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1

Serotonin and dopamine as neurotransmitters in mytilus: block of serotonin receptors by an organic mercurial.  

PubMed

The effects of mersalyl, bromo-LSD (BOL) and methysergide (UML) on the relaxation of catch by certain indole and catechol derivatives were studied in the anterior byssus retractor muscle of Mytilus. Mersalyl antagonized relaxation in response to serotonin whereas BOL and UML were less effective. Two other indole derivatives, ergotamine and gramine, were also blocked by mersalyl; BOL and UML antagonized relaxation in response to dopamine more effectively than did mersalyl. Two other catechols, epinephrine and norepinephrine, were also blocked more effectively by BOL and UML than by mersaly. Relaxation in response to neural stimulation was blocked more effectively by mersalyl than by BOL. The blocking action of mersalyl on neural relaxation reversed very poorly after washing the drug, but complete reversal was induced by brief exposure to dithiothreitol. It is concluded that the evidence supports an hypothesis that the transmitter released by relaxing nerves is serotonin. It is suggested that mersalyl blocks serotonin by combining with a sulfhydryl group at or near the site on the receptor to which the indole nitrogen attaches. PMID:16121

Twarog, B M; Muneoka, Y; Ledgere, M

1977-05-01

2

Synapsins Differentially Control Dopamine and Serotonin Release  

PubMed Central

Synapsins are a family of synaptic vesicle proteins that are important for neurotransmitter release. Here we have used triple knockout (TKO) mice lacking all three synapsin genes to determine the roles of synapsins in the release of two monoamine neurotransmitters, dopamine and serotonin. Serotonin release evoked by electrical stimulation was identical in substantia nigra pars reticulata slices prepared from TKO and wild-type mice. In contrast, release of dopamine in response to electrical stimulation was approximately doubled in striatum of TKO mice, both in vivo and in striatal slices, in comparison to wild-type controls. This was due to loss of synapsin III, because deletion of synapsin III alone was sufficient to increase dopamine release. Deletion of synapsins also increased the sensitivity of dopamine release to extracellular calcium ions. Although cocaine did not affect the release of serotonin from nigral tissue, this drug did enhance dopamine release. Cocaine-induced facilitation of dopamine release was a function of external calcium, an effect that was reduced in TKO mice. We conclude that synapsins play different roles in the control of release of dopamine and serotonin, with release of dopamine being negatively regulated by synapsins, specifically synapsin III, while serotonin release appears to be relatively independent of synapsins. These results provide further support for the concept that synapsin function in presynaptic terminals varies according to the neurotransmitter being released.

Kile, Brian M.; Guillot, Thomas S.; Venton, B. Jill; Wetsel, William C.; Augustine, George J.; Wightman, R. Mark

2010-01-01

3

Brain dopamine and serotonin differ in regulation and its consequences.  

PubMed

Dopamine and serotonin (5-hydroxytryptamine or 5-HT) are neurotransmitters that are implicated in many psychological disorders. Although dopamine transmission in the brain has been studied extensively in vivo with fast scan cyclic voltammetry, detection of 5-HT using in vivo voltammetric methods has only recently been established. In this work we use two carbon-fiber microelectrodes to simultaneously measure dopamine release in the nucleus accumbens and 5-HT release in the substantia nigra pars reticulata, using a common stimulation in a single rat. We find that 5-HT release is profoundly restricted in comparison with dopamine release despite comparable tissue content levels. Using physiological and pharmacological analysis, we find that 5-HT transmission is mostly sensitive to uptake and metabolic degradation mechanisms. In contrast, dopamine transmission is constrained by synthesis and repackaging. Finally, we show that disruption of serotonergic regulatory mechanisms by simultaneous inhibition of uptake and metabolic degradation can have severe physiological consequences that mimic serotonin syndrome. PMID:22778401

Hashemi, Parastoo; Dankoski, Elyse C; Lama, Rinchen; Wood, Kevin M; Takmakov, Pavel; Wightman, R Mark

2012-07-09

4

Brain dopamine and serotonin differ in regulation and its consequences  

PubMed Central

Dopamine and serotonin (5-hydroxytryptamine or 5-HT) are neurotransmitters that are implicated in many psychological disorders. Although dopamine transmission in the brain has been studied extensively in vivo with fast scan cyclic voltammetry, detection of 5-HT using in vivo voltammetric methods has only recently been established. In this work we use two carbon-fiber microelectrodes to simultaneously measure dopamine release in the nucleus accumbens and 5-HT release in the substantia nigra pars reticulata, using a common stimulation in a single rat. We find that 5-HT release is profoundly restricted in comparison with dopamine release despite comparable tissue content levels. Using physiological and pharmacological analysis, we find that 5-HT transmission is mostly sensitive to uptake and metabolic degradation mechanisms. In contrast, dopamine transmission is constrained by synthesis and repackaging. Finally, we show that disruption of serotonergic regulatory mechanisms by simultaneous inhibition of uptake and metabolic degradation can have severe physiological consequences that mimic serotonin syndrome.

Hashemi, Parastoo; Dankoski, Elyse C.; Lama, Rinchen; Wood, Kevin M.; Takmakov, Pavel; Wightman, R. Mark

2012-01-01

5

The Role of Serotonin and Neurotransmitters During Craniofacial Development  

Microsoft Academic Search

Several neurotransmitters, in particular serotonin (5-HT), have demonstrated multiple functions during early development and mid-gestational craniofacial morphogenesis. Early studies indicated that 5-HT is present in the oocyte, where it appears to function as a regulator of cell cleavage. Later, it has a significant role during gastrulation, during which there are significant areas of 5-HT uptake in the primitive streak. Subsequently,

Julian R. D. Moiseiwitsch

2000-01-01

6

Serotonin-S2 and dopamine-D2 receptors are the same size in membranes  

SciTech Connect

Target size analysis was used to compare the sizes of serotonin-S2 and dopamine-D2 receptors in rat brain membranes. The sizes of these receptors were standardized by comparison with the muscarinic receptor, a receptor of known size. The number of serotonin-S2 receptors labeled with (3H)ketanserin or (3H)spiperone in frontal cortex decreased as an exponential function of radiation dose, and receptor affinity was not affected. The number of dopamine-D2 receptors labeled with (3H)spiperone in striatum also decreased as an exponential function of radiation dose, and D2 and S2 receptors were equally sensitive to radiation. In both striatum and frontal cortex, the number of muscarinic receptors labeled with (3H)QNB decreased as an exponential function of radiation dose, and were much less sensitive to radiation than S2 and D2 receptors. These data indicate that in rat brain membranes, S2 and D2 receptors are of similar size, and both molecules are much larger than the muscarinic receptor.

Brann, M.R.

1985-12-31

7

Differential Contributions of Dopamine and Serotonin to Orbitofrontal Cortex Function in the Marmoset  

PubMed Central

We have shown previously that the inhibitory control functions of the orbitofrontal cortex (OFC) are disrupted by serotonin, but not dopamine depletions. However, both dopamine and serotonin terminals and receptors are present within the OFC and thus the aim of the present study was to determine the differential contributions of these neurotransmitters to orbitofrontal function. OFC and dopamine are involved in the process by which neutral stimuli take on reinforcing properties, by virtue of their prior association with reward, and guide behavior. Thus, we compared the performance of marmosets with dopaminergic or serotoninergic OFC depletions on a test of conditioned reinforcement. To further our understanding of serotonin in behavioral flexibility, the effect of these depletions was also compared on the extinction of a visual discrimination. Monkeys with serotonin depletions of the OFC displayed stimulus-bound responding on both tests of conditioned reinforcement and discrimination extinction suggesting that orbitofrontal serotonin plays a specific role in preventing competing, task irrelevant, salient stimuli from biasing responding. In contrast, monkeys with dopamine depletion were insensitive to conditioned reinforcers and displayed persistent responding in the absence of reward in extinction, a pattern of deficits that may reflect basic deficits in the associative processing of reward.

Walker, S.C.; Robbins, T.W.

2009-01-01

8

The Design, Synthesis and Structure-Activity Relationship of Mixed Serotonin, Norepinephrine and Dopamine Uptake Inhibitors  

NASA Astrophysics Data System (ADS)

The evolution of antidepressants over the past four decades has involved the replacement of drugs with a multiplicity of effects (e.g., TCAs) by those with selective actions (i.e., SSRIs). This strategy was employed to reduce the adverse effects of TCAs, largely by eliminating interactions with certain neurotransmitters or receptors. Although these more selective compounds may be better tolerated by patients, selective drugs, specifically SSRIs, are not superior to older drugs in treating depressed patients as measured by response and remission rates. It may be an advantage to increase synaptic levels of both serotonin and norepinephrine, as in the case of dual uptake inhibitors like duloxetine and venlafaxine. An important recent development has been the emergence of the triple-uptake inhibitors (TUIs/SNDRIs), which inhibit the uptake of the three neurotransmitters most closely linked to depression: serotonin, norepinephrine, and dopamine. Preclinical studies and clinical trials indicate that a drug inhibiting the reuptake of all three of these neurotransmitters could produce more rapid onset of action and greater efficacy than traditional antidepressants. This review will detail the medicinal chemistry involved in the design, synthesis and discovery of mixed serotonin, norepinephrine and dopamine transporter uptake inhibitors.

Chen, Zhengming; Yang, Ji; Skolnick, Phil

9

Dopamine D? and D? receptor subtypes functional regulation in cerebral cortex of unilateral rotenone lesioned Parkinson's rat model: Effect of serotonin, dopamine and norepinephrine.  

PubMed

Parkinson's disease is a progressive neurodegenerative disorder characterized by selective degeneration of dopaminergic neurons in substantia nigra pars compacta leading to marked reduction of dopamine levels in the cerebral cortex. The present study analysed the effect of serotonin, dopamine and norepinephrine as treatment on rotenone induced Hemi-Parkinson's disease in rats and its role in the regulation of dopamine receptor subtypes in the cerebral cortex of the experimental rats. Unilateral stereotaxic single dose infusions of rotenone were administered to the substantia nigra of adult male Wistar rats. Neurotransmitters--serotonin, dopamine and norepinephrine treatments--were given to rotenone induced Hemi-Parkinson's rats. Scatchard analysis of Dopamine D? and D? receptor showed a significant increase (p < 0.001) in the cerebral cortex of the Parkinson's rats compared to control. These altered parameters were reversed to near control in the serotonin and norepinephrine treated Parkinson's disease rats and no change was observed in dopamine treated Parkinson's rats. Real-time PCR results confirmed the receptor data. Our results showed serotonin and norepinephrine functionally reversed the dopamine receptors significantly in rotenone induced Hemi-Parkinson's rat. This has clinical significance in the therapeutic management of Parkinson's disease. PMID:21306935

Paul, Jes; Kuruvilla, Korah P; Mathew, Jobin; Kumar, Peeyush; Paulose, C S

2011-02-09

10

Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions  

Microsoft Academic Search

Serotonin, like dopamine (DA), has long been implicated in adaptive behavior, including decision making and reinforcement learning. However, although the two neuromodulators are tightly related and have a similar degree of functional importance, compared with DA, we have a much less specific understanding about the mechanisms by which serotonin affects behavior. Here, we draw on recent work on computational models

Roshan Cools; Kae Nakamura; Nathaniel D Daw

2011-01-01

11

Modulation for emergent networks: serotonin and dopamine.  

PubMed

In autonomous learning, value-sensitive experiences can improve the efficiency of learning. A learning network needs be motivated so that the limited computational resources and the limited lifetime are devoted to events that are of high value for the agent to compete in its environment. The neuromodulatory system of the brain is mainly responsible for developing such a motivation system. Although reinforcement learning has been extensively studied, many existing models are symbolic whose internal nodes or modules have preset meanings. Neural networks have been used to automatically generate internal emergent representations. However, modeling an emergent motivational system for neural networks is still a great challenge. By emergent, we mean that the internal representations emerge autonomously through interactions with the external environments. This work proposes a generic emergent modulatory system for emergent networks, which includes two subsystems - the serotonin system and the dopamine system. The former signals a large class of stimuli that are intrinsically aversive (e.g., stress or pain). The latter signals a large class of stimuli that are intrinsically appetitive (e.g., pleasure or sweet). We experimented with this motivational system for two settings. The first is a visual recognition setting to investigate how such a system can learn through interactions with a teacher, who does not directly give answers, but only punishments and rewards. The second is a setting for wandering in the presence of a friend and a foe. PMID:23294763

Weng, Juyang; Paslaski, Stephen; Daly, James; VanDam, Courtland; Brown, Jacob

2012-12-08

12

Using the neurotransmitter serotonin to target imaging agents to glioblastoma cells.  

PubMed

The neurotransmitter serotonin is involved in numerous bodily functions via seven different serotonin receptor subfamilies. Serotonin plays a role in gastrointestinal functions like intestinal secretion or peristalsis and neuropsychiatric events like depression or migraine. One of these subtypes has been found on glioblastoma cells, inducing growth promotion. In our study we attempted to target imaging agents to glioblastoma cells via the serotonin receptor. For this we coupled serotonin to the fluorescent dye rhodamine and the magnetic resonance imaging contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The cellular uptake, cytotoxicity and detection sensitivity of the conjugates were evaluated by confocal laser scanning microscopy (CLSM), cell growth analysis, flow cytometry and magnetic resonance relaxometry on U373 human glioblastoma cells. Receptor-dependency of the uptake was confirmed by competition experiments with excess of unmarked serotonin. Cellular uptake of the conjugates was found in CLSM, magnetic resonance relaxometry and flow cytometry experiments.CLSM revealed the cytoplasmic character of the uptake. In cell growth analysis experiments no adverse effect of either conjugate on the cells was observed. Competition experiments performed with the conjugates and unmarked serotonin showed decreased conjugate uptake compared to the experiments without competition. In conclusion the neurotransmitter serotonin could be successfully used to target imaging agents into human glioblastoma cells. This makes it of interest for future glioblastoma imaging methods. PMID:22212740

Sturzu, Alexander; Sheikh, Sumbla; Klose, Uwe; Echner, Hartmut; Kalbacher, Hubert; Deeg, Martin; Nägele, Thomas; Horger, Marius; Ernemann, Ulrike; Heckl, Stefan

2012-12-01

13

Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions  

PubMed Central

Serotonin, like dopamine (DA), has long been implicated in adaptive behavior, including decision making and reinforcement learning. However, although the two neuromodulators are tightly related and have a similar degree of functional importance, compared with DA, we have a much less specific understanding about the mechanisms by which serotonin affects behavior. Here, we draw on recent work on computational models of dopaminergic function to suggest a framework by which many of the seemingly diverse functions associated with both DA and serotonin—comprising both affective and activational ones, as well as a number of other functions not overtly related to either—can be seen as consequences of a single root mechanism.

