, folic acid, and dopamine, and boron/silica core/shell nanoparticles were modified with 3-(amino propyl) triethoxy silane, 3-(2-aminoethyleamino)propyltrimethoxysilane), citric acid, folic acid, amine-terminated polyethylene glycol, and O-(2-Carboxyethyl)polyethylene glycol. A UV-Vis and ATR-FTIR analysis established the success of surface modification. The cytotoxicity of water-soluble core/shell nanoparticles was studied in triple negative breast cancer cell line MDA-MB-231 and the result showed the compounds are not toxic. The second project highlights optimization of reaction conditions for the synthesis of boron nanorods. This synthesis, done via reduction of boron oxide with molten lithium, was studied to produce boron nanorods without any contamination and with a uniform size distribution. Various reaction parameters such as temperature, reaction time, and sonication were altered to find the optimal reaction conditions. Once these conditions were determined, boron nanorods were produced then functionalized with amine-terminated polyethylene glycol.

Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure.

PubMed

Dalterio, S; Steger, R; Mayfield, D; Bartke, A

1984-01-01

Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20 micrograms T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.

Novel and sensitive reversed-phase high-pressure liquid chromatography method with electrochemical detection for the simultaneous and fast determination of eight biogenic amines and metabolites in human brain tissue.

PubMed

Van Dam, Debby; Vermeiren, Yannick; Aerts, Tony; De Deyn, Peter Paul

2014-08-01

A fast and simple RP-HPLC method with electrochemical detection (ECD) and ion pair chromatography was developed, optimized and validated in order to simultaneously determine eight different biogenic amines and metabolites in post-mortem human brain tissue in a single-run analytical approach. The compounds of interest are the indolamine serotonin (5-hydroxytryptamine, 5-HT), the catecholamines dopamine (DA) and (nor)epinephrine ((N)E), as well as their respective metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), 5-hydroxy-3-indoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG). A two-level fractional factorial experimental design was applied to study the effect of five experimental factors (i.e. the ion-pair counter concentration, the level of organic modifier, the pH of the mobile phase, the temperature of the column, and the voltage setting of the detector) on the chromatographic behaviour. The cross effect between the five quantitative factors and the capacity and separation factors of the analytes were then analysed using a Standard Least Squares model. The optimized method was fully validated according to the requirements of SFSTP (Société Française des Sciences et Techniques Pharmaceutiques). Our human brain tissue sample preparation procedure is straightforward and relatively short, which allows samples to be loaded onto the HPLC system within approximately 4h. Additionally, a high sample throughput was achieved after optimization due to a total runtime of maximally 40min per sample. The conditions and settings of the HPLC system were found to be accurate with high intra and inter-assay repeatability, recovery and accuracy rates. The robust analytical method results in very low detection limits and good separation for all of the eight biogenic amines and metabolites in this complex mixture of biological analytes. Copyright © 2014 Elsevier B.V. All rights reserved.

Dopamine acting at D1-like, D2-like and α1-adrenergic receptors differentially modulates theta and gamma oscillatory activity in primary motor cortex.

PubMed

Özkan, Mazhar; Johnson, Nicholas W; Sehirli, Umit S; Woodhall, Gavin L; Stanford, Ian M

2017-01-01

The loss of dopamine (DA) in Parkinson's is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology. Recording local field potentials in deep layer V of rat M1, co-application of carbachol (CCh, 5 μM) and kainic acid (KA, 150 nM) elicited simultaneous oscillations at a frequency of 6.49 ± 0.18 Hz (theta, n = 84) and 34.97 ± 0.39 Hz (gamma, n = 84). Bath application of DA resulted in a decrease in gamma power with no change in theta power. However, application of either the D1-like receptor agonist SKF38393 or the D2-like agonist quinpirole increased the power of both theta and gamma suggesting that the DA-mediated inhibition of oscillatory power is by action at other sites other than classical DA receptors. Application of amphetamine, which promotes endogenous amine neurotransmitter release, or the adrenergic α1-selective agonist phenylephrine mimicked the action of DA and reduced gamma power, a result unaffected by prior co-application of D1 and D2 receptor antagonists SCH23390 and sulpiride. Finally, application of the α1-adrenergic receptor antagonist prazosin blocked the action of DA on gamma power suggestive of interaction between α1 and DA receptors. These results show that DA mediates complex actions acting at dopamine D1-like and D2-like receptors, α1 adrenergic receptors and possibly DA/α1 heteromultimeric receptors to differentially modulate theta and gamma activity in M1.

Mussel-inspired functionalization of graphene for synthesizing Ag-polydopamine-graphene nanosheets as antibacterial materials

NASA Astrophysics Data System (ADS)

Zhang, Zhe; Zhang, Jing; Zhang, Bailin; Tang, Jilin

2012-12-01

Mussels have been shown to attach to virtually all types of inorganic and organic surfaces via their adhesive proteins. The adhesive proteins secreted by mussels contain high concentrations of catechol and amine functional groups, which have similar functional groups with polydopamine (PDA). Inspired by mussels, a mild and environmentally friendly method was used to synthesize Ag nanoparticles (Ag NPs) on functionalized PDA-graphene nanosheets (PDA-GNS) with uniform and high dispersion. First, a uniform layer of PDA was coated on graphene oxide (GO) by polymerizing dopamine (DA) at room temperature. During the process GO was reduced by the DA. The PDA layer on the surface of GNS can be used as a nanoscale guide to form uniform Ag NPs on the surface of PDA-GNS. The obtained Ag-PDA-GNS hybrid materials are characterized by atomic force microscopy, transmission electron microscopy, UV-vis spectroscopy, Raman spectroscopy, X-ray photo-electron spectroscopy, X-ray diffraction, and thermal gravimetric analysis. The resultant Ag-PDA-GNS hybrid materials exhibited strong antibacterial properties to both Gram-negative and Gram-positive bacteria due to the synergistic effect of GNS and Ag NPs.Mussels have been shown to attach to virtually all types of inorganic and organic surfaces via their adhesive proteins. The adhesive proteins secreted by mussels contain high concentrations of catechol and amine functional groups, which have similar functional groups with polydopamine (PDA). Inspired by mussels, a mild and environmentally friendly method was used to synthesize Ag nanoparticles (Ag NPs) on functionalized PDA-graphene nanosheets (PDA-GNS) with uniform and high dispersion. First, a uniform layer of PDA was coated on graphene oxide (GO) by polymerizing dopamine (DA) at room temperature. During the process GO was reduced by the DA. The PDA layer on the surface of GNS can be used as a nanoscale guide to form uniform Ag NPs on the surface of PDA-GNS. The obtained Ag-PDA-GNS hybrid materials are characterized by atomic force microscopy, transmission electron microscopy, UV-vis spectroscopy, Raman spectroscopy, X-ray photo-electron spectroscopy, X-ray diffraction, and thermal gravimetric analysis. The resultant Ag-PDA-GNS hybrid materials exhibited strong antibacterial properties to both Gram-negative and Gram-positive bacteria due to the synergistic effect of GNS and Ag NPs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr32092d

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

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.

Bacteria isolated from Korean black raspberry vinegar with low biogenic amine production in wine.

PubMed

Song, Nho-Eul; Cho, Hyoun-Suk; Baik, Sang-Ho

2016-01-01

A high concentration of histamine, one of the biogenic amines (BAs) usually found in fermented foods, can cause undesirable physiological side effects in sensitive humans. The objective of this study is to isolate indigenous Acetobacter strains from naturally fermented Bokbunja vinegar in Korea with reduced histamine production during starter fermentation. Further, we examined its physiological and biochemical properties, including BA synthesis. The obtained strain MBA-77, identified as Acetobacter aceti by 16S rDNA homology and biochemical analysis and named A. aceti MBA-77. A. aceti MBA-77 showed optimal acidity % production at pH 5; the optimal temperature was 25°C. When we prepared and examined the BAs synthesis spectrum during the fermentation process, Bokbunja wine fermented with Saccharomyces cerevisiae showed that the histamine concentration increased from 2.72 of Bokbunja extract to 5.29mg/L and cadaverine and dopamine was decreased to 2.6 and 10.12mg/L, respectively. Bokbunja vinegar prepared by A. aceti MBA-77 as the starter, the histamine concentration of the vinegar preparation step was decreased up to 3.66mg/L from 5.29mg/L in the wine preparation step. To our knowledge, this is the first report to demonstrate acetic acid bacteria isolated from Bokbunja seed vinegar with low spectrum BA and would be useful for wellbeing vinegar preparation. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Symmetrical dimer of the human dopamine transporter revealed by cross-linking Cys-306 at the extracellular end of the sixth transmembrane segment

PubMed Central

Hastrup, Hanne; Karlin, Arthur; Javitch, Jonathan A.

2001-01-01

There is evidence both for and against Na+- and Cl−-dependent neurotransmitter transporters forming oligomers. We found that cross-linking the human dopamine transporter (DAT), which is heterologously expressed in human embryonic kidney 293 cells, either with copper phenanthroline (CuP) or the bifunctional reagent bis-(2-methanethiosulfonatoethyl)amine hydrochloride (bis-EA) increased the apparent molecular mass determined with nonreducing SDS/PAGE from ≈85 to ≈195 kDa. After cross-linking, but not before, coexpressed, differentially epitope-tagged DAT molecules, solubilized in Triton X-100, were coimmunoprecipitated. Thus, the 195-kDa complex was a homodimer. Cross-linking of DAT did not affect tyramine uptake. Replacement of Cys-306 with Ala prevented cross-linking. Replacement of all of the non-disulfide-bonded cysteines in the extracellular and membrane domains, except for Cys-306, did not prevent cross-linking. We conclude that the cross-link is between Cys-306 at the extracellular end of TM6 in each of the two DATs. The motif GVXXGVXXA occurs at the intracellular end of TM6 in DAT and is found in a number of other neurotransmitter transporters. This sequence was originally found at the dimerization interface in glycophorin A, and it promotes dimerization in model systems. Mutation of either glycine disrupted DAT expression and function. The intracellular end of TM6, like the extracellular end, is likely to be part of the dimerization interface. PMID:11526230

Symmetrical dimer of the human dopamine transporter revealed by cross-linking Cys-306 at the extracellular end of the sixth transmembrane segment.

PubMed

Hastrup, H; Karlin, A; Javitch, J A

2001-08-28

There is evidence both for and against Na(+)- and Cl(-)-dependent neurotransmitter transporters forming oligomers. We found that cross-linking the human dopamine transporter (DAT), which is heterologously expressed in human embryonic kidney 293 cells, either with copper phenanthroline (CuP) or the bifunctional reagent bis-(2-methanethiosulfonatoethyl)amine hydrochloride (bis-EA) increased the apparent molecular mass determined with nonreducing SDS/PAGE from approximately 85 to approximately 195 kDa. After cross-linking, but not before, coexpressed, differentially epitope-tagged DAT molecules, solubilized in Triton X-100, were coimmunoprecipitated. Thus, the 195-kDa complex was a homodimer. Cross-linking of DAT did not affect tyramine uptake. Replacement of Cys-306 with Ala prevented cross-linking. Replacement of all of the non-disulfide-bonded cysteines in the extracellular and membrane domains, except for Cys-306, did not prevent cross-linking. We conclude that the cross-link is between Cys-306 at the extracellular end of TM6 in each of the two DATs. The motif GVXXGVXXA occurs at the intracellular end of TM6 in DAT and is found in a number of other neurotransmitter transporters. This sequence was originally found at the dimerization interface in glycophorin A, and it promotes dimerization in model systems. Mutation of either glycine disrupted DAT expression and function. The intracellular end of TM6, like the extracellular end, is likely to be part of the dimerization interface.

Dipentylammonium Binds to the Sigma-1 Receptor and Protects Against Glutamate Toxicity, Attenuates Dopamine Toxicity and Potentiates Neurite Outgrowth in Various Cultured Cell Lines.

PubMed

Brimson, James M; Safrany, Stephen T; Qassam, Heider; Tencomnao, Tewin

2018-03-27

Alzheimer's disease is a neurodegenerative disease that affects 44 million people worldwide, costing the world $605 billion to care for those affected not taking into account the physical and psychological costs for those who care for Alzheimer's patients. Dipentylammonium is a simple amine, which is structurally similar to a number of other identified sigma-1 receptor ligands with high affinities such as (2R-trans)-2butyl-5-heptylpyrrolidine, stearylamine and dodecylamine. This study investigates whether dipentylammonium is able to provide neuroprotective effects similar to those of sigma-1 receptor agonists such as PRE-084. Here we identify dipentylammonium as a sigma-1 receptor ligand with nanomolar affinity. We have found that micromolar concentrations of dipentylammonium protect from glutamate toxicity and prevent NFκB activation in HT-22 cells. Micromolar concentrations of dipentylammonium also protect stably expressing amyloid precursor protein Swedish mutant (APP/Swe) Neuro2A cells from toxicity induced by 150 μM dopamine, suggesting that dipentylammonium may be useful for the treatment of Parkinsonian symptoms in Alzheimer's patients which are often associated with a more rapid deterioration of cognitive and physical ability. Finally, we found that low micromolar concentrations of dipentylammonium could out preform known sigma-1 receptor agonist PRE-084 in potentiating neurite outgrowth in Neuro2A cells, further suggesting that dipentylammonium has a potential use in the treatment of neurodegenerative diseases and could be acting through the sigma-1 receptor.

Investigations into the Settlement and Attachment of Biofouling Marine Invertebrates

DTIC Science & Technology

2015-12-17

attachment of biofouling marine invertebrates 5a. CONTRACT NUMBER N00014-12-1 -0432 5b. GRANT NUMBER n/a 5c. PROGRAM ELEMENT NUMBER n/a 6...larval settlement in a variety of marine invertebrate species, including B. neritina. Light also inhibits B. neritina larval settlement, yet the...underlying mechanisms by which light and adrenergic compounds exert their effects on larvae are largely unknown. Octopamine is considered the invertebrate

Octopamine: a new feeding modulator in Lymnaea

PubMed Central

Vehovszky, Á.

1998-01-01

The role of octopamine (OA) in the feeding system of the pond snail, Lymnaea stagnalis, was studied by applying behavioural tests on intact animals, and a combination of electrophysiological analysis and morphological labelling in the isolated central nervous system. OA antagonists phentolamine, demethylchlordimeform (DCDM) and 2-chloro-4-methyl-2-(phenylimino)-imidazolidine (NC-7) were injected into intact snails and the sucrose-induced feeding response of animals was monitored. Snails that received 25 to 50 mg kg-1 phentolamine did not start feeding in sucrose, and the same dose of NC-7 reduced the number of feeding animals by 80 to 90% 1 to 3 hours after injection. DCDM treatment reduced feeding by 20 to 60%. In addition, both phentolamine and NC-7 significantly decreased the feeding rate of those animals that still accepted food after 1 to 6 hours of injection. In the central nervous system a pair of buccal neurons was identified by electrophysiological and morphological criteria. After double labelling (intracellular staining with Lucifer yellow followed by OA-immunocytochemistry) these neurons were shown to be OA immunoreactive, and electrophysiological experiments confirmed that they are members of the buccal feeding system. Therefore the newly identified buccal neurons were called OC neurons (putative octopamine containing neurons or octopaminergic cells). Synchronous intracellular recordings demonstrated that the OC neurons share a common rhythm with feeding neurons either appearing spontaneously or evoked by intracellularly stimulated feeding interneurons. OC neurons also have synaptic connections with identified members of the feeding network: electrical coupling was demonstrated between OC neurons and members of the B4 cluster motoneurons, furthermore, chemically transmitted synaptic responses were recorded both on feeding motoneurons (B1, B2 cells) and the SO modulatory interneuron after the stimulation of OC neurons. However, elementary synaptic potentials could not be recorded on the follower cells of OC neurons. Prolonged (20 to 30 s) intracellular stimulation of OC cells activated the buccal feeding neurons leading to rhythmic activity pattern (fictive feeding) in a way similar to OA applied by perfusion onto isolated central nervous system (CNS) preparations. Our results suggest that OA acts as a modulatory substance in the feeding system of Lymnaea stagnalis and the newly identified pair of OC neurons belongs to the buccal feeding network.

pH-Responsive biodegradable polymeric micelles with anchors to interface magnetic nanoparticles for MR imaging in detection of cerebral ischemic area

NASA Astrophysics Data System (ADS)

Yang, Hong Yu; Jang, Moon-Sun; Gao, Guang Hui; Lee, Jung Hee; Lee, Doo Sung

2016-06-01

A novel type of pH-responsive biodegradable copolymer was developed based on methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-l-glutamate] (mPEG-b-P(DPA-DE)LG) and applied to act as an intelligent nanocarrier system for magnetic resonance imaging (MRI). The mPEG-b-P(DPA-DE)LG copolymer was synthesized by a typical ring opening polymerization of N-carboxyanhydrides (NCAs-ROP) using mPEG-NH2 as a macroinitiator, and two types of amine-terminated dopamine groups and pH-sensitive ligands were grafted onto a side chain by a sequential aminolysis reaction. This design greatly benefits from the addition of the dopamine groups to facilitate self-assembly, as these groups can act as high-affinity anchors for iron oxide nanoparticles, thereby increasing long-term stability at physiological pH. The mPEG moiety in the copolymers helped the nanoparticles to remain well-dispersed in an aqueous solution, and pH-responsive groups could control the release of hydrophobic Fe3O4 nanoparticles in an acidic environment. The particle size of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles was measured by dynamic light scattering (DLS) and cryo-TEM. The superparamagnetic properties of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles were confirmed by a superconducting quantum interference device (SQUID). T2-weighted magnetic resonance imaging (MRI) of Fe3O4-loaded mPEG-b-P(DPA-DE)LG phantoms exhibited enhanced negative contrast with an r2 relaxivity of approximately 106.7 mM-1 s-1. To assess the ability of the Fe3O4-loaded mPEG-P(DE-DPA)LG micelles to act as MRI probes, we utilized a cerebral ischemia disease rat model with acidic tissue. We found that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 h, and maximal signal loss was detected after 24 h post-injection. These results demonstrated that the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles can act as pH-triggered MRI probes for diagnostic imaging of acidic pathological tissues.A novel type of pH-responsive biodegradable copolymer was developed based on methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-l-glutamate] (mPEG-b-P(DPA-DE)LG) and applied to act as an intelligent nanocarrier system for magnetic resonance imaging (MRI). The mPEG-b-P(DPA-DE)LG copolymer was synthesized by a typical ring opening polymerization of N-carboxyanhydrides (NCAs-ROP) using mPEG-NH2 as a macroinitiator, and two types of amine-terminated dopamine groups and pH-sensitive ligands were grafted onto a side chain by a sequential aminolysis reaction. This design greatly benefits from the addition of the dopamine groups to facilitate self-assembly, as these groups can act as high-affinity anchors for iron oxide nanoparticles, thereby increasing long-term stability at physiological pH. The mPEG moiety in the copolymers helped the nanoparticles to remain well-dispersed in an aqueous solution, and pH-responsive groups could control the release of hydrophobic Fe3O4 nanoparticles in an acidic environment. The particle size of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles was measured by dynamic light scattering (DLS) and cryo-TEM. The superparamagnetic properties of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles were confirmed by a superconducting quantum interference device (SQUID). T2-weighted magnetic resonance imaging (MRI) of Fe3O4-loaded mPEG-b-P(DPA-DE)LG phantoms exhibited enhanced negative contrast with an r2 relaxivity of approximately 106.7 mM-1 s-1. To assess the ability of the Fe3O4-loaded mPEG-P(DE-DPA)LG micelles to act as MRI probes, we utilized a cerebral ischemia disease rat model with acidic tissue. We found that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 h, and maximal signal loss was detected after 24 h post-injection. These results demonstrated that the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles can act as pH-triggered MRI probes for diagnostic imaging of acidic pathological tissues. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06542a

Chemiluminescence Resonance Energy Transfer-based Detection for Microchip Electrophoresis

PubMed Central

Huang, Yong; Shi, Ming; Liu, Rongjun

2010-01-01

Since the channels in micro- and nanofluidic devices are extremely small, a sensitive detection is required following microchip electrophoresis (MCE). This work describes a highly sensitive and yet universal detection scheme based on chemiluminescence resonance energy transfer (CRET) for MCE. It was found that an efficient CRET occurred between a luminol donor and a CdTe quantum dot (QD) acceptor in the luminol-NaBrO-QD system, and that it was sensitively suppressed by the presence of certain organic compounds of biological interest including biogenic amines and thiols, amino acids, organic acids, and steroids. These findings allowed developing sensitive MCE-CL assays for the tested compounds. The proposed MCE-CL methods showed desired analytical figures of merit such as a wide concentration range of linear response. Detection limits obtained were ~10−9 M for biogenic amines including dopamine and epinephrine, and ~ 10−8 M for biogenic thiols (e.g. glutathione and acetylcysteine), organic acids (i.e. ascorbic acid and uric acid), estrogens, and native amino acids. These were 10 to 1000 times more sensitive than those of previously reported MCE-based methods with chemiluminescence, electrochemical, or laser induced fluorescence detection for quantifying corresponding compounds. To evaluate the applicability of the present MCE-CL method for analyzing real biological samples, it was used to determine amino acids in individual human red blood cells. Nine amino acids including Lys, Ser, Ala, Glu, Trp, etc. were detected. The contents ranged from 3 to 31 amol /cell. The assay proved to be simple, quick, reproducible, and very sensitive. PMID:20121202

Neuronal metabolomics by ion mobility mass spectrometry: cocaine effects on glucose and selected biogenic amine metabolites in the frontal cortex, striatum, and thalamus of the rat.

PubMed

Kaplan, Kimberly A; Chiu, Veronica M; Lukus, Peter A; Zhang, Xing; Siems, William F; Schenk, James O; Hill, Herbert H

2013-02-01

We report results of studies of global and targeted neuronal metabolomes by ambient pressure ion mobility mass spectrometry. The rat frontal cortex, striatum, and thalamus were sampled from control nontreated rats and those treated with acute cocaine or pargyline. Quantitative evaluations were made by standard additions or isotopic dilution. The mass detection limit was ~100 pmol varying with the analyte. Targeted metabolites of dopamine, serotonin, and glucose followed the rank order of distribution expected between the anatomical areas. Data was evaluated by principal component analysis on 764 common metabolites (identified by m/z and reduced mobility). Differences between anatomical areas and treatment groups were observed for 53 % of these metabolites using principal component analysis. Global and targeted metabolic differences were observed between the three anatomical areas with contralateral differences between some areas. Following drug treatments, global and targeted metabolomes were found to shift relative to controls and still maintained anatomical differences. Pargyline reduced 3,4-dihydroxyphenylacetic acid below detection limits, and 5-HIAA varied between anatomical regions. Notable findings were: (1) global metabolomes were different between anatomical areas and were altered by acute cocaine providing a broad but targeted window of discovery for metabolic changes produced by drugs of abuse; (2) quantitative analysis was demonstrated using isotope dilution and standard addition; (3) cocaine changed glucose and biogenic amine metabolism in the anatomical areas tested; and (4) the largest effect of cocaine was on the glycolysis metabolome in the thalamus confirming inferences from previous positron emission tomography studies using 2-deoxyglucose.

Chronic unpredictable mild stress-induced depressive-like behavior and dysregulation of brain levels of biogenic amines in Drosophila melanogaster.

PubMed

Araujo, Stífani Machado; Poetini, Marcia Rósula; Bortolotto, Vandreza Cardoso; de Freitas Couto, Shanda; Pinheiro, Franciane Cabral; Meichtry, Luana Barreto; de Almeida, Francielli Polet; Santos Musachio, Elize Aparecida; de Paula, Mariane Trindade; Prigol, Marina

2018-05-24

The etiopathogenesis of depression may involve repeated exposure to several unpredictable stressors. This study was conducted to investigate changes induced by chronic unpredictable mild stress (CUMS) and to assess behavioral and neurochemical changes that predict depressive-like behavior in Drosophila melanogaster. Male Drosophila melanogaster flies were exposed to CUMS with several stressors (cold, heat, starvation, and sleep deprivation) in an unpredictable and chronic manner for ten days. At the end of treatment, in vivo behavioral tests (open field, aggression, forced swimming, mating, light/dark box, male fertility evaluation, sucrose preference, weight evaluation) and ex vivo analyses (dopamine and serotonin levels) were performed. Using this CUMS model, we obtained results that contribute to the construction of a depressive model in Drosophila, where we reproduce some behavioral phenotypes corresponding to depressive symptoms, such as immobility in the forced swimming test, less exploration in the light/dark test, changes in mating behavior, changes in the aggressiveness test, reduced sucrose preference, and weight-loss, in addition to a significant reduction in the levels of serotonin and dopamine when compared to the control group. Fluoxetine was used in our study as a positive control to demonstrate that CUMS-induced depressive-like behaviors in flies can be reversed by antidepressants. In conclusion, male Drosophila melanogaster exposed to CUMS display a depressive-like phenotype, and, while this poses some limitations as an animal model for depression, it meets some of the criteria required to be a valid model, such as good face and construct validity. Copyright © 2018. Published by Elsevier B.V.

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

PubMed Central

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

2017-01-01

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 mono-amines, 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. PMID:27817108

Influence of neonatal vitamin A or vitamin D treatment on the concentration of biogenic amines and their metabolites in the adult rat brain.

PubMed

Tekes, K; Gyenge, M; Folyovich, A; Csaba, G

2009-04-01

Newborn male rats were treated with a single dose of 3 mg vitamin A (retinol) or 0.05 mg vita-min D (cholecalciferol), and three months later five brain regions (frontopolar cortex, hypothalamus, hippocampus, striatum, and brainstem) were studied for tissue levels of dopamine (DA), serotonin (5HT), and metabolites such as homovanillic acid (HVA), as well as 5-hydroxyindole-3-acetic acid (5HIAA). Vitamin A treatment as hormonal imprinting significantly decreased 5HIAA levels in each brain region. Vitamin D imprinting significantly elevated DA only in the brainstem and HVA levels in striatum and hypothalamus. Present and earlier brain-imprinting results (with brain-produced substances), show that the profound and life-long effect of neonatal hormonal imprinting on neurotransmitter production of the adult brain seems to be well established. As prophylactic treatment with these vitamins is frequent in the perinatal period, the imprinting effect of vitamin A and vitamin D must be taken into consideration.

Freeze-Drying as Sample Preparation for Micellar Electrokinetic Capillary Chromatography – Electrochemical Separations of Neurochemicals in Drosophila Brains

PubMed Central

Berglund, E. Carina; Kuklinski, Nicholas J.; Karagündüz, Ekin; Ucar, Kubra; Hanrieder, Jörg; Ewing, Andrew G.

2013-01-01

Micellar electrokinetic capillary chromatography with electrochemical detection has been used to quantify biogenic amines in freeze-dried Drosophila melanogaster brains. Freeze drying samples offers a way to preserve the biological sample while making dissection of these tiny samples easier and faster. Fly samples were extracted in cold acetone and dried in a rotary evaporator. Extraction and drying times were optimized in order to avoid contamination by red-pigment from the fly eyes and still have intact brain structures. Single freeze-dried fly-brain samples were found to produce representative electropherograms as a single hand-dissected brain sample. Utilizing the faster dissection time that freeze drying affords, the number of brains in a fixed homogenate volume can be increased to concentrate the sample. Thus, concentrated brain samples containing five or fifteen preserved brains were analyzed for their neurotransmitter content, and five analytes; dopamine N-acetyloctopamine, Nacetylserotonin, N-acetyltyramine, N-acetyldopamine were found to correspond well with previously reported values. PMID:23387977

Octopaminergic Modulation of Temporal Frequency Coding in an Identified Optic Flow-Processing Interneuron

PubMed Central

Longden, Kit D.; Krapp, Holger G.

2010-01-01

Flying generates predictably different patterns of optic flow compared with other locomotor states. A sensorimotor system tuned to rapid responses and a high bandwidth of optic flow would help the animal to avoid wasting energy through imprecise motor action. However, neural processing that covers a higher input bandwidth itself comes at higher energetic costs which would be a poor investment when the animal was not flying. How does the blowfly adjust the dynamic range of its optic flow-processing neurons to the locomotor state? Octopamine (OA) is a biogenic amine central to the initiation and maintenance of flight in insects. We used an OA agonist chlordimeform (CDM) to simulate the widespread OA release during flight and recorded the effects on the temporal frequency coding of the H2 cell. This cell is a visual interneuron known to be involved in flight stabilization reflexes. The application of CDM resulted in (i) an increase in the cell's spontaneous activity, expanding the inhibitory signaling range (ii) an initial response gain to moving gratings (20–60 ms post-stimulus) that depended on the temporal frequency of the grating and (iii) a reduction in the rate and magnitude of motion adaptation that was also temporal frequency-dependent. To our knowledge, this is the first demonstration that the application of a neuromodulator can induce velocity-dependent alterations in the gain of a wide-field optic flow-processing neuron. The observed changes in the cell's response properties resulted in a 33% increase of the cell's information rate when encoding random changes in temporal frequency of the stimulus. The increased signaling range and more rapid, longer lasting responses employed more spikes to encode each bit, and so consumed a greater amount of energy. It appears that for the fly investing more energy in sensory processing during flight is more efficient than wasting energy on under-performing motor control. PMID:21152339

Convergent evolution of neural systems in ctenophores

PubMed Central

Moroz, Leonid L.

2015-01-01

Neurons are defined as polarized secretory cells specializing in directional propagation of electrical signals leading to the release of extracellular messengers – features that enable them to transmit information, primarily chemical in nature, beyond their immediate neighbors without affecting all intervening cells en route. Multiple origins of neurons and synapses from different classes of ancestral secretory cells might have occurred more than once during ~600 million years of animal evolution with independent events of nervous system centralization from a common bilaterian/cnidarian ancestor without the bona fide central nervous system. Ctenophores, or comb jellies, represent an example of extensive parallel evolution in neural systems. First, recent genome analyses place ctenophores as a sister group to other animals. Second, ctenophores have a smaller complement of pan-animal genes controlling canonical neurogenic, synaptic, muscle and immune systems, and developmental pathways than most other metazoans. However, comb jellies are carnivorous marine animals with a complex neuromuscular organization and sophisticated patterns of behavior. To sustain these functions, they have evolved a number of unique molecular innovations supporting the hypothesis of massive homoplasies in the organization of integrative and locomotory systems. Third, many bilaterian/cnidarian neuron-specific genes and ‘classical’ neurotransmitter pathways are either absent or, if present, not expressed in ctenophore neurons (e.g. the bilaterian/cnidarian neurotransmitter, γ-amino butyric acid or GABA, is localized in muscles and presumed bilaterian neuron-specific RNA-binding protein Elav is found in non-neuronal cells). Finally, metabolomic and pharmacological data failed to detect either the presence or any physiological action of serotonin, dopamine, noradrenaline, adrenaline, octopamine, acetylcholine or histamine – consistent with the hypothesis that ctenophore neural systems evolved independently from those in other animals. Glutamate and a diverse range of secretory peptides are first candidates for ctenophore neurotransmitters. Nevertheless, it is expected that other classes of signal and neurogenic molecules would be discovered in ctenophores as the next step to decipher one of the most distinct types of neural organization in the animal kingdom. PMID:25696823

Direct and mediated electrochemistry of peroxidase and its electrocatalysis on a variety of screen-printed carbon electrodes: amperometric hydrogen peroxide and phenols biosensor.

PubMed

Chekin, Fereshteh; Gorton, Lo; Tapsobea, Issa

2015-01-01

This study compares the behaviour of direct and mediated electrochemistry of horseradish peroxidase (HRP) immobilised on screen-printed carbon electrodes (SPCEs), screen-printed carbon electrodes modified with carboxyl-functionalised multi-wall carbon nanotubes (MWCNT-SPCEs) and screen-printed carbon electrodes modified with carboxyl-functionalised single-wall carbon nanotubes (SWCNT-SPCEs). The techniques of cyclic voltammetry and amperometry in the flow mode were used to characterise the properties of the HRP immobilised on screen-printed electrodes. From measurements of the mediated and mediatorless currents of hydrogen peroxide reduction at the HRP-modified electrodes, it was concluded that the fraction of enzyme molecules in direct electron transfer (DET) contact with the electrode varies substantially for the different electrodes. It was observed that the screen-printed carbon electrodes modified with carbon nanotubes (MWCNT-SPCEs and SWCNT-SPCEs) demonstrated a substantially higher percentage (≈100 %) of HRP molecules in DET contact than the screen-printed carbon electrodes (≈60 %). The HRP-modified electrodes were used for determination of hydrogen peroxide in mediatorless mode. The SWCNT-SPCE gave the lowest detection limit (0.40 ± 0.09 μM) followed by MWCNT-SPCE (0.48 ± 0.07 μM) and SPCE (0.98 ± 0.2 μM). These modified electrodes were additionally developed for amperometric determination of phenolic compounds. It was found that the SWCNT-SPCE gave a detection limit for catechol of 110.2 ± 3.6 nM, dopamine of 640.2 ± 9.2 nM, octopamine of 3341 ± 15 nM, pyrogallol of 50.10 ± 2.9 nM and 3,4-dihydroxy-L-phenylalanine of 980.7 ± 8.7 nM using 50 μM H2O2 in the flow carrier.

De novo microdeletion of Xp11.3 exclusively encompassing the monoamine oxidase A and B genes in a male infant with episodic hypotonia: A genomics approach to personalized medicine

PubMed Central

O’Leary, Ryan E.; Shih, Jean C.; Hyland, Keith; Kramer, Nancy; Asher, Y. Jane Tavyev; Graham, John M.

2012-01-01

Monoamine oxidase A and B (MAOA and MAOB) play key roles in deaminating neurotransmitters and various other biogenic amines. Patients deficient in one or both enzymes have distinct metabolic and neurologic profiles. MAOB deficient patients exhibit normal clinical characteristics and behavior, while MAOA deficient patients have borderline intellectual deficiency and impaired impulse control. Patients who lack both MAOA and MAOB have the most extreme laboratory values (urine, blood, and CSF serotonin 4–6 times normal, with elevated O-methylated amine metabolites and reduced deaminated metabolites) in addition to severe intellectual deficiency and behavioral problems. Mice lacking maoa and moab exhibit decreased proliferation of neural stem cells beginning in late gestation and persisting into adulthood These mice show significantly increased monoamine levels, particularly serotonin, as well as anxiety-like behaviors as adults, suggesting that brain maturation in late embryonic development is adversely affected by elevated serotonin levels. We report the case of a male infant with a de novo Xp11.3 microdeletion exclusively encompassing the MAOA and MAOB genes. This newly recognized X-linked disorder is characterized by severe intellectual disability and unusual episodes of hypotonia, which resemble atonic seizures, but have no EEG correlate. A customized low dietary amine diet was implemented in an attempt to prevent the cardiovascular complications that can result from the excessive intake of these compounds. This is the second report of this deletion and the first attempt to maintain the patient’s cardiovascular health through dietary manipulation. Even though a diet low in tyramine, phenylethylamine, and dopa/dopamine is necessary for long-term management, it will not rescue the abnormal monoamine profile seen in combined MAOA and MAOB deficiency. Our patient displays markedly elevated levels of serotonin in blood, serum, urine, and CSF while on this diet. Serotonin biosynthesis inhibitors like para-chlorophenylalanine and p-ethynylphenylalanine may be needed to lower serotonin levels in patients with absent monoamine oxidase enzymes. PMID:22365943

De novo microdeletion of Xp11.3 exclusively encompassing the monoamine oxidase A and B genes in a male infant with episodic hypotonia: a genomics approach to personalized medicine.

PubMed

O'Leary, Ryan E; Shih, Jean C; Hyland, Keith; Kramer, Nancy; Asher, Y Jane Tavyev; Graham, John M

2012-05-01

Monoamine oxidase A and B (MAOA and MAOB) play key roles in deaminating neurotransmitters and various other biogenic amines. Patients deficient in one or both enzymes have distinct metabolic and neurologic profiles. MAOB deficient patients exhibit normal clinical characteristics and behavior, while MAOA deficient patients have borderline intellectual deficiency and impaired impulse control. Patients who lack both MAOA and MAOB have the most extreme laboratory values (urine, blood, and CSF serotonin 4-6 times normal, with elevated O-methylated amine metabolites and reduced deaminated metabolites) in addition to severe intellectual deficiency and behavioral problems. Mice lacking maoa and moab exhibit decreased proliferation of neural stem cells beginning in late gestation and persisting into adulthood. These mice show significantly increased monoamine levels, particularly serotonin, as well as anxiety-like behaviors as adults, suggesting that brain maturation in late embryonic development is adversely affected by elevated serotonin levels. We report the case of a male infant with a de novo Xp11.3 microdeletion exclusively encompassing the MAOA and MAOB genes. This newly recognized X-linked disorder is characterized by severe intellectual disability and unusual episodes of hypotonia, which resemble atonic seizures, but have no EEG correlate. A customized low dietary amine diet was implemented in an attempt to prevent the cardiovascular complications that can result from the excessive intake of these compounds. This is the second report of this deletion and the first attempt to maintain the patient's cardiovascular health through dietary manipulation. Even though a diet low in tyramine, phenylethylamine, and dopa/dopamine is necessary for long-term management, it will not rescue the abnormal monoamine profile seen in combined MAOA and MAOB deficiency. Our patient displays markedly elevated levels of serotonin in blood, serum, urine, and CSF while on this diet. Serotonin biosynthesis inhibitors like para-chlorophenylalanine and p-ethynylphenylalanine may be needed to lower serotonin levels in patients with absent monoamine oxidase enzymes. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Preparation of bio-compatible boron nanoparticles and novel mesoporous silica nanoparticles for bio-applications

NASA Astrophysics Data System (ADS)

Gao, Zhe

This dissertation presents the synthesis and characterization of several novel inorganic and hybrid nanoparticles, including the bio-compatible boron nanoparticles (BNPs) for boron neutron capture therapy (BNCT), tannic acid-templated mesoporous silica nanoparticles and degradable bridged silsesquioxane silica nanoparticles. Chapter 1 provides background information of BNCT and reviews the development of design and synthesizing silica nanoparticles and the study of silica material degradability. Chapter 2 describes the preparation and characterization of dopamine modified BNPs and the preliminary cell study of them. The BNPs were first produced via ball milling, with fatty acid on the surface to stabilize the combustible boron elements. This chapter will mainly focus on the ligand-exchange strategy, in which the fatty acids were replaced by non-toxic dopamines in a facile one-pot reaction. The dopamine-coated BNPs (DA-BNPs) revealed good water dispersibility and low cytotoxicity. Chapter 3 describes the synthesis of tannic acid template mesoporous silica nanoparticles (TA-TEOS SiNPs) and their application to immobilize proteins. The monodispersed TA SiNPs with uniform pore size up to approximately 13 nm were produced by utilizing tannic acid as a molecular template. We studied the influence of TA concentration and reaction time on the morphology and pore size of the particles. Furthermore, the TA-TEOS particles could subsequently be modified with amine groups allowing them to be capable of incorporating imaging ligands and other guest molecules. The ability of the TA-TEOS particles to store biomolecules was preliminarily assessed with three proteins of different charge characteristics and dimensions. The immobilization of malic dehydrogenase on TA-TEOS enhanced the stability of the enzyme at room temperature. Chapter 4 details the synthesis of several bridged silsesquioxanes and the preparation of degradable hybrid SiNPs via co-condensation of bridged silsesquioxanes with tetraethoxysilane. In vivo studies show that the solid SiNPs accumulate in many organs due to the lack of degradability. The aim of our work is to address this shortcoming by producing novel degradable SiNPs. Bridged silsesquioxanes were used as the precursors of the particles, and upon cleavage of the carbamate groups when brought into contact with aqueous media, the particles degraded into porous structures.