Cools, Roshan; Nakamura, Kae; Daw, Nathaniel D

2011-01-01

14

Interaction between the dopamine D4 receptor and the serotonin transporter promoter polymorphisms in alcohol and tobacco use among 15-year-olds  

Microsoft Academic Search

Early onset of alcohol and tobacco use during adolescence increases the risk for establishing a substance use disorder in adulthood. Both alcohol and nicotine stimulate the dopamine (DA) and the serotonin (5-HT) systems. The DA system has been implicated in the mediation of the rewarding effects of self-administered drugs of abuse. A possible role of an interaction between these neurotransmitter

M. H. Skowronek; M. Laucht; E. Hohm; K. Becker; M. H. Schmidt

2006-01-01

15

Synchronized release of dopamine and serotonin in the medial and lateral hypothalamus of rats  

Microsoft Academic Search

A positive linear correlation between dopamine and serotonin release was found in the ventromedial hypothalamus and in the lateral hypothalamic area in fasting rats and in fed rats during intermeal intervals. Dopamine release in the ventromedial hypothalamus positively correlated with dopamine and serotonin release in the lateral hypothalamic area, which occurred only during intermeal intervals and was non-significant during the

S. O Fetissov; M. M Meguid; C Chen; G Miyata

2000-01-01

16

Brain dopamine-serotonin vesicular transport disease and its treatment.  

PubMed

We describe a disease encompassing infantile-onset movement disorder (including severe parkinsonism and nonambulation), mood disturbance, autonomic instability, and developmental delay, and we describe evidence supporting its causation by a mutation in SLC18A2 (which encodes vesicular monoamine transporter 2 [VMAT2]). VMAT2 translocates dopamine and serotonin into synaptic vesicles and is essential for motor control, stable mood, and autonomic function. Treatment with levodopa was associated with worsening, whereas treatment with direct dopamine agonists was followed by immediate ambulation, near-complete correction of the movement disorder, and resumption of development. PMID:23363473

Rilstone, Jennifer J; Alkhater, Reem A; Minassian, Berge A

2013-01-30

17

MDMA induced dopamine release in vivo: role of endogenous serotonin  

Microsoft Academic Search

Summary Acting as a substrate at the serotonin (5-HT) transporter, (+)-MDMA (3,4-methylenedioxymethamphetamine), is a potent releaser of 5-HT and causes toxicity to 5-HT neurons after repeated exposure. (+)-MDMA also releases dopamine (DA), although with less potency. Since we have shown previously that the intrastriatal application of 5-HT facilitates DA release, it was hypothesized that increased release of striatal 5-HT after

S. Koch; M. P. Galloway

1997-01-01

18

Median Eminence Dopamine and Serotonin Neuronal Activity  

Microsoft Academic Search

Using a high-performance liquid chromatography (HPLC) system coupled with an electrochemical detector, the concentrations of dopamine (DA) and 5-hydroxytryptamine (5-HT) and their major specific metabolites 3,4-dihydroxy-phenylacetic acid (DOPAC) and 5-hydroxyindole-3-acetic acid (5-HIAA), respectively, were measured in the median eminence (ME) throughout the rat estrous cycle. The ME DA content remained fairly constant throughout the estrous cycle except on estrus when

Bernard Kerdelhué; Florence Bojda; Philippe Lesieur; Catherine Pasqualini; Amor El Abed; Véronique Lenoir; Patrice Douillet; Mike C. Chiueh; Miklos Palkovits

1989-01-01

19

Interactions of serotonin with multiple receptors and neurotransmitters in the guinea-pig isolated colon.  

PubMed

The motor effects of 5-hydroxytryptamine (5-HT; serotonin) on the guinea-pig isolated proximal colon were studied and analyzed. A classical organ bath setup was used to measure the longitudinal muscle responses isotonically. 5-Hydroxytryptamine induced concentration-dependent contractions which were preceded by relaxations at low concentrations. By means of the neurotoxin, tetrodotoxin, the muscarinic cholinoceptor antagonist, atropine, and selective 5-HT receptor antagonists, it was shown that the contractions to 5-HT are mediated by 5-HT2A receptors, localized on the smooth muscle, and by 5-HT3 and 5-HT4 receptors, localized on cholinergic nerves. The relaxation was abolished by tetrodotoxin and appeared to be mediated by two 5-HT receptor subtypes; the pharmacological profile of the high affinity 5-HT receptor resembled that of 5-HT2C receptors though it displayed also pronounced differences. Subsequently, it was shown that nitric oxide is the mediator released by lower concentrations of 5-HT, while, at higher concentrations, adenosine triphosphate could be involved as an end neurotransmitter as well. No evidence for a peptidergic neurotransmitter, such as vasoactive intestinal polypeptide, was obtained. Results with two 5-HT analogues confirmed the presence of a dual 5-HT receptor system (high and low affinity) regulating each the release of a different neurotransmitter (nitric oxide and adenosine triphosphate, respectively). The above described results stress the important role of 5-HT as a neurotransmitter involved in gastrointestinal motility. PMID:7639614

Briejer, M R; Akkermans, L M; Schuurkes, J A

20

Dispensable, redundant, complementary, and cooperative roles of dopamine, octopamine, and serotonin in Drosophila melanogaster.  

PubMed

To investigate the regulation of Drosophila melanogaster behavior by biogenic amines, we have exploited the broad requirement of the vesicular monoamine transporter (VMAT) for the vesicular storage and exocytotic release of all monoamine neurotransmitters. We used the Drosophila VMAT (dVMAT) null mutant to globally ablate exocytotic amine release and then restored DVMAT activity in either individual or multiple aminergic systems, using transgenic rescue techniques. We find that larval survival, larval locomotion, and female fertility rely predominantly on octopaminergic circuits with little apparent input from the vesicular release of serotonin or dopamine. In contrast, male courtship and fertility can be rescued by expressing DVMAT in octopaminergic or dopaminergic neurons, suggesting potentially redundant circuits. Rescue of major aspects of adult locomotion and startle behavior required octopamine, but a complementary role was observed for serotonin. Interestingly, adult circadian behavior could not be rescued by expression of DVMAT in a single subtype of aminergic neurons, but required at least two systems, suggesting the possibility of unexpected cooperative interactions. Further experiments using this model will help determine how multiple aminergic systems may contribute to the regulation of other behaviors. Our data also highlight potential differences between behaviors regulated by standard exocytotic release and those regulated by other mechanisms. PMID:23086220

Chen, Audrey; Ng, Fanny; Lebestky, Tim; Grygoruk, Anna; Djapri, Christine; Lawal, Hakeem O; Zaveri, Harshul A; Mehanzel, Filmon; Najibi, Rod; Seidman, Gabriel; Murphy, Niall P; Kelly, Rachel L; Ackerson, Larry C; Maidment, Nigel T; Jackson, F Rob; Krantz, David E

2012-10-19

21

Prenatal Serotonin and Neonatal Outcome: Brief Report  

PubMed Central

In a study on prenatal dopamine and its association with depression and other neurotransmitters, serotonin was a confounding variable (Field, Diego, Hernandez-Reif, Figueiredo, Deeds et al., 2007). Serotonin has long been associated with depression (Cubala & Landwski, 2006; Neumeister, 2003; Neumeister, Young, & Stastny, 2004). Serotonin receptors and serotonin transporters are reduced in depression, suggesting that serotonin systems play a key role in the pathophysiology of depression (Neumeister et al., 2004).

Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Figueiredo, Barbara; Deeds, Osvelia; Ascencio, Angela; Schanberg, Saul; Kuhn, Cynthia

2008-01-01

22

Single nucleotide polymorphisms (SNPs) in coding regions of canine dopamine- and serotonin-related genes  

PubMed Central

Background Polymorphism in genes of regulating enzymes, transporters and receptors of the neurotransmitters of the central nervous system have been associated with altered behaviour, and single nucleotide polymorphisms (SNPs) represent the most frequent type of genetic variation. The serotonin and dopamine signalling systems have a central influence on different behavioural phenotypes, both of invertebrates and vertebrates, and this study was undertaken in order to explore genetic variation that may be associated with variation in behaviour. Results Single nucleotide polymorphisms in canine genes related to behaviour were identified by individually sequencing eight dogs (Canis familiaris) of different breeds. Eighteen genes from the dopamine and the serotonin systems were screened, revealing 34 SNPs distributed in 14 of the 18 selected genes. A total of 24,895 bp coding sequence was sequenced yielding an average frequency of one SNP per 732 bp (1/732). A total of 11 non-synonymous SNPs (nsSNPs), which may be involved in alteration of protein function, were detected. Of these 11 nsSNPs, six resulted in a substitution of amino acid residue with concomitant change in structural parameters. Conclusion We have identified a number of coding SNPs in behaviour-related genes, several of which change the amino acids of the proteins. Some of the canine SNPs exist in codons that are evolutionary conserved between five compared species, and predictions indicate that they may have a functional effect on the protein. The reported coding SNP frequency of the studied genes falls within the range of SNP frequencies reported earlier in the dog and other mammalian species. Novel SNPs are presented and the results show a significant genetic variation in expressed sequences in this group of genes. The results can contribute to an improved understanding of the genetics of behaviour.

Vage, J?rn; Lingaas, Frode

2008-01-01

23

Ca 2+ channel blockade prevents lysergic acid diethylamide-induced changes in dopamine and serotonin metabolism  

Microsoft Academic Search

To investigate the effect of a single and multiple administration of lysergic acid diethylamide (LSD) on cerebral metabolism of dopamine and serotonin, male Wistar rats were treated with low and high doses (0.1 and 2.0 mg\\/kg i.p.) of LSD and the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxytyramine, serotonin and 5-hydroxyindoleacetic acid were assayed by HPLC in the nucleus

Lucyna Antkiewicz-Michaluk; Irena Roma?ska; Jerzy Vetulani

1997-01-01

24

Dopamine Regulating Genes, Negative Stressors, and Energy Balance Behaviors Among Chinese Adolescents  

Microsoft Academic Search

Context: Dopamine has been implicated as an important neurotransmitter involved in regulating appetite and food intake by modulating the reinforcement of food via the meso-limbic circuitry of the brain. Several genes have been linked with the regulation of dopamine. Monoamine oxidase A (MAOA) modulates the metabolism of serotonin and dopamine, both of which are neurotransmitters involved in the regulation of

Rosa Ahn

2012-01-01

25

Comonitoring of adenosine and dopamine using the Wireless Instantaneous Neurotransmitter Concentration System: proof of principle  

PubMed Central

Object The authors of previous studies have demonstrated that local adenosine efflux may contribute to the therapeutic mechanism of action of thalamic deep brain stimulation (DBS) for essential tremor. Real-time monitoring of the neurochemical output of DBS-targeted regions may thus advance functional neurosurgical procedures by identifying candidate neurotransmitters and neuromodulators involved in the physiological effects of DBS. This would in turn permit the development of a method of chemically guided placement of DBS electrodes in vivo. Designed in compliance with FDA-recognized standards for medical electrical device safety, the authors report on the utility of the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for real-time comonitoring of electrical stimulation–evoked adenosine and dopamine efflux in vivo, utilizing fast-scan cyclic voltammetry (FSCV) at a polyacrylonitrile-based (T-650) carbon fiber microelectrode (CFM). Methods The WINCS was used for FSCV, which consisted of a triangle wave scanned between ?0.4 and +1.5 V at a rate of 400 V/second and applied at 10 Hz. All voltages applied to the CFM were with respect to an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single T-650 carbon fiber (r = 2.5 ?m) into a glass capillary and pulling to a microscopic tip using a pipette puller. The exposed carbon fiber (the sensing region) extended beyond the glass insulation by ? 50 ?m. Proof of principle tests included in vitro measurements of adenosine and dopamine, as well as in vivo measurements in urethane-anesthetized rats by monitoring adenosine and dopamine efflux in the dorsomedial caudate putamen evoked by high-frequency electrical stimulation of the ventral tegmental area and substantia nigra. Results The WINCS provided reliable, high-fidelity measurements of adenosine efflux. Peak oxidative currents appeared at +1.5 V and at +1.0 V for adenosine, separate from the peak oxidative current at +0.6 V for dopamine. The WINCS detected subsecond adenosine and dopamine efflux in the caudate putamen at an implanted CFM during high-frequency stimulation of the ventral tegmental area and substantia nigra. Both in vitro and in vivo testing demonstrated that WINCS can detect adenosine in the presence of other easily oxidizable neurochemicals such as dopamine comparable to the detection abilities of a conventional hardwired electrochemical system for FSCV. Conclusions Altogether, these results demonstrate that WINCS is well suited for wireless monitoring of high-frequency stimulation-evoked changes in brain extracellular concentrations of adenosine. Clinical applications of selective adenosine measurements may prove important to the future development of DBS technology.

Shon, Young-Min; Chang, Su-Youne; Tye, Susannah J.; Kimble, Christopher J.; Bennet, Kevin E.; Blaha, Charles D.; Lee, Kendall H.

2010-01-01

26

GABA, glutamate, dopamine and serotonin transporters expression on forgetting.  

PubMed

Notwithstanding several neurotransmission systems are frequently related to memory formation; forgetting process and neurotransmission systems or their transporters; the role of ?-aminobutyric acid (GAT1), glutamate (EACC1), dopamine (DAT) and serotonin (SERT) is poorly understood. Hence, in this paper western-blot analysis was used to evaluate expression of GAT1, EAAC1, DAT and SERT during forgetting in trained and untrained rats treated with the selective serotonin transporter inhibitor fluoxetine, the amnesic drug d-methamphetamine (METH) and fluoxetine plus METH. Transporters expression was determined in the hippocampus (HIP), prefrontal cortex (PFC) and striatum (STR). Results indicated that forgetting of Pavlovian/instrumental autoshaping was associated to up-regulation of GAT1 (PFC and HIP) and DAT (PFC) while SERT (HIP) was down-regulated; no-changes were observed in striatum. Methamphetamine administration did not affect forgetting at 216 h post-training but up-regulated hippocampal DAT and EACC, prefrontal cortex DAT and striatal GAT1 or EACC1. Fluoxetine alone prevented forgetting, which was associated to striatal GAT1 and hippocampal DAT up-regulation, but prefrontal cortex GAT1 down-regulation. Fluoxetine plus METH administration was also able to prevent forgetting, which was associated to hippocampal DAT, prefrontal cortex SERT and striatal GAT1, DAT or SERT up-regulation, but prefrontal cortex GAT1 down-regulation. Together these data show that forgetting provokes primarily hippocampal and prefrontal cortex transporters changes; forgetting represent a behavioral process hardly modifiable and its prevention could causes different transporters expression patterns. PMID:22633984

Tellez, Ruth; Gómez-Viquez, Leticia; Liy-Salmeron, Gustavo; Meneses, Alfredo

2012-05-25

27

Implantable Microprobe with Arrayed Microsensors for Combined Amperometric Monitoring of the Neurotransmitters, Glutamate and Dopamine  

PubMed Central

An implantable, micromachined microprobe with a microsensor array for combined monitoring of the neurotransmitters, glutamate (Glut) and dopamine (DA), by constant potential amperometry has been created and characterized. Microprobe studies in vitro revealed Glut and DA microsensor sensitivities of 126±5 nA·?M?1·cm?2 and 3250±50 nA·?M?1·cm?2, respectively, with corresponding detection limits of 2.1±0.2 ?M and 62±8 nM, both at comparable ~1 sec response times. No diffusional interaction of H2O2 among arrayed microelectrodes was observed. Also, no responses from the electroactive interferents, ascorbic acid (AA), uric acid (UA), DOPA (a DA catabolite) or DOPAC (a DA precursor), over their respective physiological concentration ranges, were detected. The dual sensing microbe attributes of size, detection limit, sensitivity, response time and selectivity make it attractive for combined sensing of Glut and DA in vivo.

Tseng, Tina T.-C.

2012-01-01

28

Dopamine and Serotonin Modulate Human GABA?1 Receptors Expressed in Xenopus laevis Oocytes  

PubMed Central

GABA?1 receptors are highly expressed in bipolar neurons of the retina and to a lesser extent in several areas of the central nervous system (CNS), and dopamine and serotonin are also involved in the modulation of retinal neural transmission. Whether these biogenic amines have a direct effect on ionotropic GABA receptors was not known. Here, we report that GABA?1 receptors, expressed in X. laevis oocytes, were negatively modulated by dopamine and serotonin and less so by octopamine and tyramine. Interestingly, these molecules did not have effects on GABAA receptors. 5-Carboxamido-tryptamine and apomorphine did not exert evident effects on any of the receptors. Schild plot analyses of the inhibitory actions of dopamine and serotonin on currents elicited by GABA showed slopes of 2.7 ± 0.3 and 6.1 ± 1.8, respectively, indicating a noncompetitive mechanism of inhibition. The inhibition of GABA?1 currents was independent of the membrane potential and was insensitive to picrotoxin, a GABA receptor channel blocker and to the GABA?-specific antagonist (1,2,5,6-tetrahydropyridine-4-yl)methyl phosphinic acid (TPMPA). Dopamine and serotonin changed the sensitivity of GABA?1 receptors to the inhibitory actions of Zn2+. In contrast, La3+ potentiated the amplitude of the GABA currents generated during negative modulation by dopamine (EC50 146 ?M) and serotonin (EC50 196 ?M). The functional role of the direct modulation of GABA? receptors by dopamine and serotonin remains to be elucidated; however, it may represent an important modulatory pathway in the retina, where GABA? receptors are highly expressed and where these biogenic amines are abundant.

2011-01-01

29

Effects of acute 17a-methyltestosterone, acute 17ß-estradiol, and chronic 17a-methyltestosterone on dopamine, norepinephrine and serotonin levels in the pituitary, hypothalamus and telencephalon of rainbow trout ( Oncorhynchus mykiss )  

Microsoft Academic Search

This study investigated: (a) the effects of acute 17!-methyltestosterone (MT) or 17#-estradiol (E2) administration on norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3,4, dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) contents in the hypothalamus, telencephalon and pituitary of previtellogenic female rainbow trout Oncorhynchus mykiss, and (b) the effects of chronic MT administration on the levels of these neurotransmitters in these brain

R. Hernandez-Rauda; M. Aldegunde

2002-01-01

30

Ovarian hormones differentially influence immunoreactivity for dopamine beta- hydroxylase, choline acetyltransferase, and serotonin in the dorsolateral prefrontal cortex of adult rhesus monkeys.  

PubMed

Recent studies have shown that ovariectomy reduces, and subsequent hormone replacement restores the density of axons immunoreactive for tyrosine hydroxylase in the dorsolateral prefrontal cortex of adult female rhesus monkeys. The present study indicates that three additional extrathalamic frontal lobe afferents are also sensitive to changes in the ovarian hormone environment. Specifically, the combination of hormone manipulation with qualitative and quantitative analysis of immunocytochemistry for dopamine beta-hydroxylase, choline acetyltransferase, and serotonin in the primate prefrontal cortex revealed quantitative responses in both cholinergic and monoaminergic axons to changing ovarian hormone levels. However, whereas ovariectomy produced a modest net decrease in the density of fibers immunoreactive for choline acetyltransferase, this same treatment markedly increased the density of axons immunoreactive for dopamine beta-hydroxylase and for serotonin. Further, the effects of ovariectomy on these afferent systems were differentially attenuated by estrogen verses estrogen plus progesterone hormone replacement. Estrogen was as effective as estrogen plus progesterone in stimulating normal prefrontal immunoreactivity for choline acetyltransferase and dopamine beta-hydroxylase. The dual replacement of estrogen plus progesterone, however, was a much more potent influence than estrogen alone for serotonin immunoreactivity. Thus, ovarian hormones appear to provide stimulation that differentially affects each of four chemically identified extrathalamic prefrontal afferent systems examined to date, and may have roles in maintaining the normal balance and functional interactions between these neurotransmitter systems. PMID:10379829

Kritzer, M F; Kohama, S G

1999-07-01

31

Changes in Human In vivo Serotonin and Dopamine Transporter Availabilities during Chronic Antidepressant Administration  

Microsoft Academic Search

Few studies have demonstrated in vivo alterations of human serotonin and dopamine transporters (SERTS and DATS) during antidepressant treatment. The current study measured these transporter availabilities with [123I]?-CIT single photon emission computed tomography (SPECT) during administration of selective serotonin reuptake inhibitors (SSRIs) or a non-SSRI, bupropion. A total of 17 healthy human subjects were randomly assigned to two different treatment

Akira Kugaya; Nicholas M Seneca; Peter J Snyder; Stephen A Williams; Robert T Malison; Ronald M Baldwin; John P Seibyl; Robert B Innis

2003-01-01

32

Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia  

Microsoft Academic Search

Clozapine administration to schizophrenic patients was found to produce dopamine2 (D-2) and serotonin2 (5-HT2) receptor blockade, as evidenced by the ability to block the increases in growth hormone and cortisol secretion produced by apomorphine and MK-212, respectively, direct acting dopamine (DA) and 5-HT2 agonists. Clozapine did not increase plasma prolactin (PRL) levels nor did it block the apomorphine-induced decrease in

Herbert Y. Meltzer

1989-01-01

33

Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity.  

PubMed

Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex. PMID:21584865

Gross, Noah B; Duncker, Patrick C; Marshall, John F

2011-08-31

34

Structure-guided directed evolution of highly selective p450-based magnetic resonance imaging sensors for dopamine and serotonin.  

PubMed

New tools that allow dynamic visualization of molecular neural events are important for studying the basis of brain activity and disease. Sensors that permit ligand-sensitive magnetic resonance imaging (MRI) are useful reagents due to the noninvasive nature and good temporal and spatial resolution of MR methods. Paramagnetic metalloproteins can be effective MRI sensors due to the selectivity imparted by the protein active site and the ability to tune protein properties using techniques such as directed evolution. Here, we show that structure-guided directed evolution of the active site of the cytochrome P450-BM3 heme domain produces highly selective MRI probes with submicromolar affinities for small molecules. We report a new, high-affinity dopamine sensor as well as the first MRI reporter for serotonin, with which we demonstrate quantification of neurotransmitter release in vitro. We also present a detailed structural analysis of evolved cytochrome P450-BM3 heme domain lineages to systematically dissect the molecular basis of neurotransmitter binding affinity, selectivity, and enhanced MRI contrast activity in these engineered proteins. PMID:22659321

Brustad, Eric M; Lelyveld, Victor S; Snow, Christopher D; Crook, Nathan; Jung, Sang Taek; Martinez, Francisco M; Scholl, Timothy J; Jasanoff, Alan; Arnold, Frances H

2012-05-30

35

A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health  

PubMed Central

Mental illnesses, such as bipolar disorder, attention-deficit/hyperactivity disorder, depression and schizophrenia are a major public health concern worldwide. Several pharmacologic agents acting on monoamine neurotransmission are used for the management of these disorders. However, there is still little understanding of the ultimate molecular mechanisms responsible for the therapeutic effects of these drugs or their relations with disease etiology. Here I provide an overview of recent advances on the involvement of the signalling molecules Akt and glycogen synthase kinase-3 (GSK3) in the regulation of behaviour by the monoamine neurotransmitters dopamine (DA) and serotonin (5-HT). I examine the possible participation of these signalling molecules to the effects of antidepressants, lithium and antipsychotics, as well as their possible contribution to mental disorders. Regulation of Akt and GSK3 may constitute an important signalling hub in the subcellular integration of 5-HT and DA neurotransmission. It may also provide a link between the action of these neurotransmitters and gene products, like disrupted in schizophrenia 1 (DISC1) and neuregulin (NRG), that are associated with increased risk for mental disorders. However, changes in Akt and GSK3 signalling are not restricted to a single disorder, and their contribution to specific behavioural symptoms or therapeutic effects may be modulated by broader changes in biologic contexts or signalling landscapes. Understanding these interactions may provide a better understanding of mental illnesses, leading to better efficacy of new therapeutic approaches.

Beaulieu, Jean-Martin

2012-01-01

36

A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health.  

PubMed

Mental illnesses, such as bipolar disorder, attention-deficit/hyperactivity disorder, depression and schizophrenia are a major public health concern worldwide. Several pharmacologic agents acting on monoamine neurotransmission are used for the management of these disorders. However, there is still little understanding of the ultimate molecular mechanisms responsible for the therapeutic effects of these drugs or their relations with disease etiology. Here I provide an overview of recent advances on the involvement of the signalling molecules Akt and glycogen synthase kinase-3 (GSK3) in the regulation of behaviour by the monoamine neurotransmitters dopamine (DA) and serotonin (5-HT). I examine the possible participation of these signalling molecules to the effects of antidepressants, lithium and antipsychotics, as well as their possible contribution to mental disorders. Regulation of Akt and GSK3 may constitute an important signalling hub in the subcellular integration of 5-HT and DA neurotransmission. It may also provide a link between the action of these neurotransmitters and gene products, like disrupted in schizophrenia 1 (DISC1) and neuregulin (NRG), that are associated with increased risk for mental disorders. However, changes in Akt and GSK3 signalling are not restricted to a single disorder, and their contribution to specific behavioural symptoms or therapeutic effects may be modulated by broader changes in biologic contexts or signalling landscapes. Understanding these interactions may provide a better understanding of mental illnesses, leading to better efficacy of new therapeutic approaches. PMID:21711983

Beaulieu, Jean-Martin

2012-01-01

37

The clozapine metabolite N-desmethylclozapine displays variable activity in diverse functional assays at human dopamine D? and serotonin 5-HT?A receptors.  

PubMed

N-desmethylclozapine (NDMC or norclozapine) is the major active metabolite of the antipsychotic clozapine in humans. The activity of NDMC differs from clozapine at a number of neurotransmitter receptors, probably influencing the pharmacological effects of clozapine treatment. Here, we tested the properties of NDMC in comparison with clozapine at recombinant human dopamine D(2) and serotonin 5-HT(1A) receptors, using a panel of functional assays implicating diverse signalling pathways. At dopamine D(2) receptors, NDMC as well as clozapine did not display agonist activity in measures of G protein activation by [(35)S]GTP?S binding and in the sensitive Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) phosphorylation assay. In contrast, there were weak partial agonist actions of NDMC (but not of clozapine) for dopamine D(2)-dependent activation of Ca(2+) liberation via coexpressed chimeric G?(q/o) proteins and for G protein-coupled inward rectifier potassium channel (GIRK) current induction in Xenopus oocytes. Intriguingly, GIRK currents induced by NDMC via dopamine D(2) receptors showed a rapid and transient time course, strikingly different from currents recorded with other receptor agonists. At serotonin 5-HT(1A) receptors, NDMC was a more efficacious partial agonist than clozapine for [(35)S]GTP?S binding, ERK1/2 phosphorylation and GIRK activation. Respective low and moderate partial agonist properties of NDMC at dopamine D(2) and serotonin 5-HT(1A) receptors thus differentiate the metabolite from its parent drug and may contribute to the overall effects of clozapine pharmacotherapy. PMID:21835172

Heusler, Peter; Bruins Slot, Liesbeth; Tourette, Amélie; Tardif, Stéphanie; Cussac, Didier

2011-08-05

38

Differential regulation of MeCP2 phosphorylation in the CNS by dopamine and serotonin.  

PubMed

Systemic administration of amphetamine (AMPH) induces phosphorylation of MeCP2 at Ser421 (pMeCP2) in select populations of neurons in the mesolimbocortical brain regions. Because AMPH simultaneously activates multiple monoamine neurotransmitter systems, here we examined the ability of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) to induce pMeCP2. Selective blockade of the DA transporter (DAT) or the 5-HT transporter (SERT), but not the NE transporter (NET), was sufficient to induce pMeCP2 in the CNS. DAT blockade induced pMeCP2 in the prelimbic cortex (PLC) and nucleus accumbens (NAc), whereas SERT blockade induced pMeCP2 only in the NAc. Administration of selective DA and 5-HT receptor agonists was also sufficient to induce pMeCP2; however, the specific combination of DA and 5-HT receptors activated determined the regional- and cell-type specificity of pMeCP2 induction. The D(1)-class DA receptor agonist SKF81297 induced pMeCP2 widely; however, coadministration of the D(2)-class agonist quinpirole restricted the induction of pMeCP2 to GABAergic interneurons of the NAc. Intra-striatal injection of the adenylate cyclase activator forskolin was sufficient to induce pMeCP2 in medium-spiny neurons, suggesting that the combinatorial regulation of cAMP by different classes of DA and 5-HT receptors may contribute to the cell-type specificity of pMeCP2 induction. Consistent with the regulation of pMeCP2 by multiple monoamine neurotransmitters, genetic disruption of any single monoamine transporter in DAT-, SERT-, and NET-knockout mice failed to eliminate AMPH-induced pMeCP2 in the NAc. Together, these studies indicate that combinatorial signaling through DA and 5-HT receptors can regulate the brain region- and cell-type specific pMeCP2 in the CNS. PMID:21956448

Hutchinson, Ashley N; Deng, Jie V; Aryal, Dipendra K; Wetsel, William C; West, Anne E

2011-09-28

39

Differential Regulation of MeCP2 Phosphorylation in the CNS by Dopamine and Serotonin  

PubMed Central

Systemic administration of amphetamine (AMPH) induces phosphorylation of MeCP2 at Ser421 (pMeCP2) in select populations of neurons in the mesolimbocortical brain regions. Because AMPH simultaneously activates multiple monoamine neurotransmitter systems, here we examined the ability of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) to induce pMeCP2. Selective blockade of the DA transporter (DAT) or the 5-HT transporter (SERT), but not the NE transporter (NET), was sufficient to induce pMeCP2 in the CNS. DAT blockade induced pMeCP2 in the prelimbic cortex (PLC) and nucleus accumbens (NAc), whereas SERT blockade induced pMeCP2 only in the NAc. Administration of selective DA and 5-HT receptor agonists was also sufficient to induce pMeCP2; however, the specific combination of DA and 5-HT receptors activated determined the regional- and cell-type specificity of pMeCP2 induction. The D1-class DA receptor agonist SKF81297 induced pMeCP2 widely; however, coadministration of the D2-class agonist quinpirole restricted the induction of pMeCP2 to GABAergic interneurons of the NAc. Intra-striatal injection of the adenylate cyclase activator forskolin was sufficient to induce pMeCP2 in medium-spiny neurons, suggesting that the combinatorial regulation of cAMP by different classes of DA and 5-HT receptors may contribute to the cell-type specificity of pMeCP2 induction. Consistent with the regulation of pMeCP2 by multiple monoamine neurotransmitters, genetic disruption of any single monoamine transporter in DAT-, SERT-, and NET-knockout mice failed to eliminate AMPH-induced pMeCP2 in the NAc. Together, these studies indicate that combinatorial signaling through DA and 5-HT receptors can regulate the brain region- and cell-type specific pMeCP2 in the CNS.