Effects of Acute and Chronic Treatments with Dopamine D2 and D3 Receptor Ligands on Cocaine versus Food Choice in Rats.

PubMed

Thomsen, Morgane; Barrett, Andrew C; Butler, Paul; Negus, S Stevens; Caine, S Barak

2017-07-01

Dopamine D 3 receptor ligands are potential medications for psychostimulant addiction. Medication assessment may benefit from preclinical studies that evaluate chronic medication effects on choice between an abused drug and an alternative, nondrug reinforcer. This study compared acute and chronic effects of dopamine D 2 - and D 3 -preferring ligands on choice between intravenous cocaine and palatable food in rats. Under baseline conditions, cocaine maintained dose-dependent increases in cocaine choice and reciprocal decreases in food choice. Acutely, the D 2 agonist R -(-)-norpropylapomorphine (NPA) and antagonist L-741,626 [3-[[4-(4-chlorophenyl)-4-hydroxypiperidin-l-yl]methyl-1 H -indole] produced leftward and rightward shifts in cocaine dose-effect curves, respectively, whereas the partial agonist terguride had no effect. All three drugs dose-dependently decreased food-maintained responding. Chronically, the effects of R -(-)-norpropylapomorphine and L-741,626 on cocaine self-administration showed marked tolerance, whereas suppression of food-reinforced behavior persisted. Acute effects of the D 3 ligands were less systematic and most consistent with nonselective decreases in cocaine- and food-maintained responding. Chronically, the D 3 agonist PF-592,379 [5-[(2 R ,5 S )-5-methyl-4-propylmorpholin-2-yl]pyridin-2-amine] increased cocaine choice, whereas an intermediate dose of the D 3 antagonist PG01037 [ N -[( E )-4-[4-(2,3-dichlorophenyl)piperazin-1-yl]but-2-enyl]-4-pyridin-2-ylbenzamide] produced a therapeutically desirable decrease in cocaine choice early in treatment; however, tolerance to this effect developed, and lower and higher doses were ineffective. D 3 ligands failed to significantly modify total cocaine intake but caused persistent decreases in food intake. Thus, D 2 -and D 3 -preferring ligands showed distinct profiles, consistent with different pharmacological actions. In addition, these results highlight the role of acute versus chronic treatment as a determinant of test drug effects. With the possible exception of the D 3 antagonist PG01037, no ligand was promising in terms of cocaine addiction treatment. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss

PubMed Central

Bruinenberg, Vibeke M.; Tudor, Jennifer C.; Ferri, Sarah L.; Baumann, Arnd; Meerlo, Peter

2014-01-01

The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object–location task. Five hours of total sleep deprivation directly following training impaired the formation of object–location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation. PMID:25411499

Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss.

PubMed

Havekes, Robbert; Bruinenberg, Vibeke M; Tudor, Jennifer C; Ferri, Sarah L; Baumann, Arnd; Meerlo, Peter; Abel, Ted

2014-11-19

The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object-location task. Five hours of total sleep deprivation directly following training impaired the formation of object-location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation. Copyright © 2014 the authors 0270-6474/14/3415715-07$15.00/0.

Striatal Tyrosine Hydroxylase Is Stimulated via TAAR1 by 3-Iodothyronamine, But Not by Tyramine or β-Phenylethylamine.

PubMed

Zhang, Xiaoqun; Mantas, Ioannis; Alvarsson, Alexandra; Yoshitake, Takashi; Shariatgorji, Mohammadreza; Pereira, Marcela; Nilsson, Anna; Kehr, Jan; Andrén, Per E; Millan, Mark J; Chergui, Karima; Svenningsson, Per

2018-01-01

The trace amine-associated receptor 1 (TAAR1) is expressed by dopaminergic neurons, but the precise influence of trace amines upon their functional activity remains to be fully characterized. Here, we examined the regulation of tyrosine hydroxylase (TH) by tyramine and beta-phenylethylamine (β-PEA) compared to 3-iodothyronamine (T 1 AM). Immunoblotting and amperometry were performed in dorsal striatal slices from wild-type (WT) and TAAR1 knockout (KO) mice. T 1 AM increased TH phosphorylation at both Ser 19 and Ser 40 , actions that should promote functional activity of TH. Indeed, HPLC data revealed higher rates of L-dihydroxyphenylalanine (DOPA) accumulation in WT animals treated with T 1 AM after the administration of a DOPA decarboxylase inhibitor. These effects were abolished both in TAAR1 KO mice and by the TAAR1 antagonist, EPPTB. Further, they were specific inasmuch as Ser 845 phosphorylation of the post-synaptic GluA1 AMPAR subunit was unaffected. The effects of T 1 AM on TH phosphorylation at both Ser 19 (CamKII-targeted), and Ser 40 (PKA-phosphorylated) were inhibited by KN-92 and H-89, inhibitors of CamKII and PKA respectively. Conversely, there was no effect of an EPAC analog, 8-CPT-2Me-cAMP, on TH phosphorylation. In line with these data, T 1 AM increased evoked striatal dopamine release in TAAR1 WT mice, an action blunted in TAAR1 KO mice and by EPPTB. Mass spectrometry imaging revealed no endogenous T 1 AM in the brain, but detected T 1 AM in several brain areas upon systemic administration in both WT and TAAR1 KO mice. In contrast to T 1 AM, tyramine decreased the phosphorylation of Ser 40 -TH, while increasing Ser 845 -GluA1 phosphorylation, actions that were not blocked in TAAR1 KO mice. Likewise, β-PEA reduced Ser 40 -TH and tended to promote Ser 845 -GluA1 phosphorylation. The D 1 receptor antagonist SCH23390 blocked tyramine-induced Ser 845 -GluA1 phosphorylation, but had no effect on tyramine- or β-PEA-induced Ser 40 -TH phosphorylation. In conclusion, by intracellular cascades involving CaMKII and PKA, T 1 AM, but not tyramine and β-PEA, acts via TAAR1 to promote the phosphorylation and functional activity of TH in the dorsal striatum, supporting a modulatory influence on dopamine transmission.

Thalassiolin D: a new flavone O-glucoside Sulphate from the seagrass Thalassia hemprichii.

PubMed

Hawas, Usama W; Abou El-Kassem, Lamia T

2017-10-01

Thalassiolin D, a new flavone O-glucoside sulphate along with three flavonoids, two steroids, p-hydroxybenzoic acid, 4,4'-dihydroxybenzophenone and nitrogen compound, octopamine were isolated from the seagrass Thalassia hemprichii, collected from the Saudi Red Sea coast. By extensive spectroscopic analysis including 1D and 2D NMR and MS data, the structure of the new compound was elucidated as diosmetin 7-O-β-glucosyl-2″-sulphate. The new compound displayed moderately in vitro antiviral HCV protease activity with IC 50 value 16 μM.

Attenuation of reserpine-induced pain/depression dyad by gentiopicroside through downregulation of GluN2B receptors in the amygdala of mice.

PubMed

Liu, Shui-bing; Zhao, Rong; Li, Xu-sheng; Guo, Hong-ju; Tian, Zhen; Zhang, Nan; Gao, Guo-dong; Zhao, Ming-gao

2014-06-01

Epidemiological studies demonstrate that pain frequently occurs comorbid with depression. Gentiopicroside (Gent) is a secoiridoid compound isolated from Gentiana lutea that exhibits analgesic properties and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cortex of mice. However, the effects of Gent on the reserpine-induced pain/depression dyad and its underlying mechanisms are unclear. Reserpine administration (1 mg/kg subcutaneous daily for 3 days) caused a significant decrease in the nociceptive threshold as evidenced by the reduced paw withdrawal latency in response to a radiant heat source and mechanical allodynia. Behavioral detection indicated a significant increase in immobility time during a forced swim test, as well as decreased time in the central area and total travel distance in an open field test. Furthermore, reserpinized animals exhibited increased oxidative stress. Systemic Gent administration dose-dependently ameliorated the behavioral deficits associated with reserpine-induced pain/depression dyad. At the same time, the decrease in biogenic amine levels (norepinephrine, dopamine, and serotonin) was integrated with the increase in caspase-3 levels and GluN2B-containing NMDA receptors in the amygdala of the reserpine-injected mice. Gent significantly reversed the changes in the levels of biogenic amines, caspase-3, and GluN2B-containing NMDA receptors in amygdala. However, Gent did not affect the expression of GluN2A-containing NMDA receptors. The inhibitory effects of Gent on oxidative stress were occluded by simultaneous treatment of GluN2B receptors antagonist Ro25-6981. Our study provides strong evidence that Gent inhibits reserpine-induced pain/depression dyad by downregulating GluN2B receptors in the amygdala.

2-Phenylethylamine, a constituent of chocolate and wine, causes mitochondrial complex-I inhibition, generation of hydroxyl radicals and depletion of striatal biogenic amines leading to psycho-motor dysfunctions in Balb/c mice.

PubMed

Sengupta, T; Mohanakumar, K P

2010-11-01

Behavioral and neurochemical effects of chronic administration of high doses of 2-phenylethylamine (PEA; 25-75 mg/kg, i.p. for up to 7 days) have been investigated in Balb/c mice. Depression and anxiety, as demonstrated respectively by increased floating time in forced swim test, and reduction in number of entries and the time spent in the open arms in an elevated plus maze were observed in these animals. General motor disabilities in terms of akinesia, catalepsy and decreased swimming ability were also observed in these animals. Acute and sub-acute administration of PEA caused significant, dose-dependent depletion of striatal dopamine, and its metabolites levels. PEA caused dose-dependent generation of hydroxyl radicals in vitro in Fenton's reaction in test tubes, in isolated mitochondrial fraction, and in vivo in the striatum of mice. A significant inhibition of NADH-ubiquinone oxidoreductase (complex-I; EC: 1.6.5.3) activity suggests the inhibition in oxidative phosphorylation in the mitochondria resulting in hydroxyl radical generation. Nissl staining and TH immnunohistochemistry in brain sections failed to show any morphological aberrations in dopaminergic neurons or nerve terminals. Long-term over-consumption of PEA containing food items could be a neurological risk factor having significant pathological relevance to disease conditions such as depression or motor dysfunction. However, per-oral administration of higher doses of PEA (75-125 mg/kg; 7 days) failed to cause such overt neurochemical effects in rats, which suggested safe consumption of food items rich in this trace amine by normal population. Copyright © 2010 Elsevier Ltd. All rights reserved.

Update on the pharmacology of selective inhibitors of MAO-A and MAO-B: focus on modulation of CNS monoamine neurotransmitter release.

PubMed

Finberg, John P M

2014-08-01

Inhibitors of monoamine oxidase (MAO) were initially used in medicine following the discovery of their antidepressant action. Subsequently their ability to potentiate the effects of an indirectly-acting sympathomimetic amine such as tyramine was discovered, leading to their limitation in clinical use, except for cases of treatment-resistant depression. More recently, the understanding that: a) potentiation of indirectly-acting sympathomimetic amines is caused by inhibitors of MAO-A but not by inhibitors of MAO-B, and b) that reversible inhibitors of MAO-A cause minimal tyramine potentiation, has led to their re-introduction to clinical use for treatment of depression (reversible MAO-A inhibitors and new dose form MAO-B inhibitor) and treatment of Parkinson's disease (MAO-B inhibitors). The profound neuroprotective properties of propargyl-based inhibitors of MAO-B in preclinical experiments have drawn attention to the possibility of employing these drugs for their neuroprotective effect in neurodegenerative diseases, and have raised the question of the involvement of the MAO-mediated reaction as a source of reactive free radicals. Despite the long-standing history of MAO inhibitors in medicine, the way in which they affect neuronal release of monoamine neurotransmitters is still poorly understood. In recent years, the detailed chemical structure of MAO-B and MAO-A has become available, providing new possibilities for synthesis of mechanism-based inhibitors. This review describes the latest advances in understanding the way in which MAO inhibitors affect the release of the monoamine neurotransmitters dopamine, noradrenaline and serotonin (5-HT) in the CNS, with an accent on the importance of these effects for the clinical actions of the drugs. Copyright © 2014 Elsevier Inc. All rights reserved.

Empirical Valence Bond Simulations of the Hydride-Transfer Step in the Monoamine Oxidase A Catalyzed Metabolism of Noradrenaline.

PubMed

Poberžnik, Matic; Purg, Miha; Repič, Matej; Mavri, Janez; Vianello, Robert

2016-11-10

Monoamine oxidases (MAOs) A and B are flavoenzymes responsible for the metabolism of biogenic amines, such as dopamine, serotonin, and noradrenaline (NA), which is why they have been extensively implicated in the etiology and course of various neurodegenerative disorders and, accordingly, used as primary pharmacological targets to treat these debilitating cognitive diseases. The precise chemical mechanism through which MAOs regulate the amine concentration, which is vital for the development of novel inhibitors, is still not unambiguously determined in the literature. In this work, we present atomistic empirical valence bond simulations of the rate-limiting step of the MAO-A-catalyzed NA (norepinephrine) degradation, involving hydride transfer from the substrate α-methylene group to the flavin moiety of the flavin adenine dinucleotide prosthetic group, employing the full dimensionality and thermal fluctuations of the hydrated enzyme, with extensive configurational sampling. We show that MAO-A lowers the free energy of activation by 14.3 kcal mol -1 relative to that of the same reaction in aqueous solution, whereas the calculated activation free energy of ΔG ‡ = 20.3 ± 1.6 kcal mol -1 is found to be in reasonable agreement with the correlated experimental value of 16.5 kcal mol -1 . The results presented here strongly support the fact that both MAO-A and MAO-B isoforms function by the same hydride-transfer mechanism. We also considered a few point mutations of the "aromatic cage" tyrosine residue (Tyr444Phe, Tyr444Leu, Tyr444Trp, Tyr444His, and Tyr444Glu), and the calculated changes in the reaction barriers are in agreement with the experimental values, thus providing further support to the proposed mechanism.

Evaluation of dimethoxydop-NU as a novel anti-tumor agent.

PubMed

Mukherjee, A; Dutta, S; Sanyal, U

2007-12-01

Dimethoxydop-NU, 1-[2-{3-(2-Chloroethyl)-3-nitrosoureido}ethyl]-3,4-dimethoxy-benzene (Compound 1), was synthesized from 3,4-dimethoxy-phenethylamine as a novel anti-tumor agent based on the structures of the clinical drug CCNU and dopamine, an important endogenous biological amine having anti-angiogenesis property. In vitro screening in two human tumor cell lines, namely promyelocytic leukemia HL-60 and histiocytic lymphoma U-937, revealed its cytotoxicity greater than that of hydroxyurea and comparable to BCNU used as standards. Its in vivo anti-tumoral potency was assessed in the murine ascites tumors Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times of drug treated (T) over untreated control (C) mice. Results revealed significant tumor regression effects in these tumors. The survival time of treated mice was markedly increased by combination of the compound 1 with dopamine hydrochloride. Its toxicity was assessed in vivo in normal and EAC bearing mice by measuring drug-induced changes in hematological parameters, femoral bone marrow and splenic cellularities as well as biochemical parameters sequentially on days 9, 14 and 19 following drug treatment at the optimum dose of 30 mg/kg from day 1 to 7. Results indicated that initial suppression in the femoral bone marrow cellularity seen on day 9 reached normalcy by day 19. Other parameters were within normal limit. Histopathological studies of liver revealed mild hepatotoxicity on day 9 in treated groups that substantially recovered on day 19. Similar studies with heart and kidney revealed no cardio toxicity or nephrotoxicity. Compound 1 comparable to standards inhibited the synthesis of DNA and RNA in S-180 tumor cells.

Pharmacological characterization of ecstasy synthesis byproducts with recombinant human monoamine transporters.

PubMed

Pifl, Christian; Nagy, Gabor; Berényi, Sándor; Kattinger, Alexandra; Reither, Harald; Antus, Sándor

2005-07-01

Ecstasy samples often contain byproducts of the illegal, uncontrolled synthesis of N-methyl-3,4-methylenedioxy-amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). MDMA and eight chemically defined byproducts of MDMA synthesis were investigated for their interaction with the primary sites of action of MDMA, namely the human plasmalemmal monamine transporters for norepinephrine, serotonin, and dopamine [(norepinephrine transporter (NET), serotonin transporter (SERT), and dopamine transporter (DAT)]. SK-N-MC neuroblastoma and human embryonic kidney cells stably transfected with the transporter cDNA were used for uptake and release experiments. Two of the eight compounds, 1,3-bis (3,4-methylenedioxyphenyl)-2-propanamine (12) and N-formyl-1,3-bis (3,4-methylenedioxyphenyl)-prop-2-yl-amine (13) had uptake inhibitory potencies with IC50 values in the low micromolar range similar to MDMA. Compounds with nitro instead of amino groups and a phenylethenyl instead of a phenylethyl structure or a formamide or acetamide modification had IC50 values beyond 100 microM. MDMA, 12, and 13 were examined for induction of carrier-mediated release by superfusion of transporter expressing cells preloaded with the metabolically inert transporter substrate [3H]1-methyl-4-phenylpyridinium. MDMA induced release mediated by NET, SERT, or DAT with EC50 values of 0.64, 1.12, and 3.24 microM, respectively. 12 weakly released from NET- and SERT-expressing cells with maximum effects less than one-tenth of that of MDMA and did not release from DAT cells. 13 had no releasing activity. 12 and 13 inhibited release induced by MDMA, and the concentration dependence of this effect correlated with their uptake inhibitory potency at the various transporters. These results do not support a neurotoxic potential of the examined ecstasy synthesis byproducts and provide interesting structure-activity relationships on the transporters.

The role of monoamines in the changes in body temperature induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives

PubMed Central

Docherty, JR; Green, AR

2010-01-01

Hyperthermia is probably the most widely known acute adverse event that can follow ingestion of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) by recreational users. The effect of MDMA on body temperature is complex because the drug has actions on all three major monoamine neurotransmitters [5-hydroxytryptamine (5-HT), dopamine and noradrenaline], both by amine release and by direct receptor activation. Hyperthermia and hypothermia can be induced in laboratory animals by MDMA, depending on the ambient temperature, and involve both central thermoregulation and peripheral changes in blood flow and thermogenesis. Acute 5-HT release is not directly responsible for hyperthermia, but 5-HT receptors are involved in modulating the hyperthermic response. Impairing 5-HT function with a neurotoxic dose of MDMA or p-chlorophenylalanine alters the subsequent MDMA-induced hyperthermic response. MDMA also releases dopamine, and evidence suggests that this transmitter is involved in both the hyperthermic and hypothermic effects of MDMA in rats. The noradrenergic system is also involved in the hyperthermic response to MDMA. MDMA activates central α2A-adrenoceptors and peripheral α1-adrenoceptors to produce cutaneous vasoconstriction to restrict heat loss, and β3-adrenoceptors in brown adipose tissue to increase heat generation. The hyperthermia occurring in recreational users of MDMA can be fatal, but data reviewed here indicate that it is unlikely that any single pharmaceutical agent will be effective in reversing the hyperthermia, so careful body cooling remains the principal clinical approach. Crucially, educating recreational users about the potential dangers of hyperthermia and the control of ambient temperature should remain key approaches to prevent this potentially fatal problem. PMID:20590597

Dopamine D(3) receptor antagonists. 1. Synthesis and structure-activity relationships of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans.

PubMed

Haadsma-Svensson, S R; Cleek, K A; Dinh, D M; Duncan, J N; Haber, C L; Huff, R M; Lajiness, M E; Nichols, N F; Smith, M W; Svensson, K A; Zaya, M J; Carlsson, A; Lin, C H

2001-12-20

5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D(3) receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D(3) antagonists. Thus, combinations of various alkyl groups were generally inactive at the D(3) receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D(3) binding affinity, the D(2) affinity is also enhanced, resulting in a less than 4-fold preference for the D(3) receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D(3) antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH(3).Me(2)S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et(3)SiH to give the desired product 3 in good overall yield of ( approximately 65%) from the indanone 5c.

The newly synthesized pool of dopamine determines the severity of methamphetamine-induced neurotoxicity.

PubMed

Thomas, David M; Francescutti-Verbeem, Dina M; Kuhn, Donald M

2008-05-01

The neurotransmitter dopamine (DA) has long been implicated as a participant in the neurotoxicity caused by methamphetamine (METH), yet, its mechanism of action in this regard is not fully understood. Treatment of mice with the tyrosine hydroxylase (TH) inhibitor alpha-methyl-p-tyrosine (AMPT) lowers striatal cytoplasmic DA content by 55% and completely protects against METH-induced damage to DA nerve terminals. Reserpine, by disrupting vesicle amine storage, depletes striatal DA by more than 95% and accentuates METH-induced neurotoxicity. l-DOPA reverses the protective effect of AMPT against METH and enhances neurotoxicity in animals with intact TH. Inhibition of MAO-A by clorgyline increases pre-synaptic DA content and enhances METH striatal neurotoxicity. In all conditions of altered pre-synaptic DA homeostasis, increases or decreases in METH neurotoxicity paralleled changes in striatal microglial activation. Mice treated with AMPT, l-DOPA, or clorgyline + METH developed hyperthermia to the same extent as animals treated with METH alone, whereas mice treated with reserpine + METH were hypothermic, suggesting that the effects of alterations in cytoplasmic DA on METH neurotoxicity were not strictly mediated by changes in core body temperature. Taken together, the present data reinforce the notion that METH-induced release of DA from the newly synthesized pool of transmitter into the extracellular space plays an essential role in drug-induced striatal neurotoxicity and microglial activation. Subtle alterations in intracellular DA content can lead to significant enhancement of METH neurotoxicity. Our results also suggest that reactants derived from METH-induced oxidation of released DA may serve as neuronal signals that lead to microglial activation early in the neurotoxic process associated with METH.

Chemoselective organocatalytic aerobic oxidation of primary amines to secondary imines.

PubMed

Wendlandt, Alison E; Stahl, Shannon S

2012-06-01

Biomimetic aerobic oxidation of primary benzylic amines has been achieved by using a quinone catalyst. Excellent selectivity is observed for primary, unbranched benzylic amines relative to secondary/tertiary amines, branched benzylic amines, and aliphatic amines. The exquisite selectivity for benzylic amines enables oxidative self-sorting within dynamic mixtures of amines and imines to afford high yields of cross-coupled imine products.

Evidence for a possible neurotransmitter/neuromodulator role of tyramine on the locust oviducts.

PubMed

Donini, Andrew; Lange, Angela B

2004-04-01

Visualization of the tyraminergic innervation of the oviducts was demonstrated by immunohistochemistry, and the presence of tyramine was confirmed using high-performance liquid chromatography coupled to electrochemical detection. Oviducts incubated in high-potassium saline released tyramine in a calcium-dependent manner. Stimulation of the oviducal nerves also resulted in tyramine release, suggesting that tyramine might function as a neurotransmitter/neuromodulator at the locust oviducts. Tyramine decreased the basal tension, and also attenuated proctolin-induced contractions in a dose-dependent manner over a range of doses between 10(-7) and 10(-4) M. Low concentrations of tyramine attenuated forskolin-stimulated cyclic AMP levels in a dose-dependent manner. This effect was not blocked by yohimbine. High concentrations of tyramine increased basal cyclic AMP levels of locust oviducts in a dose-dependent manner; however, the increases in cyclic AMP were only evident at the highest concentrations tested, 5 x 10(-5) and 10(-4) M tyramine. The tyramine-induced increase in cyclic AMP shared a similar pharmacological profile with the octopamine-induced increase in cyclic AMP. Tyramine increased the amplitude of excitatory junction potentials at low concentrations while hyperpolarizing the membrane potential by 2-5 mV. A further increase in the amplitude of the excitatory junction potentials and the occurrence of an active response was seen upon washing tyramine from the preparation. These results suggest that tyramine can activate at least three different endogenous receptors on the locust oviducts a putative tyramine receptor at low concentrations, a different tyramine receptor to inhibit muscle contraction, and an octopamine receptor at high concentrations.

Wasp venom injected into the prey's brain modulates thoracic identified monoaminergic neurons.

PubMed

Rosenberg, Lior Ann; Pflüger, Hans-Joachim; Wegener, Gerhard; Libersat, Frederic

2006-02-05

The wasp Ampulex compressa injects a cocktail of neurotoxins into the brain of its cockroach prey to induce an enduring change in the execution of locomotory behaviors. Our hypothesis is that the venom injected into the brain indirectly alters the activity of monoaminergic neurons, thus changing the levels of monoamines that tune the central synapses of locomotory circuits. The purpose of the present investigation was to establish whether the venom alters the descending control, from the brain, of octopaminergic neurons in the thorax. This question was approached by recording the activity of specific identified octopaminergic neurons after removing the input from the brain or after a wasp sting into the brain. We show that the activity of these neurons is altered in stung and "brainless" animals. The spontaneous firing rate of these neurons in stung and brainless animals is approximately 20% that in control animals. Furthermore, we show that an identified octopamine neuron responds more weakly both to sensory stimuli and to direct injection of current in all treated groups. The alteration in the activity of octopamine neurons is likely to be part of the mechanism by which the wasp induces a change in the behavioral state of its prey and also affects its metabolism by reducing the potent glycolytic activator fructose 2,6-bisphosphate in leg muscle. To our knowledge, this is the first direct evidence of a change in electrical activity of specific monoaminergic neurons that can be so closely associated with a venom-induced change in behavioral state of a prey animal.

Late-life effects of chronic methamphetamine exposure during puberty on behaviour and corticostriatal mono-amines in social isolation-reared rats.

PubMed

Strauss, Laetitia; Brink, Christiaan B; Möller, Marisa; Stein, Dan J; Harvey, Brian H

2014-01-01

Chronic methamphetamine (MA) abuse results in an acute psychosis indistinguishable from paranoid schizophrenia. However, less is known of the interaction between MA use and environmental insults, and how this contributes to late-onset psychopathology. Using social isolation rearing (SIR), a neurodevelopmental animal model of schizophrenia, we investigated the association between changes in corticostriatal mono-amines and putative behaviours related to MA-induced psychosis in isolation and group-housed rats following chronic MA or saline exposure. Weaned male offspring of MA-naive female Wistar rats, either group- or isolation-housed from postnatal day (PND) +21, received saline (2 ml/kg s.c. b.i.d.) or an escalating dose of MA (0.2-6 mg/kg s.c. b.i.d.) for 16 days from PND +35 to +50. On PND +78, offspring were tested for deficits in social interactive behaviour (SIB) and prepulse inhibition (PPI) of startle, with frontal cortex and striatum harvested for the assessment of mono-amine concentrations. SIR significantly reduced rearing time, staying together, approaching and anogenital sniffing (outward-directed SIB), but increased self-grooming and locomotor activity (self-directed SIB), and also induced profound deficits in PPI. Pubertal MA exposure in group-housed animals also induced similar alterations in outward- and self-directed SIB and reduced PPI. Combined MA+SIR exposure evoked a similarly intense behavioural response as SIR or MA separately, with no exacerbation evident. Neither treatment separately nor together affected corticostriatal serotonin or noradrenaline levels, although frontal cortical dopamine (DA) levels were significantly increased in SIR and MA+group-housed animals. A trend towards further elevated frontal cortical DA was noted in the MA+SIR treatment group. Striatal DA was unaltered by all treatments. This study provides the first evidence that chronic pubertal MA exposure evokes postpubertal psychosis-like behaviours in rats of similar intensity to that induced by a neurodevelopmental animal model of schizophrenia (SIR). Moreover, the study is unique in that these behavioural changes occur together with associated changes in frontal cortical but not striatal DA, without affecting other mono-amines, and strongly implicates frontal cortical DA changes in the psychotogenic effects of early-life MA exposure or environmental insult. Although MA exposure in animals with a history of environmental insult (i.e. MA+SIR) has similar effects, combined exposure was not additive with regard to behavioural or neurochemical changes. We conclude that a ceiling effect or compensatory mechanisms prevent more pronounced neurobehavioural deficits occurring following MA+SIR treatment, at least under the current study conditions. © 2014 S. Karger AG, Basel.

[Loss of motivation in the elderly].

PubMed

Thomas, Philippe; Hazif-Thomas, Cyril; Clément, Jean-Pierre

2008-06-30

The loss of motivation is frequent in aged person and sometimes is difficult to assess. It is associated with depression but not exclusively. It overlaps with frontal brain aging consequences. Moreover, somatic problems can interfere with a loss of motivation; loss of motivation is frequent with exhausting chronic diseases, cognitive impairment and it facilitates the social withdrawal. In elderly, loss of motivation blunts the intensity of moral pain. Depressions with conative disorders can move in a dysexecutive syndrome. Even if, owing to the treatment, the cognitive disorders disappear, several years after, an authentic dementia can be diagnosed. With aging process, elderly must cope with losses, less or more balanced: affective, physical and financial losses, triggering the reject of any personal commitment. Aging process also concerns brain amines, especially dopamine, exposing old persons to depression. It alters by a similar way others brain neuro-mediator, such acetylcholine, involved in dementia. Both loss motivation and executive disorders have to be systematically assessed. An antidepressant therapeutic is necessary in case of doubt, improving patients thymic status, quality of life of patients and their family, and sometime of frontal dysfunctions.

Release of (/sup 3/H)-monoamines from superfused rat striatal slices by methylenedioxymethamphetamine (MDMA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 andmore » (/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.« less

Epidemics of mold poisoning past and present.

PubMed

Meggs, William J

2009-01-01

Molds are ubiquitous throughout the biosphere of planet earth and cause infectious, allergic, and toxic diseases. Toxic diseases arise from exposure to mycotoxins produced by molds. Throughout history, there have been a number of toxic epidemics associated with exposure to mycotoxins. Acute epidemics of ergotism are caused by consumption of grain infested by fungi of the genus Claviceps, which produce the bioactive amine ergotamine that mimics the neurotransmitters norepinephrine, serotonin, and dopamine. Acute aflatoxin outbreaks have occurred from ingestion of corn stored in damp conditions that potentiate growth of the molds of the species Aspergillus. Contemporary construction methods that use cellulose substrates such as fiber board and indoor moisture have caused an outbreak of contaminated buildings with Stachybotrys chartarum, with the extent of health effects still a subject of debate and ongoing research. This article reviews several of the more prominent epidemics and discusses the nature of the toxins. Two diseases that were leading causes of childhood mortality in England in the 1970s and vanished with changing dietary habits, putrid malignant fever, and slow nervous fever were most likely toxic mold epidemics.

Dopamine synapse is a neuroligin-2–mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures

PubMed Central

Uchigashima, Motokazu; Ohtsuka, Toshihisa; Kobayashi, Kazuto; Watanabe, Masahiko

2016-01-01

Midbrain dopamine neurons project densely to the striatum and form so-called dopamine synapses on medium spiny neurons (MSNs), principal neurons in the striatum. Because dopamine receptors are widely expressed away from dopamine synapses, it remains unclear how dopamine synapses are involved in dopaminergic transmission. Here we demonstrate that dopamine synapses are contacts formed between dopaminergic presynaptic and GABAergic postsynaptic structures. The presynaptic structure expressed tyrosine hydroxylase, vesicular monoamine transporter-2, and plasmalemmal dopamine transporter, which are essential for dopamine synthesis, vesicular filling, and recycling, but was below the detection threshold for molecules involving GABA synthesis and vesicular filling or for GABA itself. In contrast, the postsynaptic structure of dopamine synapses expressed GABAergic molecules, including postsynaptic adhesion molecule neuroligin-2, postsynaptic scaffolding molecule gephyrin, and GABAA receptor α1, without any specific clustering of dopamine receptors. Of these, neuroligin-2 promoted presynaptic differentiation in axons of midbrain dopamine neurons and striatal GABAergic neurons in culture. After neuroligin-2 knockdown in the striatum, a significant decrease of dopamine synapses coupled with a reciprocal increase of GABAergic synapses was observed on MSN dendrites. This finding suggests that neuroligin-2 controls striatal synapse formation by giving competitive advantage to heterologous dopamine synapses over conventional GABAergic synapses. Considering that MSN dendrites are preferential targets of dopamine synapses and express high levels of dopamine receptors, dopamine synapse formation may serve to increase the specificity and potency of dopaminergic modulation of striatal outputs by anchoring dopamine release sites to dopamine-sensing targets. PMID:27035941

Protecting-group-free synthesis of amines: synthesis of primary amines from aldehydes via reductive amination.

PubMed

Dangerfield, Emma M; Plunkett, Catherine H; Win-Mason, Anna L; Stocker, Bridget L; Timmer, Mattie S M

2010-08-20

New methodology for the protecting-group-free synthesis of primary amines is presented. By optimizing the metal hydride/ammonia mediated reductive amination of aldehydes and hemiacetals, primary amines were selectively prepared with no or minimal formation of the usual secondary and tertiary amine byproduct. The methodology was performed on a range of functionalized aldehyde substrates, including in situ formed aldehydes from a Vasella reaction. These reductive amination conditions provide a valuable synthetic tool for the selective production of primary amines in fewer steps, in good yields, and without the use of protecting groups.

Dopamine-Independent Locomotor Actions of Amphetamines in a Novel Acute Mouse Model of Parkinson Disease

PubMed Central

Sotnikova, Tatyana D; Beaulieu, Jean-Martin; Barak, Larry S; Wetsel, William C; Gainetdinov, Raul R

2005-01-01

Brain dopamine is critically involved in movement control, and its deficiency is the primary cause of motor symptoms in Parkinson disease. Here we report development of an animal model of acute severe dopamine deficiency by using mice lacking the dopamine transporter. In the absence of transporter-mediated recycling mechanisms, dopamine levels become entirely dependent on de novo synthesis. Acute pharmacological inhibition of dopamine synthesis in these mice induces transient elimination of striatal dopamine accompanied by the development of a striking behavioral phenotype manifested as severe akinesia, rigidity, tremor, and ptosis. This phenotype can be reversed by administration of the dopamine precursor, L-DOPA, or by nonselective dopamine agonists. Surprisingly, several amphetamine derivatives were also effective in reversing these behavioral abnormalities in a dopamine-independent manner. Identification of dopamine transporter- and dopamine-independent locomotor actions of amphetamines suggests a novel paradigm in the search for prospective anti-Parkinsonian drugs. PMID:16050778

Psychostimulants affect dopamine transmission through both dopamine transporter-dependent and independent mechanisms

PubMed Central

dela Peña, Ike; Gevorkiana, Ruzanna; Shi, Wei-Xing

2015-01-01

The precise mechanisms by which cocaine and amphetamine-like psychostimulants exert their reinforcing effects are not yet fully defined. It is widely believed, however, that these drugs produce their effects by enhancing dopamine neurotransmission in the brain, especially in limbic areas such as the nucleus accumbens, by inducing dopamine transporter-mediated reverse transport and/or blocking dopamine reuptake though the dopamine transporter. Here, we present the evidence that aside from dopamine transporter, non-dopamine transporter-mediated mechanisms also participate in psychostimulant-induced dopamine release and contribute to the behavioral effects of these drugs, such as locomotor activation and reward. Accordingly, psychostimulants could increase norepinephrine release in the prefrontal cortex, the latter then alters the firing pattern of dopamine neurons resulting in changes in action potential-dependent dopamine release. These alterations would further affect the temporal pattern of dopamine release in the nucleus accumbens, thereby modifying information processing in that area. Hence, a synaptic input to a nucleus accumbens neuron may be enhanced or inhibited by dopamine depending on its temporal relationship to dopamine release. Specific temporal patterns of dopamine release may also be required for certain forms of synaptic plasticity in the nucleus accumbens. Together, these effects induced by psychostimulants, mediated through a non-dopamine transporter-mediated mechanism involving norepinephrine and the prefrontal cortex, may also contribute importantly to the reinforcing properties of these drugs. PMID:26209364

Important roles of enthalpic and entropic contributions to CO2 capture from simulated flue gas and ambient air using mesoporous silica grafted amines.

PubMed

Alkhabbaz, Mustafa A; Bollini, Praveen; Foo, Guo Shiou; Sievers, Carsten; Jones, Christopher W

2014-09-24

The measurement of isosteric heats of adsorption of silica supported amine materials in the low pressure range (0-0.1 bar) is critical for understanding the interactions between CO2 and amine sites at low coverage and hence to the development of efficient amine adsorbents for CO2 capture from flue gas and ambient air. Heats of adsorption for an array of silica-supported amine materials are experimentally measured at low coverage using a Calvet calorimeter equipped with a customized dosing manifold. In a series of 3-aminopropyl-functionalized silica materials, higher amine densities resulted in higher isosteric heats of adsorption, clearly showing that the density/proximity of amine sites can influence the amine efficiency of adsorbents. In a series of materials with fixed amine loading but different amine types, strongly basic primary and secondary amine materials are shown to have essentially identical heats of adsorption near 90 kJ/mol. However, the adsorption uptakes vary substantially as a function of CO2 partial pressure for different primary and secondary amines, demonstrating that entropic contributions to adsorption may play a key role in adsorption at secondary amine sites, making adsorption at these sites less efficient at the low coverages that are important to the direct capture of CO2 from ambient air. Thus, while primary amines are confirmed to be the most effective amine types for CO2 capture from ambient air, this is not due to enhanced enthalpic contributions associated with primary amines over secondary amines, but may be due to unfavorable entropic factors associated with organization of the second alkyl chain on the secondary amine during CO2 adsorption. Given this hypothesis, favorable entropic factors may be the main reason primary amine based adsorbents are more effective under air capture conditions.