Hutchinson, Ashley N; Deng, Jie V; Aryal, Dipendra K; Wetsel, William C; West, Anne E

2012-01-01

40

Adult attachment and gene polymorphisms of the dopamine D4 receptor and serotonin transporter (5-HTT)  

Microsoft Academic Search

Recently, the Dopamine D4 Receptor Gene (DRD4) and the Serotonin Transporter Gene (5-HTT) have been found to be candidate genes for infant attachment disorganization. The present study aimed to explore the relationship of these genes to adult attachment representations. The Adult Attachment Interview was used to assess attachment representations in 167 German adults. DNA from buccal cells was genotyped for

Iris Reiner; Gottfried Spangler

2010-01-01

41

NORADRENALINE, DOPAMINE, SEROTONIN: DIFFERENT EFFECTS OF PSYCHOLOGICAL STRESS ON BRAIN BIOGENIC AMINES IN MICE AND RATS  

Microsoft Academic Search

The effect of restraint stress on central neurotransmission was evaluated in mice and rats. Noradrenaline (NA), dopamine (DA) and serotonin (5-HT) levels and their primary metabolites were measured in discrete brain regions following exposure to stress. Mice and rats demonstrated a similar response to stress in some brain regions. Both species responded to stress with lower NA and 5-HT in

MARIA KONSTANDI; ELIZABETH JOHNSON; MATTI A. LANG; MICHALIS MALAMAS; MARIOS MARSELOS

2000-01-01

42

Serotonin and Dopamine Transporter Binding in Children with Autism Determined by SPECT  

ERIC Educational Resources Information Center

|Disturbances in the serotonergic system have been recognized in autism. To investigate the association between serotonin and dopamine transporters and autism, we studied 15 children (14 males, one female; mean age 8y 8mo [SD 3y 10mo]) with autism and 10 non-autistic comparison children (five males, five females; mean age 9y 10mo [SD 2y 8mo])…

Makkonen, Ismo; Riikonen, Raili; Kokki, Hannu; Airaksinen, Mauno M.; Kuikka, Jyrki T.

2008-01-01

43

The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans  

Microsoft Academic Search

Neurophysiological experiments in primates, alongside neuropsychological and functional magnetic resonance investigations in humans, have significantly enhanced our understanding of the neural architecture of decision making. In this review, I consider the more limited database of experiments that have investigated how dopamine and serotonin activity influences the choices of human adults. These include those experiments that have involved the administration of

Robert D Rogers

2011-01-01

44

Altered Dopamine and Serotonin Metabolism in Motorically Asymptomatic R6\\/2 Mice  

Microsoft Academic Search

The pattern of cerebral dopamine (DA) abnormalities in Huntington disease (HD) is complex, as reflected by the variable clinical benefit of both DA antagonists and agonists in treating HD symptoms. In addition, little is known about serotonin metabolism despite the early occurrence of anxiety and depression in HD. Post-mortem enzymatic changes are likely to interfere with the in vivo profile

Fanny Mochel; Brandon Durant; Alexandra Durr; Raphael Schiffmann; David Rubinsztein

2011-01-01

45

Dopamine and serotonin release in the nucleus accumbens during starvation-induced hyperactivity  

Microsoft Academic Search

Activity-based anorexia (ABA) is considered an animal model for anorexia nervosa (AN). By scheduled feeding and voluntary wheel running, it mimics severe body weight loss and increased physical activity in AN. Pharmacological, genetic and imaging studies implicate dopamine and serotonin in the regulation of feeding behavior, food-anticipatory activity, and food reward. Previous studies propose that the nucleus accumbens (NAc) plays

Linda A. W. Verhagen; Mieneke C. M. Luijendijk; Gerdien A. H. Korte-Bouws; S. Mechiel Korte; Roger A. H. Adan

2009-01-01

46

Associations Between Dopamine and Serotonin Genes and Job Satisfaction: Preliminary Evidence From the Add Health Study  

Microsoft Academic Search

Previous behavioral genetic studies have found that job satisfaction is partially heritable. We went a step further to examine particular genetic markers that may be associated with job satisfaction. Using an oversample from the National Adolescent Longitudinal Study (Add Health Study), we found 2 genetic markers, dopamine receptor gene DRD4 VNTR and serotonin transporter gene 5-HTTLPR, to be weakly but

Zhaoli Song; Wendong Li; Richard D. Arvey

2011-01-01

47

Self-esteem in remitted patients with mood disorders is not associated with the dopamine receptor D4 and the serotonin transporter genes.  

PubMed

Disturbances of the dopaminergic and serotoninergic neurotransmitter systems have been implicated in the pathogenesis of depressive symptoms. Associations have been reported between markers of the two neurotransmitter systems and the presence of illness or severity of depressive episodes, but no attention has been focused on the periods of remission. The present report focuses on a possible association of self-esteem in remitted mood disorder patients with the functional polymorphism located in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) and the dopamine receptor D4 (DRD4). Inpatients (N=162) affected by bipolar (n=103) and unipolar (n=59) disorder (DSM III-R) were assessed by the Self-Esteem Scale (SES, Rosenberg, 1965) and were typed for DRD4 and 5-HTTLPR (n=58 subjects) variants at the third exon using polymerase chain reaction (PCR) techniques. Neither DRD4 nor 5-HTTLPR variants were associated with SES scores, and consideration of possible stratification effects such as sex and psychiatric diagnosis did not reveal any association either. The serotonin transporter and dopamine receptor D4 genes do not, therefore, influence self-esteem in remitted mood disorder subjects. PMID:9754692

Serretti, A; Macciardi, F; Di Bella, D; Catalano, M; Smeraldi, E

1998-08-17

48

EVIDENCE FOR FMRF-AMIDE AS A NEUROTRANSMITTER IN THE GILL OF APLYSIA CALIFORNICAl  

Microsoft Academic Search

In Aplysia californica, multiple regulatory mechanisms are involved in the actions of neurotransmitters on the gill. Neurotransmitter receptors and adenylate cyclase were examined in a particulate fraction of gill homogenates. The neuropeptide FMRF-amide stimulated enzyme activity 7- to &fold (EC&, 1 PM) via receptors that were pharmacologically distinct from those for dopamine and serotonin. FMRF-amide augmented cyclic AMP levels in

SAM WEISS; JEFF I. GOLDBERG; KULDIP S. CHOHAN; WILLIAM K. STELL; GEORGE I. DRUMMOND; KEN LUKOWIAK

49

The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans  

PubMed Central

Neurophysiological experiments in primates, alongside neuropsychological and functional magnetic resonance investigations in humans, have significantly enhanced our understanding of the neural architecture of decision making. In this review, I consider the more limited database of experiments that have investigated how dopamine and serotonin activity influences the choices of human adults. These include those experiments that have involved the administration of drugs to healthy controls, experiments that have tested genotypic influences upon dopamine and serotonin function, and, finally, some of those experiments that have examined the effects of drugs on the decision making of clinical samples. Pharmacological experiments in humans are few in number and face considerable methodological challenges in terms of drug specificity, uncertainties about pre- vs post-synaptic modes of action, and interactions with baseline cognitive performance. However, the available data are broadly consistent with current computational models of dopamine function in decision making and highlight the dissociable roles of dopamine receptor systems in the learning about outcomes that underpins value-based decision making. Moreover, genotypic influences on (interacting) prefrontal and striatal dopamine activity are associated with changes in choice behavior that might be relevant to understanding exploratory behaviors and vulnerability to addictive disorders. Manipulations of serotonin in laboratory tests of decision making in human participants have provided less consistent results, but the information gathered to date indicates a role for serotonin in learning about bad decision outcomes, non-normative aspects of risk-seeking behavior, and social choices involving affiliation and notions of fairness. Finally, I suggest that the role played by serotonin in the regulation of cognitive biases, and representation of context in learning, point toward a role in the cortically mediated cognitive appraisal of reinforcers when selecting between actions, potentially accounting for its influence upon the processing salient aversive outcomes and social choice.

Rogers, Robert D

2011-01-01

50

Dopamine Transporter Density in the Basal Ganglia in Obsessive-Compulsive Disorder, Measured with [123I]IPT SPECT before and after Treatment with Serotonin Reuptake Inhibitors  

Microsoft Academic Search

It has been suggested that dopamine as well as serotonin are associated with the pathophysiology of obsessive-compulsive disorder (OCD). 5-Hydroxytryptophan inhibits dopamine release in healthy persons as well as in patients with OCD, and serotonin tonic inhibition affects dopamine function in basal ganglia, indicating a close relationship between serotonin and the dopamine system. Using iodine-123-labeled N-(3-iodopropen-2-yl)-2?-carbomethoxy-3?-(4-chlorophenyl) tropane ([123I]IPT) single photon

C. H. Kim; K. A. Cheon; M.-S. Koo; Y. H. Ryu; J. D. Lee; J. W. Chang; H. S. Lee

2007-01-01

51

Serotonin, noradrenaline, dopamine metabolites in transcendental meditation-technique  

Microsoft Academic Search

Summary The highly significant increase of 5-HIAA (5-hydroxyindole-3-acetic acid) in Transcendental Meditation technique suggests systemic serotonin as “rest and fulfillment hormone” of deactivation-relaxation.

M. Bujatti; P. Biederer

1976-01-01

52

Effect of intraventricular administration of glutaurine on norepinephrine, dopamine and serotonin turnover in different brain regions in rats.  

PubMed

The effect of glutaurine (gamma-L-glutamyl-taurine, Litoralon) was studied on dopamine, norepinephrine and serotonin turnover in the hypothalamus, mesencephalon, amygdala, septum, hippocampus, cortex and cerebellum following intracerebroventricular administration. Dopamine and norepinephrine turnover, measured by alpha-methyl-paratyrosine inhibition of catecholamine synthesis, increased in the cerebellum and the norepinephrine turnover in the hypothalamus. Serotonin turnover, measured by serotonin accumulation induced by the MAO inhibitor pargyline, decreased in the mesencephalon. There was no change in catecholamine or serotonin turnover in the amygdala, septum, hippocampus and cortex. The data suggested a highly selective action of glutaurine on brain transmitters in certain brain areas, especially in the cerebellum. PMID:6650186

Feuer, L; Fekete, M; Kádár, T; Telegdy, G

1983-01-01

53

Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain  

Microsoft Academic Search

THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the

S. F. Ali; G. D. Newport; A. C. Scallet; K. W. Gee; M. G. Paule; R. M. Brown; W. Jr. Slikker

2009-01-01

54

Effects of serotonin, dopamine and ergometrine on locomotion in the pulmonate mollusc Helix lucorum.  

PubMed

The terrestrial snail Helix lucorum crawls using waves of muscular contraction (pedal waves) that spread along the sole of its foot. Crawling speed depends on wave generation frequency (step frequency) and the distance the snail moves forwards during each wave (step length). In a previous study, video recordings of a crawling snail showed that its sole length varied over a wide range and was directly correlated with mollusc speed. Speed depended on step length, which was directly related to sole length, rather than on step frequency, which remained rather constant. In the present study, the effects of dopamine, ergometrine (a blocker of dopamine receptors in molluscs) and serotonin injection on the linear relationship between sole length and locomotor speed in Helix lucorum were studied. In crawling snails, dopamine caused sole contraction, and locomotion slowed down or ceased. Ergometrine stimulated locomotion, which resembled rapid crawling with an extended sole, as observed under normal conditions. Serotonin stimulated locomotion and accelerated crawling significantly without causing changes in sole length. The acceleration of locomotion induced by serotonin injection was due to pedal wave (step) elongation. It is proposed that, during each locomotor episode, dopamine controls snail speed by regulating sole length, which determines the amplitude of contraction of the muscle cells involved in pedal waves and, as a result, step length; serotonin determines the basic step length and shifts the linear relationship between sole length and mollusc speed upwards along the axis of mollusc speed. The efficiency of the serotonergic system depends on the physiological state of the mollusc (e.g. that characteristic of summer or winter). PMID:11398751

Pavlova, G A

2001-05-01

55

Opposite modulatory effects of ovarian hormones on rat brain dopamine and serotonin transporters  

Microsoft Academic Search

The present study was designed to investigate the modulatory effect of gonadal steroids on brain dopamine (DA) and serotonin (5-HT) presynaptic transporters in female and male rats. Female and male rats were castrated and treated with either vehicle or gonadal hormones. The pharmacodynamic characteristics of the DA and 5-HT transporters were analyzed by [3H]BTCP and [3H]imipramine binding respectively. Ovariectomy (OVX)

Gitit Attali; Abraham Weizman; Irit Gil-Ad; Moshe Rehavi

1997-01-01

56

Stereoselective effects of ketamine on dopamine, serotonin and noradrenaline release and uptake in rat brain slices  

Microsoft Academic Search

Ketamine (2-(2-chlorophenyl)-(1-methylamino)-cyclohexanone) is a rapid-acting dissociative general anaesthetic whose hallucinogenic properties have made it a popular drug of abuse. Ketamine comprises two optical isomers, with differing pharmacology. In the present study, the effects of (+)- and (?)-ketamine on stimulated efflux and reuptake of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) were compared in isolated superfused slices of the rat caudatoputamen

Michelle M. Tso; Karen L. Blatchford; Luis F. Callado; Daniel P. McLaughlin; Jonathan A. Stamford

2004-01-01

57

Repeated exposure to methylenedioxymethamphetamine (MDMA) alters nucleus accumbens neuronal responses to dopamine and serotonin.  

PubMed

The purpose of this experiment was to investigate the effects of repeated exposure to methylenedioxymethamphetamine (MDMA) on responses of neurons in the nucleus accumbens of anesthetized rats to microiontophoretically-applied dopamine and serotonin. In tests conducted 1-4 days or 9-15 days following the last injection of MDMA (20 mg/kg, s.c., twice daily for 4 days), the inhibitory effects of both dopamine and serotonin on glutamate-evoked firing of nucleus accumbens cells were significantly attenuated compared to effects in control rats that were pretreated with saline injections. The inhibitory effect of the D1 receptor agonist SKF38393 was also significantly attenuated in the MDMA-pretreated rats. In contrast, the amount of inhibition of glutamate-evoked firing produced by application of GABA did not significantly differ between the MDMA-pretreated and the saline-pretreated rats. The neurotoxicity of the MDMA treatment regimen was confirmed by demonstrating that 3H-paroxetine binding was significantly decreased in the medial prefrontal cortex and the nucleus accumbens of the MDMA-pretreated rats. The mechanisms that produce the attenuated inhibitory responses to dopamine and serotonin following repeated injections of MDMA are not known. However, the results of these experiments indicate that repeated MDMA administration induces long-lasting changes in dopaminergic as well as serotonergic neurotransmission in the nucleus accumbens. PMID:9526029

Obradovic, T; Imel, K M; White, S R

1998-02-23

58

Impact of dopamine versus serotonin cell transplantation for the development of graft-induced dyskinesia in a rat Parkinson model.  

PubMed

Graft-induced dyskinesia (GID), covering a range of dystonic and choreiform involuntary movements, has been observed in some patients with Parkinson's disease (PD) after intracerebral cell transplantation. These dyskinesias have been severe in a number of patients and represent one of the main obstacles for further development of the cell therapy in PD. Serotonin neurons, included into the dopaminergic cell suspension due to the nature of the dissection process, have been suggested as a key factor for the development of GID, since the administration of the serotonin (5-HT)(1A)-receptor agonist buspirone reduced dyskinesia in transplanted PD patients. In the present study, we characterized GID in the rat PD model after transplantation of dopaminergic grafts containing different amounts of serotonin neurons. The severity of GID was significantly correlated with the amount of grafted dopamine and serotonin neurons, but the r-values were low. However, neither the innervation density of dopamine and serotonin fibers in the grafted striatum nor the dopamine-to-serotonin cell ratio correlated significantly with the severity of GID. The results extend prior knowledge of the role of dopaminergic grafts in the development of GID and show that, in the animal model, serotonin neurons within the graft suspension might be involved, but given sufficient dopamine cells, their impact on GID may be minor. PMID:22759908

García, Joanna; Carlsson, Thomas; Döbrössy, Máté; Nikkhah, Guido; Winkler, Christian

2012-07-01

59

Modulation of Drosophila heartbeat by neurotransmitters  

Microsoft Academic Search

The heart of Drosophila melanogaster is a simple muscular tube with a posterior pulsatile portion and a thoracic-cranial vessel. The pacemaker, located caudally,\\u000a is myogenic. Its rate of firing is modulated by neurotransmitters. Serotonin, octopamine, norepineph-rine, dopamine, and acetylcholine\\u000a accelerate the heart, in that order of potency. Dihydroxyphenylalanine, ?-aminobutyric acid, glutamate, and glycine have no\\u000a effect. Generally, the regularity of

E. Johnson; J. Ringo; H. Dowse

1997-01-01

60

In vivo assessment of dopamine D-2 and serotonin S-2 receptors measured by C-11 N-methylspiperone (NMSP) in manic-depressive illness  

SciTech Connect

The hypothesis has been suggested that either the dopaminergic or serotonergic neurotransmitter systems may be involved in manic-depressive illness (MD). The authors have studied 16 subjects with C-11 NMSP PET imaging. Two had never received neuroleptics; 4 were drug free for 1 month at the time of scanning; of these 3 were acutely manic; the rest were on stable lithium treatment. The dopamine and serotonin binding was estimated by the 43 min. caudate/cerebellum (Ca/Cb) and frontal/cerebellum (FC/Cb) ratios, respectively. No statistically significant difference was detected when compared to 44 age and sex matched controls. Based upon the variance in the normal data and the average age of the patient group studied, the probability of detecting a difference of >30% between patients and normals is >0.8. Hence, identification of receptor abnormalities if present will be improved with increased sample size of both normals and patients.

Wong, D.F.; Pearlson, G.; Wagner, H.N. Jr.; Dannals, R.F.; Suneja, S.; Bjorgvinsson, E.; Links, J.M.; Ravert, H.T.; Wilson, A.A.; Schaerf, F.

1985-05-01

61

Association of serotonin and dopamine gene pathways with behavioral subphenotypes in dementia.  

PubMed

Genetic association studies investigating the association between genes of serotonergic and dopaminergic systems and behavioral and psychological symptoms in dementia (BPSD) are contradictory. We have utilized 1008 probable Alzheimer's disease (AD) patients from the UK and used the 12-item Neuropsychiatric Inventory. We applied a multiple indicators-multiple causes (MIMIC) approach to investigate the effect of 11 polymorphisms on the 4 behavioral subphenotypes "psychosis", "moods", "agitation", and "behavioural dyscontrol". Significant associations were observed between the serotonin transporter gene (SERT) polymorphism STin2 and "psychosis"; the dopamine transporter gene (DAT) 3' variable number tandem repeats (VNTR) and "agitation"; and the dopamine receptor 4 (DRD4) VNTR and "moods" factors. Direct associations were identified between the dopamine receptor 3 (DRD3) BalI polymorphism and depression; the dopamine receptor 1 (DRD1) and dopamine transporter gene 3' VNTR polymorphisms and aberrant motor behavior; the DRD4 VNTR and sleep disturbances; and the SERT gene VNTR 5HTTLPR and apathy items. Significant interactions observed between polymorphisms suggested epistatic effects and interactions between polymorphisms and medications highlighted potential treatment response. This multiple indicators multiple causes (MIMIC) model efficiently captured the complexity of the interrelations between genetic variation, behavioral symptoms, and clinical variables. PMID:20685009

Proitsi, Petroula; Lupton, Michelle K; Reeves, Suzanne J; Hamilton, Gillian; Archer, Nicola; Martin, Belinda M; Iyegbe, Conrad; Hollingworth, Paul; Lawlor, Brian; Gill, Michael; Brayne, Carol; Rubinsztein, David C; Owen, Michael J; Williams, Julie; Lovestone, Simon; Powell, John F

2010-08-03

62

Genetic Polymorphisms in Dopamine- and Serotonin-Related Genes and Treatment Responses to Risperidone and Perospirone  

PubMed Central

We investigated the possible association between genetic polymorphisms in the dopamine receptor and serotonin transporter genes and the responses of schizophrenic patients treated with either risperidone or perospirone. The subjects comprised 27 patients with schizophrenia who were clinically evaluated both before and after treatment. The genotyping of the polymorphisms of the dopamine D2 receptor gene (DRD2) (rs1801028 and rs6277), the dopamine D4 receptor gene (DRD4) (120-bp tandem repeats and rs1800955), and serotonin transporter gene (5HTT)(variable number of tandem repeats; VNTR) were performed using the real-time polymerase chain reaction and sequencing. In DRD2 and 5HTT-VNTR, there were no significant correlations between clinical response and polymorphism in the case of risperidone, and for perospirone treatment it was impossible to analyze the clinical evaluation due to the absence of genotype information. On the other hand, in DRD4 there were significant correlations in the two-factor interaction effect on the Positive and Negative Syndrome Scale (PANSS) between the two drugs [120-bp tandem repeat, p=0.003; rs1800955, p=0.043]. Although the small sample represents a serious limitation, these results suggest that variants in DRD4 are a predictor of whether treatment will be more effective with risperidone or with perospirone in individual patients.

Kanazawa, Tetsufumi; Kikuyama, Hiroki; Okugawa, Gaku; Uenishi, Hiroyuki; Miyamoto, Toshio; Matsumoto, Naoki; Koh, Jun; Shinosaki, Kazuhiro; Kishimoto, Toshifumi; Yoneda, Hiroshi; Kinoshita, Toshihiko

2009-01-01

63

Serotonin-dopamine interactions in the control of conditioned reinforcement and motor behavior.  

PubMed

These studies addressed the question of serotonin (5-HT)-dopamine (DA) interactions with regard to reward-related behavior and motor activity in rats. The first experiment evaluated the effect of chronic treatment with fluoxetine (7 mg/kg/day), a serotonin-selective reuptake inhibitor, and buproprion (15 mg/kg/day), a dopamine reuptake inhibitor, on responding for conditioned reinforcement (CR). Chronic fluoxetine, but not buproprion, enhanced CR responding, and also potentiated cocaine-induced increases in CR responding. In the second experiment, animals received intra-accumbens infusions of either 5-HT (0, 1, 5, and 10 microg) or DA (10, 20 microg) prior to the conditioned reinforcement test. Dopamine, but not 5-HT, selectively facilitated CR responding, although 5-HT non-specifically increased responding as well. In the third and fourth experiments, it was demonstrated that intra-accumbens 5-HT causes increased motor activity, which was partially blocked by DA antagonists. The results suggest that chronically increased levels of 5-HT may facilitate reward-related behavior, but most likely via indirect modulatory mechanisms affecting general arousal and motor tone. PMID:11522471

Sasaki-Adams, D M; Kelley, A E

2001-09-01

64

Fluvoxamine, a selective serotonin reuptake inhibitor, suppresses tetrahydrobiopterin levels and dopamine as well as serotonin turnover in the mesoprefrontal system of mice  

Microsoft Academic Search

Rationale Tetrahydrobiopterin (BH 4) is a coenzyme of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), rate-limiting enzymes of monoamine biosynthesis. According to the monoamine hypothesis of depression, antidepressants will restore the function of the brain monoaminergic system, and BH 4 concentration. Objective To investigate the effects of fluvoxamine on BH 4 levels and dopamine (DA) and serotonin (5-HT) turnover in

H. Miura; H. Qiao; T. Kitagami; T. Ohta; N. Ozaki

2005-01-01

65

The establishment of a sensitive method in determining different neurotransmitters simultaneously in rat brains by using liquid chromatography–electrospray tandem mass spectrometry  

Microsoft Academic Search

An effective way to determine the amount of different neurotransmitters is vital to the study of brain function. Here, a highly sensitive HPLC–MS\\/MS method was developed to simultaneously measure ?-aminobutyric acid, dopamine, epinephrine, norepinepherine, glutamate and serotonin in one sample. The quantification of the neurotransmitters was achieved by a tandem mass spectrometer using the selected reaction monitoring scan mode. The

Kevin Y. Zhu; Qiang Fu; K. Wing Leung; Zack C. F. Wong; Roy C. Y. Choi; Karl W. K. Tsim

2011-01-01

66

Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain  

Microsoft Academic Search

The cannabinoid receptor type 1 (CB1) displays unusual properties, including the dual capacity to inhibit or stimulate adenylate cyclase and a brain density considerably higher than the majority of G protein-coupled receptors. Together with overlapping expression patterns of dopamine and serotonin receptors this suggests a potential of CB1 to modulate the function of the dopamine and serotonin system. Indeed, pharmacological

H Hermann; G Marsicano; B Lutz

2002-01-01

67

The Mechanistic Basis for Noncompetitive Ibogaine Inhibition of Serotonin and Dopamine Transporters*  

PubMed Central

Ibogaine, a hallucinogenic alkaloid proposed as a treatment for opiate withdrawal, has been shown to inhibit serotonin transporter (SERT) noncompetitively, in contrast to all other known inhibitors, which are competitive with substrate. Ibogaine binding to SERT increases accessibility in the permeation pathway connecting the substrate-binding site with the cytoplasm. Because of the structural similarity between ibogaine and serotonin, it had been suggested that ibogaine binds to the substrate site of SERT. The results presented here show that ibogaine binds to a distinct site, accessible from the cell exterior, to inhibit both serotonin transport and serotonin-induced ionic currents. Ibogaine noncompetitively inhibited transport by both SERT and the homologous dopamine transporter (DAT). Ibogaine blocked substrate-induced currents also in DAT and increased accessibility of the DAT cytoplasmic permeation pathway. When present on the cell exterior, ibogaine inhibited SERT substrate-induced currents, but not when it was introduced into the cytoplasm through the patch electrode. Similar to noncompetitive transport inhibition, the current block was not reversed by increasing substrate concentration. The kinetics of inhibitor binding and dissociation, as determined by their effect on SERT currents, indicated that ibogaine does not inhibit by forming a long-lived complex with SERT, but rather binds directly to the transporter in an inward-open conformation. A kinetic model for transport describing the noncompetitive action of ibogaine and the competitive action of cocaine accounts well for the results of the present study.

Bulling, Simon; Schicker, Klaus; Zhang, Yuan-Wei; Steinkellner, Thomas; Stockner, Thomas; Gruber, Christian W.; Boehm, Stefan; Freissmuth, Michael; Rudnick, Gary; Sitte, Harald H.; Sandtner, Walter

2012-01-01

68

In vivo binding of /sup 3/H-N-methylspiperone to dopamine and serotonin receptors  

SciTech Connect

/sup 3/H-N-methylspiperone (/sup 3/H-NMSP) was used to label dopamine-2 and serotonin-2 in vivo in the mouse. The striatum/cerebellum binding ratio reached a maximum of 80 eight hours after intravenous administration of /sup 3/H-NMSP. The frontal cortex/cerebellum ratio was 5 one hour after injection. The binding of /sup 3/H-NMSP was saturable in the frontal cortex and cerebellum between doses of 10 and 1000 ..mu..g/kg. Between 0.01 and 10 ..mu..g/kg the ratio total/nonspecific binding increased from 14 to 21. Inhibition of /sup 3/H-NMSP binding in the frontal cortex and striatum by ketanserin, a selective serotonin-2 antagonist, demonstrated that 20% of the total binding in the striatum was to serotonin-2 rectors and 91% of the total binding in the frontal cortex was to serotonin-2 receptors. Compared to /sup 3/H-spiperone, /sup 3/H-NMSP 1) results in a much higher specific/nonspecific binding ratio in the striatum and frontal cortex and 2) displays more than a two-fold higher brain uptake. 18 references, 4 figures.

Frost, J.J.; Smith, A.C.; Kuhar, M.J.; Dannals, R.F.; Wagner, H.N. Jr.

1987-03-09

69

Amisulpride-induced acute akathisia in OCD: an example of dysfunctional dopamine-serotonin interactions?  

PubMed Central

We report about a clinical observation in a well-characterized group of patients with obsessive–compulsive disorder (OCD) during an experimental medicine study in which a single dose of amisulpride (a selective D2/3 antagonist) was administered. Almost half of the OCD patients, in particular those with less severe obsessive–compulsive symptoms, experienced acute akathisia in response to the amisulpride challenge. This unexpectedly high incidence of akathisia in the selective serotonin reuptake inhibitor (SSRI)-treated patients with OCD suggests that individual differences in dopamine–serotonin interactions underlie the clinical heterogeneity of OCD, and may thus explain the insufficiency of SSRI monotherapy in those patients not experiencing a satisfactory outcome in symptom reduction. We further speculate about the neuropathology possibly underlying this clinical observation and outline a testable hypothesis for future molecular imaging studies.

Ersche, Karen D; Cumming, Paul; Craig, Kevin J; Muller, Ulrich; Fineberg, Naomi A; Bullmore, Edward T; Robbins, Trevor W

2013-01-01

70

Amisulpride-induced acute akathisia in OCD: an example of dysfunctional dopamine-serotonin interactions?  