Trimethylaluminum and borane complexes of primary amines.

PubMed

Németh, Balázs; Guégan, Jean-Paul; Veszprémi, Tamás; Guillemin, Jean-Claude

2013-01-07

Trimethylaluminum (TMA) complexes of methyl-, n-propyl-, cyclopropyl-, allyl-, and propargylamine were synthesized and their experimental properties and theoretical characteristics were compared with the respective amine-borane analogues. The amine ligand of an amine-TMA Lewis acid-base complex can be easily changed by another amine through a 2:1 amine-TMA intermediate in pentane at room temperature. The exchange of the same ligands in the case of amine-boranes requires remarkably more time in line with the calculated relative energy of the respective transition state. The (1)H and (13)C NMR experiments examining the addition of one or more equivalent of amine to the respective Lewis acid-base complex conclude in the fast exchange of the amine ligand in the NMR time scale only in the cases of amine-TMA complexes, which could also be caused by similar 2:1 complexes. However, in gas phase, only 1:1 amine-TMA complexes are present as evidenced by ultraviolet photoelectron spectroscopy (UPS). The observed UP spectra, which are the first recorded photoelectron spectra of primary amine-TMA compounds, indicate that the stabilization effect of the lone electron pair of nitrogen atom in amines during the borane complexation is stronger than that of the TMA complexation. In line with this observation, the destabilization of the σ(Al-C) orbitals is lower than that of σ(B-H) orbitals during the formation of amine-TMA and amine-borane complexes, respectively. As showed by theoretical calculations, the CH(4) elimination of the studied amine-TMA complexes is exothermic, indicating the possibility of using these compounds in metal organic chemical vapor deposition techniques (MOCVD). On the other hand, our experimental conditions avoid this methane elimination and constitutes the first procedure employing distillation to isolate primary amine-TMA complexes.

Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids

PubMed Central

Covey, Dan P.; Bunner, Kendra D.; Schuweiler, Douglas R.; Cheer, Joseph F.; Garris, Paul A.

2018-01-01

The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement. PMID:27038339

Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

PubMed

Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

2016-06-01

The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Atmospheric Amines and Ammonia Measured with a Chemical Ionization Mass Spectrometer (CIMS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

You, Y.; Kanawade, V. P.; de Gouw, J. A.

We report ambient measurements of amines and ammonia with a fast response chemical ionization mass spectrometer (CIMS) in a Southeastern U.S. forest in Alabama and a moderately polluted Midwestern site during the summer. In the Alabama forest, mostly C3-amines (from pptv to tens of pptv) and ammonia (up to 2 ppbv) were detected on a daily basis. C3-amines and ammonia showed similar diurnal trends and temperature and wind direction dependences, and were not associated with transported CO and SO2 plumes. Consistent with temperature dependences, amine and ammonia in the gas and aerosol phases showed opposite diurnal trends, indicating gas-to-particle partitioningmore » of amines and ammonia. Temperature dependences also imply reversible processes of amines and ammonia evaporation from soil surfaces in daytime and deposition of amines and ammonia to soil surfaces at nighttime. Various amines (C1-C6) at the pptv level were observed in the transported biomass burning plumes, showing that biomass burning can be a substantial source of amines in the Southeast U.S. At the moderately polluted Kent site, higher concentrations of amines (C1-C6, from pptv to tens of pptv) and ammonia (up to 6 ppbv) were detected. Diurnal variations of C1- to C3-amines and ammonia were correlated with the ambient temperature. C4- to C6-amines showed abrupt increases during the nighttime, suggesting that they were emitted from local sources. These abundant amines and ammonia may in part explain the frequent new particle formation events reported from Kent. Lower amine concentrations at the rural forested site highlight the importance of constraining anthropogenic sources of amines.« less

Development of a general non-noble metal catalyst for the benign amination of alcohols with amines and ammonia.

PubMed

Cui, Xinjiang; Dai, Xingchao; Deng, Youquan; Shi, Feng

2013-03-11

The N-alkylation of amines or ammonia with alcohols is a valuable route for the synthesis of N-alkyl amines. However, as a potentially clean and economic choice for N-alkyl amine synthesis, non-noble metal catalysts with high activity and good selectivity are rarely reported. Normally, they are severely limited due to low activity and poor generality. Herein, a simple NiCuFeOx catalyst was designed and prepared for the N-alkylation of ammonia or amines with alcohol or primary amines. N-alkyl amines with various structures were successfully synthesized in moderate to excellent yields in the absence of organic ligands and bases. Typically, primary amines could be efficiently transformed into secondary amines and N-heterocyclic compounds, and secondary amines could be N-alkylated to synthesize tertiary amines. Note that primary and secondary amines could be produced through a one-pot reaction of ammonia and alcohols. In addition to excellent catalytic performance, the catalyst itself possesses outstanding superiority, that is, it is air and moisture stable. Moreover, the magnetic property of this catalyst makes it easily separable from the reaction mixture and it could be recovered and reused for several runs without obvious deactivation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals

PubMed Central

Daberkow, DP; Brown, HD; Bunner, KD; Kraniotis, SA; Doellman, MA; Ragozzino, ME; Garris, PA; Roitman, MF

2013-01-01

Drugs of abuse hijack brain reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting non-exocytotic dopamine efflux via reverse transport. This mechanism of AMPH action, though, is inconsistent with its therapeutic effects and addictive properties - which are thought to be reliant on phasic dopamine signaling. Here we used fast-scan cyclic voltammetry in freely moving rats to interrogate principal neurochemical responses to AMPH in the striatum and relate these changes to behavior. First, we showed that AMPH dose-dependently enhanced evoked dopamine responses to phasic-like current pulse trains for up to two hours. Modeling the data revealed that AMPH inhibited dopamine uptake but also unexpectedly potentiated vesicular dopamine release. Second, we found that AMPH increased the amplitude, duration and frequency of spontaneous dopamine transients, the naturally occurring, non-electrically evoked, phasic increases in extracellular dopamine. Finally, using an operant sucrose reward paradigm, we showed that low-dose AMPH augmented dopamine transients elicited by sucrose-predictive cues. However, operant behavior failed at high-dose AMPH, which was due to phasic dopamine hyperactivity and the decoupling of dopamine transients from the reward predictive cue. These findings identify up-regulation of exocytotic dopamine release as a key AMPH action in behaving animals and support a unified mechanism of abused drugs to activate phasic dopamine signaling. PMID:23303926

Acute fasting increases somatodendritic dopamine release in the ventral tegmental area

PubMed Central

2015-01-01

Fasting and food restriction alter the activity of the mesolimbic dopamine system to affect multiple reward-related behaviors. Food restriction decreases baseline dopamine levels in efferent target sites and enhances dopamine release in response to rewards such as food and drugs. In addition to releasing dopamine from axon terminals, dopamine neurons in the ventral tegmental area (VTA) also release dopamine from their soma and dendrites, and this somatodendritic dopamine release acts as an autoinhibitory signal to inhibit neighboring VTA dopamine neurons. It is unknown whether acute fasting also affects dopamine release, including the local inhibitory somatodendritic dopamine release in the VTA. In these studies, I have tested whether fasting affects the inhibitory somatodendritic dopamine release within the VTA by examining whether an acute 24-h fast affects the inhibitory postsynaptic current mediated by evoked somatodendritic dopamine release (D2R IPSC). Fasting increased the contribution of the first action potential to the overall D2R IPSC and increased the ratio of repeated D2R IPSCs evoked at short intervals. Fasting also reduced the effect of forskolin on the D2R IPSC and led to a significantly bigger decrease in the D2R IPSC in low extracellular calcium. Finally, fasting resulted in an increase in the D2R IPSCs when a more physiologically relevant train of D2R IPSCs was used. Taken together, these results indicate that fasting caused a change in the properties of somatodendritic dopamine release, possibly by increasing dopamine release, and that this increased release can be sustained under conditions where dopamine neurons are highly active. PMID:26084913

Allylic aminations with hindered secondary amine nucleophiles catalyzed by heterobimetallic Pd-Ti complexes.

PubMed

Walker, Whitney K; Anderson, Diana L; Stokes, Ryjul W; Smith, Stacey J; Michaelis, David J

2015-02-06

Phosphinoamide-scaffolded heterobimetallic palladium-titanium complexes are highly effective catalysts for allylic aminations of allylic chlorides with hindered secondary amine nucleophiles. Three titanium-containing ligands are shown to assemble active catalysts in situ and enable catalysis at room temperature. A variety of sterically bulky secondary amines are efficiently allylated in high yields with as little as 1 mol % palladium catalyst. Piperidine and pyrrolidine products are also efficiently generated via intramolecular aminations with hindered amine nucleophiles.

Drosophila insulin-producing cells are differentially modulated by serotonin and octopamine receptors and affect social behavior.

PubMed

Luo, Jiangnan; Lushchak, Oleh V; Goergen, Philip; Williams, Michael J; Nässel, Dick R

2014-01-01

A set of 14 insulin-producing cells (IPCs) in the Drosophila brain produces three insulin-like peptides (DILP2, 3 and 5). Activity in IPCs and release of DILPs is nutrient dependent and controlled by multiple factors such as fat body-derived proteins, neurotransmitters, and neuropeptides. Two monoamine receptors, the octopamine receptor OAMB and the serotonin receptor 5-HT1A, are expressed by the IPCs. These receptors may act antagonistically on adenylate cyclase. Here we investigate the action of the two receptors on activity in and output from the IPCs. Knockdown of OAMB by targeted RNAi led to elevated Dilp3 transcript levels in the brain, whereas 5-HT1A knockdown resulted in increases of Dilp2 and 5. OAMB-RNAi in IPCs leads to extended survival of starved flies and increased food intake, whereas 5-HT1A-RNAi produces the opposite phenotypes. However, knockdown of either OAMB or 5-HT1A in IPCs both lead to increased resistance to oxidative stress. In assays of carbohydrate levels we found that 5-HT1A knockdown in IPCs resulted in elevated hemolymph glucose, body glycogen and body trehalose levels, while no effects were seen after OAMB knockdown. We also found that manipulations of the two receptors in IPCs affected male aggressive behavior in different ways and 5-HT1A-RNAi reduced courtship latency. Our observations suggest that activation of 5-HT1A and OAMB signaling in IPCs generates differential effects on Dilp transcription, fly physiology, metabolism and social interactions. However the findings do not support an antagonistic action of the two monoamines and their receptors in this particular system.

Decoding the Dopamine Signal in Macaque Prefrontal Cortex: A Simulation Study Using the Cx3Dp Simulator

PubMed Central

Spühler, Isabelle Ayumi; Hauri, Andreas

2013-01-01

Dopamine transmission in the prefrontal cortex plays an important role in reward based learning, working memory and attention. Dopamine is thought to be released non-synaptically into the extracellular space and to reach distant receptors through diffusion. This simulation study examines how the dopamine signal might be decoded by the recipient neuron. The simulation was based on parameters from the literature and on our own quantified, structural data from macaque prefrontal area 10. The change in extracellular dopamine concentration was estimated at different distances from release sites and related to the affinity of the dopamine receptors. Due to the sparse and random distribution of release sites, a transient heterogeneous pattern of dopamine concentration emerges. Our simulation predicts, however, that at any point in the simulation volume there is sufficient dopamine to bind and activate high-affinity dopamine receptors. We propose that dopamine is broadcast to its distant receptors and any change from the local baseline concentration might be decoded by a transient change in the binding probability of dopamine receptors. Dopamine could thus provide a graduated ‘teaching’ signal to reinforce concurrently active synapses and cell assemblies. In conditions of highly reduced or highly elevated dopamine levels the simulations predict that relative changes in the dopamine signal can no longer be decoded, which might explain why cognitive deficits are observed in patients with Parkinson’s disease, or induced through drugs blocking dopamine reuptake. PMID:23951205

Amine dehydrogenases: efficient biocatalysts for the reductive amination of carbonyl compounds.

PubMed

Knaus, Tanja; Böhmer, Wesley; Mutti, Francesco G

2017-01-21

Amines constitute the major targets for the production of a plethora of chemical compounds that have applications in the pharmaceutical, agrochemical and bulk chemical industries. However, the asymmetric synthesis of α-chiral amines with elevated catalytic efficiency and atom economy is still a very challenging synthetic problem. Here, we investigated the biocatalytic reductive amination of carbonyl compounds employing a rising class of enzymes for amine synthesis: amine dehydrogenases (AmDHs). The three AmDHs from this study - operating in tandem with a formate dehydrogenase from Candida boidinii (Cb-FDH) for the recycling of the nicotinamide coenzyme - performed the efficient amination of a range of diverse aromatic and aliphatic ketones and aldehydes with up to quantitative conversion and elevated turnover numbers (TONs). Moreover, the reductive amination of prochiral ketones proceeded with perfect stereoselectivity, always affording the ( R )-configured amines with more than 99% enantiomeric excess. The most suitable amine dehydrogenase, the optimised catalyst loading and the required reaction time were determined for each substrate. The biocatalytic reductive amination with this dual-enzyme system (AmDH-Cb-FDH) possesses elevated atom efficiency as it utilizes the ammonium formate buffer as the source of both nitrogen and reducing equivalents. Inorganic carbonate is the sole by-product.

Dopamine D1 and D2 Receptor Immunoreactivities in the Arcuate-Median Eminence Complex and their Link to the Tubero-Infundibular Dopamine Neurons

PubMed Central

Romero-Fernandez, W.; Borroto-Escuela, D.O.; Vargas-Barroso, V.; Narváez, M.; Di Palma, M.; Agnati, L.F.; Sahd, J. Larriva

2014-01-01

Dopamine D1 and D2 receptor immunohistochemistry and Golgi techniques were used to study the structure of the adult rat arcuate-median eminence complex, and determine the distribution of the dopamine D1 and D2 receptor immunoreactivities therein, particularly in relation to the tubero-infundibular dopamine neurons. Punctate dopamine D1 and D2 receptor immunoreactivities, likely located on nerve terminals, were enriched in the lateral palisade zone built up of nerve terminals, while the densities were low to modest in the medial palisade zone. A codistribution of dopamine D1 receptor or dopamine D2 receptor immunoreactive puncta with tyrosine hydroxylase immunoreactive nerve terminals was demonstrated in the external layer. Dopamine D1 receptor but not dopamine D2 receptor immnunoreactivites nerve cell bodies were found in the ventromedial part of the arcuate nucleus and in the lateral part of the internal layer of the median eminence forming a continuous cell mass presumably representing neuropeptide Y immunoreactive nerve cell bodies. The major arcuate dopamine/ tyrosine hydroxylase nerve cell group was found in the dorsomedial part. A large number of tyrosine hydroxylase immunoreactive nerve cell bodies in this region demonstrated punctate dopamine D1 receptor immunoreactivity but only a few presented dopamine D2 receptor immunoreactivity which were mainly found in a substantial number of tyrosine hydroxylase cell bodies of the ventral periventricular hypothalamic nucleus, also belonging to the tuberoinfundibular dopamine neurons. Structural evidence for projections of the arcuate nerve cells into the median eminence was also obtained. Distal axons formed horizontal axons in the internal layer issuing a variable number of collaterals classified into single or multiple strands located in the external layer increasing our understanding of the dopamine nerve terminal networks in this region. Dopamine D1 and D2 receptors may therefore directly and differentially modulate the activity and/or Dopamine synthesis of substantial numbers of tubero-infundibular dopamine neurons at the somatic and terminal level. The immunohistochemical work also gives support to the view that dopamine D1 receptors and/or dopamine D2 receptors in the lateral palisade zone by mediating dopamine volume transmission may contribute to the inhibition of luteinizing hormone releasing hormone release from nerve terminals in this region. PMID:25308843

Dopamine D1 and D2 receptor immunoreactivities in the arcuate-median eminence complex and their link to the tubero-infundibular dopamine neurons.

PubMed

Romero-Fernandez, W; Borroto-Escuela, D O; Vargas-Barroso, V; Narváez, M; Di Palma, M; Agnati, L F; Larriva Sahd, J; Fuxe, K

2014-07-18

Dopamine D1 and D2 receptor immunohistochemistry and Golgi techniques were used to study the structure of the adult rat arcuate-median eminence complex, and determine the distribution of the dopamine D1 and D2 receptor immunoreactivities therein, particularly in relation to the tubero-infundibular dopamine neurons. Punctate dopamine D1 and D2 receptor immunoreactivities, likely located on nerve terminals, were enriched in the lateral palisade zone built up of nerve terminals, while the densities were low to modest in the medial palisade zone. A codistribution of dopamine D1 receptor or dopamine D2 receptor immunoreactive puncta with tyrosine hydroxylase immunoreactive nerve terminals was demonstrated in the external layer. Dopamine D1 receptor but not dopamine D2 receptor immnunoreactivites nerve cell bodies were found in the ventromedial part of the arcuate nucleus and in the lateral part of the internal layer of the median eminence forming a continuous cell mass presumably representing neuropeptide Y immunoreactive nerve cell bodies. The major arcuate dopamine/ tyrosine hydroxylase nerve cell group was found in the dorsomedial part. A large number of tyrosine hydroxylase immunoreactive nerve cell bodies in this region demonstrated punctate dopamine D1 receptor immunoreactivity but only a few presented dopamine D2 receptor immunoreactivity which were mainly found in a substantial number of tyrosine hydroxylase cell bodies of the ventral periventricular hypothalamic nucleus, also belonging to the tubero-infundibular dopamine neurons. Structural evidence for projections of the arcuate nerve cells into the median eminence was also obtained. Distal axons formed horizontal axons in the internal layer issuing a variable number of collaterals classified into single or multiple strands located in the external layer increasing our understanding of the dopamine nerve terminal networks in this region.  Dopamine D1 and D2 receptors may therefore directly and differentially modulate the activity and /or Dopamine synthesis of substantial numbers of tubero-infundibular dopamine neurons at the somatic and terminal level. The immunohistochemical work also gives support to the view that dopamine D1 receptors and/or dopamine D2 receptors in the lateral palisade zone by mediating dopamine volume transmission may contribute to the inhibition of luteinizing hormone releasing hormone release from nerve terminals in this region.

Cholinergic Interneurons Underlie Spontaneous Dopamine Release in Nucleus Accumbens

PubMed Central

2017-01-01

The release of dopamine from terminals in the NAc is regulated by a number of factors, including voltage-gated ion channels, D2-autoreceptors, and nAChRs. Cholinergic interneurons (CINs) drive dopamine release through activation of nAChRs on dopamine terminals. Using cyclic voltammetry in mouse brain slices, nAChR-dependent spontaneous dopamine transients and the mechanisms underlying the origin were examined in the NAc. Spontaneous events were infrequent (0.3 per minute), but the rate and amplitude were increased after blocking Kv channels with 4-aminopyridine. Although the firing frequency of CINs was increased by blocking glutamate reuptake with TBOA and the Sk blocker apamin, only 4-aminopyridine increased the frequency of dopamine transients. In contrast, inhibition of CIN firing with the μ/δ selective opioid [Met5]enkephalin (1 μm) decreased spontaneous dopamine transients. Cocaine increased the rate and amplitude of dopamine transients, suggesting that the activity of the dopamine transporter limits the detection of these events. In the presence of cocaine, the rate of spontaneous dopamine transients was further increased after blocking D2-autoreceptors. Blockade of muscarinic receptors had no effect on evoked dopamine release, suggesting that feedback inhibition of acetylcholine release was not involved. Thus, although spontaneous dopamine transients are reliant on nAChRs, the frequency was not strictly governed by the activity of CINs. The increase in frequency of spontaneous dopamine transients induced by cocaine was not due to an increase in cholinergic tone and is likely a product of an increase in detection resulting from decreased dopamine reuptake. SIGNIFICANCE STATEMENT The actions of dopamine in the NAc are thought to be responsible for endogenous reward and the reinforcing properties of drugs of abuse, such as psychostimulants. The present work examines the mechanisms underlying nAChR-induced spontaneous dopamine release. This study demonstrates that spontaneous dopamine release is (1) dependent of the activation of nicotinic receptors, (2) independent on the spontaneous activity of cholinergic interneurons, and (3) that cocaine increased the detection of dopamine transients by prolonging the presence and increasing the diffusion of dopamine in the extracellular space. The release of acetylcholine is therefore responsible for spontaneous dopamine transients, and cocaine augments dopamine tone without altering activity of cholinergic interneurons. PMID:28115487

Metal and base free synthesis of primary amines via ipso amination of organoboronic acids mediated by [bis(trifluoroacetoxy)iodo]benzene (PIFA).

PubMed

Chatterjee, Nachiketa; Goswami, Avijit

2015-08-07

A metal and base free synthesis of primary amines has been developed at ambient temperature through ipso amination of diversely functionalized organoboronic acids, employing a combination of [bis(trifluoroacetoxy)iodo]benzene (PIFA)-N-bromosuccinimide (NBS) and methoxyamine hydrochloride as the aminating reagent. The amines were primarily obtained as their trifluoroacetate salts which on subsequent aqueous alkaline work up provided the corresponding free amines. The combination of PIFA-NBS is found to be the mildest choice compared to the commonly used strong bases (e.g. n-BuLi, Cs2CO3) for activating the aminating agent. The reaction is expected to proceed via activation of the aminating reagent followed by B-N 1,2-aryl migration.

Opposite initialization to novel cues in dopamine signaling in ventral and posterior striatum in mice

PubMed Central

Menegas, William; Babayan, Benedicte M; Uchida, Naoshige; Watabe-Uchida, Mitsuko

2017-01-01

Dopamine neurons are thought to encode novelty in addition to reward prediction error (the discrepancy between actual and predicted values). In this study, we compared dopamine activity across the striatum using fiber fluorometry in mice. During classical conditioning, we observed opposite dynamics in dopamine axon signals in the ventral striatum (‘VS dopamine’) and the posterior tail of the striatum (‘TS dopamine’). TS dopamine showed strong excitation to novel cues, whereas VS dopamine showed no responses to novel cues until they had been paired with a reward. TS dopamine cue responses decreased over time, depending on what the cue predicted. Additionally, TS dopamine showed excitation to several types of stimuli including rewarding, aversive, and neutral stimuli whereas VS dopamine showed excitation only to reward or reward-predicting cues. Together, these results demonstrate that dopamine novelty signals are localized in TS along with general salience signals, while VS dopamine reliably encodes reward prediction error. DOI: http://dx.doi.org/10.7554/eLife.21886.001 PMID:28054919

Role of amine structure on carbon dioxide adsorption from ultradilute gas streams such as ambient air.

PubMed

Didas, Stephanie A; Kulkarni, Ambarish R; Sholl, David S; Jones, Christopher W

2012-10-01

A fundamental study on the adsorption properties of primary, secondary, and tertiary amine materials is used to evaluate what amine type(s) are best suited for ultradilute CO(2) capture applications. A series of comparable materials comprised of primary, secondary, or tertiary amines ligated to a mesoporous silica support via a propyl linker are used to systematically assess the role of amine type. Both CO(2) and water adsorption isotherms are presented for these materials in the range relevant to CO(2) capture from ambient air and it is demonstrated that primary amines are the best candidates for CO(2) capture from air. Primary amines possess both the highest amine efficiency for CO(2) adsorption as well as enhanced water affinity compared to other amine types or the bare silica support. The results suggest that the rational design of amine adsorbents for the extraction of CO(2) from ambient air should focus on adsorbents rich in primary amines. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The direct reductive amination of electron-deficient amines with aldehydes: the unique reactivity of the Re2O7 catalyst.

PubMed

Das, Braja Gopal; Ghorai, Prasanta

2012-08-25

An unprecedented direct reductive amination of electron-deficient amines such as Cbz-, Boc-, EtOCO-, Fmoc-, Bz-, ArSO(2)-, Ar(2)PO-, etc. protected amines with aldehydes is achieved using the Re(2)O(7) catalyst and silanes as the hydride source. Excellent regioselective mono-alkylation and chemoselective reductive-amination were observed.

Ventral tegmental ionotropic glutamate receptor stimulation of nucleus accumbens tonic dopamine efflux blunts hindbrain-evoked phasic neurotransmission: implications for dopamine dysregulation disorders.

PubMed

Tye, S J; Miller, A D; Blaha, C D

2013-11-12

Activation of glutamate receptors within the ventral tegmental area (VTA) stimulates extrasynaptic (basal) dopamine release in terminal regions, including the nucleus accumbens (NAc). Hindbrain inputs from the laterodorsal tegmental nucleus (LDT) are critical for elicitation of phasic VTA dopamine cell activity and consequent transient dopamine release. This study investigated the role of VTA ionotropic glutamate receptor (iGluR) stimulation on both basal and LDT electrical stimulation-evoked dopamine efflux in the NAc using in vivo chronoamperometry and fixed potential amperometry in combination with stearate-graphite paste and carbon fiber electrodes, respectively. Intra-VTA infusion of the iGluR agonists (±)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; 1 μg/μl) or N-methyl-d-aspartic acid (NMDA; 2 μg/μl) enhanced basal NAc dopamine efflux. This iGluR-mediated potentiation of basal dopamine efflux was paralleled by an attenuation of LDT-evoked transient NAc dopamine efflux, suggesting that excitation of basal activity effectively inhibited the capacity of hindbrain afferents to elicit transient dopamine efflux. In line with this, post-NMDA infusion of the dopamine D2 autoreceptor (D2R) agonist quinpirole (1 μg/μl; intra-VTA) partially recovered NMDA-mediated attenuation of LDT-evoked NAc dopamine, while concurrently attenuating NMDA-mediated potentiation of basal dopamine efflux. Post-NMDA infusion of quinpirole (1 μg/μl) alone attenuated basal and LDT-evoked dopamine efflux. Taken together, these data reveal that hyperstimulation of basal dopamine transmission can stunt hindbrain burst-like stimulation-evoked dopamine efflux. Inhibitory autoreceptor mechanisms within the VTA help to partially recover the magnitude of phasic dopamine efflux, highlighting the importance of both iGluRs and D2 autoreceptors in maintaining the functional balance of tonic and phasic dopamine neurotransmission. Dysregulation of this balance may have important implications for disorders of dopamine dysregulation such as attention deficit hyperactivity disorder. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Concentration, size distribution and dry deposition of amines in atmospheric particles of urban Guangzhou, China

NASA Astrophysics Data System (ADS)

Liu, Fengxian; Bi, Xinhui; Zhang, Guohua; Peng, Long; Lian, Xiufeng; Lu, Huiying; Fu, Yuzhen; Wang, Xinming; Peng, Ping'an; Sheng, Guoying

2017-12-01

Size-segregated PM10 samples were collected in Guangzhou, China during autumn of 2014. Nine amines, including seven aliphatic amines and two heterocyclic amines, were detected using a gas chromatography-mass spectrometer after derivatization by benzenesulfonyl chloride. The total concentration of the nine amines (Ʃamines) was 79.6-140.9 ng m-3 in PM10. The most abundant species was methylamine (MA), which had a concentration of 29.2-70.1 ng m-3. MA, dimethylamine (DMA), diethylamine (DEA) and dibutylamine (DBA) were the predominant amines in the samples and accounted for approximately 80% of Ʃamines in each size segment. Two heterocyclic amines, pyrrolidine (PYR) and morpholine (MOR), were detected in all samples and had average concentrations of 1.14 ± 0.37 and 1.89 ± 0.64 ng m-3, respectively, in particles with aerodynamic diameters < 3 μm. More than 80% of Ʃamines were found in particles with diameters <1.5 μm, indicating that amines are mainly enriched in fine particles. All amines exhibited a bimodal distribution with a fine mode at 0.49-1.5 μm and a coarse mode at 7.2-10 μm. The maximum contributions of amines to particles (0.21%) and amines-N to water-soluble organic nitrogen (WSON) (3.1%) were found at the sizes < 0.49 μm. The maximum contribution of amines-C to water-soluble organic carbon (WSOC) was 1.6% over the size range of 0.95-1.5 μm. The molar ratio of Ʃamines to ammonium ranged from 0.0068 to 0.0107 in particles with diameters <1.5 μm, and the maximum ratio occurred in the smallest particles (diameter< 0.49 μm). The average dry deposition flux and velocity of Ʃamines in PM10 were 7.9 ± 1.6 μg m-2 d-1 and 0.084 ± 0.0021 cm s-1, respectively. The results of this study provide essential information on the contribution of amines to secondary organic aerosols and dry removal mechanisms in urban areas.

Lack of dopamine supersensitivity in rats after chronic administration of blonanserin: Comparison with haloperidol.

PubMed

Hashimoto, Takashi; Baba, Satoko; Ikeda, Hiroko; Oda, Yasunori; Hashimoto, Kenji; Shimizu, Isao

2018-07-05

Long-term treatment with antipsychotic drugs in patients with schizophrenia can lead to dopamine supersensitivity psychosis. It is reported that repeated administration of haloperidol caused dopamine supersensitivity in rats. Blonanserin is an atypical antipsychotic drug with high affinity for dopamine D 2 , D 3 and serotonin 2A receptors. In this study, we investigated whether chronic administration of blonanserin leads to dopamine supersensitivity. Following oral treatment with blonanserin (0.78 mg/kg) or haloperidol (1.1 mg/kg) twice daily for 28 days, the dopamine D 2 agonist quinpirole-induced hyperlocomotion test and a dopamine D 2 receptor binding assay were conducted. We found that haloperidol significantly enhanced both quinpirole-induced hyperlocomotion and striatal dopamine D 2 receptor density in rats. On the other hand, repeated administration of blonanserin had no effect on either locomotor activity or striatal dopamine D 2 receptor density. Further, our results show that mRNA levels of dopamine D 2 and D 3 receptors in several brain regions were unaffected by repeated administration of both agents. In addition, we examined the effect of the dopamine D 3 receptor antagonist PG-01037 on development of dopamine supersensitivity induced by chronic haloperidol treatment and showed that PG-01037 prevents the development of supersensitivity to quinpirole in chronic haloperidol-treated rats. Given the higher affinity of blonanserin at dopamine D 3 receptors than haloperidol, antagonism of blonanserin at dopamine D 3 receptors may play a role in lack of dopamine supersensitivity after chronic administration. The present findings suggest long-term treatment with antipsychotic dose of blonanserin may be unlikely to lead to dopamine supersensitivity. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

PET evaluation of the dopamine system of the human brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volkow, N.D.; Fowler, J.S.; Gatley, S.

1996-07-01

Dopamine plays a pivotal role in the regulation and control of movement, motivation and cognition. It also is closely linked to reward, reinforcement and addiction. Abnormalities in brain dopamine are associated with many neurological and psychiatric disorders including Parkinson`s disease, schizophrenia and substance abuse. This close association between dopamine and neurological and psychiatric diseases and with substance abuse make it an important topic in research in the neurosciences and an important molecular target in drug development. PET enables the direct measurement of components of the dopamine system in the living human brain. It relies on radiotracers which label dopamine receptors,more » dopamine transporters, precursors of dopamine or compounds which have specificity for the enzymes which degrade dopamine. Additionally, by using tracers that provide information on regional brain metabolism or blood flow as well as neurochemically specific pharmacological interventions, PET can be used to assess the functional consequences of change in brain dopamine activity. PET dopamine measurements have been used to investigate the normal human brain and its involvement in psychiatric and neurological diseases. It has also been used in psychopharmacological research to investigate dopamine drugs used in the treatment of Parkinson`s disease and of schizophrenia as well as to investigate the effects of drugs of abuse on the dopamine system. Since various functional and neurochemical parameters can be studied in the same subject, PET enables investigation of the functional integrity of the dopamine system in the human brain and investigation of the interactions of dopamine with other neurotransmitters. This paper summarizes the different tracers and experimental strategies developed to evaluate the various elements of the dopamine system in the human brain with PET and their applications to clinical research. 254 refs., 7 figs., 3 tabs.« less

Adenosine transiently modulates stimulated dopamine release in the caudate putamen via A1 receptors

PubMed Central

Ross, Ashley E.; Venton, B. Jill

2014-01-01

Adenosine modulates dopamine in the brain via A1 and A2A receptors, but that modulation has only been characterized on a slow time scale. Recent studies have characterized a rapid signaling mode of adenosine that suggests a possible rapid modulatory role. Here, fast-scan cyclic voltammetry was used to characterize the extent to which transient adenosine changes modulate stimulated dopamine release (5 pulses at 60 Hz) in rat caudate putamen brain slices. Exogenous adenosine was applied and dopamine concentration monitored. Adenosine only modulated dopamine when it was applied 2 or 5 s before stimulation. Longer time intervals and bath application of 5 µM adenosine did not decrease dopamine release. Mechanical stimulation of endogenous adenosine 2s before dopamine stimulation also decreased stimulated dopamine release by 41 ± 7 %, similar to the 54 ± 6 % decrease in dopamine after exogenous adenosine application. Dopamine inhibition by transient adenosine was recovered within 10 minutes. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) blocked the dopamine modulation, whereas dopamine modulation was unaffected by the A2A receptor antagonist SCH 442416. Thus, transient adenosine changes can transiently modulate phasic dopamine release via A1 receptors. These data demonstrate that adenosine has a rapid, but transient, modulatory role in the brain. PMID:25219576

The Role of D2-Autoreceptors in Regulating Dopamine Neuron Activity and Transmission

PubMed Central

Ford, Christopher P

2014-01-01

Dopamine D2-autoreceptors play a key role in regulating the activity of dopamine neurons and control the synthesis, release and uptake of dopamine. These Gi/o-coupled inhibitory receptors play a major part in shaping dopamine transmission. Found at both somatodendritic and axonal sites, autoreceptors regulate the firing patterns of dopamine neurons and control the timing and amount of dopamine released from their terminals in target regions. Alterations in the expression and activity of autoreceptors are thought to contribute to Parkinson’s disease as well as schizophrenia, drug addiction and attention deficit hyperactivity disorder (ADHD), which emphasizes the importance of D2-autoreceptors in regulating the dopamine system. This review will summarize the cellular actions of dopamine autoreceptors and discuss recent advances that have furthered our understanding of the mechanisms by which D2-receptors control dopamine transmission. PMID:24463000

Dynamic nigrostriatal dopamine biases action selection

PubMed Central

Howard, Christopher D.; Li, Hao; Geddes, Claire E.; Jin, Xin

2017-01-01

Summary Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here, we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn’t reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons, or optogenetic manipulation of dopamine concentration, alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions and have important implications for neurological disorders including Parkinson’s disease and substance dependence. PMID:28285820

Dynamic Nigrostriatal Dopamine Biases Action Selection.

PubMed

Howard, Christopher D; Li, Hao; Geddes, Claire E; Jin, Xin

2017-03-22

Dopamine is thought to play a critical role in reinforcement learning and goal-directed behavior, but its function in action selection remains largely unknown. Here we demonstrate that nigrostriatal dopamine biases ongoing action selection. When mice were trained to dynamically switch the action selected at different time points, changes in firing rate of nigrostriatal dopamine neurons, as well as dopamine signaling in the dorsal striatum, were found to be associated with action selection. This dopamine profile is specific to behavioral choice, scalable with interval duration, and doesn't reflect reward prediction error, timing, or value as single factors alone. Genetic deletion of NMDA receptors on dopamine or striatal neurons or optogenetic manipulation of dopamine concentration alters dopamine signaling and biases action selection. These results unveil a crucial role of nigrostriatal dopamine in integrating diverse information for regulating upcoming actions, and they have important implications for neurological disorders, including Parkinson's disease and substance dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

Ruthenium-catalyzed regioselective allylic amination of 2,3,3-trifluoroallylic carbonates.

PubMed

Isobe, Shin-Ichi; Terasaki, Shou; Hanakawa, Taisyun; Mizuno, Shota; Kawatsura, Motoi

2017-04-05

We demonstrated the ruthenium-catalyzed allylic amination of 2,3,3-trifluoroallylic carbonates with several types of amines. The reactions proceeded with several types of amines, and succeeded in obtaining polyfluorinated terminal alkenes possessing branched allylic amines as a single regioisomer.

A one-pot parallel reductive amination of aldehydes with heteroaromatic amines.

PubMed

Bogolubsky, Andrey V; Moroz, Yurii S; Mykhailiuk, Pavel K; Panov, Dmitriy M; Pipko, Sergey E; Konovets, Anzhelika I; Tolmachev, Andrey

2014-08-11

A parallel reductive amination of heteroaromatic amines has been performed using a combination of ZnCl2-TMSOAc (activating agents) and NaBH(OAc)3 (reducing agent). A library of diverse secondary amines was easily prepared on a 50-300 mg scale.

Putting desire on a budget: dopamine and energy expenditure, reconciling reward and resources

PubMed Central

Beeler, Jeff A.; Frazier, Cristianne R. M.; Zhuang, Xiaoxi

2012-01-01

Accumulating evidence indicates integration of dopamine function with metabolic signals, highlighting a potential role for dopamine in energy balance, frequently construed as modulating reward in response to homeostatic state. Though its precise role remains controversial, the reward perspective of dopamine has dominated investigation of motivational disorders, including obesity. In the hypothesis outlined here, we suggest instead that the primary role of dopamine in behavior is to modulate activity to adapt behavioral energy expenditure to the prevailing environmental energy conditions, with the role of dopamine in reward and motivated behaviors derived from its primary role in energy balance. Dopamine has long been known to modulate activity, exemplified by psychostimulants that act via dopamine. More recently, there has been nascent investigation into the role of dopamine in modulating voluntary activity, with some investigators suggesting that dopamine may serve as a final common pathway that couples energy sensing to regulated voluntary energy expenditure. We suggest that interposed between input from both the internal and external world, dopamine modulates behavioral energy expenditure along two axes: a conserve-expend axis that regulates generalized activity and an explore-exploit axes that regulates the degree to which reward value biases the distribution of activity. In this view, increased dopamine does not promote consumption of tasty food. Instead increased dopamine promotes energy expenditure and exploration while decreased dopamine favors energy conservation and exploitation. This hypothesis provides a mechanistic interpretation to an apparent paradox: the well-established role of dopamine in food seeking and the findings that low dopaminergic functions are associated with obesity. Our hypothesis provides an alternative perspective on the role of dopamine in obesity and reinterprets the “reward deficiency hypothesis” as a perceived energy deficit. We propose that dopamine, by facilitating energy expenditure, should be protective against obesity. We suggest the apparent failure of this protective mechanism in Western societies with high prevalence of obesity arises as a consequence of sedentary lifestyles that thwart energy expenditure. PMID:22833718

Amine dehydrogenases: efficient biocatalysts for the reductive amination of carbonyl compounds

PubMed Central

Mutti, Francesco G.

2017-01-01

Amines constitute the major targets for the production of a plethora of chemical compounds that have applications in the pharmaceutical, agrochemical and bulk chemical industries. However, the asymmetric synthesis of α-chiral amines with elevated catalytic efficiency and atom economy is still a very challenging synthetic problem. Here, we investigated the biocatalytic reductive amination of carbonyl compounds employing a rising class of enzymes for amine synthesis: amine dehydrogenases (AmDHs). The three AmDHs from this study – operating in tandem with a formate dehydrogenase from Candida boidinii (Cb-FDH) for the recycling of the nicotinamide coenzyme – performed the efficient amination of a range of diverse aromatic and aliphatic ketones and aldehydes with up to quantitative conversion and elevated turnover numbers (TONs). Moreover, the reductive amination of prochiral ketones proceeded with perfect stereoselectivity, always affording the (R)-configured amines with more than 99% enantiomeric excess. The most suitable amine dehydrogenase, the optimised catalyst loading and the required reaction time were determined for each substrate. The biocatalytic reductive amination with this dual-enzyme system (AmDH–Cb-FDH) possesses elevated atom efficiency as it utilizes the ammonium formate buffer as the source of both nitrogen and reducing equivalents. Inorganic carbonate is the sole by-product. PMID:28663713

Control of extracellular dopamine at dendrite and axon terminals

PubMed Central

Ford, Christopher P.; Gantz, Stephanie C.; Phillips, Paul E. M.; Williams, John T.

2010-01-01

Midbrain dopamine neurons release dopamine from both axons and dendrites. The mechanism underlying release at these different sites has been proposed to differ. This study used electrochemical and electrophysiological methods to compare the time course and calcium-dependence of somatodendritc dopamine release in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) to that of axonal dopamine release in the dorsal striatum. The amount of dopamine released in the striatum was ~20 fold greater than in cell body regions of the VTA or SNc. However the calcium dependence and time to peak of the dopamine transients were similar. These results illustrate an unexpected overall similarity in the mechanisms of dopamine release in the striatum and cell body regions. To examine how diffusion regulates the time course of dopamine following release, dextran was added to the extracellular solution to slow diffusion. In the VTA, dextran slowed the rate of rise and fall of the extracellular dopamine transient as measured by fast-scan cyclic voltammetry (FSCV) yet did not alter the kinetics of the dopamine dependent inhibitory post-synaptic current (IPSC). Dextran failed to significantly alter the time course of the rise and fall of the dopamine transient in the striatum suggesting a more influential role for reuptake in the striatum. The conclusion is that the time course of dopamine within the extracellular space of the VTA is dependent on both diffusion and reuptake, whereas the activation of D2-receptors on dopamine neurons is primarily limited by reuptake. PMID:20484639

A Mobile Device App to Reduce Medication Errors and Time to Drug Delivery During Pediatric Cardiopulmonary Resuscitation: Study Protocol of a Multicenter Randomized Controlled Crossover Trial.

PubMed

Siebert, Johan N; Ehrler, Frederic; Lovis, Christian; Combescure, Christophe; Haddad, Kevin; Gervaix, Alain; Manzano, Sergio

2017-08-22

During pediatric cardiopulmonary resuscitation (CPR), vasoactive drug preparation for continuous infusions is complex and time-consuming. The need for individual specific weight-based drug dose calculation and preparation places children at higher risk than adults for medication errors. Following an evidence-based and ergonomic driven approach, we developed a mobile device app called Pediatric Accurate Medication in Emergency Situations (PedAMINES), intended to guide caregivers step-by-step from preparation to delivery of drugs requiring continuous infusion. In a prior single center randomized controlled trial, medication errors were reduced from 70% to 0% by using PedAMINES when compared with conventional preparation methods. The purpose of this study is to determine whether the use of PedAMINES in both university and smaller hospitals reduces medication dosage errors (primary outcome), time to drug preparation (TDP), and time to drug delivery (TDD) (secondary outcomes) during pediatric CPR when compared with conventional preparation methods. This is a multicenter, prospective, randomized controlled crossover trial with 2 parallel groups comparing PedAMINES with a conventional and internationally used drug infusion rate table in the preparation of continuous drug infusion. The evaluation setting uses a simulation-based pediatric CPR cardiac arrest scenario with a high-fidelity manikin. The study involving 120 certified nurses (sample size) will take place in the resuscitation rooms of 3 tertiary pediatric emergency departments and 3 smaller hospitals. After epinephrine-induced return of spontaneous circulation, nurses will be asked to prepare a continuous infusion of dopamine using either PedAMINES (intervention group) or the infusion table (control group) and then prepare a continuous infusion of norepinephrine by crossing the procedure. The primary outcome is the medication dosage error rate. The secondary outcome is the time in seconds elapsed since the oral prescription by the physician to drug delivery by the nurse in each allocation group. TDD includes TDP. Stress level during the resuscitation scenario will be assessed for each participant by questionnaire and recorded by the heart rate monitor of a fitness watch. The study is formatted according to the Consolidated Standards of Reporting Trials Statement for Randomized Controlled Trials of Electronic and Mobile Health Applications and Online TeleHealth (CONSORT-EHEALTH) and the Reporting Guidelines for Health Care Simulation Research. Enrollment and data analysis started in March 2017. We anticipate the intervention will be completed in late 2017, and study results will be submitted in early 2018 for publication expected in mid-2018. Results will be reported in line with recommendations from CONSORT-EHEALTH and the Reporting Guidelines for Health Care Simulation Research . This paper describes the protocol used for a clinical trial assessing the impact of a mobile device app to reduce the rate of medication errors, time to drug preparation, and time to drug delivery during pediatric resuscitation. As research in this area is scarce, results generated from this study will be of great importance and might be sufficient to change and improve the pediatric emergency care practice. ClinicalTrials.gov NCT03021122; https://clinicaltrials.gov/ct2/show/NCT03021122 (Archived by WebCite at http://www.webcitation.org/6nfVJ5b4R). ©Johan N Siebert, Frederic Ehrler, Christian Lovis, Christophe Combescure, Kevin Haddad, Alain Gervaix, Sergio Manzano. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 22.08.2017.

Initial elevations in glutamate and dopamine neurotransmission decline with age, as does exploratory behavior, in LRRK2 G2019S knock-in mice

PubMed Central

Kuhlmann, Naila; Kadgien, Chelsie A; Tatarnikov, Igor; Fox, Jesse; Khinda, Jaskaran; Mitchell, Emma; Bergeron, Sabrina; Melrose, Heather

2017-01-01

LRRK2 mutations produce end-stage Parkinson’s disease (PD) with reduced nigrostriatal dopamine, whereas, asymptomatic carriers have increased dopamine turnover and altered brain connectivity. LRRK2 pathophysiology remains unclear, but reduced dopamine and mitochondrial abnormalities occur in aged G2019S mutant knock-in (GKI) mice. Conversely, cultured GKI neurons exhibit increased synaptic transmission. We assessed behavior and synaptic glutamate and dopamine function across a range of ages. Young GKI mice exhibit more vertical exploration, elevated glutamate and dopamine transmission, and aberrant D2-receptor responses. These phenomena decline with age, but are stable in littermates. In young GKI mice, dopamine transients are slower, independent of dopamine transporter (DAT), increasing the lifetime of extracellular dopamine. Slowing of dopamine transients is observed with age in littermates, suggesting premature ageing of dopamine synapses in GKI mice. Thus, GKI mice exhibit early, but declining, synaptic and behavioral phenotypes, making them amenable to investigation of early pathophysiological, and later parkinsonian-like, alterations. This model will prove valuable in efforts to develop neuroprotection for PD. PMID:28930069

The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation

PubMed Central

Jennings, Katie A.; Platt, Nicola J.; Cragg, Stephanie J.

2015-01-01

Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD. PMID:26117304

Initial elevations in glutamate and dopamine neurotransmission decline with age, as does exploratory behavior, in LRRK2 G2019S knock-in mice.

PubMed

Volta, Mattia; Beccano-Kelly, Dayne A; Paschall, Sarah A; Cataldi, Stefano; MacIsaac, Sarah E; Kuhlmann, Naila; Kadgien, Chelsie A; Tatarnikov, Igor; Fox, Jesse; Khinda, Jaskaran; Mitchell, Emma; Bergeron, Sabrina; Melrose, Heather; Farrer, Matthew J; Milnerwood, Austen J

2017-09-20

LRRK2 mutations produce end-stage Parkinson's disease (PD) with reduced nigrostriatal dopamine, whereas, asymptomatic carriers have increased dopamine turnover and altered brain connectivity. LRRK2 pathophysiology remains unclear, but reduced dopamine and mitochondrial abnormalities occur in aged G2019S mutant knock-in (GKI) mice. Conversely, cultured GKI neurons exhibit increased synaptic transmission. We assessed behavior and synaptic glutamate and dopamine function across a range of ages. Young GKI mice exhibit more vertical exploration, elevated glutamate and dopamine transmission, and aberrant D2-receptor responses. These phenomena decline with age, but are stable in littermates. In young GKI mice, dopamine transients are slower, independent of dopamine transporter (DAT), increasing the lifetime of extracellular dopamine. Slowing of dopamine transients is observed with age in littermates, suggesting premature ageing of dopamine synapses in GKI mice. Thus, GKI mice exhibit early, but declining, synaptic and behavioral phenotypes, making them amenable to investigation of early pathophysiological, and later parkinsonian-like, alterations. This model will prove valuable in efforts to develop neuroprotection for PD.

In vitro and in vivo evaluation of poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate)/dopamine-coated electrodes for dopamine delivery.

PubMed

Sui, L; Song, X J; Ren, J; Cai, W J; Ju, L H; Wang, Y; Wang, L Y; Chen, M

2014-06-01

Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly(styrene sulfonate) (PSS) has a variety of chemical and biomedical applications. The application of PEDOT/PSS polymers in drug delivery has attracted attention. However, whether conducting polymers of PEDOT/PSS could be used for dopamine delivery has not clear. In the present study, the PEDOT/PSS coatings incorporated with dopamine were fabricated on 0.5 mm diameter platinum electrodes, electrochemical properties, and dopamine delivery capacities of these electrodes were evaluated in vitro and in vivo through implanting these electrodes into brain striatum area. The findings demonstrated that the PEDOT/PSS/dopamine coatings on platinum electrodes could reduce electrodes impedances, increase charge storage capacities, and release significant levels of dopamine upon electrical stimulation of these electrodes. These results indicated that polymers of PEDOT/PSS/dopamine could be used for dopamine delivery, implicating potential application of PEDOT/PSS/dopamine-coated implantable electrodes in the treatment of some diseases associated with dopamine deficits, such as, electrodes for the treatment of Parkinson's disease during deep brain stimulation. Copyright © 2013 Wiley Periodicals, Inc.

A Catalyst-Free Amination of Functional Organolithium Reagents by Flow Chemistry.

PubMed

Kim, Heejin; Yonekura, Yuya; Yoshida, Jun-Ichi

2018-04-03

Reported is the electrophilic amination of functional organolithium intermediates with well-designed aminating reagents under mild reaction conditions using flow microreactors. The aminating reagents were optimized to achieve efficient C-N bond formation without using any catalyst. The electrophilic amination reactions of functionalized aryllithiums were successfully conducted under mild reaction conditions, within 1 minute, by using flow microreactors. The aminating reagent was also prepared by the flow method. Based on stopped-flow NMR analysis, the reaction time for the preparation of the aminating reagent was quickly optimized without the necessity of work-up. Integrated one-flow synthesis consisting of the generation of an aryllithium, the preparation of an aminating reagent, and their combined reaction was successfully achieved to give the desired amine within 5 minutes of total reaction time. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermometric titrations of amines with nitrosyl perchlorate in acetonitrile solvent.

PubMed

Gündüz, T; Kiliç, E; Cakirer, O

1996-05-01

Thirteen aliphatic and four aromatic amines, namely diethylamine, triethylamine, n-propylamine, di-n-propylamine, tri-n-butylamine, isopropylamine, di-isopropylamine, n-butylamine, di-n-butylamine, tri-n-butylamine, isobutylamine, sec-butylamine, tert-butylamine, aniline, N,N-dimethylaniline, 2-nitroaniline and 4-nitroaniline were titrated thermometrically with nitrosyl perchlorate in acetonitrile solvent. All the aliphatic amines gave very well-shaped thermometric titration curves. The calculated recovery values of the amines were very good. In comparison, the aromatic amines, aniline and N,N-dimethylaniline gave rather well-shaped titration curves, but the recovery values were fairly low. 2-Nitro- and 4-nitro anilines gave no thermometric response at all. The heats of reaction of the amines with nitrosyl perchlorate are rather high. However, the average heat of reaction of the aromatic amines is approximately two-thirds that of the average heat of the aliphatic amines. To support this method all the amines were also titrated potentiometrically and very similar results to those obtained with the thermometric method are seen. The nitrosyl ion is a Lewis acid, strong enough to titrate quantitatively aliphatic amines in acetonitrile solvent, but not strong enough to titrate aromatic amines at the required level in the same solvent.

Trans-blood brain barrier delivery of dopamine-loaded nanoparticles reverses functional deficits in parkinsonian rats.

PubMed

Pahuja, Richa; Seth, Kavita; Shukla, Anshi; Shukla, Rajendra Kumar; Bhatnagar, Priyanka; Chauhan, Lalit Kumar Singh; Saxena, Prem Narain; Arun, Jharna; Chaudhari, Bhushan Pradosh; Patel, Devendra Kumar; Singh, Sheelendra Pratap; Shukla, Rakesh; Khanna, Vinay Kumar; Kumar, Pradeep; Chaturvedi, Rajnish Kumar; Gupta, Kailash Chand

2015-05-26

Sustained and safe delivery of dopamine across the blood brain barrier (BBB) is a major hurdle for successful therapy in Parkinson's disease (PD), a neurodegenerative disorder. Therefore, in the present study we designed neurotransmitter dopamine-loaded PLGA nanoparticles (DA NPs) to deliver dopamine to the brain. These nanoparticles slowly and constantly released dopamine, showed reduced clearance of dopamine in plasma, reduced quinone adduct formation, and decreased dopamine autoxidation. DA NPs were internalized in dopaminergic SH-SY5Y cells and dopaminergic neurons in the substantia nigra and striatum, regions affected in PD. Treatment with DA NPs did not cause reduction in cell viability and morphological deterioration in SH-SY5Y, as compared to bulk dopamine-treated cells, which showed reduced viability. Herein, we report that these NPs were able to cross the BBB and capillary endothelium in the striatum and substantia nigra in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Systemic intravenous administration of DA NPs caused significantly increased levels of dopamine and its metabolites and reduced dopamine-D2 receptor supersensitivity in the striatum of parkinsonian rats. Further, DA NPs significantly recovered neurobehavioral abnormalities in 6-OHDA-induced parkinsonian rats. Dopamine delivered through NPs did not cause additional generation of ROS, dopaminergic neuron degeneration, and ultrastructural changes in the striatum and substantia nigra as compared to 6-OHDA-lesioned rats. Interestingly, dopamine delivery through nanoformulation neither caused alterations in the heart rate and blood pressure nor showed any abrupt pathological change in the brain and other peripheral organs. These results suggest that NPs delivered dopamine into the brain, reduced dopamine autoxidation-mediated toxicity, and ultimately reversed neurochemical and neurobehavioral deficits in parkinsonian rats.

Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain

PubMed Central

Purves-Tyson, T D; Owens, S J; Rothmond, D A; Halliday, G M; Double, K L; Stevens, J; McCrossin, T; Shannon Weickert, C

2017-01-01

The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes. Gene expression of 12 dopamine-related molecules was examined in post-mortem midbrain (28 antipsychotic-treated schizophrenia cases/29 controls) using quantitative PCR. TH and the synaptic dopamine transporter (DAT) proteins were examined in post-mortem midbrain (26 antipsychotic-treated schizophrenia cases per 27 controls) using immunoblotting. TH and aromatic acid decarboxylase (AADC) mRNA and TH protein were unchanged in the midbrain in schizophrenia compared with controls. Dopamine receptor D2 short, vesicular monoamine transporter (VMAT2) and DAT mRNAs were significantly decreased in schizophrenia, with no change in DRD3 mRNA, DRD3nf mRNA and DAT protein between diagnostic groups. However, DAT protein was significantly increased in putatively treatment-resistant cases of schizophrenia compared to putatively treatment-responsive cases. Midbrain monoamine oxidase A (MAOA) mRNA was increased, whereas MAOB and catechol-O-methyl transferase mRNAs were unchanged in schizophrenia. We conclude that, whereas some mRNA changes are consistent with increased dopamine action (decreased DAT mRNA), others suggest reduced dopamine action (increased MAOA mRNA) in the midbrain in schizophrenia. Here, we identify a molecular signature of dopamine dysregulation in the midbrain in schizophrenia that mainly includes gene expression changes of molecules involved in dopamine synthesis and in regulating the time course of dopamine action. PMID:28094812

Treatment of Parkinson’s disease: nanostructured sol–gel silica–dopamine reservoirs for controlled drug release in the central nervous system

PubMed Central

López, Tessy; Bata-García, José L; Esquivel, Dulce; Ortiz-Islas, Emma; Gonzalez, Richard; Ascencio, Jorge; Quintana, Patricia; Oskam, Gerko; Álvarez-Cervera, Fernando J; Heredia-López, Francisco J; Góngora-Alfaro, José L

2011-01-01

Introduction We have evaluated the use of silica–dopamine reservoirs synthesized by the sol–gel approach with the aim of using them in the treatment of Parkinson’s disease, specifically as a device for the controlled release of dopamine in the striatum. Theoretical calculations illustrate that dopamine is expected to assume a planar structure and exhibit weak interactions with the silica surface. Methods Several samples were prepared by varying the wt% of dopamine added during the hydrolysis of tetraethyl orthosilicate. The silica–dopamine reservoirs were characterized by N2 adsorption, scanning and transmission electron microscopy, and Fourier transform infrared spectroscopy. The in vitro release profiles were determined using ultraviolet visible absorbance spectroscopy. The textural analyses showed a maximum value for the surface area of 620 m2/g nanostructured silica materials. The stability of dopamine in the silica network was confirmed by infrared and 13C-nuclear magnetic resonance spectroscopy. The reservoirs were evaluated by means of apomorphine-induced rotation behavior in hemiparkisonian rats. Results The in vitro dopamine delivery profiles indicate two regimes of release, a fast and sustained dopamine delivery was observed up to 24 hours, and after this time the rate of delivery became constant. Histologic analysis of formalin-fixed brains performed 24–32 weeks after reservoir implantation revealed that silica–dopamine implants had a reddish-brown color, suggesting the presence of oxidized dopamine, likely caused by the fixation procedure, while implants without dopamine were always translucent. Conclusion The major finding of the study was that intrastriatal silica–dopamine implants reversed the rotational asymmetry induced by apomorphine, a dopamine agonist, in hemiparkinsonian rats. No dyskinesias or other motor abnormalities were observed in animals implanted with silica or silica–dopamine. PMID:21289978

Midbrain dopamine neurons signal aversion in a reward-context-dependent manner

PubMed Central

Matsumoto, Hideyuki; Tian, Ju; Uchida, Naoshige; Watabe-Uchida, Mitsuko

2016-01-01

Dopamine is thought to regulate learning from appetitive and aversive events. Here we examined how optogenetically-identified dopamine neurons in the lateral ventral tegmental area of mice respond to aversive events in different conditions. In low reward contexts, most dopamine neurons were exclusively inhibited by aversive events, and expectation reduced dopamine neurons’ responses to reward and punishment. When a single odor predicted both reward and punishment, dopamine neurons’ responses to that odor reflected the integrated value of both outcomes. Thus, in low reward contexts, dopamine neurons signal value prediction errors (VPEs) integrating information about both reward and aversion in a common currency. In contrast, in high reward contexts, dopamine neurons acquired a short-latency excitation to aversive events that masked their VPE signaling. Our results demonstrate the importance of considering the contexts to examine the representation in dopamine neurons and uncover different modes of dopamine signaling, each of which may be adaptive for different environments. DOI: http://dx.doi.org/10.7554/eLife.17328.001 PMID:27760002

Cross-hemispheric dopamine projections have functional significance

PubMed Central

Fox, Megan E.; Mikhailova, Maria A.; Bass, Caroline E.; Takmakov, Pavel; Gainetdinov, Raul R.; Budygin, Evgeny A.; Wightman, R. Mark

2016-01-01

Dopamine signaling occurs on a subsecond timescale, and its dysregulation is implicated in pathologies ranging from drug addiction to Parkinson’s disease. Anatomic evidence suggests that some dopamine neurons have cross-hemispheric projections, but the significance of these projections is unknown. Here we report unprecedented interhemispheric communication in the midbrain dopamine system of awake and anesthetized rats. In the anesthetized rats, optogenetic and electrical stimulation of dopamine cells elicited physiologically relevant dopamine release in the contralateral striatum. Contralateral release differed between the dorsal and ventral striatum owing to differential regulation by D2-like receptors. In the freely moving animals, simultaneous bilateral measurements revealed that dopamine release synchronizes between hemispheres and intact, contralateral projections can release dopamine in the midbrain of 6-hydroxydopamine–lesioned rats. These experiments are the first, to our knowledge, to show cross-hemispheric synchronicity in dopamine signaling and support a functional role for contralateral projections. In addition, our data reveal that psychostimulants, such as amphetamine, promote the coupling of dopamine transients between hemispheres. PMID:27298371

Mesolimbic Dopamine Signals the Value of Work

PubMed Central

Hamid, Arif A.; Pettibone, Jeffrey R.; Mabrouk, Omar S.; Hetrick, Vaughn L.; Schmidt, Robert; Vander Weele, Caitlin M.; Kennedy, Robert T.; Aragona, Brandon J.; Berke, Joshua D.

2015-01-01

Dopamine cell firing can encode errors in reward prediction, providing a learning signal to guide future behavior. Yet dopamine is also a key modulator of motivation, invigorating current behavior. Existing theories propose that fast (“phasic”) dopamine fluctuations support learning, while much slower (“tonic”) dopamine changes are involved in motivation. We examined dopamine release in the nucleus accumbens across multiple time scales, using complementary microdialysis and voltammetric methods during adaptive decision-making. We first show that minute-by-minute dopamine levels covary with reward rate and motivational vigor. We then show that second-by-second dopamine release encodes an estimate of temporally-discounted future reward (a value function). We demonstrate that changing dopamine immediately alters willingness to work, and reinforces preceding action choices by encoding temporal-difference reward prediction errors. Our results indicate that dopamine conveys a single, rapidly-evolving decision variable, the available reward for investment of effort, that is employed for both learning and motivational functions. PMID:26595651

A peptide disrupting the D2R-DAT interaction protects against dopamine neurotoxicity.

PubMed

Su, Ping; Liu, Fang

2017-09-01

Dopamine reuptake from extracellular space to cytosol leads to accumulation of dopamine, which triggers neurotoxicity in dopaminergic neurons. Previous studies have shown that both dopamine D2 receptor (D2R) and dopamine transporter (DAT) are involved in dopamine neurotoxicity. However, blockade of either D2R or DAT causes side effects due to antagonism of other physiological functions of these two proteins. We previously found that DAT can form a protein complex with D2R and its cell surface expression is facilitated via D2R-DAT interaction, which regulates dopamine reuptake and intracellular dopamine levels. Here we found that an interfering peptide (DAT-S1) disrupting the D2R-DAT interaction protects neurons against dopamine neurotoxicity, and this effect is mediated by inhibiting DAT cell surface expression and inhibiting both caspase-3 and PARP-1 cleavage. This study demonstrates the role of the D2R-DAT complex in dopamine neurotoxicity and investigated the potential mechanisms, which might help better understand the mechanisms of dopamine neurotoxicity. The peptide may provide some insights to improve treatments for dopamine neurotoxicity and related diseases, such as Parkinson's disease, as well as methamphetamine- and 3,4-methsylenedioxy methamphetamine-induced neurotoxicity. Copyright © 2017. Published by Elsevier Inc.

Adding Dopamine to Proxymetacaine or Oxybuprocaine Solutions Potentiates and Prolongs the Cutaneous Antinociception in Rats.

PubMed

Chen, Yu-Wen; Chiu, Chong-Chi; Lin, Heng-Teng; Wang, Jhi-Joung; Hung, Ching-Hsia

2018-05-01

We evaluated the interaction of dopamine-proxymetacaine and dopamine- oxybuprocaine antinociception using isobolograms. This experiment uses subcutaneous drug (proxymetacaine, oxybuprocaine, and dopamine) injections under the skin of the rat's back, thus simulating infiltration blocks. The dose-related antinociceptive curves of proxymetacaine and oxybuprocaine alone and in combination with dopamine were constructed, and then the antinociceptive interactions between the local anesthetic and dopamine were analyzed using isobolograms. Subcutaneous proxymetacaine, oxybuprocaine, and dopamine produced a sensory block to local skin pinpricks in a dose-dependent fashion. The rank order of potency was proxymetacaine (0.57 [0.52-0.63] μmol/kg) > oxybuprocaine (1.05 [0.96-1.15] μmol/kg) > dopamine (165 [154-177] μmol/kg; P < .01 for each comparison) based on the 50% effective dose values. On the equianesthetic basis (25% effective dose, 50% effective dose, and 75% effective dose), the nociceptive block duration of proxymetacaine or oxybuprocaine was shorter than that of dopamine (P < .01). Oxybuprocaine or proxymetacaine coinjected with dopamine elicited a synergistic antinociceptive effect and extended the duration of action. Oxybuprocaine and proxymetacaine had a higher potency and provoked a shorter duration of sensory block compared with dopamine. The use of dopamine increased the quality and duration of skin antinociception caused by oxybuprocaine and proxymetacaine.

Use of fast-scan cyclic voltammetry to assess phasic dopamine release in rat models of early postpartum maternal behavior and neglect.

PubMed

Shnitko, Tatiana A; Mace, Kyla D; Sullivan, Kaitlin M; Martin, W Kyle; Andersen, Elizabeth H; Williams Avram, Sarah K; Johns, Josephine M; Robinson, Donita L

2017-12-01

Maternal behavior (MB) is a complex response to infant cues, orchestrated by postpartum neurophysiology. Although mesolimbic dopamine contributes toward MB, little is known about real-time dopamine fluctuations during the postpartum period. Thus, we used fast-scan cyclic voltammetry to measure individual dopamine transients in the nucleus accumbens of early postpartum rats and compared them with dopamine transients in virgins and in postpartum females exposed to cocaine during pregnancy, which is known to disrupt MB. We hypothesized that dopamine transients are normally enhanced postpartum and support MB. In anesthetized rats, electrically evoked dopamine release was larger and clearance was faster in postpartum females than in virgins and gestational cocaine exposure blocked the change in clearance. In awake rats, control mothers showed more dopamine transients than cocaine-exposed mothers during MB. Salient pup-produced stimuli may contribute toward differences in maternal phasic dopamine by evoking dopamine transients; supporting the feasibility of this hypothesis, urine composition (glucose, ketones, and leukocytes) differed between unexposed and cocaine-exposed infants. These data, resulting from the novel application of fast-scan cyclic voltammetry to models of MB, support the hypothesis that phasic dopamine signaling is enhanced postpartum. Future studies with additional controls can delineate which aspects of gestational cocaine reduce dopamine clearance and transient frequency.

Identification of amines in wintertime ambient particulate material using high resolution aerosol mass spectrometry

NASA Astrophysics Data System (ADS)

Bottenus, Courtney L. H.; Massoli, Paola; Sueper, Donna; Canagaratna, Manjula R.; VanderSchelden, Graham; Jobson, B. Thomas; VanReken, Timothy M.

2018-05-01

Significant amounts of amines were detected in fine particulate matter (PM) during ambient wintertime conditions in Yakima, WA, using a high resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). Positive matrix factorization (PMF) of the organic aerosol (OA) signal resulted in a six-factor solution that included two previously unreported amine OA factors. The contributions of the amine factors were strongly episodic, but the concentration of the combined amine factors was as high as 10-15 μg m-3 (2-min average) during those episodes. In one occasion, the Amine-II component was 45% of total OA signal. The Amine-I factor was dominated by spectral peaks at m/z 86 (C5H12N+) and m/z 100 (C6H14N+), while the Amine-II factor was dominated by spectral peaks at m/z 58 (C3H8N+ and C2H6N2+) and m/z 72 (C4H10N+ and C3H8N2+). The ions dominating each amine factor showed distinct time traces, suggesting different sources or formation processes. Investigation into the chemistry of the amine factors suggests a correlation with inorganic anions for Amine-I, but no evidence that the Amine-II was being neutralized by the same inorganic ions. We also excluded the presence of organonitrates (ON) in the OA. The presence of C2H4O2+ at m/z 60 (a levoglucosan fragment) in the Amine-I spectrum suggests some influence of biomass burning emissions (more specifically residential wood combustion) in this PMF factor, but wind direction suggested that the most likely sources of these amines were agricultural activities and feedlots to the S-SW of the site.

Acute phenylalanine/tyrosine depletion of phasic dopamine in the rat brain.

PubMed

Shnitko, Tatiana A; Taylor, Sarah C; Stringfield, Sierra J; Zandy, Shannon L; Cofresí, Roberto U; Doherty, James M; Lynch, William B; Boettiger, Charlotte A; Gonzales, Rueben A; Robinson, Donita L

2016-06-01

Dopamine plays a critical role in striatal and cortical function, and depletion of the dopamine precursors phenylalanine and tyrosine is used in humans to temporarily reduce dopamine and probe the role of dopamine in behavior. This method has been shown to alter addiction-related behaviors and cognitive functioning presumably by reducing dopamine transmission, but it is unclear what specific aspects of dopamine transmission are altered. We performed this study to confirm that administration of an amino acid mixture omitting phenylalanine and tyrosine (Phe/Tyr[-]) reduces tyrosine tissue content in the prefrontal cortex (PFC) and nucleus accumbens (NAc), and to test the hypothesis that Phe/Tyr[-] administration reduces phasic dopamine release in the NAc. Rats were injected with a Phe/Tyr[-] amino acid mixture, a control amino acid mixture, or saline. High-performance liquid chromatography was used to determine the concentration of tyrosine, dopamine, or norepinephrine in tissue punches from the PFC and ventral striatum. In a separate group of rats, phasic dopamine release was measured with fast-scan cyclic voltammetry in the NAc core after injection with either the Phe/Tyr[-] mixture or the control amino acid solution. Phe/Tyr[-] reduced tyrosine content in the PFC and NAc, but dopamine and norepinephrine tissue content were not reduced. Moreover, Phe/Tyr[-] decreased the frequency of dopamine transients, but not their amplitude, in freely moving rats. These results indicate that depletion of tyrosine via Phe/Tyr[-] decreases phasic dopamine transmission, providing insight into the mechanism by which this method modifies dopamine-dependent behaviors in human imaging studies.

Systemic effects of low-dose dopamine during administration of cytarabine.

PubMed

Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

2017-09-01

Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

Brain dopamine neurone 'damage': methamphetamine users vs. Parkinson's disease - a critical assessment of the evidence.

PubMed

Kish, Stephen J; Boileau, Isabelle; Callaghan, Russell C; Tong, Junchao

2017-01-01

The objective of this review is to evaluate the evidence that recreational methamphetamine exposure might damage dopamine neurones in human brain, as predicted by experimental animal findings. Brain dopamine marker data in methamphetamine users can now be compared with those in Parkinson's disease, for which the Oleh Hornykiewicz discovery in Vienna of a brain dopamine deficiency is established. Whereas all examined striatal (caudate and putamen) dopamine neuronal markers are decreased in Parkinson's disease, levels of only some (dopamine, dopamine transporter) but not others (dopamine metabolites, synthetic enzymes, vesicular monoamine transporter 2) are below normal in methamphetamine users. This suggests that loss of dopamine neurones might not be characteristic of methamphetamine exposure in at least some human drug users. In methamphetamine users, dopamine loss was more marked in caudate than in putamen, whereas in Parkinson's disease, the putamen is distinctly more affected. Substantia nigra loss of dopamine-containing cell bodies is characteristic of Parkinson's disease, but similar neuropathological studies have yet to be conducted in methamphetamine users. Similarly, it is uncertain whether brain gliosis, a common feature of brain damage, occurs after methamphetamine exposure in humans. Preliminary epidemiological findings suggest that methamphetamine use might increase risk of subsequent development of Parkinson's disease. We conclude that the available literature is insufficient to indicate that recreational methamphetamine exposure likely causes loss of dopamine neurones in humans but does suggest presence of a striatal dopamine deficiency that, in principle, could be corrected by dopamine substitution medication if safety and subject selection considerations can be resolved. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

A Simple Secondary Amine Synthesis: Reductive Amination Using Sodium Triacetoxyborohydride

NASA Astrophysics Data System (ADS)

Carlson, Merle W.; Ciszewski, James T.; Bhatti, Micah M.; Swanson, Wesley F.; Wilson, Anne M.

2000-02-01

We present a reductive amination experiment for a second-semester organic chemistry class. It utilizes an imine intermediate and sodium triacetoxyborohydride, a mild reducing agent. The progress of the reaction is followed by TLC as the starting materials (the aldehyde and primary amine), the imine intermediate, and the secondary amine product are visible under ultraviolet light. This experiment provides an introduction to the observation of intermediates, the synthesis of amines, and the concept of mild reducing agents.

Role of Amine Functionality for CO2 Chemisorption on Silica.

PubMed

Hahn, Maximilian W; Jelic, Jelena; Berger, Edith; Reuter, Karsten; Jentys, Andreas; Lercher, Johannes A

2016-03-03

The mechanism of CO2 adsorption on primary, secondary, and bibasic aminosilanes synthetically functionalized in porous SiO2 was qualitatively and quantitatively investigated by a combination of IR spectroscopy, thermogravimetry, and quantum mechanical modeling. The mode of CO2 adsorption depends particularly on the nature of the amine group and the spacing between the aminosilanes. Primary amines bonded CO2 preferentially through the formation of intermolecular ammonium carbamates, whereas CO2 was predominantly stabilized as carbamic acid, when interacting with secondary amines. Ammonium carbamate formation requires the transfer of the carbamic acid proton to a second primary amine group to form the ammonium ion and hence two (primary) amine groups are required to bind one CO2 molecule. The higher base strength of secondary amines enables the stabilization of carbamic acid, which is thereby hindered to interact further with nearby amine functions, because their association with Si-OH groups (either protonation or hydrogen bonding) does not allow further stabilization of carbamic acid as carbamate. Steric hindrance of the formation of intermolecular ammonium carbamates leads to higher uptake capacities for secondary amines functionalized in porous SiO2 at higher amine densities. In aminosilanes possessing a primary and a secondary amine group, the secondary amine group tends to be protonated by Si-OH groups and therefore does not substantially interact with CO2.

Prefrontal and Striatal Glutamate Differently Relate to Striatal Dopamine: Potential Regulatory Mechanisms of Striatal Presynaptic Dopamine Function?

PubMed

Gleich, Tobias; Deserno, Lorenz; Lorenz, Robert Christian; Boehme, Rebecca; Pankow, Anne; Buchert, Ralph; Kühn, Simone; Heinz, Andreas; Schlagenhauf, Florian; Gallinat, Jürgen

2015-07-01

Theoretical and animal work has proposed that prefrontal cortex (PFC) glutamate inhibits dopaminergic inputs to the ventral striatum (VS) indirectly, whereas direct VS glutamatergic afferents have been suggested to enhance dopaminergic inputs to the VS. In the present study, we aimed to investigate relationships of glutamate and dopamine measures in prefrontostriatal circuitries of healthy humans. We hypothesized that PFC and VS glutamate, as well as their balance, are differently associated with VS dopamine. Glutamate concentrations in the left lateral PFC and left striatum were assessed using 3-Tesla proton magnetic resonance spectroscopy. Striatal presynaptic dopamine synthesis capacity was measured by fluorine-18-l-dihydroxyphenylalanine (F-18-FDOPA) positron emission tomography. First, a negative relationship was observed between glutamate concentrations in lateral PFC and VS dopamine synthesis capacity (n = 28). Second, a positive relationship was revealed between striatal glutamate and VS dopamine synthesis capacity (n = 26). Additionally, the intraindividual difference between PFC and striatal glutamate concentrations correlated negatively with VS dopamine synthesis capacity (n = 24). The present results indicate an involvement of a balance in PFC and striatal glutamate in the regulation of VS dopamine synthesis capacity. This notion points toward a potential mechanism how VS presynaptic dopamine levels are kept in a fine-tuned range. A disruption of this mechanism may account for alterations in striatal dopamine turnover as observed in mental diseases (e.g., in schizophrenia). The present work demonstrates complementary relationships between prefrontal and striatal glutamate and ventral striatal presynaptic dopamine using human imaging measures: a negative correlation between prefrontal glutamate and presynaptic dopamine and a positive relationship between striatal glutamate and presynaptic dopamine are revealed. The results may reflect a regulatory role of prefrontal and striatal glutamate for ventral striatal presynaptic dopamine levels. Such glutamate-dopamine relationships improve our understanding of neurochemical interactions in prefrontostriatal circuits and have implications for the neurobiology of mental disease. Copyright © 2015 the authors 0270-6474/15/359615-07$15.00/0.