PubMed

We report about a clinical observation in a well-characterized group of patients with obsessive-compulsive disorder (OCD) during an experimental medicine study in which a single dose of amisulpride (a selective D?/? antagonist) was administered. Almost half of the OCD patients, in particular those with less severe obsessive-compulsive symptoms, experienced acute akathisia in response to the amisulpride challenge. This unexpectedly high incidence of akathisia in the selective serotonin reuptake inhibitor (SSRI)-treated patients with OCD suggests that individual differences in dopamine-serotonin interactions underlie the clinical heterogeneity of OCD, and may thus explain the insufficiency of SSRI monotherapy in those patients not experiencing a satisfactory outcome in symptom reduction. We further speculate about the neuropathology possibly underlying this clinical observation and outline a testable hypothesis for future molecular imaging studies. PMID:21746752

Ersche, Karen D; Cumming, Paul; Craig, Kevin J; Müller, Ulrich; Fineberg, Naomi A; Bullmore, Edward T; Robbins, Trevor W

2011-07-11

71

Recognition Properties and Competitive Assays of a Dual Dopamine/Serotonin Selective Molecularly Imprinted Polymer  

PubMed Central

A molecularly imprinted polymer (MIP) with dual dopamine/serotonin-like binding sites (DS-MIP) was synthesized for use as a receptor model of study the drug-interaction of biological mixed receptors at a molecular level. The polymer material was produced using methacrylic acid (MAA) and acrylamide (ACM) as functional monomers, N,N?-methylene bisacrylamide (MBAA) as cross-linker, methanol/water mixture (4:1, v/v) as porogen and a mixture of dopamine (D) and serotonin (S) as templates. The prepared DS-MIP exhibited the greatest rebinding of the template(s) in aqueous methanol solution with decreased recognition in acetonitrile, water and methanol solvent. The binding affinity and binding capacity of DS-MIP with S were found to be higher than those of DS-MIP with D. The selectivity profiles of DS-MIP suggest that the D binding site of DS-MIP has sufficient integrity to discriminate between species of non-optimal functional group orientation, whilst the S binding site of DS-MIP is less selective toward species having structural features and functional group orientations different from S. The ligand binding activities of a series of ergot derivatives (ergocryptine, ergocornine, ergocristine, ergonovine, agroclavine, pergolide and terguride) have been studied with the DS-MIP using a competitive ligand binding assay protocol. The binding affinities of DS-MIP were demonstrated in the micro- or submicro-molar range for a series of ergot derivatives, whereas the binding affinities were considerably greater to natural receptors derived from the rat hypothalamus. The DS-MIP afforded the same pattern of differentiation as the natural receptors, i.e. affinity for the clavines > lysergic acid derivatives > ergopeptines. The results suggest that the discrimination for the ergot derivatives by the dopamine and serotonin sites of DS-MIP is due to the structural features and functional orientation of the phenylethylamine and indolylethylamine entities at the binding sites, and the fidelity of the dopamine and serotonin imprinted cavities.

Suedee, Roongnapa; Seechamnanturakit, Vatcharee; Suksuwan, Acharee; Canyuk, Bhutorn

2008-01-01

72

Striatal dopamine release and genetic variation of the serotonin 2C receptor in humans  

PubMed Central

Mesoaccumbal and nigrostriatal projections are sensitive to stress, and heightened stress sensitivity is thought to confer risk for neuropsychiatric disorders. Serotonin 2C (5-HT2C) receptors mediate the inhibitory effects of serotonin on dopaminergic circuitry in experimental animals, and preclinical findings have implicated 5-HT2C receptors in motivated behaviors and psychotropic drug mechanisms. In humans, a common missense single-nucleotide change (rs6318, Cys23Ser) in the 5-HT2C receptor gene (HTR2C) has been associated with altered activity in vitro and with clinical mood disorders. We hypothesized that dopaminergic circuitry would be more sensitive to stress in humans carrying the Ser23 variant. To test this hypothesis, we studied 54 healthy humans using positron emission tomography and the displaceable D2/D3 receptor radiotracer [11C]raclopride. Binding potential (BPND) was quantified before and after a standardized stress challenge consisting of 20 minutes of moderate deep muscular pain, and reduction in BPND served as an index of dopamine release. The Cys23Ser variant was genotyped on a custom array, and ancestry informative markers were used to control for population stratification. We found greater dopamine release in the nucleus accumbens, caudate nucleus, and putamen among Ser23 carriers, after controlling for sex, age, and ancestry. Genotype accounted for 12% of the variance in dopamine release in the nucleus accumbens. There was no association of Cys23Ser with baseline BPND. These findings indicate that a putatively functional HTR2C variant (Ser23) is associated with greater striatal dopamine release during pain in healthy humans. Mesoaccumbal stress sensitivity may mediate the effects of HTR2C variation on risk of neuropsychiatric disorders.

Mickey, Brian J; Sanford, Benjamin J; Love, Tiffany M; Shen, Pei-Hong; Hodgkinson, Colin; Stohler, Christian S; Goldman, David; Zubieta, Jon-Kar

2012-01-01

73

Optimal physical performance in athletes: key roles of dopamine in a specific neurotransmitter\\/hormonal mechanism  

Microsoft Academic Search

It is proposed that exercise training leads to resetting of the central autonomic nervous system (ANS) status, modifies neuroendocrine function and consistently results in upgraded efficiency of physiological\\/metabolic regulations. The initiating neurotransmitter mechanism is widely held to be due, essentially, to activation of certain brain cholinergic neurons (amygdala n.), stimulation of the hypothalamic-pituitary-adrenocortical pathway, and to cortisol as the dominant

Christine Gilbert

1995-01-01

74

Linking cognitive aging to alterations in dopamine neurotransmitter functioning: Recent data and future avenues  

Microsoft Academic Search

Molecular-imaging studies of dopaminergic neurotransmission measure biomarkers of dopamine (DA), such as the DA transporter and D1 and D2 receptor densities in the living brain. These studies indicate that individual differences in DA functions are linked to cognitive performance irrespective of age, and serve as powerful mediators of age-related decline in executive functioning, episodic memory, and perceptual speed. This focused

Lars Bäckman; Ulman Lindenberger; Shu-Chen Li; Lars Nyberg

2010-01-01

75

Cell Lineage, Cell Death, and the Developmental Origin of ldenti Serotonin and Dopamine-Containing Neurons in the Leech  

Microsoft Academic Search

The nervous system of the glossiphoniid leech includes segmentally iterated neurons that contain serotonin (5HT) and dopamine. These have been investigated in Helobdella triserialis, Theromyzon rude, and Haementeria ghilianii. Five types of 5-HT neurons are identified by immunocytochem- istry in the abdominal ganglia of the ventral nerve cord: the bilaterally paired Retzius, anteromedial, ventrolateral and dorsolateral neurons, and the unpaired

Duncan K. Stuart; Seth S. Blair; David A. Weisblatb

1987-01-01

76

Effect of Green Tea Catechins Intake on Brain Pattern of Certain Neurotransmitters in Stz Diabetic Rats  

Microsoft Academic Search

3 Abstract: Present work aimed to illustrate the changes in neurotransmitters secretion mainly noradrenaline, serotonin and dopamine as re levant to ox idative stress that induced i n STZ r ats. This was followed by intake of green tea extract (Catechin) in a dose level 50mg\\/kg body weight daily for 10 weeks. Collected data showed a significant decrease in blood

Mohamed M. Elseweidy; Atef E. Abd El-Bak; Ahmed Abdullah

2009-01-01

77

Extracellular serotonin, dopamine and glutamate levels are elevated in the hypothalamus in a serotonin syndrome animal model induced by tranylcypromine and fluoxetine  

Microsoft Academic Search

Serotonin (5-HT) syndrome is a potentially fatal condition associated with various combinations of serotonergic drugs. The present study was undertaken to demonstrate that nervous systems other than the 5-HT system also participate in the pathophysiology of 5-HT syndrome. Concentrations of 5-HT, dopamine (DA) and glutamate in the hypothalamus were measured in two different 5-HT syndrome animal models using a microdialysis

Katsutoshi Shioda; Koichi Nisijima; Tatsuki Yoshino; Satoshi Kato

2004-01-01

78

Long-term gonadectomy affects the density of tyrosine hydroxylase- but not dopamine-beta-hydroxylase-, choline acetyltransferase- or serotonin-immunoreactive axons in the medial prefrontal cortices of adult male rats.  

PubMed

The rat prefrontal cortices participate in cognitive, affective and mnemonic functions. The importance of dopamine innervation for these computations is illustrated in studies showing that both supranormal levels and chemical lesions of prefrontal dopamine induce severe behavioral deficits. Observed hormone effects on some of these same behaviors suggest that the prefrontal cortices are also sensitive to gonadal steroids. These two influences seem to converge in recent evidence of increased dopamine axon density in representative prefrontal but not sensory or motor cortices in gonadectomized adult male rats. The seeming selectivity of these effects was further explored here using immunocytochemistry for tyrosine hydroxylase, dopamine-b-hydroxylase, serotonin and choline acetyltransferase to label neurochemically identified afferents in remaining, unstudied prefrontal fields of rat cortex in animals that were sham-operated or gonadectomized and given placebo, testosterone propionate, estradiol or dihydrotestosterone 28 days before being killed. Group comparisons revealed that across prefrontal zones, gonadectomy produced androgen-sensitive increases in presumed dopamine axon density, but did not affect the other afferents. These findings thus bolster evidence for a targeted gonadal steroid influence involving the prefrontal cortices and a neurotransmitter essential for their normal operations and implicated in their dysfunction in disorders such as schizophrenia as well. PMID:12571118

Kritzer, M F

2003-03-01

79

Caenorhabditis elegans selects distinct crawling and swimming gaits via dopamine and serotonin.  

PubMed

Many animals, including humans, select alternate forms of motion (gaits) to move efficiently in different environments. However, it is unclear whether primitive animals, such as nematodes, also use this strategy. We used a multifaceted approach to study how the nematode Caenorhabditis elegans freely moves into and out of water. We demonstrate that C. elegans uses biogenic amines to switch between distinct crawling and swimming gaits. Dopamine is necessary and sufficient to initiate and maintain crawling after swimming. Serotonin is necessary and sufficient to transition from crawling to swimming and to inhibit a set of crawl-specific behaviors. Further study of locomotory switching in C. elegans and its dependence on biogenic amines may provide insight into how gait transitions are performed in other animals. PMID:21969584

Vidal-Gadea, Andrés; Topper, Stephen; Young, Layla; Crisp, Ashley; Kressin, Leah; Elbel, Erin; Maples, Thomas; Brauner, Martin; Erbguth, Karen; Axelrod, Abram; Gottschalk, Alexander; Siegel, Dionicio; Pierce-Shimomura, Jonathan T

2011-10-03

80

Associations between dopamine and serotonin genes and job satisfaction: preliminary evidence from the Add Health Study.  

PubMed

Previous behavioral genetic studies have found that job satisfaction is partially heritable. We went a step further to examine particular genetic markers that may be associated with job satisfaction. Using an oversample from the National Adolescent Longitudinal Study (Add Health Study), we found 2 genetic markers, dopamine receptor gene DRD4 VNTR and serotonin transporter gene 5-HTTLPR, to be weakly but significantly associated with job satisfaction. Furthermore, we found study participants' level of pay to mediate the DRD4 and job satisfaction relationship. However, we found no evidence that self-esteem mediated the relationships between these 2 genes and job satisfaction. The study represents an initial effort to introduce a molecular genetics approach to the fields of organizational psychology and organizational behavior. PMID:21766995

Song, Zhaoli; Li, Wendong; Arvey, Richard D

2011-07-18

81

Human genetics and pharmacology of neurotransmitter transporters.  

PubMed

Biogenic amine neurotransmitters are released from nerve terminals and activate pre- and postsynaptic receptors. Released neurotransmitters are sequestered by transporters into presynaptic neurons, a major mode of their inactivation in the brain. Genetic studies of human biogenic amine transporter genes, including the dopamine transporter (hDAT; SLC6A3), the serotonin transporter (hSERT; SLC6A4), and the norepinephrine transporter (hNET; SLC6A2) have provided insight into how genomic variations in these transporter genes influence pharmacology and brain physiology. Genetic variants can influence transporter function by various mechanisms, including substrate affinities, transport velocity, transporter expression levels (density), extracellular membrane expression, trafficking and turnover, and neurotransmitter release. It is increasingly apparent that genetic variants of monoamine transporters also contribute to individual differences in behavior and neuropsychiatric disorders. This chapter summarizes current knowledge of transporters with a focus on genomic variations, expression variations, pharmacology of protein variants, and known association with human diseases. PMID:16722243

Lin, Z; Madras, B K

2006-01-01

82

Molecular mechanisms of cocaine reward: Combined dopamine and serotonin transporter knockouts eliminate cocaine place preference  

PubMed Central

Cocaine blocks uptake by neuronal plasma membrane transporters for dopamine (DAT), serotonin (SERT), and norepinephrine (NET). Cocaine reward/reinforcement has been linked to actions at DAT or to blockade of SERT. However, knockouts of neither DAT, SERT, or NET reduce cocaine reward/reinforcement, leaving substantial uncertainty about cocaine's molecular mechanisms for reward. Conceivably, the molecular bases of cocaine reward might display sufficient redundancy that either DAT or SERT might be able to mediate cocaine reward in the other's absence. To test this hypothesis, we examined double knockout mice with deletions of one or both copies of both the DAT and SERT genes. These mice display viability, weight gain, histologic features, neurochemical parameters, and baseline behavioral features that allow tests of cocaine influences. Mice with even a single wild-type DAT gene copy and no SERT copies retain cocaine reward/reinforcement, as measured by conditioned place-preference testing. However, mice with no DAT and either no or one SERT gene copy display no preference for places where they have previously received cocaine. The serotonin dependence of cocaine reward in DAT knockout mice is thus confirmed by the elimination of cocaine place preference in DAT/SERT double knockout mice. These results provide insights into the brain molecular targets necessary for cocaine reward in knockout mice that develop in their absence and suggest novel strategies for anticocaine medication development.

Sora, Ichiro; Hall, F. Scott; Andrews, Anne M.; Itokawa, Masanari; Li, Xiao-Fei; Wei, Hong-Bing; Wichems, Christine; Lesch, Klaus-Peter; Murphy, Dennis L.; Uhl, George R.

2001-01-01

83

[Association between dopamine (DRD2) and serotonin (5HTR2A) gene polymorphisms with the indicators of adolescent behavior adaptiveness].  