Stimulus-Dependent Dopamine Release in Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Sikstrom, Sverker; Soderlund, Goran

2007-01-01

Attention-deficit/hyperactivity disorder (ADHD) is related to an attenuated and dysfunctional dopamine system. Normally, a high extracellular dopamine level yields a tonic dopaminergic input that down-regulates stimuli-evoked phasic dopamine responses through autoreceptors. Abnormally low tonic extracellular dopamine in ADHD up-regulates the…

Azobisisobutyronitrile initiated aerobic oxidative transformation of amines: coupling of primary amines and cyanation of tertiary amines.

PubMed

Liu, Lianghui; Wang, Zikuan; Fu, Xuefeng; Yan, Chun-Hua

2012-11-16

In the presence of a catalytic amount of radical initiator AIBN, primary amines are oxidatively coupled to imines and tertiary amines are cyanated to α-aminonitriles. These "metal-free" aerobic oxidative coupling reactions may find applications in a wide range of "green" oxidation chemistry.

Readily Available Chiral Benzimidazoles-Derived Guanidines as Organocatalysts in the Asymmetric α-Amination of 1,3-Dicarbonyl Compounds.

PubMed

Benavent, Llorenç; Puccetti, Francesco; Baeza, Alejandro; Gómez-Martínez, Melania

2017-08-11

The synthesis and the evaluation as organocatalysts of new chiral guanidines derived from benzimidazoles in the enantioselective α-amination of 1,3-dicarbonyl compounds using di- t -butylazodicarboxylate as aminating agent is herein disclosed. The catalysts are readily synthesized through the reaction of 2-chlorobezimidazole and a chiral amine in moderate-to-good yields. Among all of them, those derived from ( R )-1-phenylethan-1-amine ( 1 ) and ( S )-1-(2-naphthyl)ethan-1-amine ( 3 ) turned out to be the most efficient for such asymmetric transformation, rendering good-to-high yields and moderate-to-good enantioselectivities for the amination products.

[Effects of dopamine and adenosine on regulation of water-electrolyte exchange in Amoeba proteus].

PubMed

Bagrov, Ia Iu; Manusova, N B

2014-01-01

Dopamine and adenosine both regulate transport of sodium chloride in the renal tubules in mammals. We have studied the effect of dopamine and adenosine on spontaneous activity of contractile vacuole of Amoeba proteous. Both substances stimulated contractile vacuole. The effect of dopamine was suppressed by D2 receptor antagonist, haloperidol, but not by D1 antagonist, SCH 39166. Adenylate cyclase inhibitor, 2.5-dideoxyadenosine, suppressed the effect of dopamine, but not of adenosine. Inhibitor of protein kinase C, staurosporine, in contrast, blocked the effect of adenosine, but not dopamine. Notably, dopamine opposed effect of adenosine and vice versa. These results suggest that similar effects of dopamine and adenosine could be mediated by different intracellulare mechanisms.

Dopamine, reward learning, and active inference

PubMed Central

FitzGerald, Thomas H. B.; Dolan, Raymond J.; Friston, Karl

2015-01-01

Temporal difference learning models propose phasic dopamine signaling encodes reward prediction errors that drive learning. This is supported by studies where optogenetic stimulation of dopamine neurons can stand in lieu of actual reward. Nevertheless, a large body of data also shows that dopamine is not necessary for learning, and that dopamine depletion primarily affects task performance. We offer a resolution to this paradox based on an hypothesis that dopamine encodes the precision of beliefs about alternative actions, and thus controls the outcome-sensitivity of behavior. We extend an active inference scheme for solving Markov decision processes to include learning, and show that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning. Furthermore, simulated dopamine depletion impairs performance but spares learning, while simulated excitation of dopamine neurons drives reward learning, through aberrant inference about outcome states. Our formal approach provides a novel and parsimonious reconciliation of apparently divergent experimental findings. PMID:26581305

Dopamine, reward learning, and active inference.

PubMed

FitzGerald, Thomas H B; Dolan, Raymond J; Friston, Karl

2015-01-01

Temporal difference learning models propose phasic dopamine signaling encodes reward prediction errors that drive learning. This is supported by studies where optogenetic stimulation of dopamine neurons can stand in lieu of actual reward. Nevertheless, a large body of data also shows that dopamine is not necessary for learning, and that dopamine depletion primarily affects task performance. We offer a resolution to this paradox based on an hypothesis that dopamine encodes the precision of beliefs about alternative actions, and thus controls the outcome-sensitivity of behavior. We extend an active inference scheme for solving Markov decision processes to include learning, and show that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning. Furthermore, simulated dopamine depletion impairs performance but spares learning, while simulated excitation of dopamine neurons drives reward learning, through aberrant inference about outcome states. Our formal approach provides a novel and parsimonious reconciliation of apparently divergent experimental findings.

The role of dopamine in human addiction: from reward to motivated attention.

PubMed

Franken, Ingmar H A; Booij, Jan; van den Brink, Wim

2005-12-05

There is general consensus among preclinical researchers that dopamine plays an important role in the development and persistence of addiction. However, the precise role of dopamine in addictive behaviors is far from clear and only a few clinical studies on the role of dopamine in human addiction have been conducted so far. The present paper reviews studies addressing the role of dopamine in humans. There is substantial and consistent evidence that dopamine is involved in the experience of drug reward in humans. Dopamine may also be involved in motivational processes such as drug craving. However, given the inconsistent findings of studies using dopamine receptor (ant)agonists, the role of dopamine in the experience of craving is far from resolved. Recent theories claiming that dopamine signals salience and makes the brain paying attention to biological relevant stimuli may provide an interesting framework for explaining addictive behaviors. There is accumulating evidence that patients with drug and alcohol addiction have an aberrant focus on drug-related stimuli. Although there is some preliminary support for the role of dopamine in these attention processes, more studies have to be carried out in order to test the validity of these theories in human subjects.

Dopamine and extinction: a convergence of theory with fear and reward circuitry.

PubMed

Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

2014-02-01

Research on dopamine lies at the intersection of sophisticated theoretical and neurobiological approaches to learning and memory. Dopamine has been shown to be critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in reward-related tasks. A parallel and growing literature indicates that dopamine is involved in fear conditioning and extinction. These studies are consistent with long-standing ideas about appetitive-aversive interactions in learning theory and they speak to the general nature of cellular and molecular processes that underlie behavior. We review the behavioral and neurobiological literature showing a role for dopamine in fear conditioning and extinction. At a cellular level, we review dopamine signaling and receptor pharmacology, cellular and molecular events that follow dopamine receptor activation, and brain systems in which dopamine functions. At a behavioral level, we describe theories of learning and dopamine function that could describe the fundamental rules underlying how dopamine modulates different aspects of learning and memory processes. Copyright © 2013 Elsevier Inc. All rights reserved.

The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors.

PubMed

Fortin, Samantha M; Chartoff, Elena H; Roitman, Mitchell F

2016-02-01

Unconditioned rewarding stimuli evoke phasic increases in dopamine concentration in the nucleus accumbens (NAc) while discrete aversive stimuli elicit pauses in dopamine neuron firing and reductions in NAc dopamine concentration. The unconditioned effects of more prolonged aversive states on dopamine release dynamics are not well understood and are investigated here using the malaise-inducing agent lithium chloride (LiCl). We used fast-scan cyclic voltammetry to measure phasic increases in NAc dopamine resulting from electrical stimulation of dopamine cell bodies in the ventral tegmental area (VTA). Systemic LiCl injection reduced electrically evoked dopamine release in the NAc of both anesthetized and awake rats. As some behavioral effects of LiCl appear to be mediated through glucagon-like peptide-1 receptor (GLP-1R) activation, we hypothesized that the suppression of phasic dopamine by LiCl is GLP-1R dependent. Indeed, peripheral pretreatment with the GLP-1R antagonist exendin-9 (Ex-9) potently attenuated the LiCl-induced suppression of dopamine. Pretreatment with Ex-9 did not, however, affect the suppression of phasic dopamine release by the kappa-opioid receptor agonist, salvinorin A, supporting a selective effect of GLP-1R stimulation in LiCl-induced dopamine suppression. By delivering Ex-9 to either the lateral or fourth ventricle, we highlight a population of central GLP-1 receptors rostral to the hindbrain that are involved in the LiCl-mediated suppression of NAc dopamine release.

Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum.

PubMed

Goutier, W; Lowry, J P; McCreary, A C; O'Connor, J J

2016-05-01

Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release.

Greater Ethanol Inhibition of Presynaptic Dopamine Release in C57BL/6J than DBA/2J Mice: Role of Nicotinic Acetylcholine Receptors

PubMed Central

Yorgason, Jordan T.; Rose, Jamie H.; McIntosh, J. Michael; Ferris, Mark J.; Jones, Sara R.

2014-01-01

The mesolimbic dopamine system, originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc), has been heavily implicated in the reinforcing effects of ethanol. Recent slice voltammetry studies have shown that ethanol inhibits dopamine release selectively during highfrequency activity that elicits phasic dopamine release shown to be important for learning and reinforcement. Presently, we examined ethanol inhibition of electrically evoked NAc dopamine in two mouse strains with divergent dopamine responses to ethanol, C57BL/6 (C57) and DBA/2J (DBA) mice. Previous electrophysiology and microdialysis studies have demonstrated greater ethanol induced VTA dopaminergic firing and NAc dopamine elevations in DBA compared to C57 mice. Additionally, DBA mice have greater ethanol responses in dopamine-related behaviors, including hyperlocomotion and conditioned place preference. Currently, we demonstrate greater sensitivity of ethanol inhibition of NAc dopamine signaling in C57 compared to DBA mice. The reduced sensitivity to ethanol inhibition in DBA mice may contribute to the overall greater ethanol-induced dopamine signaling and related behaviors observed in this strain. NAc cholinergic activity is known to potently modulate terminal dopamine release. Additionally, ethanol is known to interact with multiple aspects of nicotinic acetylcholine receptor activity. Therefore, we examined ethanol-mediated inhibition of dopamine release at two ethanol concentrations (80 and 160mM) during bath application of the non-selective nicotinic receptor antagonist mecamylamine, as well as compounds selective for the β2- (DhβE) and α6- (α-conotoxin MII [H9A; L15A]) subunit-containing receptors. Mecamylamine and DhβE decreased dopamine release and reduced ethanol's inhibitory effects on dopamine in both DBA and C57 mice. Further, α-conotoxin also reduced the dopamine release and the dopamine-inhibiting effects of ethanol at the 80mM, but not 160mM, concentration. These data suggest that ethanol is acting in part through nicotinic acetylcholine receptors, or downstream effectors, to reduce dopamine release during high-frequency activity. PMID:25451295

Effects of Modafinil on Dopamine and Dopamine Transporters in the Male Human Brain: Clinical Implications

PubMed Central

Volkow, Nora D.; Fowler, Joanna S.; Logan, Jean; Alexoff, David; Zhu, Wei; Telang, Frank; Wang, Gene-Jack; Jayne, Millard; Hooker, Jacob M.; Wong, Christopher; Hubbard, Barbara; Carter, Pauline; Warner, Donald; King, Payton; Shea, Colleen; Xu, Youwen; Muench, Lisa; Apelskog-Torres, Karen

2009-01-01

Context Modafinil, a wake-promoting drug used to treat narcolepsy, is increasingly being used as a cognitive enhancer. Although initially launched as distinct from stimulants that increase extracellular dopamine by targeting dopamine transporters, recent preclinical studies suggest otherwise. Objective To measure the acute effects of modafinil at doses used therapeutically (200 mg and 400 mg given orally) on extracellular dopamine and on dopamine transporters in the male human brain. Design, Setting, and Participants Positron emission tomography with [11C]raclopride (D2/D3 radioligand sensitive to changes in endogenous dopamine) and [11C]cocaine (dopamine transporter radioligand) was used to measure the effects of modafinil on extracellular dopamine and on dopamine transporters in 10 healthy male participants. The study took place over an 8-month period (2007–2008) at Brookhaven National Laboratory. Main Outcome Measures Primary outcomes were changes in dopamine D2/D3 receptor and dopamine transporter availability (measured by changes in binding potential) after modafinil when compared with after placebo. Results Modafinil decreased mean (SD) [11C]raclopride binding potential in caudate (6.1% [6.5%]; 95% confidence interval [CI], 1.5% to 10.8%; P=.02), putamen (6.7% [4.9%]; 95% CI, 3.2% to 10.3%; P=.002), and nucleus accumbens (19.4% [20%]; 95% CI, 5% to 35%; P=.02), reflecting increases in extracellular dopamine. Modafinil also decreased [11C]cocaine binding potential in caudate (53.8% [13.8%]; 95% CI, 43.9% to 63.6%; P<.001), putamen (47.2% [11.4%]; 95% CI, 39.1% to 55.4%; P<.001), and nucleus accumbens (39.3% [10%]; 95% CI, 30% to 49%; P=.001), reflecting occupancy of dopamine transporters. Conclusions In this pilot study, modafinil blocked dopamine transporters and increased dopamine in the human brain (including the nucleus accumbens). Because drugs that increase dopamine in the nucleus accumbens have the potential for abuse, and considering the increasing use of modafinil, these results highlight the need for heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations. PMID:19293415

Sequential Metabolism of Secondary Alkyl Amines to Metabolic-Intermediate Complexes: Opposing Roles for the Secondary Hydroxylamine and Primary Amine Metabolites of Desipramine, (S)-Fluoxetine, and N-Desmethyldiltiazem

PubMed Central

Hanson, Kelsey L.; VandenBrink, Brooke M.; Babu, Kantipudi N.; Allen, Kyle E.; Nelson, Wendel L.

2010-01-01

Three secondary amines desipramine (DES), (S)-fluoxetine [(S)-FLX], and N-desmethyldiltiazem (MA) undergo N-hydroxylation to the corresponding secondary hydroxylamines [N-hydroxydesipramine, (S)-N-hydroxyfluoxetine, and N-hydroxy-N-desmethyldiltiazem] by cytochromes P450 2C11, 2C19, and 3A4, respectively. The expected primary amine products, N-desmethyldesipramine, (S)-norfluoxetine, and N,N-didesmethyldiltiazem, are also observed. The formation of metabolic-intermediate (MI) complexes from these substrates and metabolites was examined. In each example, the initial rates of MI complex accumulation followed the order secondary hydroxylamine > secondary amine ≫ primary amine, suggesting that the primary amine metabolites do not contribute to formation of MI complexes from these secondary amines. Furthermore, the primary amine metabolites, which accumulate in incubations of the secondary amines, inhibit MI complex formation. Mass balance studies provided estimates of the product ratios of N-dealkylation to N-hydroxylation. The ratios were 2.9 (DES-CYP2C11), 3.6 [(S)-FLX-CYP2C19], and 0.8 (MA-CYP3A4), indicating that secondary hydroxylamines are significant metabolites of the P450-mediated metabolism of secondary alkyl amines. Parallel studies with N-methyl-d3-desipramine and CYP2C11 demonstrated significant isotopically sensitive switching from N-demethylation to N-hydroxylation. These findings demonstrate that the major pathway to MI complex formation from these secondary amines arises from N-hydroxylation rather than N-dealkylation and that the primary amines are significant competitive inhibitors of MI complex formation. PMID:20200233

Sequential metabolism of secondary alkyl amines to metabolic-intermediate complexes: opposing roles for the secondary hydroxylamine and primary amine metabolites of desipramine, (s)-fluoxetine, and N-desmethyldiltiazem.

PubMed

Hanson, Kelsey L; VandenBrink, Brooke M; Babu, Kantipudi N; Allen, Kyle E; Nelson, Wendel L; Kunze, Kent L

2010-06-01

Three secondary amines desipramine (DES), (S)-fluoxetine [(S)-FLX], and N-desmethyldiltiazem (MA) undergo N-hydroxylation to the corresponding secondary hydroxylamines [N-hydroxydesipramine, (S)-N-hydroxyfluoxetine, and N-hydroxy-N-desmethyldiltiazem] by cytochromes P450 2C11, 2C19, and 3A4, respectively. The expected primary amine products, N-desmethyldesipramine, (S)-norfluoxetine, and N,N-didesmethyldiltiazem, are also observed. The formation of metabolic-intermediate (MI) complexes from these substrates and metabolites was examined. In each example, the initial rates of MI complex accumulation followed the order secondary hydroxylamine > secondary amine > primary amine, suggesting that the primary amine metabolites do not contribute to formation of MI complexes from these secondary amines. Furthermore, the primary amine metabolites, which accumulate in incubations of the secondary amines, inhibit MI complex formation. Mass balance studies provided estimates of the product ratios of N-dealkylation to N-hydroxylation. The ratios were 2.9 (DES-CYP2C11), 3.6 [(S)-FLX-CYP2C19], and 0.8 (MA-CYP3A4), indicating that secondary hydroxylamines are significant metabolites of the P450-mediated metabolism of secondary alkyl amines. Parallel studies with N-methyl-d(3)-desipramine and CYP2C11 demonstrated significant isotopically sensitive switching from N-demethylation to N-hydroxylation. These findings demonstrate that the major pathway to MI complex formation from these secondary amines arises from N-hydroxylation rather than N-dealkylation and that the primary amines are significant competitive inhibitors of MI complex formation.

Formation of N-alkylpyrroles via intermolecular redox amination.

PubMed

Pahadi, Nirmal K; Paley, Miranda; Jana, Ranjan; Waetzig, Shelli R; Tunge, Jon A

2009-11-25

A wide variety of aldehydes, ketones, and lactols undergo redox amination when allowed to react with 3-pyrroline in the presence of a mild Brønsted acid catalyst. This reaction utilizes the inherent reducing power of 3-pyrroline to perform the equivalent of a reductive amination to form alkyl pyrroles. In doing so, the reaction avoids stoichiometric reducing agents that are typically associated with reductive aminations. Moreover, the redox amination protocol allows access to alkyl pyrroles that cannot be made via standard reductive amination.

Effect of salt-tolerant yeast of Candida versatilis and Zygosaccharomyces rouxii on the production of biogenic amines during soy sauce fermentation.

PubMed

Qi, Wei; Hou, Li-Hua; Guo, Hong-Lian; Wang, Chun-Ling; Fan, Zhen-Chuan; Liu, Jin-Fu; Cao, Xiao-Hong

2014-06-01

This study aimed to enhance and improve the quality and safety of soy sauce. In the present work, the change of biogenic amines, such as histamine, tyramine, cadaverine, spermidine, was examined by the treatment of Candida versatilis and Zygosaccharomyces rouxii, and the influence of salt-tolerant yeast on biogenic amines was analysed during the whole fermentation process. The results showed that the content of biogenic amines was elevated after yeast treatment and the content of biogenic amines was influenced by using yeast. The dominating biogenic amine in soy sauce was tyramine. At the end of fermentation, the concentrations of biogenic amines produced by Zygosaccharomyces rouxii and Candida versatilis in the soy mash were 122.71 mg kg(-1) and 69.96 mg kg(-1) . The changes of biogenic amines in high-salt liquid soy mash during fermentation process indicated that a variety of biogenic amines were increased in the fermentation ageing period, which may be due to amino acid decarboxylation to form biogenic amines by yeast decarboxylase. The fermentation period of soy sauce should be longer than 5 months because biogenic amines began to decline after this time period. © 2013 Society of Chemical Industry.

Presence and function of dopamine transporter (DAT) in stallion sperm: dopamine modulates sperm motility and acrosomal integrity.

PubMed

Urra, Javier A; Villaroel-Espíndola, Franz; Covarrubias, Alejandra A; Rodríguez-Gil, Joan Enric; Ramírez-Reveco, Alfredo; Concha, Ilona I

2014-01-01

Dopamine is a catecholamine with multiple physiological functions, playing a key role in nervous system; however its participation in reproductive processes and sperm physiology is controversial. High dopamine concentrations have been reported in different portions of the feminine and masculine reproductive tract, although the role fulfilled by this catecholamine in reproductive physiology is as yet unknown. We have previously shown that dopamine type 2 receptor is functional in boar sperm, suggesting that dopamine acts as a physiological modulator of sperm viability, capacitation and motility. In the present study, using immunodetection methods, we revealed the presence of several proteins important for the dopamine uptake and signalling in mammalian sperm, specifically monoamine transporters as dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporters in equine sperm. We also demonstrated for the first time in equine sperm a functional dopamine transporter using 4-[4-(Dimethylamino)styryl]-N-methylpyridinium iodide (ASP(+)), as substrate. In addition, we also showed that dopamine (1 mM) treatment in vitro, does not affect sperm viability but decreases total and progressive sperm motility. This effect is reversed by blocking the dopamine transporter with the selective inhibitor vanoxerine (GBR12909) and non-selective inhibitors of dopamine reuptake such as nomifensine and bupropion. The effect of dopamine in sperm physiology was evaluated and we demonstrated that acrosome integrity and thyrosine phosphorylation in equine sperm is significantly reduced at high concentrations of this catecholamine. In summary, our results revealed the presence of monoamine transporter DAT, NET and SERT in equine sperm, and that the dopamine uptake by DAT can regulate sperm function, specifically acrosomal integrity and sperm motility.

Presence and Function of Dopamine Transporter (DAT) in Stallion Sperm: Dopamine Modulates Sperm Motility and Acrosomal Integrity

PubMed Central

Covarrubias, Alejandra A.; Rodríguez-Gil, Joan Enric; Ramírez-Reveco, Alfredo; Concha, Ilona I.

2014-01-01

Dopamine is a catecholamine with multiple physiological functions, playing a key role in nervous system; however its participation in reproductive processes and sperm physiology is controversial. High dopamine concentrations have been reported in different portions of the feminine and masculine reproductive tract, although the role fulfilled by this catecholamine in reproductive physiology is as yet unknown. We have previously shown that dopamine type 2 receptor is functional in boar sperm, suggesting that dopamine acts as a physiological modulator of sperm viability, capacitation and motility. In the present study, using immunodetection methods, we revealed the presence of several proteins important for the dopamine uptake and signalling in mammalian sperm, specifically monoamine transporters as dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporters in equine sperm. We also demonstrated for the first time in equine sperm a functional dopamine transporter using 4-[4-(Dimethylamino)styryl]-N-methylpyridinium iodide (ASP+), as substrate. In addition, we also showed that dopamine (1 mM) treatment in vitro, does not affect sperm viability but decreases total and progressive sperm motility. This effect is reversed by blocking the dopamine transporter with the selective inhibitor vanoxerine (GBR12909) and non-selective inhibitors of dopamine reuptake such as nomifensine and bupropion. The effect of dopamine in sperm physiology was evaluated and we demonstrated that acrosome integrity and thyrosine phosphorylation in equine sperm is significantly reduced at high concentrations of this catecholamine. In summary, our results revealed the presence of monoamine transporter DAT, NET and SERT in equine sperm, and that the dopamine uptake by DAT can regulate sperm function, specifically acrosomal integrity and sperm motility. PMID:25402186

Enhanced dopamine D2 autoreceptor function in the adult prefrontal cortex contributes to dopamine hypoactivity following adolescent social stress.

PubMed

Weber, Matthew A; Graack, Eric T; Scholl, Jamie L; Renner, Kenneth J; Forster, Gina L; Watt, Michael J

2018-06-14

Adult psychiatric disorders characterized by cognitive deficits reliant on prefrontal cortex (PFC) dopamine are promoted by teenage bullying. Similarly, male Sprague-Dawley rats exposed to social defeat in mid-adolescence (P35-39) show impaired working memory in adulthood (P56-70), along with decreased medial PFC (mPFC) dopamine activity that results in part from increased dopamine transporter-mediated clearance. Here, we determined if dopamine synthesis and D2 autoreceptor-mediated inhibition of dopamine release in the adult mPFC are also enhanced by adolescent defeat to contribute to later dopamine hypofunction. Control and previously defeated rats did not differ in either DOPA accumulation following amino acid decarboxylase inhibition (NSD-1015 100 mg/kg ip.) or total/phosphorylated tyrosine hydroxylase protein expression, suggesting dopamine synthesis in the adult mPFC is not altered by adolescent defeat. However, exposure to adolescent defeat caused greater decreases in extracellular dopamine release (measured using in vivo chronoamperometry) in the adult mPFC upon local infusion of the D2 receptor agonist quinpirole (3 nM), implying greater D2 autoreceptor function. Equally enhanced D2 autoreceptor-mediated inhibition of dopamine release is seen in the adolescent (P40 or P49) mPFC, which declines in control rats by adulthood. However, this developmental decrease in autoreceptor function is absent following adolescent defeat, suggesting retention of an adolescent-like phenotype into adulthood. Current and previous findings indicate adolescent defeat decreases extracellular dopamine availability in the adult mPFC via both enhanced inhibition of dopamine release and increased dopamine clearance, which may be viable targets for improving treatment of cognitive deficits seen in neuropsychiatric disorders promoted by adolescent stress. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Blockade of dopamine D1-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels.

PubMed

Milienne-Petiot, Morgane; Groenink, Lucianne; Minassian, Arpi; Young, Jared W

2017-10-01

Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D 1 -family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice. Dopamine transporter knockdown and wild-type littermate mice were tested in mouse versions of the Iowa Gambling Task (risk-taking), Progressive Ratio Breakpoint Test (effortful motivation), and Behavioral Pattern Monitor (activity). Prior to testing, the mice were treated with the dopamine D 1 -family receptor antagonist SCH 23390 hydrochloride (0.03, 0.1, or 0.3 mg/kg), or vehicle. Dopamine transporter knockdown mice exhibited hyperactivity and hyperexploration, hypermotivation, and risk-taking preference compared with wild-type littermates. SCH 23390 hydrochloride treatment decreased premature responding in dopamine transporter knockdown mice and attenuated their hypermotivation. SCH 23390 hydrochloride flattened the safe/risk preference, while reducing activity and exploratory levels of both genotypes similarly. Dopamine transporter knockdown mice exhibited mania-relevant behavior compared to wild-type mice. Systemic dopamine D 1 -family receptor antagonism attenuated these behaviors in dopamine transporter knockdown, but not all effects were specific to only the knockdown mice. The normalization of behavior via blockade of dopamine D 1 -family receptors supports the hypothesis that D 1 and/or D 5 receptors could contribute to the mania-relevant behaviors of dopamine transporter knockdown mice.

Nitrosamine formation in amine scrubbing at desorber temperatures.

PubMed

Fine, Nathan A; Goldman, Mark J; Rochelle, Gary T

2014-01-01

Amine scrubbing is a thermodynamically efficient and industrially proven method for carbon capture, but amine solvents can nitrosate in the desorber, forming potentially carcinogenic nitrosamines. The kinetics of reactions involving nitrite and monoethanolamine (MEA), diethanolamine (DEA), methylethanolamine (MMEA), and methyldiethanolamine (MDEA) were determined under desorber conditions. The nitrosations of MEA, DEA, and MMEA are first order in nitrite, carbamate species, and hydronium ion. Nitrosation of MDEA, a tertiary amine, is not catalyzed by the addition of CO2 since it cannot form a stable carbamate. Concentrated and CO2 loaded MEA was blended with low concentrations of N-(2-hydroxyethyl) glycine (HeGly), hydroxyethyl-ethylenediamine (HEEDA), and DEA, secondary amines common in MEA degradation. Nitrosamine yield was proportional to the concentration of secondary amine and was a function of CO2 loading and temperature. Blends of tertiary amines with piperazine (PZ) showed n-nitrosopiperazine (MNPZ) yields close to unity, validating the slow nitrosation rates hypothesized for tertiary amines. These results provide a useful tool for estimating nitrosamine accumulation over a range of amine solvents.

Enhanced Striatal Dopamine Release During Food Stimulation in Binge Eating Disorder

PubMed Central

Wang, Gene-Jack; Geliebter, Allan; Volkow, Nora D.; Telang, Frank W.; Logan, Jean; Jayne, Millard C.; Galanti, Kochavi; Selig, Peter A.; Han, Hao; Zhu, Wei; Wong, Christopher T.; Fowler, Joanna S.

2011-01-01

Subjects with binge eating disorder (BED) regularly consume large amounts of food in short time periods. The neurobiology of BED is poorly understood. Brain dopamine, which regulates motivation for food intake, is likely to be involved. We assessed the involvement of brain dopamine in the motivation for food consumption in binge eaters. Positron emission tomography (PET) scans with [11C]raclopride were done in 10 obese BED and 8 obese subjects without BED. Changes in extracellular dopamine in the striatum in response to food stimulation in food-deprived subjects were evaluated after placebo and after oral methylphenidate (MPH), a drug that blocks the dopamine reuptake transporter and thus amplifies dopamine signals. Neither the neutral stimuli (with or without MPH) nor the food stimuli when given with placebo increased extracellular dopamine. The food stimuli when given with MPH significantly increased dopamine in the caudate and putamen in the binge eaters but not in the nonbinge eaters. Dopamine increases in the caudate were significantly correlated with the binge eating scores but not with BMI. These results identify dopamine neurotransmission in the caudate as being of relevance to the neurobiology of BED. The lack of correlation between BMI and dopamine changes suggests that dopamine release per se does not predict BMI within a group of obese individuals but that it predicts binge eating. PMID:21350434

Microencapsulation of dopamine neurons derived from human induced pluripotent stem cells.

PubMed

Konagaya, Shuhei; Iwata, Hiroo

2015-01-01

Dopamine neurons derived from induced pluripotent stem cells have been widely studied for the treatment of Parkinson's disease. However, various difficulties remain to be overcome, such as tumor formation, fragility of dopamine neurons, difficulty in handling large numbers of dopamine neurons, and immune reactions. In this study, human induced pluripotent stem cell-derived precursors of dopamine neurons were encapsulated in agarose microbeads. Dopamine neurons in microbeads could be handled without specific protocols, because the microbeads protected the fragile dopamine neurons from mechanical stress. hiPS cells were seeded on a Matrigel-coated dish and cultured to induce differentiation into a dopamine neuronal linage. On day 18 of culture, cells were collected from the culture dishes and seeded into U-bottom 96-well plates to induce cell aggregate formation. After 5 days, cell aggregates were collected from the plates and microencapsulated in agarose microbeads. The microencapsulated aggregates were cultured for an additional 45 days to induce maturation of dopamine neurons. Approximately 60% of all cells differentiated into tyrosine hydroxylase-positive neurons in agarose microbeads. The cells released dopamine for more than 40 days. In addition, microbeads containing cells could be cryopreserved. hiPS cells were successfully differentiated into dopamine neurons in agarose microbeads. Agarose microencapsulation provides a good supporting environment for the preparation and storage of dopamine neurons. Copyright © 2014 Elsevier B.V. All rights reserved.

Dopamine receptors – IUPHAR Review 13

PubMed Central

Beaulieu, Jean-Martin; Espinoza, Stefano; Gainetdinov, Raul R

2015-01-01

The variety of physiological functions controlled by dopamine in the brain and periphery is mediated by the D1, D2, D3, D4 and D5 dopamine GPCRs. Drugs acting on dopamine receptors are significant tools for the management of several neuropsychiatric disorders including schizophrenia, bipolar disorder, depression and Parkinson's disease. Recent investigations of dopamine receptor signalling have shown that dopamine receptors, apart from their canonical action on cAMP-mediated signalling, can regulate a myriad of cellular responses to fine-tune the expression of dopamine-associated behaviours and functions. Such signalling mechanisms may involve alternate G protein coupling or non-G protein mechanisms involving ion channels, receptor tyrosine kinases or proteins such as β-arrestins that are classically involved in GPCR desensitization. Another level of complexity is the growing appreciation of the physiological roles played by dopamine receptor heteromers. Applications of new in vivo techniques have significantly furthered the understanding of the physiological functions played by dopamine receptors. Here we provide an update of the current knowledge regarding the complex biology, signalling, physiology and pharmacology of dopamine receptors. PMID:25671228

Renal dopamine containing nerves. What is their functional significance?

PubMed

DiBona, G F

1990-06-01

Biochemical and morphological studies indicate that there are nerves within the kidney that contain dopamine and that various structures within the kidney contain dopamine receptors. However, the functional significance of these renal dopamine containing nerves in relation to renal dopamine receptors is unknown. The functional significance could be defined by demonstrating that an alteration in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves is dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors. Thus, the hypothesis becomes: reflex or electrical activation of efferent renal nerves causes alterations in renal function (eg, renal blood flow, water and solute handling) that are inhibited by specific and selective dopamine receptor antagonists. As reviewed herein, the published experimental data do not support the hypothesis. Therefore, the view that alterations in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves are dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors remains unproven.

Neuroprotective efficiency of Mangifera indica leaves extract on cadmium-induced cortical damage in rats.

PubMed

Al Omairi, Naif E; Radwan, Omyma K; Alzahrani, Yahea A; Kassab, Rami B

2018-03-20

Due to the high ability of cadmium to cross the blood-brain barrier, cadmium (Cd) causes severe neurological damages. Hence, the purpose of this study was to investigate the possible protective effect of Mangifera indica leaf extract (MLE) against Cd-induced neurotoxicity. Rats were divided into eight groups. Group 1 served as vehicle control group, groups 2, 3 and 4 received MLE (100, 200, 300 mg /kg b.wt, respectively). Group 5 was treated with CdCl 2 (5 mg/kg b.wt). Groups 6, 7 and 8 were co-treated with MLE and CdCl 2 using the same doses. All treatments were orally administered for 28 days. Cortical oxidative stress biomarkers [Malondialdehyde (MDA), nitric oxide (NO), glutathione content (GSH), oxidized form of glutathione (GSSG), 8-hydroxy-2-deoxyguanosine (8-OHdG), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], inflammatory cytokines [tumor necrosis factor (TNF-α) and interlukin-1β (IL-1β)], biogenic amines [norepinephrine (NE), dopamine (DA) and serotonin (5-HT)], some biogenic metabolites [3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA)], acetylcholine esterase activity (AChE) and purinergic compound [adenosine triphosphate (ATP)] were determined in frontal cortex of rats. Results indicated that Cd increased levels of the oxidative biomarkers (MDA, NO, GSSG and 8-OHdG) and the inflammatory mediators (TNF-α and IL-1β), while lowered GSH, SOD, CAT, GPx and ATP levels. Also, Cd significantly decreased the AChE activity and the tested biogenic amines while elevated the tested metabolites in the frontal cortex. Levels of all disrupted cortical parameters were alleviated by MLE co-administration. The MLE induced apparent protective effect on Cd-induced neurotoxicity in concern with its medium and higher doses which may be due to its antioxidant and anti-inflammatory activities.

Banana (Musa spp) from peel to pulp: ethnopharmacology, source of bioactive compounds and its relevance for human health.

PubMed

Pereira, Aline; Maraschin, Marcelo

2015-02-03

Banana is a fruit with nutritional properties and also with acclaimed therapeutic uses, cultivated widely throughout the tropics as source of food and income for people. Banana peel is known by its local and traditional use to promote wound healing mainly from burns and to help overcome or prevent a substantial number of illnesses, as depression. This review critically assessed the phytochemical properties and biological activities of Musa spp fruit pulp and peel. A survey on the literature on banana (Musa spp, Musaceae) covering its botanical classification and nomenclature, as well as the local and traditional use of its pulp and peel was performed. Besides, the current state of art on banana fruit pulp and peel as interesting complex matrices sources of high-value compounds from secondary metabolism was also approached. Dessert bananas and plantains are systematic classified into four sections, Eumusa, Rhodochlamys, Australimusa, and Callimusa, according to the number of chromosomes. The fruits differ only in their ploidy arrangement and a single scientific name can be given to all the edible bananas, i.e., Musa spp. The chemical composition of banana's peel and pulp comprise mostly carotenoids, phenolic compounds, and biogenic amines. The biological potential of those biomasses is directly related to their chemical composition, particularly as pro-vitamin A supplementation, as potential antioxidants attributed to their phenolic constituents, as well as in the treatment of Parkinson's disease considering their contents in l-dopa and dopamine. Banana's pulp and peel can be used as natural sources of antioxidants and pro-vitamin A due to their contents in carotenoids, phenolics, and amine compounds, for instance. For the development of a phytomedicine or even an allopathic medicine, e.g., banana fruit pulp and peel could be of interest as raw materials riches in beneficial bioactive compounds. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Impact of experimental hypothyroidism on monoamines level in discrete brain regions and other peripheral tissues of young and adult male rats.

PubMed

Hassan, Wafaa A; Aly, Mona S; Rahman, Taghride Abdel; Shahat, Asmaa S

2013-06-01

The levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats were measured following experimentally induced hypothyroidism. Hypothyroidism induced by daily oral administration of propylthiouracil (PTU, 5mg/kg body wt) caused a significant reduction in DA levels in most of the tissues examined of both young and adult rats after 21 and 28 days, in NE levels after all the time intervals studied in young rats, and after 21 and 28 days in adult rats. 5-HT exhibited a significant reduction in the selected brain regions and blood plasma after 21 and 28 days and in cardiac muscle after all the time intervals in the two age groups of animals. It may be suggested that the changes in monoamine levels induced by hypothyroidism may be due to disturbance in the synthesis and release of these amines through the neurons impairment or may be due to an alteration pattern of their synthesizing and/or degradative enzymes. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

An integrated scheme for the simultaneous determination of biogenic amines, precursor amino acids, and related metabolites by liquid chromatography with electrochemical detection.

PubMed

Oka, K; Kojima, K; Togari, A; Nagatsu, T; Kiss, B

1984-06-08

A new method using high-performance liquid chromatography with electrochemical detection (HPLC-ED) for the simultaneous determination of monoamines, their precursor amino acids, and related major metabolites in small samples of brain tissue weighing from 0.5 to 50 mg is described. The method is based on the preliminary isolation of monoamines (dopamine, norepinephrine, epinephrine, and serotonin), their precursor amino acids (tyrosine, 3,4-dihydroxyphenylalanine, tryptophan and 5-hydroxytryptophan), and their major metabolites (3-methoxytyramine, normetanephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, vanillylmandelic acid, 3-methoxy-4-hydroxyphenylethyleneglycol, and 5-hydroxyindoleacetic acid) by chromatography on small columns of Amberlite CG-50 and Dowex 50W, and by ethyl acetate extraction. All the compounds in the four isolated fractions were measured by HPLC-ED on a reversed-phase column under four different conditions. The sensitivity was from 0.1 to 40 pmol, depending on the substances analysed. This newly established method was applied to the study of the effects of an aromatic L-amino acid decarboxylase inhibitor (NSD-1015) and a monoamine oxidase inhibitor (pargyline) on the levels of monoamines, their precursor amino acids and their major metabolites in brain regions of mice.

Polysulfone thin film composite nanofiltration membranes for removal of textile dyes wastewater

NASA Astrophysics Data System (ADS)

Sutedja, Andrew; Aileen Josephine, Claresta; Mangindaan, Dave

2017-12-01

This research was conducted to produce nanofiltration (NF) membranes, which have good performance in terms of removal of textile dye (Reactive Red 120, RR120) from simulated wastewater as one of several eco-engineering developments for sustainable water resource management. Phase inversion technique was utilized to fabricate the membrane with polysulfone (PSF) support, dissolved in N-methyl-2 pyrollidone (NMP) solvent, and diethylene glycol (DEG) as non-solvent additive. The fabricated membrane then modified with the additional of dopamine coating and further modified by interfacial polymerization (IP) to form a thin film composite (TFC)-NF membrane with PSF substrate. TFC was formed from interaction between amine monomer (2 %-weight of m-phenylenediamine (MPD) in deionized water) and acyl chloride (0.2 %-weight of trimesoyl chloride (TMC) in hexane). From this study, the fabricated PSF-TFC membrane could remove dyestuff from RR120 wastewater by 88% rejection at 120 psi. The result of this study is promising to be applied in Indonesia where researches on removal of dyes from textile wastewater by using membranes are still quite rare. Therefore, this paper may open new avenues for development of eco-engineering development in Indonesia.

Sub-second changes in accumbal dopamine during sexual behavior in male rats.

PubMed

Robinson, D L; Phillips, P E; Budygin, E A; Trafton, B J; Garris, P A; Wightman, R M

2001-08-08

Transient (200--900 ms), high concentrations (200--500 nM) of dopamine, measured using fast-scan cyclic voltammetry, occurred in the nucleus accumbens core of male rats at the presentation of a receptive female. Additional dopamine signals were observed during subsequent approach behavior. Background-subtracted cyclic voltammograms of the naturally-evoked signals matched those of electrically-evoked dopamine measured at the same recording sites. Administration of nomifensine amplified natural and evoked dopamine release, and increased the frequency of detectable signals. While gradual changes in dopamine concentration during sexual behavior have been well established, these findings dramatically improve the time resolution. The observed dopamine transients, probably resulting from neuronal burst firing, represent the first direct correlation of dopamine with sexual behavior on a sub-second time scale.

Distribution of messenger RNAs for D1 dopamine receptors and DARPP-32 in striatum and cerebral cortex of the cynomolgus monkey: relationship to D1 dopamine receptors.

PubMed

Brené, S; Hall, H; Lindefors, N; Karlsson, P; Halldin, C; Sedvall, G

1995-07-01

Messenger RNAs for the D1 dopamine receptor and dopamine- and cyclic AMP-regulated phosphoprotein of relative mass 32,000 (DARPP-32) were examined by in situ hybridization in the cynomolgus monkey brain. The messenger RNA distribution was compared to the distribution of D1 dopamine receptors using [3H]SCH 23390 autoradiography. In the caudate nucleus and putamen, D1 dopamine receptor messenger RNA-positive cells were unevenly distributed. Clusters of cells with an approximately three-fold higher intensity of labeling, as compared to surrounding regions, were found. Some of these D1 dopamine receptor messenger RNA intensive cell clusters in the caudate nucleus appeared to some extent to be matched to regions of higher intensity of [3H]SCH 23390 binding. The distribution of cells expressing DARPP-32 messenger RNA in the caudate nucleus and putamen was found to be non-clustered. In neocortical regions, cells of different sizes expressing D1 dopamine receptor messenger RNA were present in layers II-VI. D1 dopamine receptor messenger RNA-positive cells were most abundant in layer V. Unexpectedly, no DARPP-32 messenger RNA signal was detected in neocortex. Chronic SCH 23390 administration did not change the relative levels of messenger RNAs for the D1 dopamine receptor and DARPP-32 or [3H]SCH 23390 binding as measured by quantitative image analysis. The clustered distribution of D1 dopamine receptor messenger RNA is in contrast to that of DARPP-32 messenger RNA. This suggests that D1 dopamine receptors may play a more significant role in regulating DARPP-32 function in patch regions as compared to matrix regions. D1 dopamine receptor messenger RNA-expressing cells could also be visualized in several layers of the primate neocortex, implying that dopamine acts through D1 dopamine receptors within functionally different neuronal circuits of the neocortex.

Striking Confinement Effect: AuCl[subscript 4][superscript -] Binding to Amines in a Nanocage Cavity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henao, Juan D.; Suh, Young-Woong; Lee, Jeong-Kyu

2009-02-23

Binding of AuCl{sub 4}{sup -} to amine groups tethered to the interior of a 2 nm siloxane nanocage was determined in solutions containing various concentrations of acid. The mode of binding was inferred from EXAFS and UV-vis spectra to be by ligand exchange of amine for chloride, which implies that the amines remain unprotonated. Cyclic voltammetry confirmed that the Au complexes bind to the nanocage interior and established a 1:1 relationship between bound Au complex and amine groups. The results suggested a 5-7 pH unit shift in the protonation constant of the interior amines relative to free amines in solution.

Divergent Effects of Anandamide Transporter Inhibitors with Different Target Selectivity on Social Play Behavior in Adolescent Rats

PubMed Central

Trezza, Viviana; Vanderschuren, Louk J. M. J.

2009-01-01

The endocannabinoid system plays an important role in the modulation of affect, motivation, and emotion. Social play behavior is a natural reinforcer in adolescent rats, and we have recently shown that interacting endocannabinoid, opioid, and dopamine systems modulate social play. In the present study, we tested the hypothesis that, in contrast to administration of exogenous cannabinoid agonists, increasing local endocannabinoid signaling through anandamide transporter inhibition enhances social play. To this aim, we tested the effects of two anandamide transporter inhibitors with different target selectivity on social play behavior in adolescent rats. Interestingly, we found that the prototypical anandamide transporter inhibitor N-(4-hydroxyphenyl)-arachidonamide (AM404) reduced social play, whereas its more selective analog N-arachidonoyl-(2-methyl-4-hydroxyphenyl)amine (VDM11) enhanced it. The effects of AM404 were not mediated through its known pharmacological targets, since they were not blocked by the CB1 cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A), the CB2 cannabinoid receptor antagonist N-(1,3,3-trimethylbicyclo(2.2.1)heptan-2-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide (SR144528), or by the transient receptor potential vanilloid 1 receptor antagonist capsazepine. In contrast, the increase in social play induced by VDM11 was dependent on cannabinoid, opioid, and dopaminergic neurotransmission, since it was blocked by the CB1 cannabinoid receptor antagonist SR141716A, the opioid receptor antagonist naloxone, and the dopamine receptor antagonist α-flupenthixol. These findings support the notion that anandamide plays an important role in the modulation of social interaction in adolescent rats, and they suggest that selective anandamide transporter inhibitors might be useful for the treatment of social dysfunctions. Furthermore, these results suggest that off-target effects may be responsible for some of the conflicting effects of anandamide transporter inhibitors on behavior. PMID:18948500

The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors.

PubMed

De Gregorio, Danilo; Posa, Luca; Ochoa-Sanchez, Rafael; McLaughlin, Ryan; Maione, Sabatino; Comai, Stefano; Gobbi, Gabriella

2016-11-01

d-lysergic diethylamide (LSD) is a hallucinogenic drug that interacts with the serotonin (5-HT) system binding to 5-HT 1 and 5-HT 2 receptors. Little is known about its potential interactions with the dopamine (DA) neurons of the ventral tegmental area (VTA). Using in-vivo electrophysiology in male adult rats, we evaluated the effects of cumulative doses of LSD on VTA DA neuronal activity, compared these effects to those produced on 5-HT neurons in the dorsal raphe nucleus (DRN), and attempted to identify the mechanism of action mediating the effects of LSD on VTA DA neurons. LSD, at low doses (5-20μg/kg, i.v.) induced a significant decrease of DRN 5-HT firing activity through 5-HT 2A and D 2 receptors. At these low doses, LSD did not alter VTA DA neuronal activity. On the contrary, at higher doses (30-120μg/kg, i.v.), LSD dose-dependently decreased VTA DA firing activity. The depletion of 5-HT with p-chlorophenylalanine did not modulate the effects of LSD on DA firing activity. The inhibitory effects of LSD on VTA DA firing activity were prevented by the D 2 receptor antagonist haloperidol (50μg/kg, i.v.) and by the 5-HT 1A receptor antagonist WAY-100,635 (500μg/kg, i.v.). Notably, pretreatment with the trace amine-associate receptor 1 (TAAR 1 ) antagonist EPPTB (5mg/kg, i.v.) blocked the inhibitory effect of LSD on VTA DA neurons. These results suggest that LSD at high doses strongly affects DA mesolimbic neuronal activity in a 5-HT independent manner and with a pleiotropic mechanism of action involving 5-HT 1A, D 2 and TAAR 1 receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transition Metal Free C-N Bond Forming Dearomatizations and Aryl C-H Aminations by in Situ Release of a Hydroxylamine-Based Aminating Agent.

PubMed

Farndon, Joshua J; Ma, Xiaofeng; Bower, John F

2017-10-11

We outline a simple protocol that accesses directly unprotected secondary amines by intramolecular C-N bond forming dearomatization or aryl C-H amination. The method is dependent on the generation of a potent electrophilic aminating agent released by in situ deprotection of O-Ts activated N-Boc hydroxylamines.

Bioinspired organocatalytic aerobic C-H oxidation of amines with an ortho-quinone catalyst.

PubMed

Qin, Yan; Zhang, Long; Lv, Jian; Luo, Sanzhong; Cheng, Jin-Pei

2015-03-20

A simple bioinspired ortho-quinone catalyst for the aerobic oxidative dehydrogenation of amines to imines is reported. Without any metal cocatalysts, the identified optimal ortho-quinone catalyst enables the oxidations of α-branched primary amines and cyclic secondary amines. Mechanistic studies have disclosed the origins of different performances of ortho-quinone vs para-quinone in biomimetic amine oxidations.

Experimental investigation and DFT calculation of different amine/ammonium salts adsorption on kaolinite

NASA Astrophysics Data System (ADS)

Chen, Jun; Min, Fan-fei; Liu, Lingyun; Liu, Chunfu; Lu, Fangqin

2017-10-01

The adsorption of four different amine/ammonium salts of DDA (Dodecyl amine), MDA (N-methyldodecyl amine), DMDA (N,N-dimethyldodecyl amine) and DTAC (Dodecyl trimethyl ammonium chloride) on kaolinite particles was investigated in the study through the measurement of contact angles, zeta potentials, aggregation observation, adsorption and sedimentation. The results show that different amine/ammonium salts can adsorb on the kaolinite surface to enhance the hydrophobicity and reduce the electronegativity of kaolinite particle surface, and thus induce a strong hydrophobic aggregation of kaolinite particles which promotes the settlement of kaolinite. To explore the adsorption mechanism of these four amine/ammonium salts on kaolinite surfaces, the adsorptions of DDA+, MDA+, DMDA+ and DTAC+ on kaolinite (001) surface and (00 1 bar) surface are calculated with DFT (Density functional theory). The DFT calculation results indicate that different amine/ammonium cations can strongly adsorbed on kaolinite (001) surface and (00 1 bar) surface by forming Nsbnd H⋯O strong hydrogen bonds or Csbnd H⋯O weak hydrogen bonds, and there are strongly electrostatic attractions between different amine/ammonium cations and kaolinite surfaces. The main adsorption mechanism of amine/ammonium cations on kaolinite is hydrogen-bond interaction and electrostatic attraction.

Oxidations of N-(3-indoleethyl) cyclic aliphatic amines by horseradish peroxidase: the indole ring binds to the enzyme and mediates electron-transfer amine oxidation.

PubMed

Ling, Ke-Qing; Li, Wen-Shan; Sayre, Lawrence M

2008-01-23

Although oxidations of aromatic amines by horseradish peroxidase (HRP) are well-known, typical aliphatic amines are not substrates of HRP. In this study, the reactions of N-benzyl and N-methyl cyclic amines with HRP were found to be slow, but reactions of N-(3-indoleethyl) cyclic amines were 2-3 orders of magnitude faster. Analyses of pH-rate profiles revealed a dominant contribution to reaction by the amine-free base forms, the only species found to bind to the enzyme. A metabolic study on a family of congeneric N-(3-indoleethyl) cyclic amines indicated competition between amine and indole oxidation pathways. Amine oxidation dominated for the seven- and eight-membered azacycles, where ring size supports the change in hybridization from sp3 to sp2 that occurs upon one-electron amine nitrogen oxidation, whereas only indole oxidation was observed for the six-membered ring congener. Optical difference spectroscopic binding data and computational docking simulations suggest that all the arylalkylamine substrates bind to the enzyme through their aromatic termini with similar binding modes and binding affinities. Kinetic saturation was observed for a particularly soluble substrate, consistent with an obligatory role of an enzyme-substrate complexation preceding electron transfer. The significant rate enhancements seen for the indoleethylamine substrates suggest the ability of the bound indole ring to mediate what amounts to medium long-range electron-transfer oxidation of the tertiary amine center by the HRP oxidants. This is the first systematic investigation to document aliphatic amine oxidation by HRP at rates consistent with normal metabolic turnover, and the demonstration that this is facilitated by an auxiliary electron-rich aromatic ring.

Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis.

PubMed

Egerton, Alice; Howes, Oliver D; Houle, Sylvain; McKenzie, Kwame; Valmaggia, Lucia R; Bagby, Michael R; Tseng, Huai-Hsuan; Bloomfield, Michael A P; Kenk, Miran; Bhattacharyya, Sagnik; Suridjan, Ivonne; Chaddock, Chistopher A; Winton-Brown, Toby T; Allen, Paul; Rusjan, Pablo; Remington, Gary; Meyer-Lindenberg, Andreas; McGuire, Philip K; Mizrahi, Romina

2017-03-01

Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case-control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capacity) in immigrants compared to nonimmigrants were performed in Canada and the United Kingdom. The Canadian dopamine release study included 25 immigrant and 31 nonmigrant Canadians. These groups included 23 clinical high risk (CHR) subjects, 9 antipsychotic naïve patients with schizophrenia, and 24 healthy volunteers. The UK dopamine synthesis study included 32 immigrants and 44 nonimmigrant British. These groups included 50 CHR subjects and 26 healthy volunteers. Both striatal stress-induced dopamine release and dopamine synthesis capacity were significantly elevated in immigrants compared to nonimmigrants, independent of clinical status. These data provide the first evidence that the effect of migration on the risk of developing psychosis may be mediated by an elevation in brain dopamine function. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Consequences of peripheral chemoreflex inhibition with low-dose dopamine in humans

PubMed Central

Niewinski, Piotr; Tubek, Stanislaw; Banasiak, Waldemar; Paton, Julian F R; Ponikowski, Piotr

2014-01-01

Low-dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double-blind, placebo-controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low-dose dopamine (2 μg kg–1 min–1) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function. PMID:24396060

Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes Autistic-Like Behaviors.

PubMed

Lee, Yunjin; Kim, Hannah; Kim, Ji-Eun; Park, Jin-Young; Choi, Juli; Lee, Jung-Eun; Lee, Eun-Hwa; Han, Pyung-Lim

2018-07-01

The dopamine system has been characterized in motor function, goal-directed behaviors, and rewards. Recent studies recognize various dopamine system genes as being associated with autism spectrum disorder (ASD). However, how dopamine system dysfunction induces ASD pathophysiology remains unknown. In the present study, we demonstrated that mice with increased dopamine functions in the dorsal striatum via the suppression of dopamine transporter expression in substantia nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry exhibited sociability deficits and repetitive behaviors relevant to ASD pathology in animal models, while these behavioral changes were blocked by a D1 receptor antagonist. Pharmacological activation of D1 dopamine receptors in normal mice or the genetic knockout (KO) of D2 dopamine receptors also produced typical autistic-like behaviors. Moreover, the siRNA-mediated inhibition of D2 dopamine receptors in the dorsal striatum was sufficient to replicate autistic-like phenotypes in D2 KO mice. Intervention of D1 dopamine receptor functions or the signaling pathways-related D1 receptors in D2 KO mice produced anti-autistic effects. Together, our results indicate that increased dopamine function in the dorsal striatum promotes autistic-like behaviors and that the dorsal striatum is the neural correlate of ASD core symptoms.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, g.j.; Wang, G.-J.; Geliebter, A.

Subjects with binge eating disorder (BED) regularly consume large amounts of food in short time periods. The neurobiology of BED is poorly understood. Brain dopamine, which regulates motivation for food intake, is likely to be involved. We assessed the involvement of brain dopamine in the motivation for food consumption in binge eaters. Positron emission tomography (PET) scans with [{sup 11}C]raclopride were done in 10 obese BED and 8 obese subjects without BED. Changes in extracellular dopamine in the striatum in response to food stimulation in food-deprived subjects were evaluated after placebo and after oral methylphenidate (MPH), a drug that blocksmore » the dopamine reuptake transporter and thus amplifies dopamine signals. Neither the neutral stimuli (with or without MPH) nor the food stimuli when given with placebo increased extracellular dopamine. The food stimuli when given with MPH significantly increased dopamine in the caudate and putamen in the binge eaters but not in the nonbinge eaters. Dopamine increases in the caudate were significantly correlated with the binge eating scores but not with BMI. These results identify dopamine neurotransmission in the caudate as being of relevance to the neurobiology of BED. The lack of correlation between BMI and dopamine changes suggests that dopamine release per se does not predict BMI within a group of obese individuals but that it predicts binge eating.« less

RECOVERY OF URANIUM FROM AQUEOUS PHOSPHATE-CONTAINING SOLUTIONS

DOEpatents

Igelsrud, I.; Stephen, E.F.

1959-08-11

ABS>A method is presented for recovering hexavalent uranium from an acidic phosphaie solution. A high molecular weight amine, such as a mixture of cccoanut oil amines, is added to the solution in such amount as to give a ratio of about 2000 parts by weight of amine to 1 part by weight of uranium. The uranium is precipitated with the amines and the whole filtered from the solution. The uranium is leached from the amine mass by washing with aqueous sodium carbonate solution; and the amine mixture is available for reuse.

Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions.

PubMed

Mingote, Susana; Chuhma, Nao; Kusnoor, Sheila V; Field, Bianca; Deutch, Ariel Y; Rayport, Stephen

2015-12-09

In the ventral tegmental area (VTA), a subpopulation of dopamine neurons express vesicular glutamate transporter 2 and make glutamatergic connections to nucleus accumbens (NAc) and olfactory tubercle (OT) neurons. However, their glutamatergic connections across the forebrain have not been explored systematically. To visualize dopamine neuron forebrain projections and to enable photostimulation of their axons independent of transmitter status, we virally transfected VTA neurons with channelrhodopsin-2 fused to enhanced yellow fluorescent protein (ChR2-EYFP) and used DAT(IREScre) mice to restrict expression to dopamine neurons. ChR2-EYFP-expressing neurons almost invariably stained for tyrosine hydroxylase, identifying them as dopaminergic. Dopamine neuron axons visualized by ChR2-EYFP fluorescence projected most densely to the striatum, moderately to the amygdala and entorhinal cortex (ERC), sparsely to prefrontal and cingulate cortices, and rarely to the hippocampus. Guided by ChR2-EYFP fluorescence, we recorded systematically from putative principal neurons in target areas and determined the incidence and strength of glutamatergic connections by activating all dopamine neuron terminals impinging on recorded neurons with wide-field photostimulation. This revealed strong glutamatergic connections in the NAc, OT, and ERC; moderate strength connections in the central amygdala; and weak connections in the cingulate cortex. No glutamatergic connections were found in the dorsal striatum, hippocampus, basolateral amygdala, or prefrontal cortex. These results indicate that VTA dopamine neurons elicit widespread, but regionally distinct, glutamatergic signals in the forebrain and begin to define the dopamine neuron excitatory functional connectome. Dopamine neurons are important for the control of motivated behavior and are involved in the pathophysiology of several major neuropsychiatric disorders. Recent studies have shown that some ventral midbrain dopamine neurons are capable of glutamate cotransmission. With conditional expression of channelrhodopsin in dopamine neurons, we systematically explored dopamine neuron connections in the forebrain and identified regionally specific dopamine neuron excitatory connections. Establishing that only a subset of forebrain regions receive excitatory connections from dopamine neurons will help to determine the function of dopamine neuron glutamate cotransmission, which likely involves transmission of precise temporal signals and enhancement of the dynamic range of dopamine neuron signals. Copyright © 2015 the authors 0270-6474/15/3516259-13$15.00/0.

Dopamine-dependent effects on basal and glutamate stimulated network dynamics in cultured hippocampal neurons.

PubMed

Li, Yan; Chen, Xin; Dzakpasu, Rhonda; Conant, Katherine

2017-02-01

Oscillatory activity occurs in cortical and hippocampal networks with specific frequency ranges thought to be critical to working memory, attention, differentiation of neuronal precursors, and memory trace replay. Synchronized activity within relatively large neuronal populations is influenced by firing and bursting frequency within individual cells, and the latter is modulated by changes in intrinsic membrane excitability and synaptic transmission. Published work suggests that dopamine, a potent modulator of learning and memory, acts on dopamine receptor 1-like dopamine receptors to influence the phosphorylation and trafficking of glutamate receptor subunits, along with long-term potentiation of excitatory synaptic transmission in striatum and prefrontal cortex. Prior studies also suggest that dopamine can influence voltage gated ion channel function and membrane excitability in these regions. Fewer studies have examined dopamine's effect on related endpoints in hippocampus, or potential consequences in terms of network burst dynamics. In this study, we record action potential activity using a microelectrode array system to examine the ability of dopamine to modulate baseline and glutamate-stimulated bursting activity in an in vitro network of cultured murine hippocampal neurons. We show that dopamine stimulates a dopamine type-1 receptor-dependent increase in number of overall bursts within minutes of its application. Notably, however, at the concentration used herein, dopamine did not increase the overall synchrony of bursts between electrodes. Although the number of bursts normalizes by 40 min, bursting in response to a subsequent glutamate challenge is enhanced by dopamine pretreatment. Dopamine-dependent potentiation of glutamate-stimulated bursting was not observed when the two modulators were administered concurrently. In parallel, pretreatment of murine hippocampal cultures with dopamine stimulated lasting increases in the phosphorylation of the glutamate receptor subunit GluA1 at serine 845. This effect is consistent with the possibility that enhanced membrane insertion of GluAs may contribute to a more slowly evolving dopamine-dependent potentiation of glutamate-stimulated bursting. Together, these results are consistent with the possibility that dopamine can influence hippocampal bursting by at least two temporally distinct mechanisms, contributing to an emerging appreciation of dopamine-dependent effects on network activity in the hippocampus. © 2016 International Society for Neurochemistry.

The Transfection of BDNF to Dopamine Neurons Potentiates the Effect of Dopamine D3 Receptor Agonist Recovering the Striatal Innervation, Dendritic Spines and Motor Behavior in an Aged Rat Model of Parkinson’s Disease

PubMed Central

Razgado-Hernandez, Luis F.; Espadas-Alvarez, Armando J.; Reyna-Velazquez, Patricia; Sierra-Sanchez, Arturo; Anaya-Martinez, Veronica; Jimenez-Estrada, Ismael; Bannon, Michael J.; Martinez-Fong, Daniel; Aceves-Ruiz, Jorge

2015-01-01

The progressive degeneration of the dopamine neurons of the pars compacta of substantia nigra and the consequent loss of the dopamine innervation of the striatum leads to the impairment of motor behavior in Parkinson’s disease. Accordingly, an efficient therapy of the disease should protect and regenerate the dopamine neurons of the substantia nigra and the dopamine innervation of the striatum. Nigral neurons express Brain Derived Neurotropic Factor (BDNF) and dopamine D3 receptors, both of which protect the dopamine neurons. The chronic activation of dopamine D3 receptors by their agonists, in addition, restores, in part, the dopamine innervation of the striatum. Here we explored whether the over-expression of BDNF by dopamine neurons potentiates the effect of the activation of D3 receptors restoring nigrostriatal innervation. Twelve-month old Wistar rats were unilaterally injected with 6-hydroxydopamine into the striatum. Five months later, rats were treated with the D3 agonist 7-hydroxy-N,N-di-n-propy1-2-aminotetralin (7-OH-DPAT) administered i.p. during 4½ months via osmotic pumps and the BDNF gene transfection into nigral cells using the neurotensin-polyplex nanovector (a non-viral transfection) that selectively transfect the dopamine neurons via the high-affinity neurotensin receptor expressed by these neurons. Two months after the withdrawal of 7-OH-DPAT when rats were aged (24 months old), immunohistochemistry assays were made. The over-expression of BDNF in rats receiving the D3 agonist normalized gait and motor coordination; in addition, it eliminated the muscle rigidity produced by the loss of dopamine. The recovery of motor behavior was associated with the recovery of the nigral neurons, the dopamine innervation of the striatum and of the number of dendritic spines of the striatal neurons. Thus, the over-expression of BDNF in dopamine neurons associated with the chronic activation of the D3 receptors appears to be a promising strategy for restoring dopamine neurons in Parkinson’s disease. PMID:25693197

Controlling Nitrosamines, Nitramines, and Amines in Amine-Based CO₂ Capture Systems with Continuous Ultraviolet and Ozone Treatment of Washwater.

PubMed

Dai, Ning; Mitch, William A

2015-07-21

Formation of nitrosamines and nitramines from reactions between flue gas NOx and the amines used in CO2 capture units has arisen as a significant concern. Washwater scrubbers can capture nitrosamines and nitramines. They can also capture amines, preventing formation of nitrosamines and nitramines downwind by amine reactions with ambient NOx. The continuous application of UV alone, or a combination of UV and ozone to the return line of a washwater treatment unit was evaluated to control the accumulation of nitrosamines, nitramines and amines in a laboratory-scale washwater unit. With model secondary amine solvents ranging from nonvolatile diethanolamine to volatile morpholine, application of 272-537 mJ/cm(2) UV incident fluence alone reduced the accumulation of nitrosamines and nitramines by approximately an order of magnitude. Modeling indicated that the gains achieved by UV treatment should increase over time, because UV treatment converts the time dependence of nitrosamine accumulation from a quadratic to a linear function. Ozone (21 mg/L) maintained low steady-state concentrations of amines in the washwater. While modeling indicated that more than 80% of nitrosamine accumulation in the washwater was associated with reaction of washwater amines with residual NOx, a reduction in nitrosamine accumulation rates due to ozone oxidation of amines was not fully realized because the ozonation products of amines reduced nitrosamine photolysis rates by competing for photons.

SO 2-Resistant Immobilized Amine Sorbents for CO 2 Capture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tumuluri, Uma

2014-01-01

The solid amine sorbent for CO 2 capture process has advantages of simplicity and low operating cost compared to the MEA (monoethanolamine) process. Solid amine sorbents reported so far suffered from either low CO 2 capture capacity or low stability in the flue gas environment. This project is aimed at developing a SO 2-resistant solid amine sorbent for capturing CO 2 from coal–fired power plants with SCR/FGD which emits SO 2ranging from 15 to 30 ppm and NO ranging from 5 to 10 ppm. The amine sorbent we developed in a previous project degraded rapidly with 65% decrease in themore » initial capture capacity in presence of 1% SO 2. This amine sorbent was further modified by coating with polyethyleneglycol (PEG) to increase the SO 2-resistance. Polyethylene glycol (PEG) was found to decrease the SO 2-amine interaction, resulting in the decrease in the maximum SO desorption temperature (Tmax ) of amine sorbent. The PEG-coated amine sorbent exhibited higher stability with only 40% decrease in the initial capture capacity compared to un-coated amine sorbents. The cost of the solid amine sorbent developed in this project is estimated to be less than $7.00/lb; the sorbent exhibited CO 2 capture capacity more than 2.3 mmol/g. The results of this study provided the scientific basis for further development of SO 2-resistant sorbents.« less

Phasic dopamine release drives rapid activation of striatal D2-receptors

PubMed Central

Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P

2014-01-01

Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

Factors influencing the regioselectivity of the oxidation of asymmetric secondary amines with singlet oxygen.

PubMed

Ushakov, Dmitry B; Plutschack, Matthew B; Gilmore, Kerry; Seeberger, Peter H

2015-04-20

Aerobic amine oxidation is an attractive and elegant process for the α functionalization of amines. However, there are still several mechanistic uncertainties, particularly the factors governing the regioselectivity of the oxidation of asymmetric secondary amines and the oxidation rates of mixed primary amines. Herein, it is reported that singlet-oxygen-mediated oxidation of 1° and 2° amines is sensitive to the strength of the α-C-H bond and steric factors. Estimation of the relative bond dissociation energy by natural bond order analysis or by means of one-bond C-H coupling constants allowed the regioselectivity of secondary amine oxidations to be explained and predicted. In addition, the findings were utilized to synthesize highly regioselective substrates and perform selective amine cross-couplings to produce imines. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Methamphetamine Regulation of Firing Activity of Dopamine Neurons

PubMed Central

Lin, Min; Sambo, Danielle

2016-01-01

Methamphetamine (METH) is a substrate for the dopamine transporter that increases extracellular dopamine levels by competing with dopamine uptake and increasing reverse transport of dopamine via the transporter. METH has also been shown to alter the excitability of dopamine neurons. The mechanism of METH regulation of the intrinsic firing behaviors of dopamine neurons is less understood. Here we identified an unexpected and unique property of METH on the regulation of firing activity of mouse dopamine neurons. METH produced a transient augmentation of spontaneous spike activity of midbrain dopamine neurons that was followed by a progressive reduction of spontaneous spike activity. Inspection of action potential morphology revealed that METH increased the half-width and produced larger coefficients of variation of the interspike interval, suggesting that METH exposure affected the activity of voltage-dependent potassium channels in these neurons. Since METH has been shown to affect Ca2+ homeostasis, the unexpected findings that METH broadened the action potential and decreased the amplitude of afterhyperpolarization led us to ask whether METH alters the activity of Ca2+-activated potassium (BK) channels. First, we identified BK channels in dopamine neurons by their voltage dependence and their response to a BK channel blocker or opener. While METH suppressed the amplitude of BK channel-mediated unitary currents, the BK channel opener NS1619 attenuated the effects of METH on action potential broadening, afterhyperpolarization repression, and spontaneous spike activity reduction. Live-cell total internal reflection fluorescence microscopy, electrophysiology, and biochemical analysis suggest METH exposure decreased the activity of BK channels by decreasing BK-α subunit levels at the plasma membrane. SIGNIFICANCE STATEMENT Methamphetamine (METH) competes with dopamine uptake, increases dopamine efflux via the dopamine transporter, and affects the excitability of dopamine neurons. Here, we identified an unexpected property of METH on dopamine neuron firing activity. METH transiently increased the spontaneous spike activity of dopamine neurons followed by a progressive reduction of the spontaneous spike activity. METH broadened the action potentials, increased coefficients of variation of the interspike interval, and decreased the amplitude of afterhyperpolarization, which are consistent with changes in the activity of Ca2+-activated potassium (BK) channels. We found that METH decreased the activity of BK channels by stimulating BK-α subunit trafficking. Thus, METH modulation of dopamine neurotransmission and resulting behavioral responses is, in part, due to METH regulation of BK channel activity. PMID:27707972

Differential degradation of motor deficits during gradual dopamine depletion with 6-hydroxydopamine in mice

PubMed Central

Willard, Amanda M.; Bouchard, Rachel S.; Gittis, Aryn H.

2015-01-01

Parkinson’s disease (PD) is a movement disorder whose cardinal motor symptoms arise due to the progressive loss of dopamine. Although this dopamine loss typically progresses slowly over time, currently there are very few animal models that enable incremental dopamine depletion over time within the same animal. This type of gradual dopamine depletion model would be useful in studies aimed at the prodromal phase of PD, when dopamine levels are pathologically low but motor symptoms have not yet presented. Utilizing the highly characterized neurotoxin 6-hydroxydopamine (6-OHDA), we have developed a paradigm to gradually deplete dopamine levels in the striatum over a user-defined time course – spanning weeks to months – in C57BL/6 mice. Dopamine depletions were achieved by administration of five low dose injections (0.75 µg) of 6-OHDA through an implanted intracranial bilateral cannula targeting the medial forebrain bundle. Levels of dopamine within the striatum declined linearly with successive injections, quantified using tyrosine hydroxylase immunostaining and high-performance liquid chromatography. Behavioral testing was carried out at each time point to study the onset and progression of motor impairments as a function of dopamine loss over time. We found that spontaneous locomotion, measured in an open field, was robust to loss of dopamine until ~70% of striatal dopamine was lost. Beyond this point, additional dopamine loss caused a sharp decline in motor performance, reaching a final level comparable to that of acutely depleted mice. Similarly, although rearing behavior was more sensitive to dopamine loss and declined linearly as a function of dopamine levels, it eventually declined to levels similar to that seen in acutely depleted mice. In contrast, motor coordination, measured on a vertical pole task, was only moderately impaired in gradually depleted mice, despite severe impairments observed in acutely depleted mice. These results demonstrate the importance of the temporal profile of dopamine loss on the magnitude and progression of behavioral impairments. Our gradual depletion model thus establishes a new paradigm with which to study how circuits respond and adapt to dopamine loss over time, information which could uncover important cellular events during the prodromal phase of PD that ultimately impact the presentation or treatability of behavioral symptoms. PMID:26067595

Knölker's iron complex: an efficient in situ generated catalyst for reductive amination of alkyl aldehydes and amines.

PubMed

Pagnoux-Ozherelyeva, Anastassiya; Pannetier, Nicolas; Mbaye, Mbaye Diagne; Gaillard, Sylvain; Renaud, Jean-Luc

2012-05-14

An aminated series: a well-defined iron-catalyzed reductive amination reaction of aldehydes and ketones with aliphatic amines using molecular hydrogen is presented. Under mild conditions, good yields for a broad range of alkyl ketones as well as aldehydes were achieved. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organization of monosynaptic inputs to the serotonin and dopamine neuromodulatorysystems

PubMed Central

Ogawa, Sachie K.; Cohen, Jeremiah Y.; Hwang, Dabin; Uchida, Naoshige; Watabe-Uchida, Mitsuko

2014-01-01

SUMMARY Serotonin and dopamine are major neuromodulators. Here we used a modified rabies virus to identify monosynaptic inputs to serotonin neurons in the dorsal and median raphe (DR and MR). We found that inputs to DR and MR serotonin neurons are spatially shiftedin the forebrain, with MRserotonin neurons receiving inputs from more medial structures. We then compared these data with inputs to dopamine neurons in the ventral tegmental area (VTA) and substantianigra pars compacta (SNc). We found that DR serotonin neurons receive inputs from a remarkably similar set of areas as VTA dopamine neurons, apart from the striatum, which preferentially targets dopamine neurons. Ourresults suggest three majorinput streams: amedial stream regulates MR serotonin neurons, anintermediate stream regulatesDR serotonin and VTA dopamine neurons, and alateral stream regulatesSNc dopamine neurons. These results providefundamental organizational principlesofafferent control forserotonin and dopamine. PMID:25108805

The dopamine theory of addiction: 40 years of highs and lows.

PubMed

Nutt, David J; Lingford-Hughes, Anne; Erritzoe, David; Stokes, Paul R A

2015-05-01

For several decades, addiction has come to be viewed as a disorder of the dopamine neurotransmitter system; however, this view has not led to new treatments. In this Opinion article, we review the origins of the dopamine theory of addiction and discuss the ability of addictive drugs to elicit the release of dopamine in the human striatum. There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels. Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions.

Selective detection of dopamine in the presence of ascorbic acid via fluorescence quenching of InP/ZnS quantum dots.

PubMed

Ankireddy, Seshadri Reddy; Kim, Jongsung

2015-01-01

Dopamine is a neurotransmitter of the catecholamine family and has many important roles, especially in human brain. Several diseases of the nervous system, such as Parkinson's disease, attention deficit hyperactivity disorder, restless legs syndrome, are believed to be related to deficiency of dopamine. Several studies have been performed to detect dopamine by using electrochemical analysis. In this study, quantum dots (QDs) were used as sensing media for the detection of dopamine. The surface of the QDs was modified with l-cysteine by coupling reaction to increase the selectivity of dopamine. The fluorescence of cysteine-capped indium phosphide/zinc sulfide QDs was quenched by dopamine with various concentrations in the presence of ascorbic acid. This method shows good selectivity for dopamine detection, and the detection limit was 5 nM.

Dopamine dependency for acquisition and performance of Pavlovian conditioned response

PubMed Central

Darvas, Martin; Wunsch, Amanda M.; Gibbs, Jeffrey T.; Palmiter, Richard D.

2014-01-01

During Pavlovian conditioning, pairing of a neutral conditioned stimulus (CS) with a reward leads to conditioned reward-approach responses (CRs) that are elicited by presentation of the CS. CR behaviors can be sign tracking, in which animals engage the CS, or goal tracking, in which animals go to the reward location. We investigated CR behaviors in mice with only ∼5% of normal dopamine in the striatum using a Pavlovian conditioning paradigm. These mice had severely impaired acquisition of the CR, which was ameliorated by pharmacological restoration of dopamine synthesis with l-dopa. Surprisingly, after they had learned the CR, its expression decayed only gradually in following sessions that were conducted without l-dopa treatment. To assess specific contributions of dopamine signaling in the dorsal or ventral striatum, we performed virus-mediated restoration of dopamine synthesis in completely dopamine-deficient (DD) mice. Mice with dopamine signaling only in the dorsal striatum did not acquire a CR, whereas mice with dopamine signaling only in in the ventral striatum acquired a CR. The CR in mice with dopamine signaling only in the dorsal striatum was restored by subjecting the mice to instrumental training in which they had to interact with the CS to obtain rewards. We conclude that dopamine is essential for learning and performance of CR behavior that is predominantly goal tracking. Furthermore, although dopamine signaling in the ventral striatum is sufficient to support a CR, dopamine signaling only in the dorsal striatum can also support a CR under certain circumstances. PMID:24550305

Involvement of Infralimbic Prefrontal Cortex but not Lateral Habenula in Dopamine Attenuation After Chronic Mild Stress.