PubMed

The paper gives the results of a study of the impact of dopamine (DRD2) and serotonin (5HTR2A) genes on the development of personality characteristics in adolescents, by applying the Cattell (16PF) questionnaire. The study was performed in a group of 360 Moscow teenagers (185 girls and 175 boys) aged 14-17 years. The boys carrying the A1 allelle of the DRD2 gene were found to have a lower self-control, indiscipline, and impulsiveness. An association between the indicators of unconscientiousness, social introversion, and group independence was established in the girls with the G/G genotype of the 5HTR2A gene. Thus, gender differences have been revealed from the impact of dopamine and serotonin gene polymorphisms on the teenagers' personality characteristics that characterize the forms of disadaptive behavior, such as unconscientiousness, indiscipline, low self-control, and impulsiveness. PMID:21384582

Barski?, V I; Aksenova, M G; Kozlova, O B; Kirillov, A V; Demin, A A; Il'inykh, L M

84

Sustained Administration of Pramipexole Modifies the Spontaneous Firing of Dopamine, Norepinephrine, and Serotonin Neurons in the Rat Brain  

Microsoft Academic Search

Pramipexole (PPX) is a D2\\/D3 receptor agonist that has been shown to be effective in the treatment of depression. Serotonin (5-HT), norepinephrine (NE) and dopamine (DA) systems are known to be involved in the pathophysiology and treatment of depression. Due to reciprocal interactions between these neuronal systems, drugs selectively targeting one system-specific receptor can indirectly modify the firing activity of

O Chernoloz; M El Mansari; P Blier

2009-01-01

85

Interactions between Serotonin and Dopamine in the Control of Impulsive Choice in Rats: Therapeutic Implications for Impulse Control Disorders  

Microsoft Academic Search

Forebrain serotonergic lesions attenuate the ability of d-amphetamine to decrease impulsivity in a delay-discounting paradigm, potentially through interactions between the serotonin (5-HT) and dopamine (DA) systems. Nucleus accumbens (NAC) lesions increase impulsivity, but the extent to which accumbal DA is involved in regulating impulsive choice is unknown. In the current study, the effects of intra-accumbal infusions of 6-hydroxydopamine (6-OHDA) on

Catharine A Winstanley; David E H Theobald; Jeffrey W Dalley; Trevor W Robbins

2005-01-01

86

GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenylalaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia  

Microsoft Academic Search

A 4-year-old patient is described with hyperphenylalaninemia, severe retardation in development, severe muscular hypotonia of the trunk and hypertonia of the extremities, convulsions, and frequent episodes of hyperthermia without infections. Urinary excretion of neopterin, biopterin, pterin, isoxanthopterin, dopamine, and serotonin was very low, although the relative proportions of pterins were normal. In lumbar cerebrospinal fluid, homovanillic acid, 5-hydroxy-indoleacetic acid, neopterin

A. Niederwieser; N. Blau; M. Wang; P. Joller; M. Atarés; J. Cardesa-Garcia

1984-01-01

87

Midbrain serotonin and striatum dopamine transporter binding in double depression: A one-year follow-up study  

Microsoft Academic Search

Data on neurobiological differences between major depression (MD) and double depression (DD) are scarce. We examined the striatum dopamine (DAT) and midbrain serotonin transporter (SERT) binding of [123I] nor-?-CIT in DD patients (n=8) and compared it to that in MD patients (n=11) and healthy controls (n=19). Drug-naïve patients and controls were imaged by single-photon emission computed tomography at baseline, and

Soili M. Lehto; Tommi Tolmunen; Jyrki Kuikka; Minna Valkonen-Korhonen; Mikko Joensuu; Pirjo I. Saarinen; Ritva Vanninen; Pasi Ahola; Jari Tiihonen; Johannes Lehtonen

2008-01-01

88

Overoxidized polypyrrole film directed DNA immobilization for construction of electrochemical micro-biosensors and simultaneous determination of serotonin and dopamine  

Microsoft Academic Search

A promising electrochemical microsensor was fabricated by electrochemical immobilization of calf-thymus DNA on a carbon fiber electrode (CFE) through an overoxidized polypyrrole (PPyox) template for simultaneous determination of serotonin (5-HT) and dopamine (DA). Such a DNA–PPyox biocomposite modification layer of nano-thickness exhibited superior selectivity and sensitivity towards these neuronal amines comparing with a simple PPyox or DNA coating. This microsensor

Xiaohua Jiang; Xiangqin Lin

2005-01-01

89

Risperidone: regional effects in vivo on release and metabolism of dopamine and serotonin in the rat brain  

Microsoft Academic Search

The antipsychotic drug risperidone shows high affinity for both central serotonin (5-HT)2A and dopamine (DA)-D2 receptors in vivo. By employing microdialysis in freely moving rats, the effects of acute risperidone administration on regional brain DA and 5-HT release and metabolism were compared with the corresponding effects of the atypical antipsychotic drug clozapine as well as amperozide, the selective DA-D2 receptor

P. Hertel; G. G. Nomikos; M. Iurlo; T. H. Svensson

1996-01-01

90

Methamphetamine-elicited alterations of dopamine- and serotonin-metabolite levels within ? -opioid receptor knockout mice: a microdialysis study  

Microsoft Academic Search

?-Opioid receptors (?-ORs) modulate methamphetamine (MA)-induced behavioral responses, increased locomotor activity and stereotyped\\u000a behavior in the mouse model. We investigated the changes in dopamine (DA) and serotonin (5-HT) metabolism in the striatum\\u000a following either acute or repeated MA treatment using in vivo microdialysis. We also studied the role of ?-ORs in the modulation\\u000a of MA-induced DA and 5-HT metabolism within ?-OR

Kuo-Cheng Lan; Tangeng Ma; Shoei-Yn Lin-Shiau; Shing-Hwa Liu; Ing-Kang Ho

2008-01-01

91

A Nonoxidative Electrochemical Sensor Based on a Self-Doped Polyaniline/Carbon Nanotube Composite for Sensitive and Selective Detection of the Neurotransmitter Dopamine: A Review  

PubMed Central

Most of the current techniques for in vivo detection of dopamine exploit the ease of oxidation of this compound. The major problem during the detection is the presence of a high concentration of ascorbic acid that is oxidized at nearly the same potential as dopamine on bare electrodes. Furthermore, the oxidation product of dopamine reacts with ascorbic acid present in samples and regenerates dopamine again, which severely limits the accuracy of the detection. Meanwhile, the product could also form a melanin-like insulating film on the electrode surface, which decreases the sensitivity of the electrode. Various surface modifications on the electrode, new materials for making the electrodes, and new electrochemical techniques have been exploited to solve these problems. Recently we developed a new electrochemical detection method that did not rely on direct oxidation of dopamine on electrodes, which may naturally solve these problems. This approach takes advantage of the high performance of our newly developed poly(anilineboronic acid)/carbon nanotube composite and the excellent permselectivity of the ion-exchange polymer Nafion. The high affinity binding of dopamine to the boronic acid groups of the polymer affects the electrochemical properties of the polyaniline backbone, which act as the basis for the transduction mechanism of this non-oxidative dopamine sensor. The unique reduction capability and high conductivity of single-stranded DNA functionalized single-walled carbon nanotubes greatly improved the electrochemical activity of the polymer in a physiologically-relevant buffer, and the large surface area of the carbon nanotubes increased the density of the boronic acid receptors. The high sensitivity and selectivity of the sensor show excellent promise toward molecular diagnosis of Parkinson's disease. In this review, we will focus on the discussion of this novel detection approach, the new interferences in this detection approach, and how to eliminate these interferences toward in vivo and in vitro detection of the neurotransmitter dopamine.

Ali, Shah R.; Parajuli, Rishi R.; Balogun, Yetunde; Ma, Yufeng; He, Huixin

2008-01-01

92

Differential effects of adjunctive methylphenidate and citalopram on extracellular levels of serotonin, noradrenaline and dopamine in the rat brain.  

PubMed

Several clinical studies have suggested that the combined treatment with methylphenidate and citalopram may accelerate the onset of antidepressant action and induce an improvement even in treatment-refractory patients. In the present study, in vivo microdialysis was used to monitor the extracellular levels of serotonin, noradrenaline and dopamine in the prefrontal cortex, hippocampus, nucleus accumbens and striatum of the rat. Administration of methylphenidate (2.5 mg/kg s.c.) with citalopram (5 mg/kg i.p.) compared to methylphenidate alone caused a marked enhancement of dopamine levels in the prefrontal cortex, n. accumbens and hippocampus, but not in the striatum. Citalopram-induced increase in serotonin levels was strongly enhanced by adjunctive methylphenidate in the hippocampus, but attenuated in the cortex. These findings suggest that the proposed augmentation effects of adjuvant methylphenidate to citalopram are most likely associated with enhanced dopamine transmission in the corticolimbic areas, whereas serotonin and noradrenaline levels show differential and region specific responses. PMID:17383162

Weikop, Pia; Yoshitake, Takashi; Kehr, Jan

2007-03-26

93

Mutations in the Sepiapterin Reductase Gene Cause a Novel Tetrahydrobiopterin-Dependent Monoamine-Neurotransmitter Deficiency without Hyperphenylalaninemia  

Microsoft Academic Search

Classic tetrahydrobiopterin (BH4) deficiencies are characterized by hyperphenylalaninemia and deficiency of mono- amine neurotransmitters. In this article, we report two patients with progressive psychomotor retardation, dystonia, severe dopamine and serotonin deficiencies (low levels of 5-hydroxyindoleacetic and homovanillic acids), and abnormal pterin pattern (high levels of biopterin and dihydrobiopterin) in cerebrospinal fluid. Furthermore, they presented with normal urinary pterins and without

Luisa Bonafé; Beat Thöny; Johann M. Penzien; Barbara Czarnecki; Nenad Blau

2001-01-01

94

Application of carboxymethyl-?-cyclodextrin as a chiral selector in capillary electrophoresis for enantiomer separation of selected neurotransmitters  

Microsoft Academic Search

The aim of this work was to optimize conditions for capillary electrophoresis separation of different neurotransmitters (serotonin, phenylalanine, dopamine, adrenaline, ephedrine, propranolol and DOPA) in a single run, including separation of existing enantiomers. As chiral selectors added to the borate background, electrolyte unsubstituted ?-, ?- and ?-cyclodextrins (CDs), methyl-, dimethyl-, and trimethyl-substituted ?-CDs, and hydroxypropyl-substituted ?-, ?- and ?-CDs were

Wioleta Maruszak; Marek Trojanowicz; Magdalena Margasi?ska; Hans Engelhardt

2001-01-01

95

[Effects of schizandrol A on monoamine neurotransmitters in the central nervous system].  

PubMed

Schizandrol A (2',3',4',1",2",3"-hexamethoxy-6, 7-dimethyl-1,2,3,4-dibenzo-1,3-cyclooctadien-6-ol) is one of the effective components in the dried fruit of Schizandra chinensis Bail. Previous studies have found that schizandrol A exerts inhibitory effects on the central nervous system (CNS). For the purpose of elucidating the mechanism of inhibition, the concentrations of monoamine neurotransmitters and their metabolites in rat brain and the effects of schizandrol A on some receptors were determined by the ion-pairing reversed-phase liquid chromatography with electrochemical detection method and competitive binding assay. In the neurotransmitter studies, significant elevations of dopamine and its metabolite DOPAC (in striatum) and DA (in hypothalamus) were observed after i.p. administration of 50 mg/kg or 100 mg/kg of schizandrol A. But the receptor binding experiments showed that schizandrol A had no affinity for dopamine D1 and D2 receptors. Serotonin receptors and alpha 1-,alpha 2-adrenergic receptors, and it did not affect the binding of dopamine to dopamine D1 or D2 receptors. These results indicate that the inhibition exerted by schizandrol A on the CNS may be related to the dopamine system, and the increase of dopamine turnover has nothing to do with dopamine receptors. The concentrations of the norepinephrine metabolite MHPG and the serotonin metabolite 5-HIAA showed changes in rat striatum and hypothalamus after schizandrol A treatment, but norepinephrine and serotonin levels were unaffected. PMID:1678991

Zhang, L; Niu, X

1991-02-01

96

GABA, glutamate, dopamine and serotonin transporters expression on memory formation and amnesia.  

PubMed

Notwithstanding several neurotransmission systems are frequently related to memory formation, amnesia and/or therapeutic targets for memory alterations, the role of transporters ?-aminobutyric acid (GABA, GAT1), glutamate (neuronal glutamate transporter excitatory amino acid carrier; EACC1), dopamine (DAT) and serotonin (SERT) is poorly understood. Hence, in this paper Western-blot analysis was used to evaluate expression changes on them during memory formation in trained and untrained rats treated with the selective serotonin transporter inhibitor fluoxetine, the amnesic drug d-methamphetamine (METH) and fluoxetine plus METH. Transporters expression was evaluated in the hippocampus, prefrontal cortex and striatum. Data indicated that in addition of memory performance other behavioral parameters (e.g., explorative behavior, food-intake, etc.) that memory formation was recorded. Thus, memory formation in a Pavlovian/instrumental autoshaping was associated to up-regulation of prefrontal cortex GAT1 and EAAC1, striatal SERT, DAT and EACC1; while, hippocampal EACC1, GAT1 and SERT were down-regulated. METH impaired short (STM) and long-term memory (LTM), at 24 or 48h. The METH-induced amnesia down-regulated SERT, DAT, EACC1 and GAT1 in hippocampus and the GAT1 in striatum; no-changes were observed in prefrontal cortex. Post-training administration of fluoxetine improved LTM (48h), which was associated to DAT, GAT1 (prefrontal cortex) up-regulation, but GAT1 (striatum) and SERT (hippocampus) down-regulation. Fluoxetine plus METH administration was able to prevent amnesia, which was associated to DAT, EACC1 and GAT1 (prefrontal cortex), SERT and DAT (hippocampus) and EACC1 or DAT (striatal) up-regulation. Together these data show that memory formation, amnesia and anti-amnesic effects are associated to specific patters of transporters expression. PMID:22183017

Tellez, Ruth; Gómez-Víquez, Leticia; Meneses, Alfredo

2011-12-13

97

Novel receptor site involved in enhancement of stimulus-induced acetylcholine, dopamine, and serotonin release  

SciTech Connect

The cognitive enhancer DuP 996 (3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one) and its structural analogs enhance the K(+)-stimulated release of acetylcholine, dopamine, and serotonin in brain slices, without effect on basal release. A novel receptor site labeled by (3H)DuP 996 has been identified. The (3H)DuP 996 binding site has a Kd of 19 nM and a Bmax of 102 fmol/mg of protein. Binding to this site is specific, saturable, reversible, and time, pH, and temperature dependent. Specific binding is decreased by treatment with trypsin and not affected by phospholipase C. Specific binding is inhibited by Ca2+ and increased by Mn2+ but not affected by Na+, K+, or Mg2+. The (3H)DuP 996 binding sites are heterogeneously distributed in brain, with striatum and hypothalamus having highest density and cerebellum lowest. The (3H)DuP 996 binding site does not belong to any known class of receptor site, because (3H)DuP 996 binding could not be displaced by a broad variety of standard pharmacological agents and neuropeptides. Physiological significance of this binding site is suggested by the excellent correlation between the binding affinity for this site and the potency to enhance K(+)-stimulated release of acetylcholine for a series of DuP 996 analogs. Ligands for this receptor site may have therapeutic potential for the treatment of cognitive deficits and neurodegenerative diseases.

Tam, S.W.; Rominger, D.; Nickolson, V.J. (Central Nervous System Diseases Research, Du Pont Merck Pharmaceutical Company, Wilmington, DE (USA))

1991-07-01

98

Evaluation of metaiodobenzylguanidine uptake by the norepinephrine, dopamine and serotonin transporters.  