PubMed

Moreines, Jared L; Owrutsky, Zoe L; Grace, Anthony A

2017-03-01

Emerging evidence supports a role for dopamine in major depressive disorder (MDD). We recently reported fewer spontaneously active ventral tegmental area (VTA) dopamine neurons (ie, reduced dopamine neuron population activity) in the chronic mild stress (CMS) rodent model of MDD. In this study, we examined the role of two brain regions that have been implicated in MDD in humans, the infralimbic prefrontal cortex (ILPFC)-that is, rodent homolog of Brodmann area 25 (BA25), and the lateral habenula (LHb) in the CMS-induced attenuation of dopamine neuron activity. The impact of activating the ILPFC or LHb was evaluated using single-unit extracellular recordings of identified VTA dopamine neurons. The involvement of each region in dopamine neuron attenuation following 5-7 weeks of CMS was then evaluated by selective inactivation. Activation of either ILPFC or LHb in normal rats potently suppressed dopamine neuron population activity, but in unique patterns. ILPFC activation selectively inhibited dopamine neurons in medial VTA, which were most impacted by CMS. Conversely, LHb activation selectively inhibited dopamine neurons in lateral VTA, which were unaffected by CMS. Moreover, only ILPFC inactivation restored dopamine neuron population activity to normal levels following CMS; LHb inactivation had no restorative effect. These data suggest that, in the CMS model of MDD, the ILPFC is the primary driver of diminished dopamine neuron responses. These findings support a neural substrate for ILPFC/BA25 linking affective and motivational circuitry dysfunction in MDD.

Iron-catalyzed synthesis of secondary amines: on the way to green reductive aminations.

PubMed

Stemmler, Tobias; Surkus, Annette-Enrika; Pohl, Marga-Martina; Junge, Kathrin; Beller, Matthias

2014-11-01

Amines represent important intermediates in chemical and biological processes. Herein, we describe the use of a nanostructured iron-based catalyst for the tandem reductive amination between nitroarenes and aldehydes using hydrogen as reductant. The nanostructured iron-catalyst is prepared by immobilization of an iron-phenanthroline complex onto a commercially available carbon support. In the reaction sequence a primary amine is formed in situ from the corresponding nitro compound. Reversible condensation with aldehydes forms the respective imines, which are finally reduced to the desired secondary amine. This synthesis of secondary amines is atom-economical and environmentally attractive using cheap and readily available organic compounds as starting materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The dopamine D1 receptor is expressed and facilitates relaxation in airway smooth muscle.

PubMed

Mizuta, Kentaro; Zhang, Yi; Xu, Dingbang; Mizuta, Fumiko; D'Ovidio, Frank; Masaki, Eiji; Emala, Charles W

2013-09-02

Dopamine signaling is mediated by Gs protein-coupled "D1-like" receptors (D1 and D5) and Gi-coupled "D2-like" receptors (D2-4). In asthmatic patients, inhaled dopamine induces bronchodilation. Although the Gi-coupled dopamine D2 receptor is expressed and sensitizes adenylyl cyclase activity in airway smooth muscle (ASM) cells, the Gs-coupled dopamine D1-like receptor subtypes have never been identified on these cells. Activation of Gs-coupled receptors stimulates cyclic AMP (cAMP) production through the stimulation of adenylyl cyclase, which promotes ASM relaxation. We questioned whether the dopamine D1-like receptor is expressed on ASM, and modulates its function through Gs-coupling. The mRNA and protein expression of dopamine D1-like receptor subtypes in both native human and guinea pig ASM tissue and cultured human ASM (HASM) cells was measured. To characterize the stimulation of cAMP through the dopamine D1 receptor, HASM cells were treated with dopamine or the dopamine D1-like receptor agonists (A68930 or SKF38393) before cAMP measurements. To evaluate whether the activation of dopamine D1 receptor induces ASM relaxation, guinea pig tracheal rings suspended under isometric tension in organ baths were treated with cumulatively increasing concentrations of dopamine or A68930, following an acetylcholine-induced contraction with or without the cAMP-dependent protein kinase (PKA) inhibitor Rp-cAMPS, the large-conductance calcium-activated potassium (BKCa) channel blocker iberiotoxin, or the exchange proteins directly activated by cAMP (Epac) antagonist NSC45576. Messenger RNA encoding the dopamine D1 and D5 receptors were detected in native human ASM tissue and cultured HASM cells. Immunoblots confirmed the protein expression of the dopamine D1 receptor in both native human and guinea pig ASM tissue and cultured HASM cells. The dopamine D1 receptor was also immunohistochemically localized to both human and guinea pig ASM. The dopamine D1-like receptor agonists stimulated cAMP production in HASM cells, which was reversed by the selective dopamine D1-like receptor antagonists SCH23390 or SCH39166. A68930 relaxed acetylcholine-contracted guinea pig tracheal rings, which was attenuated by Rp-cAMPS but not by iberiotoxin or NSC45576. These results demonstrate that the dopamine D1 receptors are expressed on ASM and regulate smooth muscle force via cAMP activation of PKA, and offer a novel target for therapeutic relaxation of ASM.

The dopamine D1 receptor is expressed and facilitates relaxation in airway smooth muscle

PubMed Central

2013-01-01

Background Dopamine signaling is mediated by Gs protein-coupled “D1-like” receptors (D1 and D5) and Gi-coupled “D2-like” receptors (D2-4). In asthmatic patients, inhaled dopamine induces bronchodilation. Although the Gi-coupled dopamine D2 receptor is expressed and sensitizes adenylyl cyclase activity in airway smooth muscle (ASM) cells, the Gs-coupled dopamine D1-like receptor subtypes have never been identified on these cells. Activation of Gs-coupled receptors stimulates cyclic AMP (cAMP) production through the stimulation of adenylyl cyclase, which promotes ASM relaxation. We questioned whether the dopamine D1-like receptor is expressed on ASM, and modulates its function through Gs-coupling. Methods The mRNA and protein expression of dopamine D1-like receptor subtypes in both native human and guinea pig ASM tissue and cultured human ASM (HASM) cells was measured. To characterize the stimulation of cAMP through the dopamine D1 receptor, HASM cells were treated with dopamine or the dopamine D1-like receptor agonists (A68930 or SKF38393) before cAMP measurements. To evaluate whether the activation of dopamine D1 receptor induces ASM relaxation, guinea pig tracheal rings suspended under isometric tension in organ baths were treated with cumulatively increasing concentrations of dopamine or A68930, following an acetylcholine-induced contraction with or without the cAMP-dependent protein kinase (PKA) inhibitor Rp-cAMPS, the large-conductance calcium-activated potassium (BKCa) channel blocker iberiotoxin, or the exchange proteins directly activated by cAMP (Epac) antagonist NSC45576. Results Messenger RNA encoding the dopamine D1 and D5 receptors were detected in native human ASM tissue and cultured HASM cells. Immunoblots confirmed the protein expression of the dopamine D1 receptor in both native human and guinea pig ASM tissue and cultured HASM cells. The dopamine D1 receptor was also immunohistochemically localized to both human and guinea pig ASM. The dopamine D1-like receptor agonists stimulated cAMP production in HASM cells, which was reversed by the selective dopamine D1-like receptor antagonists SCH23390 or SCH39166. A68930 relaxed acetylcholine-contracted guinea pig tracheal rings, which was attenuated by Rp-cAMPS but not by iberiotoxin or NSC45576. Conclusions These results demonstrate that the dopamine D1 receptors are expressed on ASM and regulate smooth muscle force via cAMP activation of PKA, and offer a novel target for therapeutic relaxation of ASM. PMID:24004608

Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory

PubMed Central

Kempadoo, Kimberly A.; Mosharov, Eugene V.; Choi, Se Joon; Sulzer, David; Kandel, Eric R.

2016-01-01

Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC). Photostimulation of LC axons produced an increase in dopamine release in the dorsal hippocampus as revealed by high-performance liquid chromatography. Furthermore, optogenetically induced release of dopamine from the LC into the dorsal hippocampus enhanced selective attention and spatial object recognition via the dopamine D1/D5 receptor. These results suggest that spatial learning and memory are energized by the release of dopamine in the dorsal hippocampus from noradrenergic neurons of the LC. The present findings are critical for identifying the neural circuits that enable proper attention selection and successful learning and memory. PMID:27930324

Dopamine and extinction: A convergence of theory with fear and reward circuitry

PubMed Central

Abraham, Antony D.; Neve, Kim A.; Lattal, K. Matthew

2014-01-01

Research on dopamine lies at the intersection of sophisticated theoretical and neurobiological approaches to learning and memory. Dopamine has been shown to be critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine’s function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in reward-related tasks. A parallel and growing literature indicates that dopamine is involved in fear conditioning and extinction. These studies are consistent with long-standing ideas about appetitive-aversive interactions in learning theory and they speak to the general nature of cellular and molecular processes that underlie behavior. We review the behavioral and neurobiological literature showing a role for dopamine in fear conditioning and extinction. At a cellular level, we review dopamine signaling and receptor pharmacology, cellular and molecular events that follow dopamine receptor activation, and brain systems in which dopamine functions. At a behavioral level, we describe theories of learning and dopamine function that could describe the fundamental rules underlying how dopamine modulates different aspects of learning and memory processes. PMID:24269353

Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory.

PubMed

Kempadoo, Kimberly A; Mosharov, Eugene V; Choi, Se Joon; Sulzer, David; Kandel, Eric R

2016-12-20

Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC). Photostimulation of LC axons produced an increase in dopamine release in the dorsal hippocampus as revealed by high-performance liquid chromatography. Furthermore, optogenetically induced release of dopamine from the LC into the dorsal hippocampus enhanced selective attention and spatial object recognition via the dopamine D1/D5 receptor. These results suggest that spatial learning and memory are energized by the release of dopamine in the dorsal hippocampus from noradrenergic neurons of the LC. The present findings are critical for identifying the neural circuits that enable proper attention selection and successful learning and memory.

Cutaneous synergistic analgesia of bupivacaine in combination with dopamine in rats.

PubMed

Tzeng, Jann-Inn; Wang, Jieh-Neng; Wang, Jhi-Joung; Chen, Yu-Wen; Hung, Ching-Hsia

2016-05-04

The main goal of the study was to investigate the interaction between bupivacaine and dopamine on local analgesia. After the blockade of the cutaneous trunci muscle reflex (CTMR) responses, which occurred following the drugs were subcutaneously injected in rats, the cutaneous analgesic effect of dopamine in a dosage-dependent fashion was compared to that of bupivacaine. Drug-drug interactions were evaluated by isobolographic methods. We showed the dose-dependent effects of dopamine on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was bupivacaine (1.99 [1.92-2.09] μmol/kg) greater than dopamine (190 [181-203] μmol/kg) (P<0.01). At the equianalgesic doses (ED25, ED50, and ED75), dopamine elicited a similar duration of cutaneous analgesia compared with bupivacaine. The addition of dopamine to the bupivacaine solution exhibited a synergistic effect. Our pre-clinical data showed that dopamine produced a dose-dependent effect in producing cutaneous analgesia. When compared with bupivacaine, dopamine produced a lesser potency with a similar duration of cutaneous analgesia. Dopamine added to the bupivacaine preparation resulted in a synergistic analgesic effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An electrochemical dopamine sensor based on the ZnO/CuO nanohybrid structures.

PubMed

Khun, K; Ibupoto, Z H; Liu, X; Mansor, N A; Turner, A P F; Beni, V; Willander, M

2014-09-01

The selective detection of dopamine (DA) is of great importance in the modern medicine because dopamine is one of the main regulators in human behaviour. In this study, ZnO/CuO nanohybrid structures, grown on the gold coated glass substrate, have been investigated as a novel electrode material for the electrochemical detection of dopamine. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) techniques were used for the material characterization and the obtained results are in good agreement. The selective determination of dopamine was demonstrated by cyclic voltammetry (CV) and amperometric experiments. The amperometric response was linear for dopamine concentrations between 1.0 x 10(-3) and 8.0 mM with a sensitivity of 90.9 μA mM(-1) cm(-2). The proposed dopamine biosensor is very stable, selective over common interferents as glucose, uric acid and ascorbic acid, and also good reproducibility was observed for seven electrodes. Moreover, the dopamine sensor exhibited a fast response time of less than 10 s. The wide range and acceptable sensitivity of the presented dopamine sensor provide the possible application in analysing the dopamine from the real samples.

Attenuating GABAA Receptor Signaling in Dopamine Neurons Selectively Enhances Reward Learning and Alters Risk Preference in Mice

PubMed Central

Parker, Jones G.; Wanat, Matthew J.; Soden, Marta E.; Ahmad, Kinza; Zweifel, Larry S.; Bamford, Nigel S.; Palmiter, Richard D.

2011-01-01

Phasic dopamine transmission encodes the value of reward-predictive stimuli and influences both learning and decision-making. Altered dopamine signaling is associated with psychiatric conditions characterized by risky choices such as pathological gambling. These observations highlight the importance of understanding how dopamine neuron activity is modulated. While excitatory drive onto dopamine neurons is critical for generating phasic dopamine responses, emerging evidence suggests that inhibitory signaling also modulates these responses. To address the functional importance of inhibitory signaling in dopamine neurons, we generated mice lacking the β3 subunit of the GABAA receptor specifically in dopamine neurons (β3-KO mice) and examined their behavior in tasks that assessed appetitive learning, aversive learning, and risk preference. Dopamine neurons in midbrain slices from β3-KO mice exhibited attenuated GABA-evoked inhibitory post-synaptic currents. Furthermore, electrical stimulation of excitatory afferents to dopamine neurons elicited more dopamine release in the nucleus accumbens of β3-KO mice as measured by fast-scan cyclic voltammetry. β3-KO mice were more active than controls when given morphine, which correlated with potential compensatory upregulation of GABAergic tone onto dopamine neurons. β3-KO mice learned faster in two food-reinforced learning paradigms, but extinguished their learned behavior normally. Enhanced learning was specific for appetitive tasks, as aversive learning was unaffected in β3-KO mice. Finally, we found that β3-KO mice had enhanced risk preference in a probabilistic selection task that required mice to choose between a small certain reward and a larger uncertain reward. Collectively, these findings identify a selective role for GABAA signaling in dopamine neurons in appetitive learning and decision-making. PMID:22114279

Interaction of childhood urbanicity and variation in dopamine genes alters adult prefrontal function as measured by functional magnetic resonance imaging (fMRI).

PubMed

Reed, Jessica L; D'Ambrosio, Enrico; Marenco, Stefano; Ursini, Gianluca; Zheutlin, Amanda B; Blasi, Giuseppe; Spencer, Barbara E; Romano, Raffaella; Hochheiser, Jesse; Reifman, Ann; Sturm, Justin; Berman, Karen F; Bertolino, Alessandro; Weinberger, Daniel R; Callicott, Joseph H

2018-01-01

Brain phenotypes showing environmental influence may help clarify unexplained associations between urban exposure and psychiatric risk. Heritable prefrontal fMRI activation during working memory (WM) is such a phenotype. We hypothesized that urban upbringing (childhood urbanicity) would alter this phenotype and interact with dopamine genes that regulate prefrontal function during WM. Further, dopamine has been hypothesized to mediate urban-associated factors like social stress. WM-related prefrontal function was tested for main effects of urbanicity, main effects of three dopamine genes-catechol-O-methyltransferase (COMT), dopamine receptor D1 (DRD1), and dopamine receptor D2 (DRD2)-and, importantly, dopamine gene-by-urbanicity interactions. For COMT, three independent human samples were recruited (total n = 487). We also studied 253 subjects genotyped for DRD1 and DRD2. 3T fMRI activation during the N-back WM task was the dependent variable, while childhood urbanicity, dopamine genotype, and urbanicity-dopamine interactions were independent variables. Main effects of dopamine genes and of urbanicity were found. Individuals raised in an urban environment showed altered prefrontal activation relative to those raised in rural or town settings. For each gene, dopamine genotype-by-urbanicity interactions were shown in prefrontal cortex-COMT replicated twice in two independent samples. An urban childhood upbringing altered prefrontal function and interacted with each gene to alter genotype-phenotype relationships. Gene-environment interactions between multiple dopamine genes and urban upbringing suggest that neural effects of developmental environmental exposure could mediate, at least partially, increased risk for psychiatric illness in urban environments via dopamine genes expressed into adulthood.

Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques

PubMed Central

Siciliano, Cody A.; Calipari, Erin S.; Yorgason, Jordan T.; Lovinger, David M.; Mateo, Yolanda; Jimenez, Vanessa A.; Helms, Christa M.; Grant, Kathleen A.; Jones, Sara R.

2016-01-01

Rationale Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use, and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are unknown. Objective Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Methods Female rhesus macaques completed one year of daily (22 hr/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa-opioid receptor agonist) induced inhibition of dopamine release. Results Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa-opioid receptors, which both act as negative regulators of presynaptic dopamine release, were moderately and robustly enhanced in ethanol drinkers. Conclusions Greater uptake rates and sensitivity to D2-type autoreceptor and kappa-opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system, and suggest that the dopamine and dynorphin/kappa-opioid receptor systems may be efficacious pharmcotherapeutic targets in the treatment of alcohol use disorders. PMID:26892380

Single cocaine exposure does not alter striatal pre-synaptic dopamine function in mice: an [18 F]-FDOPA PET study.

PubMed

Bonsall, David R; Kokkinou, Michelle; Veronese, Mattia; Coello, Christopher; Wells, Lisa A; Howes, Oliver D

2017-12-01

Cocaine is a recreational drug of abuse that binds to the dopamine transporter, preventing reuptake of dopamine into pre-synaptic terminals. The increased presence of synaptic dopamine results in stimulation of both pre- and post-synaptic dopamine receptors, considered an important mechanism by which cocaine elicits its reinforcing properties. However, the effects of acute cocaine administration on pre-synaptic dopamine function remain unclear. Non-invasive imaging techniques such as positron emission tomography have revealed impaired pre-synaptic dopamine function in chronic cocaine users. Similar impairments have been seen in animal studies, with microdialysis experiments indicating decreased basal dopamine release. Here we use micro positron emission tomography imaging techniques in mice to measure dopamine synthesis capacity and determine the effect of acute cocaine administration of pre-synaptic dopamine function. We show that a dose of 20 mg/kg cocaine is sufficient to elicit hyperlocomotor activity, peaking 15-20 min post treatment (p < 0.001). However, dopamine synthesis capacity in the striatum was not significantly altered by acute cocaine treatment (KiCer: 0.0097 per min vs. 0.0112 per min in vehicle controls, p > 0.05). Furthermore, expression levels of two key enzymes related to dopamine synthesis, tyrosine hydroxylase and aromatic l-amino acid decarboxylase, within the striatum of scanned mice were not significantly affected by acute cocaine pre-treatment (p > 0.05). Our findings suggest that while the regulation of dopamine synthesis and release in the striatum have been shown to change with chronic cocaine use, leading to a reduced basal tone, these adaptations to pre-synaptic dopaminergic neurons are not initiated following a single exposure to the drug. © 2017 International Society for Neurochemistry.

Continuous cerebroventricular administration of dopamine: A new treatment for severe dyskinesia in Parkinson's disease?

PubMed

Laloux, C; Gouel, F; Lachaud, C; Timmerman, K; Do Van, B; Jonneaux, A; Petrault, M; Garcon, G; Rouaix, N; Moreau, C; Bordet, R; Duce, J A; Devedjian, J C; Devos, D

2017-07-01

In Parkinson's disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia. We aim to overcome prior challenges by demonstrating treatment feasibility and efficacy of continuous i.c.v. of dopamine close to the striatum. Dopamine prepared either anaerobically (A-dopamine) or aerobically (O-dopamine) in the presence or absence of a conservator (sodium metabisulfite, SMBS) was assessed upon acute MPTP and chronic 6-OHDA lesioning and compared to peripheral l-dopa treatment. A-dopamine restored motor function and induced a dose dependent increase of nigro-striatal tyrosine hydroxylase positive neurons in mice after 7days of MPTP insult that was not evident with either O-dopamine or l-dopa. In the 6-OHDA rat model, continuous circadian i.c.v. injection of A-dopamine over 30days also improved motor activity without occurrence of tachyphylaxia. This safety profile was highly favorable as A-dopamine did not induce dyskinesia or behavioral sensitization as observed with peripheral l-dopa treatment. Indicative of a new therapeutic strategy for patients suffering from l-dopa related complications with dyskinesia, continuous i.c.v. of A-dopamine has greater efficacy in mediating motor impairment over a large therapeutic index without inducing dyskinesia and tachyphylaxia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Sleep Deprivation Decreases [11C]Raclopride’s Binding to Dopamine D2/D3 Receptors in the Human Brain

PubMed Central

Volkow, Nora D.; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S.; Logan, Jean; Wong, Christopher; Ma, Jim; Pradhan, Kith; Tomasi, Dardo; Thanos, Peter K.; Ferré, Sergi; Jayne, Millard

2009-01-01

Sleep deprivation can markedly impair human performance contributing to accidents and poor productivity. The mechanisms underlying this impairment are not well understood but brain dopamine systems have been implicated. Here we test whether one night of sleep deprivation changes dopamine brain activity. We studied fifteen healthy subjects using positron emission tomography and [11C]raclopride (dopamine D2/3 receptor radioligand) and [11C]cocaine (dopamine transporter radioligand). Subjects were tested twice; after one night of rested sleep and after on night of sleep deprivation. [11C]Raclopride’s specific binding in striatum and thalamus were significantly reduced after sleep deprivation and the magnitude of this reduction correlated with increases in fatigue (tiredness and sleepiness) and with deterioration in cognitive performance (visual attention and working memory). In contrast sleep deprivation did not affect the specific binding of [11C]cocaine in striatum. Since [11C]raclopride competes with endogenous dopamine for binding to D2/D3 receptors, we interpret the decreases in binding to reflect dopamine increases with sleep deprivation. However, we can not rule out the possibility that decreased [11C]raclopride binding reflects decreases in receptor levels or affinity. Sleep deprivation did not affect dopamine transporters (target for most wake-promoting medications) and thus dopamine increases are likely to reflect increases in dopamine cell firing and/or release rather than decreases in dopamine reuptake. Inasmuch as dopamine-enhancing drugs increase wakefulness we postulate that dopamine increases after sleep deprivation is a mechanism by which the brain maintains arousal as the drive to sleep increases but one that is insufficient to counteract behavioral and cognitive impairment. PMID:18716203

Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques.

PubMed

Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T; Lovinger, David M; Mateo, Yolanda; Jimenez, Vanessa A; Helms, Christa M; Grant, Kathleen A; Jones, Sara R

2016-04-01

Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are not fully understood. Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self-administration. Female rhesus macaques completed 1 year of daily (22 h/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa opioid receptor agonist) induced inhibition of dopamine release. Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa opioid receptors, which both act as negative regulators of presynaptic dopamine release, was moderately and robustly enhanced in ethanol drinkers. Greater uptake rates and sensitivity to D2-type autoreceptor and kappa opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol-induced hypofunction of the dopamine system and suggest that the dopamine and dynorphin/kappa opioid receptor systems may be efficacious pharmacotherapeutic targets in the treatment of alcohol use disorders.

Adolescent binge-like alcohol alters sensitivity to acute alcohol effects on dopamine release in the nucleus accumbens of adult rats

PubMed Central

Shnitko, Tatiana A.; Spear, Linda P.; Robinson, Donita L.

2015-01-01

Rationale Early onset of alcohol drinking has been associated with alcohol abuse in adulthood. The neurobiology of this phenomenon is unclear, but mesolimbic dopamine pathways, which are dynamic during adolescence, may play a role. Objectives We investigated the impact of adolescent binge-like alcohol on phasic dopaminergic neurotransmission during adulthood. Methods Rats received intermittent intragastric ethanol, water or nothing during adolescence. In adulthood, electrically-evoked dopamine release and subsequent uptake were measured in the nucleus accumbens core at baseline and after acute challenge of ethanol or saline. Results Adolescent ethanol exposure did not alter basal measures of evoked dopamine release or uptake. Ethanol challenge dose-dependently decreased the amplitude of evoked dopamine release in rats by 30–50% in control groups, as previously reported, but did not alter evoked release in ethanol-exposed animals. To address the mechanism by which ethanol altered dopamine signaling, the evoked signals were modeled to estimate dopamine efflux per impulse and the velocity of the dopamine transporter. Dopamine uptake was slower in all exposure groups after ethanol challenge compared to saline, while dopamine efflux per pulse of electrical stimulation was reduced by ethanol only in ethanol-naive rats. Conclusions The results demonstrate that exposure to binge levels of ethanol during adolescence blunts the effect of ethanol challenge to reduce the amplitude of phasic dopamine release in adulthood. Large dopamine transients may result in more extracellular dopamine after alcohol challenge in adolescent-exposed rats, and may be one mechanism by which alcohol is more reinforcing in people who initiated drinking at an early age. PMID:26487039

Rotigotine is a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors.

PubMed

Wood, Martyn; Dubois, Vanessa; Scheller, Dieter; Gillard, Michel

2015-02-01

Rotigotine acts as a dopamine receptor agonist with high affinity for the dopamine D2, D3, D4 and D5 receptors but with a low affinity for the dopamine D1 receptor. We have investigated this further in radioligand binding and functional studies and compared the profile of rotigotine with that of other drugs used in the treatment of Parkinson's disease (PD). The binding of rotigotine to human dopamine D1, D2, D3, D4 and D5 receptors was determined in radioligand binding studies using [(3)H]rotigotine and compared with that of standard antagonist radioligands. Functional interactions of rotigotine with human dopamine receptors was also determined. [(3)H]rotigotine can be used as an agonist radioligand to label all dopamine receptor subtypes and this can be important to derive agonist affinity estimates. Rotigotine maintains this high affinity in functional studies at all dopamine receptors especially D1, D2 and D3 receptors and, to a lesser extent, D4 and D5 receptors. Rotigotine, like apomorphine but unlike ropinirole and pramipexole, was a potent agonist at all dopamine receptors. Rotigotine is a high-potency agonist at human dopamine D1, D2 and D3 receptors with a lower potency at D4 and D5 receptors. These studies differentiate rotigotine from conventional dopamine D2 agonists, used in the treatment of PD, such as ropinirole and pramipexole which lack activity at the D1 and D5 receptors, but resembles that of apomorphine which has greater efficacy in PD than other dopamine agonists but has suboptimal pharmacokinetic properties. © 2014 The British Pharmacological Society.

Rotigotine is a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors

PubMed Central

Wood, Martyn; Dubois, Vanessa; Scheller, Dieter; Gillard, Michel

2015-01-01

Background and Purpose Rotigotine acts as a dopamine receptor agonist with high affinity for the dopamine D2, D3, D4 and D5 receptors but with a low affinity for the dopamine D1 receptor. We have investigated this further in radioligand binding and functional studies and compared the profile of rotigotine with that of other drugs used in the treatment of Parkinson's disease (PD). Experimental Approach The binding of rotigotine to human dopamine D1, D2, D3, D4 and D5 receptors was determined in radioligand binding studies using [3H]rotigotine and compared with that of standard antagonist radioligands. Functional interactions of rotigotine with human dopamine receptors was also determined. Key Results [3H]rotigotine can be used as an agonist radioligand to label all dopamine receptor subtypes and this can be important to derive agonist affinity estimates. Rotigotine maintains this high affinity in functional studies at all dopamine receptors especially D1, D2 and D3 receptors and, to a lesser extent, D4 and D5 receptors. Rotigotine, like apomorphine but unlike ropinirole and pramipexole, was a potent agonist at all dopamine receptors. Conclusions and Implications Rotigotine is a high-potency agonist at human dopamine D1, D2 and D3 receptors with a lower potency at D4 and D5 receptors. These studies differentiate rotigotine from conventional dopamine D2 agonists, used in the treatment of PD, such as ropinirole and pramipexole which lack activity at the D1 and D5 receptors, but resembles that of apomorphine which has greater efficacy in PD than other dopamine agonists but has suboptimal pharmacokinetic properties. PMID:25339241

Neuromolecular imaging, a nanobiotechnology for Parkinson's disease: advancing pharmacotherapy for personalized medicine.

PubMed

Broderick, P A; Wenning, L; Li, Y-S

2017-01-01

Evaluating each patient and animal as its own control achieves personalized medicine, which honors the hippocratic philosophy, explaining that "it is far more important to know what person has the disease than what disease the person has." Similarly, individualizing molecular signaling directly from the patient's brain in real time is essential for providing prompt, patient-based treatment as dictated by the point of care. Fortunately, nanotechnology effectively treats many neurodegenerative diseases. In particular, the new medicinal frontier for the discovery of therapy for Parkinson's disease is nanotechnology and nanobiotechnology. Indeed, the unique nanotechnology of neuromolecular imaging combined with the series of nanobiosensors enables continuous videotracking of molecular neurotransmitters in both the normal physiologic and disease states with long-term electrochemical operational stability. This nanobiotechnology is able to track a signal in real time with excellent temporal and spatial resolution directly from each patient's brain to a computer as subjects are behaving during movement, normal and/or dysfunctional including prion-like Parkinson's behavioral biometrics. Moreover, the molecular signaling performed by these nanobiosensors live streams directly online and originates from precise neuroanatomic brain sites such as, in this case, the dorsal striatum in basal ganglia. Thus, the nanobiotechnology studies discussed herein imaged neuromolecules with and without L-3,4-dihydroxyphenylalanine (L-DOPA) in dorsal striatal basal ganglia neurons. Parkinsonian and non-Parkinsonian animals were video-tracked, and images were readily seen on a laptop via a potentiostat using a semiderivative electrical circuit. Administered L-DOPA doses were 50 and 100 mg/kg intraperitoneally (ip); the same experimental paradigm was used to image and then contrast data. Results showed that the baseline release of biogenic amine molecules was significantly above detection limits in non-Parkinsonian animals. After administration of L-DOPA, biogenic amines significantly increased in these non-Parkinson's animals. Nevertheless, it is intriguing to see that L-DOPA could not enable synaptic dopamine release in Parkinson's animals, thereby demonstrating that biogenic amines are biomarkers for Parkinson's disease. Biomarkers are biochemical, genetic, or molecular measures of biological reactions. Importantly, there were other significant biomarkers present in Parkinsonian animals and absent in non-Parkinsonian animals; these were peptide neurotransmitters that include dynorphin and somatostatin in the brain with detection limits of 40 nM for dynorphin and 37 nM for somatostatin (see Table 1). Furthermore, L-DOPA significantly increased these peptide biomarkers, dynorphin and somatostatin, in Parkinson's animals. Targeting biomarkers enables new diagnostic devices and treatments for Parkinson's disease through nanotechnology and nanobiotechnology.

Atmospheric chemistry and environmental impact of the use of amines in carbon capture and storage (CCS).

PubMed

Nielsen, Claus J; Herrmann, Hartmut; Weller, Christian

2012-10-07

This critical review addresses the atmospheric gas phase and aqueous phase amine chemistry that is relevant to potential emissions from amine-based carbon capture and storage (CCS). The focus is on amine, nitrosamine and nitramine degradation, and nitrosamine and nitramine formation processes. A comparison between the relative importance of the various atmospheric sinks for amines, nitrosamines and nitramines is presented.

High capacity immobilized amine sorbents

DOEpatents

Gray, McMahan L [Pittsburgh, PA; Champagne, Kenneth J [Fredericktown, PA; Soong, Yee [Monroeville, PA; Filburn, Thomas [Granby, CT

2007-10-30

A method is provided for making low-cost CO.sub.2 sorbents that can be used in large-scale gas-solid processes. The improved method entails treating an amine to increase the number of secondary amine groups and impregnating the amine in a porous solid support. The method increases the CO.sub.2 capture capacity and decreases the cost of utilizing an amine-enriched solid sorbent in CO.sub.2 capture systems.

Photoredox-catalyzed Direct Reductive Amination of Aldehydes without an External Hydrogen/Hydride Source.

PubMed

Alam, Rauful; Molander, Gary A

2018-05-04

The direct reductive amination of aromatic aldehydes has been realized using a photocatalyst under visible light irradiation. The single electron oxidation of an in situ formed aminal species generates the putative α-amino radical that eventually delivers the reductive amination product. This method is operationally simple, highly selective, and functional group tolerant, which allows the direct synthesis of benzylic amines by a unique mechanistic pathway.

Blonanserin Ameliorates Phencyclidine-Induced Visual-Recognition Memory Deficits: the Complex Mechanism of Blonanserin Action Involving D3-5-HT2A and D1-NMDA Receptors in the mPFC

PubMed Central

Hida, Hirotake; Mouri, Akihiro; Mori, Kentaro; Matsumoto, Yurie; Seki, Takeshi; Taniguchi, Masayuki; Yamada, Kiyofumi; Iwamoto, Kunihiro; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

2015-01-01

Blonanserin differs from currently used serotonin 5-HT2A/dopamine-D2 receptor antagonists in that it exhibits higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT2A receptor agonist) and 7-OH-DPAT (a dopamine-D3 receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D1 receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr197 and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser897 by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser896 by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D1-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D3 and serotonin 5-HT2A receptors in the mPFC. PMID:25120077

Selective effects of buspirone and molindone on dopamine metabolism and function in the striatum and frontal cortex of the rat.

PubMed

McMillen, B A; McDonald, C C

1983-03-01

The hypothesis that the nerve endings of the dopamine projection of the frontal cortex lack autoreceptors for regulation of tyrosine hydroxylase was tested by using the preferential inhibitors of dopamine autoreceptors, molindole and buspirone. In contrast to haloperidol, which elevates dopamine metabolism in the striatum and frontal cortex, both molindone and buspirone elicited little change in dopamine metabolism in the frontal cortex at doses up to 3.0 mg/kg, which cause the same maximal response in the corpus striatum as does haloperidol. Thus, the lack of autoreceptors in the frontal cortex is of pharmacological importance. That preferential inhibition of striatal dopamine autoreceptors may reverse catalepsy by enhancing synthesis and release of dopamine was tested by first inducing catalepsy with different drugs and then administering molindone or buspirone. Only buspirone (1.0 mg/kg) reversed catalepsy. This effect does not require presynaptic dopamine as catalepsy was reversed by buspirone in the dopamine-depleted rat (with 2.0 mg/kg R04-1284) as well as after postsynaptic dopamine receptor blockade by haloperidol of cis-flupenthixol. Thus, the mechanism for the reversal of catalepsy appears to be located efferent from the dopamine neuron. Buspirone, a non-benzodiazepine anti-anxiety drug, may prove useful for treatment of extrapyramidal motor disorders of either iatrogenic or idiosyncratic origin.

Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors

PubMed Central

Mikhailova, Maria A.; Bass, Caroline E.; Grinevich, Valentina P.; Chappell, Ann M.; Deal, Alex L.; Bonin, Keith D.; Weiner, Jeff L.; Gainetdinov, Raul R.; Budygin, Evgeny A.

2016-01-01

Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats. We used optical activation of this dopamine circuit to mimic tonic dopamine release in the nucleus accumbens and to explore the causal relationship between this form of dopamine signaling within the ventral tegmental area (VTA)-nucleus accumbens projection and consumption of a natural reward. Using a two bottle choice paradigm (sucrose vs. water), the experiments revealed that tonic optogenetic stimulation of mesolimbic dopamine transmission significantly decreased reward consummatory behaviors. Specifically, there was a significant decrease in the number of bouts, licks and amount of sucrose obtained during the drinking session. Notably, activation of VTA dopamine cell bodies or dopamine terminals in the nucleus accumbens resulted in identical behavioral consequences. No changes in the water intake were evident under the same experimental conditions. Collectively, these data demonstrate that tonic optogenetic stimulation of VTA-nucleus accumbens dopamine release is sufficient to inhibit reward consummatory behavior, possibly by preventing this circuit from engaging in phasic activity that is thought to be essential for reward-based behaviors. PMID:27421228

Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

PubMed Central

Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

2014-01-01

Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

Tyrosine - Effects on catecholamine release

NASA Technical Reports Server (NTRS)

Acworth, Ian N.; During, Matthew J.; Wurtman, Richard J.

1988-01-01

Tyrosine administration elevates striatal levels of dopamine metabolites in animals given treatments that accelerate nigrostriatal firing, but not in untreated rats. We examined the possibility that the amino acid might actually enhance dopamine release in untreated animals, but that the technique of measuring striatal dopamine metabolism was too insensitive to demonstrate such an effect. Dopamine release was assessed directly, using brain microdialysis of striatal extracellular fluid. Tyrosine administration (50-200 mg/kg IP) did indeed cause a dose related increase in extracellular fluid dopamine levels with minor elevations in levels of DOPAC and HVA, its major metabolites, which were not dose-related. The rise in dopamine was short-lived, suggesting that receptor-mediated feedback mechanisms responded to the increased dopamine release by diminishing neuronal firing or sensitivity to tyrosine. These observations indicate that measurement of changes in striatal DOPAC and HVA, if negative, need not rule out increases in nigrostriatal dopamine release.

Selective detection of dopamine in the presence of ascorbic acid via fluorescence quenching of InP/ZnS quantum dots

PubMed Central

Ankireddy, Seshadri Reddy; Kim, Jongsung

2015-01-01

Dopamine is a neurotransmitter of the catecholamine family and has many important roles, especially in human brain. Several diseases of the nervous system, such as Parkinson’s disease, attention deficit hyperactivity disorder, restless legs syndrome, are believed to be related to deficiency of dopamine. Several studies have been performed to detect dopamine by using electrochemical analysis. In this study, quantum dots (QDs) were used as sensing media for the detection of dopamine. The surface of the QDs was modified with l-cysteine by coupling reaction to increase the selectivity of dopamine. The fluorescence of cysteine-capped indium phosphide/zinc sulfide QDs was quenched by dopamine with various concentrations in the presence of ascorbic acid. This method shows good selectivity for dopamine detection, and the detection limit was 5 nM. PMID:26347250

Potential occupational risk of amines in carbon capture for power generation.

PubMed

Gentry, P Robinan; House-Knight, Tamara; Harris, Angela; Greene, Tracy; Campleman, Sharan

2014-08-01

While CO2 capture and storage (CCS) technology has been well studied in terms of its efficacy and cost of implementation, there is limited available data concerning the potential for occupational exposure to amines, mixtures of amines, or degradation of by-products from the CCS process. This paper is a critical review of the available data concerning the potential effects of amines and CCS-degradation by-products. A comprehensive review of the occupational health and safety issues associated with exposure to amines and amine by-products at CCS facilities was performed, along with a review of the regulatory status and guidelines of amines, by-products, and CCS process vapor mixtures. There are no specific guidelines or regulations regarding permissible levels of exposure via air for amines and degradation products that could form atmospheric oxidation of amines released from post-combustion CO2 capture plants. While there has been a worldwide effort to develop legal and regulatory frameworks for CCS, none are directly related to occupational exposures. By-products of alkanolamine degradation may pose the most significant health hazard to workers in CCS facilities, with several aldehydes, amides, nitramines, and nitrosamines classified as either known or potential/possible human carcinogens. The absence of large-scale CCS facilities; absence and unreliability of reported data in the literature from pilot facilities; and proprietary amine blends make it difficult to estimate potential amine exposures and predict formation and exposure to degradation products.

Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons.

PubMed

Yapo, Cedric; Nair, Anu G; Clement, Lorna; Castro, Liliana R; Hellgren Kotaleski, Jeanette; Vincent, Pierre

2017-12-15

Brief dopamine events are critical actors of reward-mediated learning in the striatum; the intracellular cAMP-protein kinase A (PKA) response of striatal medium spiny neurons to such events was studied dynamically using a combination of biosensor imaging in mouse brain slices and in silico simulations. Both D1 and D2 medium spiny neurons can sense brief dopamine transients in the sub-micromolar range. While dopamine transients profoundly change cAMP levels in both types of medium spiny neurons, the PKA-dependent phosphorylation level remains unaffected in D2 neurons. At the level of PKA-dependent phosphorylation, D2 unresponsiveness depends on protein phosphatase-1 (PP1) inhibition by DARPP-32. Simulations suggest that D2 medium spiny neurons could detect transient dips in dopamine level. The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of the dopamine effect on intracellular signalling remains poorly understood. We used genetically encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation levels, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D 1 or D 2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively. Transient dopamine showed similar sub-micromolar efficacies on cAMP in both D1 and D2 MSNs, thus challenging the commonly accepted notion that dopamine efficacy is much higher on D 2 than on D 1 receptors. However, in D2 MSNs, the large decrease in cAMP level triggered by transient dopamine did not translate to a decrease in PKA-dependent phosphorylation level, owing to the efficient inhibition of protein phosphatase 1 by DARPP-32. Simulations further suggested that D2 MSNs can also operate in a 'tone-sensing' mode, allowing them to detect transient dips in basal dopamine. Overall, our results show that D2 MSNs may sense much more complex patterns of dopamine than previously thought. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

40 CFR 721.7285 - Amines, N-cocoalkyltrimethylenedi-, citrates.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Amines, N-cocoalkyltrimethylenedi... Specific Chemical Substances § 721.7285 Amines, N-cocoalkyltrimethylenedi-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines, N...

40 CFR 721.7286 - Amines, N-tallowalkyltripropylenetetra-, citrates.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Amines, N-tallowalkyltripropylenetetra... Specific Chemical Substances § 721.7286 Amines, N-tallowalkyltripropylenetetra-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines, N...

40 CFR 721.7285 - Amines, N-cocoalkyltrimethylenedi-, citrates.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amines, N-cocoalkyltrimethylenedi... Specific Chemical Substances § 721.7285 Amines, N-cocoalkyltrimethylenedi-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines, N...

40 CFR 721.7286 - Amines, N-tallowalkyltripropylenetetra-, citrates.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amines, N-tallowalkyltripropylenetetra... Specific Chemical Substances § 721.7286 Amines, N-tallowalkyltripropylenetetra-, citrates. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified as amines, N...

Oral Administration of Methylphenidate Blocks the Effect of Cocaine on Uptake at the Drosophila Dopamine Transporter

PubMed Central

2013-01-01

Although our understanding of the actions of cocaine in the brain has improved, an effective drug treatment for cocaine addiction has yet to be found. Methylphenidate binds the dopamine transporter and increases extracellular dopamine levels in mammalian central nervous systems similar to cocaine, but it is thought to elicit fewer addictive and reinforcing effects owing to slower pharmacokinetics for different routes of administration between the drugs. This study utilizes the fruit fly model system to quantify the effects of oral methylphenidate on dopamine uptake during direct cocaine exposure to the fly CNS. The effect of methylphenidate on the dopamine transporter has been explored by measuring the uptake of exogenously applied dopamine. The data suggest that oral consumption of methylphenidate inhibits the Drosophila dopamine transporter and the inhibition is concentration dependent. The peak height increased to 150% of control when cocaine was used to block the dopamine transporter for untreated flies but only to 110% for methylphenidate-treated flies. Thus, the dopamine transporter is mostly inhibited for the methylphenidate-fed flies before the addition of cocaine. The same is true for the rate of the clearance of dopamine measured by amperometry. For untreated flies the rate of clearance changes 40% when the dopamine transporter is inhibited with cocaine, and for treated flies the rate changes only 10%. The results were correlated to the in vivo concentration of methylphenidate determined by CE-MS. Our data suggest that oral consumption of methylphenidate inhibits the Drosophila dopamine transporter for cocaine uptake, and the inhibition is concentration dependent. PMID:23402315

Long-Term Stimulant Treatment Affects Brain Dopamine Transporter Level in Patients with Attention Deficit Hyperactive Disorder

PubMed Central

Wang, Gene-Jack; Volkow, Nora D.; Wigal, Timothy; Kollins, Scott H.; Newcorn, Jeffrey H.; Telang, Frank; Logan, Jean; Jayne, Millard; Wong, Christopher T.; Han, Hao; Fowler, Joanna S.; Zhu, Wei; Swanson, James M.

2013-01-01

Objective Brain dopamine dysfunction in attention deficit/hyperactivity disorder (ADHD) could explain why stimulant medications, which increase dopamine signaling, are therapeutically beneficial. However while the acute increases in dopamine induced by stimulant medications have been associated with symptom improvement in ADHD the chronic effects have not been investigated. Method We used positron emission tomography and [11C]cocaine (dopamine transporter radioligand) to measure dopamine transporter availability in the brains of 18 never-medicated adult ADHD subjects prior to and after 12 months of treatment with methylphenidate and in 11 controls who were also scanned twice at 12 months interval but without stimulant medication. Dopamine transporter availability was quantified as non-displaceable binding potential using a kinetic model for reversible ligands. Results Twelve months of methylphenidate treatment increased striatal dopamine transporter availability in ADHD (caudate, putamen and ventral striatum: +24%, p<0.01); whereas there were no changes in control subjects retested at 12-month interval. Comparisons between controls and ADHD participants revealed no significant difference in dopamine transporter availability prior to treatment but showed higher dopamine transporter availability in ADHD participants than control after long-term treatment (caudate: p<0.007; putamen: p<0.005). Conclusion Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories. PMID:23696790

A transient dopamine signal encodes subjective value and causally influences demand in an economic context

PubMed Central

Schelp, Scott A.; Pultorak, Katherine J.; Rakowski, Dylan R.; Gomez, Devan M.; Krzystyniak, Gregory; Das, Raibatak; Oleson, Erik B.

2017-01-01

The mesolimbic dopamine system is strongly implicated in motivational processes. Currently accepted theories suggest that transient mesolimbic dopamine release events energize reward seeking and encode reward value. During the pursuit of reward, critical associations are formed between the reward and cues that predict its availability. Conditioned by these experiences, dopamine neurons begin to fire upon the earliest presentation of a cue, and again at the receipt of reward. The resulting dopamine concentration scales proportionally to the value of the reward. In this study, we used a behavioral economics approach to quantify how transient dopamine release events scale with price and causally alter price sensitivity. We presented sucrose to rats across a range of prices and modeled the resulting demand curves to estimate price sensitivity. Using fast-scan cyclic voltammetry, we determined that the concentration of accumbal dopamine time-locked to cue presentation decreased with price. These data confirm and extend the notion that dopamine release events originating in the ventral tegmental area encode subjective value. Using optogenetics to augment dopamine concentration, we found that enhancing dopamine release at cue made demand more sensitive to price and decreased dopamine concentration at reward delivery. From these observations, we infer that value is decreased because of a negative reward prediction error (i.e., the animal receives less than expected). Conversely, enhancing dopamine at reward made demand less sensitive to price. We attribute this finding to a positive reward prediction error, whereby the animal perceives they received a better value than anticipated. PMID:29109253

Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder.

PubMed

Wang, Gene-Jack; Volkow, Nora D; Wigal, Timothy; Kollins, Scott H; Newcorn, Jeffrey H; Telang, Frank; Logan, Jean; Jayne, Millard; Wong, Christopher T; Han, Hao; Fowler, Joanna S; Zhu, Wei; Swanson, James M

2013-01-01

Brain dopamine dysfunction in attention deficit/hyperactivity disorder (ADHD) could explain why stimulant medications, which increase dopamine signaling, are therapeutically beneficial. However while the acute increases in dopamine induced by stimulant medications have been associated with symptom improvement in ADHD the chronic effects have not been investigated. We used positron emission tomography and [(11)C]cocaine (dopamine transporter radioligand) to measure dopamine transporter availability in the brains of 18 never-medicated adult ADHD subjects prior to and after 12 months of treatment with methylphenidate and in 11 controls who were also scanned twice at 12 months interval but without stimulant medication. Dopamine transporter availability was quantified as non-displaceable binding potential using a kinetic model for reversible ligands. Twelve months of methylphenidate treatment increased striatal dopamine transporter availability in ADHD (caudate, putamen and ventral striatum: +24%, p<0.01); whereas there were no changes in control subjects retested at 12-month interval. Comparisons between controls and ADHD participants revealed no significant difference in dopamine transporter availability prior to treatment but showed higher dopamine transporter availability in ADHD participants than control after long-term treatment (caudate: p<0.007; putamen: p<0.005). Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories.

Carbon Dioxide-Mediated C(sp3)-H Arylation of Amine Substrates.

PubMed

Kapoor, Mohit; Liu, Daniel; Young, Michael C

2018-05-25

Elaborating amines via C-H functionalization has been an important area of research over the past decade but has generally relied on an added directing group or sterically hindered amine approach. Since free-amine-directed C(sp 3 )-H activation is still primarily limited to cyclization reactions and to improve the sustainability and reaction scope of amine-based C-H activation, we present a strategy using CO 2 in the form of dry ice that facilitates intermolecular C-H arylation. This methodology has been used to enable an operationally simple procedure whereby 1° and 2° aliphatic amines can be arylated selectively at their γ-C-H positions. In addition to potentially serving as a directing group, CO 2 has also been demonstrated to curtail the oxidation of sensitive amine substrates.

A general catalytic β-C-H carbonylation of aliphatic amines to β-lactams.

PubMed

Willcox, Darren; Chappell, Ben G N; Hogg, Kirsten F; Calleja, Jonas; Smalley, Adam P; Gaunt, Matthew J

2016-11-18

Methods for the synthesis and functionalization of amines are intrinsically important to a variety of chemical applications. We present a general carbon-hydrogen bond activation process that combines readily available aliphatic amines and the feedstock gas carbon monoxide to form synthetically versatile value-added amide products. The operationally straightforward palladium-catalyzed process exploits a distinct reaction pathway, wherein a sterically hindered carboxylate ligand orchestrates an amine attack on a palladium anhydride to transform aliphatic amines into β-lactams. The reaction is successful with a wide range of secondary amines and can be used as a late-stage functionalization tactic to deliver advanced, highly functionalized amine products of utility for pharmaceutical research and other areas. Copyright © 2016, American Association for the Advancement of Science.

Conversion of alcohols to enantiopure amines through dual enzyme hydrogen-borrowing cascades

PubMed Central

Mutti, Francesco G.; Knaus, Tanja; Scrutton, Nigel S.; Breuer, Michael; Turner, Nicholas J.

2016-01-01

α-Chiral amines are key intermediates for the synthesis of a plethora of chemical compounds on industrial scale. Here we present a biocatalytic hydrogen-borrowing amination of primary and secondary alcohols that allows for the efficient and environmentally benign production of enantiopure amines. The method relies on the combination of an alcohol dehydrogenase (ADHs from Aromatoleum sp., Lactobacillus sp. and Bacillus sp.) enzyme operating in tandem with an amine dehydrogenase (AmDHs engineered from Bacillus sp.) to aminate a structurally diverse range of aromatic and aliphatic alcohols (up to 96% conversion and 99% enantiomeric excess). Furthermore, primary alcohols are aminated with high conversion (up to 99%). This redox self-sufficient network possesses high atom efficiency, sourcing nitrogen from ammonium and generating water as the sole by-product. PMID:26404833

Dopamine Signaling Regulates Fat Content through β-Oxidation in Caenorhabditis elegans

PubMed Central

Barros, Alexandre Guimarães de Almeida; Bridi, Jessika Cristina; de Souza, Bruno Rezende; de Castro Júnior, Célio; de Lima Torres, Karen Cecília; Malard, Leandro; Jorio, Ado; de Miranda, Débora Marques; Ashrafi, Kaveh; Romano-Silva, Marco Aurélio

2014-01-01

The regulation of energy balance involves an intricate interplay between neural mechanisms that respond to internal and external cues of energy demand and food availability. Compelling data have implicated the neurotransmitter dopamine as an important part of body weight regulation. However, the precise mechanisms through which dopamine regulates energy homeostasis remain poorly understood. Here, we investigate mechanisms through which dopamine modulates energy storage. We showed that dopamine signaling regulates fat reservoirs in Caenorhabditis elegans. We found that the fat reducing effects of dopamine were dependent on dopaminergic receptors and a set of fat oxidation enzymes. Our findings reveal an ancient role for dopaminergic regulation of fat and suggest that dopamine signaling elicits this outcome through cascades that ultimately mobilize peripheral fat depots. PMID:24465759

Dopamine D2 receptors photolabeled by iodo-azido-clebopride.

PubMed

Niznik, H B; Dumbrille-Ross, A; Guan, J H; Neumeyer, J L; Seeman, P

1985-04-19

Iodo-azido-clebopride, a photoaffinity compound for dopamine D2 receptors, had high affinity for canine brain striatal dopamine D2 receptors with a dissociation constant (Kd) of 14 nM. Irradiation of striatal homogenate with iodo-azido-clebopride irreversibly inactivated 50% of dopamine D2 receptors at 20 nM (as indicated by subsequent [3H]spiperone binding). Dopamine agonists and antagonists prevented this photo-inactivation with the appropriate rank-order of potency. Striatal dopamine D1, serotonin (S2), alpha 1- and beta-adrenoceptors were not significantly inactivated following irradiation with iodo-azido-clebopride. Thus, iodo-azido-clebopride is a selective photoaffinity probe for dopamine D2 receptors, the radiolabelled form of which may aid in the molecular characterization of these proteins.

A novel assay to measure tertiary and quaternary amines in wastewater: An indicator for NDMA wastewater precursors.

PubMed

Woods-Chabane, Gwen C; Glover, Caitlin M; Marti, Erica J; Dickenson, Eric R V

2017-07-01

This study examined the potential of using a novel bulk amine assay as an approximation for the tertiary and quaternary amine load in wastewaters and surface water samples, and this approximation was compared to N-nitrosodimethylamine (NDMA) formation potential using chloramines. An existing colorimetric method was examined and optimized for the detection of amines in environmental water samples. The method consists of liquid-liquid extraction followed by a catalyzed reaction to form a yet-undefined product that is known to be both a strong chromophore and fluorophore. Previous work verified that this reaction was effectively catalyzed by a number of compounds containing tertiary and quaternary amine moieties. Many tertiary and quaternary compounds are also efficient producers of NDMA under chloramination conditions, and a linear correlation was consequently derived from the bulk amine signals vs. NDMA formation potential in various wastewater samples (R 2  = 0.74; n = 24; p-value < 0.05). The results provide evidence that approximately 2% of the tertiary and quaternary amines measured can form NDMA and an estimated 0.01-1.3% of nitrogen in dissolved organic nitrogen originates from these bulk amines. The normalization of NDMA concentration by the amine measurement revealed that ozone effectively destroyed those tertiary and quaternary amine structures more likely to form NDMA in treated wastewater samples. This bulk amine assay illustrates that proxy measurements of tertiary and quaternary amines can be linked to the NDMA formation potential of a given sample, and this approach may prove useful as a characterizing tool for NDMA precursors in wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antagonistic effects of beta-phenylethylamine on quinpirole- and (-)-sulpiride-induced changes in evoked dopamine release from rat striatal slices.

PubMed

Yamada, S; Harano, M; Tanaka, M

1998-02-19

To assess the role of beta-phenylethylamine in aspects of dopamine release, we measured the level of beta-phenylethylamine in the rat striatum after killing the rats by microwave irradiation. We then investigated the effect of beta-phenylethylamine on electrically evoked dopamine release from rat striatal slices in vitro. The striatal beta-phenylethylamine level was 46.5 +/- 3.5 ng/g wet tissue, equivalent to 0.3 micromol/l. Superfusion with low concentrations of beta-phenylethylamine up to 1 micromol/l had no effect on spontaneous or electrically evoked dopamine release from striatal slices. Quinpirole reduced the evoked dopamine release from slices in a concentration-dependent manner. The quinpirole-induced reduction of evoked dopamine release was attenuated 30% by superfusion with 0.3 micromol/l beta-phenylethylamine. Moreover, the (-)-sulpiride (0.1 micromol/l)-induced increase in evoked dopamine release was also attenuated by superfusion with 0.3 micromol/l beta-phenylethylamine. These data indicate that submicromolar levels of beta-phenylethylamine could modify the dopamine autoreceptor mediated changes in evoked dopamine release from rat striatal slices.

The protective effect of dopamine on ventilator-induced lung injury via the inhibition of NLRP3 inflammasome.

PubMed

Yang, Xiaomei; Sun, Xiaotong; Chen, Hongli; Xi, Guangmin; Hou, Yonghao; Wu, Jianbo; Liu, Dejie; Wang, Huanliang; Hou, Yuedong; Yu, Jingui

2017-04-01

Dopamine (DA), a neurotransmitter, was previously shown to have anti-inflammatory effects. However, its role in ventilator-induced lung injury (VILI) has not been explicitly demonstrated. This study aimed to investigate the therapeutic efficacy and molecular mechanisms of dopamine in VILI. Rats were treated with dopamine during mechanical ventilation. Afterwards, the influence of dopamine on histological changes, pulmonary edema, the lung wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, polymorphonuclear(PMN)counts, inflammatory cytokine levels, and NLRP3 inflammasome protein expression were examined. Our results showed that dopamine significantly attenuated lung tissue injury, the lung W/D ratio, MPO activity and neutrophil infiltration. Moreover, it inhibited inflammatory cytokine levels in the Bronchoalveolar lavage fluid (BAL). In addition, dopamine significantly inhibited ventilation-induced NLRP3 activation. Our experimental findings demonstrate that dopamine exerted protective effects in VILI by alleviating the inflammatory response through inhibition of NLRP3 signaling pathways. The present study indicated that dopamine could be a potential effective therapeutic strategy for the treatment of VILI. Copyright © 2017 Elsevier B.V. All rights reserved.

Soda-amine pulping : reaction of amines with free phenolic [beta]-[omicron]-4 ethers

Treesearch

John R. Obst

1981-01-01

The quinone methide from guaiacylglycol-ß-guaiacyl ether underwent nucleophilic addition to the a-carbon with primary and secondary amines at 40°C. At pulping temperature, 170°C, only the primary amine adduct was detected. The quinone methide from guaiacylglycerol-ß-guaiacyl ether gave analogous adducts at 40°C, but no quinone methide-amine adducts were detected at 170...

Aminative umpolung of aldehydes to α-amino anion equivalents for Pd-catalyzed allylation: an efficient synthesis of homoallylic amines.

PubMed

Ding, Lei; Chen, Jing; Hu, Yifan; Xu, Juan; Gong, Xing; Xu, Dongfang; Zhao, Baoguo; Li, Hexing

2014-02-07

An attractive strategy for generation of α-amino anions from aldehydes with applications in synthesis of homoallylic amines is described. Aromatic aldehydes can be converted to α-amino anion equivalents via amination with 2,2-diphenylglycine and subsequent decarboxylation. The in situ generated α-imino anions are highly reactive for Pd-catalyzed allylation, forming the corresponding homoallylic amines in high yields with excellent regioselectivity.

40 CFR 721.1625 - Alkylbenzene sulfonate, amine salt.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkylbenzene sulfonate, amine salt... Substances § 721.1625 Alkylbenzene sulfonate, amine salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkylbenzene sulfonate, amine...

40 CFR 721.1625 - Alkylbenzene sulfonate, amine salt.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkylbenzene sulfonate, amine salt... Substances § 721.1625 Alkylbenzene sulfonate, amine salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkylbenzene sulfonate, amine...

Evaluation of a Liquid Amine System for Spacecraft Carbon Dioxide Control

NASA Technical Reports Server (NTRS)

Breaux, D. K.; Friedel, P.; Hwang, K. C.; Probert, G.; Ruder, J. M.; Sawamura, L.

1974-01-01

The analytical and experimental studies are described which were directed toward the acquisition of basic information on utilizing a liquid amine sorbent for in use in a CO2 removal system for manned spacecraft. Liquid amine systems are successfully used on submarines for control of CO2 generated by the crew, but liquid amines were not previously considered for spacecraft applications due to lack of development of satisfactory rotary phase separators. Developments in this area now make consideration of liquid amines practical for spacecraft system CO2 removal. The following major tasks were performed to evaluate liquid amine systems for spacecraft: (1) characterization, through testing, of the basic physical and thermodynamic properties of the amine solution; (2) determination of the dynamic characteristics of a cocurrent flow absorber; and (3) evaluation, synthesis, and selection of a liquid amine system concept oriented toward low power requirements. A low weight, low power system concept was developed. Numerical and graphical data are accompanied by pertinent observations.

Bioactive amines in sorghum: method optimisation and influence of line, tannin and hydric stress.

PubMed

Paiva, Caroline Liboreiro; Evangelista, Warlley Pinheiro; Queiroz, Valéria Aparecida Vieira; Glória, Maria Beatriz Abreu

2015-04-15

The profile and levels of bioactive amines in different sorghum lines were reported for the first time. The amines were quantified by ion-pair HPLC, post-column derivatisation with o-phthalaldehyde and fluorimetric detection. The extraction procedure was optimised: 420 μm particle size, extraction with 5% trichloroacetic acid and three extractions. The screening of 22 sorghum lines showed that four of the ten amines investigated were detected. Spermine and spermidine were the prevalent amines (100%), followed by putrescine (77%) and cadaverine (14%). Total amines ranged from 5.8 to 41.4 mg/100 g, and the polyamines represented 60-100% of the total. Sorghum without tannin had higher amines levels compared to sorghum with tannin and cadaverine was specific to samples without tannin. Hydric stress caused accumulation of spermidine in the grains and affected the levels of other amines at rates depending on the presence or not of tannin. Sorghum is a significant source of polyamines. Copyright © 2014 Elsevier Ltd. All rights reserved.

Basic biogenic aerosol precursors: Agricultural source attribution of volatile amines revised

NASA Astrophysics Data System (ADS)

Kuhn, U.; Sintermann, J.; Spirig, C.; Jocher, M.; Ammann, C.; Neftel, A.

2011-08-01

Despite recent evidence on an important role of volatile amines in the nucleation of particulate matter, very scarce information is available on their atmospheric abundance and source distribution. Previous measurements in animal housings had identified livestock husbandry as the main amine source, with trimethylamine (TMA) being the key component. This has led to the assumption that the agricultural sources for amines are similar as for ammonia, emitted throughout the cascade of animal excretion, storage and application in the field. In this study, we present the first micrometeorological flux measurements as well as dynamic enclosure experiments showing that the amine source strength from stored slurry is negligible, implying significant consequences for the global amine emission inventory. In the case of cattle, amine production is attributed to the animal's rumination activity and exhalation is suggested to be an important emission pathway, similar to the greenhouse gas methane. Fodder like hay and silage also emits volatile amines, potentially assigning these alkaloid compounds a key function in enhancing particle formation in remote areas.

Quantitative effects of amination degree on the magnetic iron oxide nanoparticles (MIONPs) using as adsorbents to remove aqueous heavy metal ions.

PubMed

Lin, Sen; Xu, Meng; Zhang, Wei; Hua, Xiufu; Lin, Kuangfei

2017-08-05

The hierarchical effect of amine-functionalization on nanoparticle properties, magnetism especially, and adsorption of Cu 2+ , Ni 2+ , Pb 2+ and Zn 2+ by aminated MIONPs were investigated elaboratively. The results reflected that the dispersibility and stability of nanoparticles in aqueous solution were both enhanced as MIONPs grafted with amine groups, while saturation magnetism and magnetic recovery conveniences had a negatively correlative relation with the amination degree. In addition, the adsorption performances of Cu 2+ , Ni 2+ , Pb 2+ and Zn 2+ by different aminated MIONPs were also studied comprehensively. The results showed that the initial adsorption rates and adsorption capacities of heavy metal ions increased with the amination degree. In addition, the quantitative correlation between amination degree and adsorption capacities of different heavy metal ions could be described well by a model built on basis of adsorption processes. Copyright © 2017. Published by Elsevier B.V.

Michael Addition Polymerization of Trifunctional Amine and Acrylic Monomer: A Versatile Platform for Development of Biomaterials.

PubMed

Cheng, Weiren; Wu, Decheng; Liu, Ye

2016-10-10

Michael addition polymerizations of amines and acrylic monomers are versatile approaches to biomaterials for various applications. A combinatorial library of poly(β-amino ester)s and diverse poly(amido amine)s from diamines and diacrylates or bis(acrylamide)s have been reported, respectively. Furthermore, novel linear and hyperbranched polymers from Michael addition polymerizations of trifunctional amines and acrylic monomers significantly enrich this category of biomaterials. In this Review, we focus on the biomaterials from Michael addition polymerizations of trifunctional amines and acrylic monomers. First we discuss how the polymerization mechanisms, which are determined by the reactivity sequence of the three types of amines of trifunctional amines, i.e., secondary (2°) amines (original), primary (1°) amines, and 2° amines (formed), are affected by the chemistry of monomers, reaction temperature, and solvent. Then we update how to design and synthesize linear and hyperbranched polymers based on the understanding of polymerization mechanisms. Linear polymers containing 2° amines in the backbones can be obtained from polymerizations of diacrylates or bis(acrylamide)s with equimolar trifunctional amine, and several approaches, e.g., 2A 2 +BB'B″, A 3 +2BB'B', A 2 +BB'B″, to hyperbranched polymers are developed. Further through molecular design of monomers, conjugation of functional species to 2° amines in the backbones of linear polymers and the abundant terminal groups of hyperbranched polymers, the amphiphilicity of polymers can be adjusted, and additional stimuli, e.g., thermal, redox, reactive oxidation species (ROS), and light, responses can be integrated with the intrinsic pH response. Finally we discuss the applications of the polymers for gene/drug delivery and bioimaging through exploring their self-assemblies in various motifs, e.g., micelles, polyplexes particles/nanorings and hydrogels. Redox-responsive hyperbranched polymers can display 300 times higher in vitro gene transfection efficiency and provide a higher in vivo siRNA efficacy than PEI. Also redox-responsive micelle carriers can improve the efficacy of anticancer drug and the bioimaging contrast. Further molecular design and optimization of this category of polymers together with in vivo studies should provide safe and efficient biomaterials for clinical applications.

Genetics Home Reference: dopa-responsive dystonia

MedlinePlus

... neurotransmitters called dopamine and serotonin. Among their many functions, dopamine transmits signals within the brain to produce smooth ... production of a tyrosine hydroxylase enzyme with reduced function, which leads to a decrease in dopamine production. A reduction in the amount of dopamine ...

Mutation of Drosophila dopamine receptor DopR leads to male-male courtship behavior.

PubMed

Chen, Bin; Liu, He; Ren, Jing; Guo, Aike

2012-07-06

In Drosophila, dopamine plays important roles in many biological processes as a neuromodulator. Previous studies showed that dopamine level could affect fly courtship behaviors. Disturbed dopamine level leads to abnormal courtship behavior in two different ways. Dopamine up-regulation induces male-male courtship behavior, while down-regulation of dopamine level results in increased sexual attractiveness of males towards other male flies. Until now, the identity of the dopamine receptor involved in this abnormal male-male courtship behavior remains unknown. Here we used genetic approaches to investigate the role of dopamine receptors in fly courtship behavior. We found that a dopamine D1-like receptor, DopR, was involved in fly courtship behavior. DopR mutant male flies display male-male courtship behavior. This behavior is mainly due to the male's increased propensity to court other males. Expression of functional DopR successfully rescued this mutant phenotype. Knock-down of D2-like receptor D2R and another D1-like receptor, DAMB, did not induce male-male courtship behavior, indicating the receptor-type specificity of this phenomenon. Our findings provide insight into a possible link between dopamine level disturbance and the induced male-male courtship behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

Development and function of the midbrain dopamine system: what we know and what we need to.

PubMed

Bissonette, G B; Roesch, M R

2016-01-01

The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson's disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, including drug addiction, autism and schizophrenia. Understanding dopamine neuron ontogeny and how dopamine connections and circuitry develops may provide us with key insights into potentially important avenues of research for other dopamine-related disorders. This review will provide a brief overview of the major molecular and genetic players throughout the development of midbrain dopamine neurons and what we know about the behavioral- and disease-related implications associated with perturbations to midbrain dopamine neuron development. We intend to combine the knowledge of two broad fields of neuroscience, both developmental and behavioral, with the intent on fostering greater discussion between branches of neuroscience in the service of addressing complex cognitive questions from a developmental perspective and identifying important gaps in our knowledge for future study. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Membrane transporters as mediators of synaptic dopamine dynamics: implications for disease

PubMed Central

Lohr, Kelly M.; Masoud, Shababa T.; Salahpour, Ali; Miller, Gary W.

2016-01-01

Dopamine was first identified as a neurotransmitter localized to the midbrain over 50 years ago. The dopamine transporter (DAT; SLC6A3) and the vesicular monoamine transporter 2 (VMAT2; SLC18A2) are two regulators of dopamine homeostasis in the presynaptic neuron. DAT transports dopamine from the extracellular space into the cytosol of the presynaptic terminal. VMAT2 then packages this cytosolic dopamine into vesicular compartments for subsequent release upon neurotransmission. Thus, DAT and VMAT2 act in concert to move transmitter efficiently throughout the neuron. The accumulation of dopamine in the neuronal cytosol can trigger oxidative stress and neurotoxicity, suggesting that the proper compartmentalization of dopamine is critical for neuron function and risk of disease. For decades, studies have examined the effects of reduced transporter function in mice (e.g. DAT-KO, VMAT2-KO, VMAT2-deficient). However, we have only recently been able to assess the effects of elevated transporter expression using BAC transgenic methods (DAT-tg, VMAT2-HI mice). Complemented with in vitro work and neurochemical techniques to assess dopamine compartmentalization, a new focus on the importance of transporter proteins as both models of human disease and potential drug targets has emerged. Here we review the importance of DAT and VMAT2 function in the delicate balance of neuronal dopamine. PMID:27520881

Dopamine dynamics and cocaine sensitivity differ between striosome and matrix compartments of the striatum

PubMed Central

Salinas, Armando G.; Davis, Margaret I.; Lovinger, David M.; Mateo, Yolanda

2016-01-01

The striatum is typically classified according to its major output pathways, which consist of dopamine D1 and D2 receptor-expressing neurons. The striatum is also divided into striosome and matrix compartments, based on the differential expression of a number of proteins, including the mu opioid receptor, dopamine transporter (DAT), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1). Numerous functional differences between the striosome and matrix compartments are implicated in dopamine-related neurological disorders including Parkinson’s disease and addiction. Using Nr4a1-eGFP mice, we provide evidence that electrically evoked dopamine release differs between the striosome and matrix compartments in a regionally-distinct manner. We further demonstrate that this difference is not due to differences in inhibition of dopamine release by dopamine autoreceptors or nicotinic acetylcholine receptors. Furthermore, cocaine enhanced extracellular dopamine in striosomes to a greater degree than in the matrix and concomitantly inhibited dopamine uptake in the matrix to a greater degree than in striosomes. Importantly, these compartment differences in cocaine sensitivity were limited to the dorsal striatum. These findings demonstrate a level of exquisite microanatomical regulation of dopamine by the DAT in striosomes relative to the matrix. PMID:27036891

Orbitofrontal Dopamine Depletion Upregulates Caudate Dopamine and Alters Behavior via Changes in Reinforcement Sensitivity

PubMed Central

Cardinal, R. N.; Rygula, R.; Hong, Y. T.; Fryer, T. D.; Sawiak, S. J.; Ferrari, V.; Cockcroft, G.; Aigbirhio, F. I.; Robbins, T. W.; Roberts, A. C.

2014-01-01

Schizophrenia is associated with upregulation of dopamine (DA) release in the caudate nucleus. The caudate has dense connections with the orbitofrontal cortex (OFC) via the frontostriatal loops, and both areas exhibit pathophysiological change in schizophrenia. Despite evidence that abnormalities in dopaminergic neurotransmission and prefrontal cortex function co-occur in schizophrenia, the influence of OFC DA on caudate DA and reinforcement processing is poorly understood. To test the hypothesis that OFC dopaminergic dysfunction disrupts caudate dopamine function, we selectively depleted dopamine from the OFC of marmoset monkeys and measured striatal extracellular dopamine levels (using microdialysis) and dopamine D2/D3 receptor binding (using positron emission tomography), while modeling reinforcement-related behavior in a discrimination learning paradigm. OFC dopamine depletion caused an increase in tonic dopamine levels in the caudate nucleus and a corresponding reduction in D2/D3 receptor binding. Computational modeling of behavior showed that the lesion increased response exploration, reducing the tendency to persist with a recently chosen response side. This effect is akin to increased response switching previously seen in schizophrenia and was correlated with striatal but not OFC D2/D3 receptor binding. These results demonstrate that OFC dopamine depletion is sufficient to induce striatal hyperdopaminergia and changes in reinforcement learning relevant to schizophrenia. PMID:24872570

Modulation of motor behavior by dopamine and the D1-like dopamine receptor AmDOP2 in the honey bee

PubMed Central

Mustard, Julie A.; Pham, Priscilla M.; Smith, Brian H.

2009-01-01

Determining the specific molecular pathways through which dopamine affects behavior has been complicated by the presence of multiple dopamine receptor subtypes that couple to different second messenger pathways. The observation of freely moving adult bees in an arena was used to investigate the role of dopamine signaling in regulating the behavior of the honey bee. Dopamine or the dopamine receptor antagonist flupenthixol was injected into the hemolymph of worker honey bees. Significant differences between treated and control bees were seen for all behaviors (walking, stopped, upside down, grooming, flying and fanning), and behavioral shifts were dependent on drug dosage and time after injection. To examine the role of dopamine signaling through a specific dopamine receptor in the brain, RNA interference was used to reduce expression levels of a D1-like receptor, AmDOP2. Injection of Amdop2 dsRNA into the mushroom bodies reduced the levels of Amdop2 mRNA and produced significant changes in the amount of time honey bees spent performing specific behaviors with reductions in time spent walking offset by increases in grooming or time spent stopped. Taken together these results establish that dopamine plays an important role in regulating motor behavior of the honey bee. PMID:19945462

Modulation of motor behavior by dopamine and the D1-like dopamine receptor AmDOP2 in the honey bee.

PubMed

Mustard, Julie A; Pham, Priscilla M; Smith, Brian H

2010-04-01

Determining the specific molecular pathways through which dopamine affects behavior has been complicated by the presence of multiple dopamine receptor subtypes that couple to different second messenger pathways. The observation of freely moving adult bees in an arena was used to investigate the role of dopamine signaling in regulating the behavior of the honey bee. Dopamine or the dopamine receptor antagonist flupenthixol was injected into the hemolymph of worker honey bees. Significant differences between treated and control bees were seen for all behaviors (walking, stopped, upside down, grooming, flying and fanning), and behavioral shifts were dependent on drug dosage and time after injection. To examine the role of dopamine signaling through a specific dopamine receptor in the brain, RNA interference was used to reduce expression levels of a D1-like receptor, AmDOP2. Injection of Amdop2 dsRNA into the mushroom bodies reduced the levels of Amdop2 mRNA and produced significant changes in the amount of time honey bees spent performing specific behaviors with reductions in time spent walking offset by increases in grooming or time spent stopped. Taken together these results establish that dopamine plays an important role in regulating motor behavior of the honey bee. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Teaching Old Compounds New Tricks: DDQ-Photocatalyzed C-H Amination of Arenes with Carbamates, Urea, and N-Heterocycles.

PubMed

Das, Somnath; Natarajan, Palani; König, Burkhard

2017-12-22

The C-H amination of benzene derivatives was achieved using DDQ as photocatalyst and BocNH 2 as the amine source under aerobic conditions and visible light irradiation. Electron-deficient and electron-rich benzenes react as substrates with moderate to good product yields. The amine scope of the reaction comprises Boc-amine, carbamates, pyrazoles, sulfonimides and urea. Preliminary mechanistic investigations indicate arene oxidation by the triplet of DDQ to radical cations with different electrophilicity and a charge transfer complex between the amine and DDQ as intermediate of the reaction. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sillica Gel-Amine from Geothermal Sludge

NASA Astrophysics Data System (ADS)

Muljani, S.; Pujiastuti, C.; Wicaksono, P.; Lutfianingrum, R.

2018-01-01

Silica Gel-Amine (SGA) has been made from geothermal sludge by grafting amine method. Sodium silicate solution is prepared by extracted geothermal sludge powder using sodium hidroxide solution then acidification in the range of pH 5 - 9 by using tartaric acid 1N. The grafting process uses 1 ml of ammonia solution and 10 ml of toluene at a rate of 0.1 ml min-1 accompanied by a reflux process. The amine grafting is done in two methods. The first method is grafting amine in silicate solution and the second method is grafting amine in washed gel. Product SGA was confirmed by FTIR, TGA-DTG and BET characterization. The results show that the pH affects the amount of amine that is grafted onto silica gel. Differences in grafting method affect the size of the pore and surface area. SGA product prepared by grafting washed gel at pH 8 have pore diameter of 12.06 nm, surface area of 173.44 m2g-1, and mass of decomposed amine compound 0.4 mg. In the presence of amine groups on the silica gel surface, these adsorbents may be able to selectively adsorb CO2 gas from natural gas.