PubMed

Metaiodobenzylguanidine (MIBG) is taken up by sympathetic neurons, but the precise mechanism of uptake has not been elucidated. Uptake of monoamines by presynaptic neurons is mediated by plasma membrane proteins, the monoamine transporters. The human norepinephrine transporter (hNET), the bovine dopamine transporter (bDAT) and the rat serotonin transporter (r5HTT) have been cloned, sequenced and expressed in various cell lines. This study involves the measurement of MIBG uptake by cell lines that have been transfected with complementary DNAs encoding these monoamine transporters. At 20 nM MIBG, hNET transfected cells demonstrate a ninefold greater uptake of MIBG than nontransfected cells. MIBG uptake in hNET transfected cells is inhibited by 3 x 10(-6) M norepinephrine (87% inhibition) and by hNET transport inhibitors: 10(-7) M desipramine (94% inhibition) and 10(-7) M mazindol (97% inhibition). hNET transfected cells exhibit a Km for MIBG transport of 264 nM. Percent nonspecific uptake rises with increasing concentrations of MIBG while specific uptake is saturable. There is no significant uptake by bDAT or r5HTT. The NET appears to be responsible for the specific uptake of MIBG. PMID:8315492

Glowniak, J V; Kilty, J E; Amara, S G; Hoffman, B J; Turner, F E

1993-07-01

99

Characterization of the effects of serotonin on the release of (/sup 3/H)dopamine from rat nucleus accumbens and striatal slices  

SciTech Connect

The effect of serotonin agonists on the depolarization (K+)-induced, calcium-dependent, release of (/sup 3/H)dopamine (DA) from rat nucleus accumbens and striatal slices was investigated. Serotonin enhanced basal /sup 3/H overflow and reduced K+-induced release of (/sup 3/H)DA from nucleus accumbens slices. The effect of serotonin on basal /sup 3/H overflow was not altered by the serotonin antagonist, methysergide, or the serotonin re-uptake blocker, chlorimipramine, but was reversed by the DA re-uptake carrier inhibitors nomifensine and benztropine. With the effect on basal overflow blocked, serotonin did not modulate K+-induced release of (/sup 3/H)DA in the nucleus accumbens or striatum. The serotonin agonists, quipazine (in the presence of nomifensine) and 5-methoxytryptamine, did not significantly affect K+-induced release of (/sup 3/H)DA in the nucleus accumbens. This study does not support suggestions that serotonin receptors inhibit the depolarization-induced release of dopamine in the nucleus accumbens or striatum of the rat brain. The present results do not preclude the possibility that serotonin may affect the mesolimbic reward system at a site which is post-synaptic to dopaminergic terminals in the nucleus accumbens.

Nurse, B.; Russell, V.A.; Taljaard, J.J.

1988-05-01

100

Cloning of the cocaine-sensitive bovine dopamine transporter  

SciTech Connect

A cDNA encoding the dopamine transporter from bovine brain substantia nigra was identified on the basis of its structural homology to other, recently cloned, neurotransmitter transporters. The sequence of the 693-amino acid protein is quite similar to those of the rat {gamma}-aminobutyric acid, human norepinephrine, and rat serotonin transporters. Dopamine transporter mRNA was detected by in situ hybridization in the substantia nigra but not in the locus coeruleus, raphe, caudate, or other brain areas. ({sup 3}H)Dopamine accumulation in tissue culture cells transfected with the cDNA was inhibited by amphetamine, cocaine, and specific inhibitors of dopamine transports, including GBR12909.

Usdin, T.B.; Chen, C.; Brownstein, M.J.; Hoffman, B.J. (National Inst. of Mental Health, Bethesda, MD (United States)); Mezey, E. (Semmelweis Univ., Budapest (Hungary))

1991-12-15

101

A Bacoside containing Bacopa monnieri extract reduces both morphine hyperactivity plus the elevated striatal dopamine and serotonin turnover.  

PubMed

Bacopa monnieri (BM) has been used in Ayurvedic medicine as a nootropic, anxiolytic, antiepileptic and antidepressant. An n-butanol extract of the plant (nBt-ext BM) was analysed and found to contain Bacoside A (Bacoside A3, Bacopaside II and Bacopasaponin C). The effects of the BM extract were then studied on morphine-induced hyperactivity as well as dopamine and serotonin turnover in the striatum since these parameters have a role in opioid sensitivity and dependence. Mice were pretreated with saline or nBt-ext BM (5, 10 and 15 mg/kg, orally), 60 min before morphine administration and locomotor activity was subsequently recorded. Immediately after testing, striatal tissues were analysed for dopamine (DA), serotonin (5HT) and their metabolites using HPLC coupled with electrochemical detection. The results indicated that nBt-ext BM significantly (p < 0.001) decreased locomotor activity in both the saline and morphine treated groups. Additionally, nBt-ext BM significantly lowered morphine-induced dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-H1AA) upsurges in the striatum but failed to affect DA, 5-HT and their metabolites in the saline treated group. These findings suggest that nBt-ext BM has an antidopaminergic/serotonergic effect and may have potential beneficial effects in the treatment of morphine dependence. PMID:22105846

Rauf, Khalid; Subhan, Fazal; Sewell, Robert D E

2011-11-22

102

Neurotransmitters, psychotropic drugs and microglia: clinical implications for psychiatry.  

PubMed

Psychiatric disorders have long and dominantly been regarded to be induced by disturbances of neuronal networks including synapses and neurotransmitters. Thus, the effects of psychotropic drugs such as antipsychotics and antidepressants have been understood to modulate synaptic regulation via receptors and transporters of neurotransmitters such as dopamine and serotonin. Recently, microglia, immunological/inflammatory cells in the brain, have been indicated to have positive links to psychiatric disorders. Positron emission tomography (PET) imaging and postmortem studies have revealed microglial activation in the brain of neuropsychiatric disorders such as schizophrenia, depression and autism. Animal models of neuropsychiatric disorders have revealed the underlying microglial pathologies. In addition, various psychotropic drugs have been suggested to have direct effects on microglia. Until now, the relationship between microglia, neurotransmitters and psychiatric disorders has not been well understood. Therefore, in this review, at first, we summarize recent findings of interaction between microglia and neurotransmitters such as dopamine, serotonin, norepinephrine, acetylcholine and glutamate. Next, we introduce up-to-date knowledge of the effects of psychotropic drugs such as antipsychotics, antidepressants and antiepileptics on microglial modulation. Finally, we propose the possibility that modulating microglia may be a key target in the treatment of various psychiatric disorders. Further investigations and clinical trials should be conducted to clarify this perspective, using animal in vivo studies and imaging studies with human subjects. PMID:23157624

Kato, T A; Yamauchi, Y; Horikawa, H; Monji, A; Mizoguchi, Y; Seki, Y; Hayakawa, K; Utsumi, H; Kanba, S

2013-01-01

103

Comodulation of dopamine and serotonin on prefrontal cortical rhythms: a theoretical study  

PubMed Central

The prefrontal cortex (PFC) is implicated to play an important role in cognitive control. Abnormal PFC activities and rhythms have been observed in some neurological and neuropsychiatric disorders, and evidences suggest influences from the neuromodulators dopamine (DA) and serotonin (5-HT). Despite the high level of interest in these brain systems, the combined effects of DA and 5-HT modulation on PFC dynamics remain unknown. In this work, we build a mathematical model that incorporates available experimental findings to systematically study the comodulation of DA and 5-HT on the network behavior, focusing on beta and gamma band oscillations. Single neuronal model shows pyramidal cells with 5-HT1A and 2A receptors can be non-monotonically modulated by 5-HT. Two-population excitatory-inhibitory type network consisting of pyramidal cells with D1 receptors can provide rich repertoires of oscillatory behavior. In particular, 5-HT and DA can modulate the amplitude and frequency of the oscillations, which can emerge or cease, depending on receptor types. Certain receptor combinations are conducive for the robustness of the oscillatory regime, or the existence of multiple discrete oscillatory regimes. In a multi-population heterogeneous model that takes into account possible combination of receptors, we demonstrate that robust network oscillations require high DA concentration. We also show that selective D1 receptor antagonists (agonists) tend to suppress (enhance) network oscillations, increase the frequency from beta toward gamma band, while selective 5-HT1A antagonists (agonists) act in opposite ways. Selective D2 or 5-HT2A receptor antagonists (agonists) can lead to decrease (increase) in oscillation amplitude, but only 5-HT2A antagonists (agonists) can increase (decrease) the frequency. These results are comparable to some pharmacological effects. Our work illustrates the complex mechanisms of DA and 5-HT when operating simultaneously through multiple receptors.

Wang, Da-Hui; Wong-Lin, KongFatt

2013-01-01

104

Running wheel exercise ameliorates methamphetamine-induced damage to dopamine and serotonin terminals.  

PubMed

Repeated administration of methamphetamine (mAMPH) to rodents in a single-day "binge" produces long-lasting damage to dopaminergic and serotonergic terminals. Because previous research has demonstrated that physical activity can ameliorate nigrostriatal injury, this study investigated whether voluntary exercise in rats can alter the monoaminergic damage resulting from a neurotoxic mAMPH binge. Adult male rats were allowed constant access to running wheels or kept in nonwheel cages for three weeks, then given a binge dosing regimen of mAMPH or saline. The rats were returned to their original environments for three additional weeks post-mAMPH. [(125) I]RTI-55 binding and autoradiography was used to quantify dopamine transporters (DAT), and radioimmunocytochemistry was used to quantify striatal tyrosine hydroxylase (TH). Binge mAMPH treatment significantly reduced striatal DAT and TH in a regionally specific pattern; with greatest effects in ventral caudate-putamen (CP) and relative sparing of the nucleus accumbens septi (NAc). The effects of mAMPH on striatal DAT and TH were ameliorated in the running, compared to the sedentary, animals. Also, mAMPH was found to reduce [(125) I]RTI-55 binding to serotonin transporters (SERT) in frontoparietal cortex, and this too was significantly attenuated by exercise. Additional correlational analyses showed that the post-mAMPH running of individual animals predicted the amelioration of striatal DAT and TH as well as frontoparietal SERT. Overall, voluntary exercise significantly diminished mAMPH-induced forebrain monoaminergic damage. The significant correlations between post-mAMPH exercise and markers of monoaminergic terminal integrity provide novel evidence that voluntary exercise may exert beneficial effects on behavior in recovering mAMPH addicts. PMID:21953518

O'Dell, Steven J; Galvez, Bryan A; Ball, Alexander J; Marshall, John F

2011-11-03

105

Lack of evidence for reduced prefrontal cortical serotonin and dopamine efflux after acute tryptophan depletion  

PubMed Central

Rationale Acute tryptophan depletion (ATD) is a widely used method to study the role of serotonin (5-HT) in affect and cognition. ATD results in a strong but transient decrease in plasma tryptophan and central 5-HT synthesis and availability. Although its use is widespread, the evidence that the numerous functional effects of ATD are caused by actual changes in 5-HT neuronal release is not very strong. Thus far, decreases in 5-HT efflux (thought to reflect synaptic release) were only reported after chronic tryptophan depletion or when ATD was combined with blockade of 5-HT reuptake. Objective With the current experiment, we aimed to study the validity of the method of ATD by measuring the extent to which it reduces the efflux of 5-HT (and dopamine) in the prefrontal cortex in the absence of reuptake blockage. Materials and methods We simultaneously measured in freely moving animals plasma tryptophan via a catheter in the jugular vein and 5-HT and DA efflux in the medial prefrontal cortex through microdialysis after ATD treatment. Results ATD reduced plasma tryptophan to less than 30% of control, without affecting 5-HT or DA efflux in the prefrontal cortex, indicating that even strong reductions of plasma tryptophan do not necessarily result in decreases in central 5-HT efflux. Conclusion The present experiment showed that reductions in plasma tryptophan, similar to values associated with behavioural effects, do not necessarily reduce 5-HT efflux and suggest that the cognitive and behavioural effects of ATD may not be (exclusively) due to alterations in 5-HT release.

Meerkerk, Dorie (T). J.; Lieben, Cindy K. J.; Blokland, Arjan; Feenstra, Matthijs G. P.

2007-01-01

106

Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients  

Microsoft Academic Search

Rationale  Perphenazine, a classical antipsychotic drug, has the potential to induce extrapyramidal side effects (EPS). Dopaminergic\\u000a and serotonergic pathways are involved in the therapeutic and adverse effects of the drug.\\u000a \\u000a \\u000a \\u000a Objectives  To evaluate the impact of polymorphisms in the dopamine D2 and D3 and serotonin 2A and 2C receptor genes (DRD2, DRD3, HTR2A, and HTR2C) on short-term effects of perphenazine monotherapy in

Arzu Gunes; Maria Gabriella Scordo; Peeter Jaanson; Marja-Liisa Dahl

2007-01-01

107

Pharmacodynamic interactions between MDMA and concomitants in MDMA tablets on extracellular dopamine and serotonin in the rat brain.  

PubMed

3,4-methylenedioxymethamphetamine (MDMA) is a psychoactive stimulant abused by young people as the recreational drug ecstasy. Other compounds, either deliberately added or present as byproducts, are often found in MDMA tablets and can unexpectedly interact with each other. The aim of this study was to evaluate the pharmacodynamic effects of interactions caused by concomitants in MDMA tablets on extracellular dopamine and serotonin (5-HT) by microdialysis in the striatum of ethylcarbamate-anesthetized rats. Baseline levels of dopamine and 5-HT in the striatum were 16.5±7.7 and 3.5±1.7 nM (mean±standard deviation), respectively. After a single administration of MDMA (10 mg/kg, i.p.), a dramatic increase in extracellular dopamine (Cmax: 36.1-fold vs. baseline) and 5-HT levels (Cmax: 9.3-fold vs. baseline) was observed. When rats were co-administered with methamphetamine (1, 5 or 10 mg/kg) with MDMA, the dopamine levels induced by MDMA increased in a methamphetamine-dose-dependent manner (Cmax: 2.5-, 3.5-, and 3.8-fold vs. MDMA). A similar trend was observed in 5-HT levels (Cmax: 1.1-, 1.3-, and 1.8-fold vs. MDMA). In contrast, ketamine and caffeine showed synergistic effects on the monoamine levels induced by MDMA, whereas the individual administration of either of these compounds did not affect monoamine levels. Ketamine (1, 5 mg/kg) decreased the dopamine levels induced by MDMA (Cmax: 0.9- and 0.7-fold vs. MDMA) and increased the 5-HT levels induced by MDMA (Cmax: 1.4- and 1.6-fold vs. MDMA), and co-administration of caffeine (20 mg/kg) with MDMA increased dopamine levels (Cmax: 1.7-fold vs. MDMA). These results suggest that exposure to multiple drugs in addition to MDMA can have neurotoxic effects. PMID:21497593

Ikeda, Rie; Igari, Yoshiko; Fuchigami, Yuki; Wada, Mitsuhiro; Kuroda, Naotaka; Nakashima, Kenichiro

2011-04-09

108

Serotonin Promotes the Differentiation of Glutamate Neurons in Organotypic Slice Cultures of the Developing Cerebral Cortex  

Microsoft Academic Search

The monoamines serotonin (5-HT), noradrenaline (NA), and dopamine (DA), which are present in the developing brain ap- parently before they assume their neurotransmitter functions, are regarded as strong candidates for a role in the maturation of the cerebral cortex. Here we sought to investigate their effects on the generation and differentiation of cortical cell types. Slice cultures, prepared from the

Alexandros A. Lavdas; Mary E. Blue; Jill Lincoln; John G. Parnavelas

1997-01-01

109

Neurotrophic actions of dopamine on the development of a serotonergic feeding circuit in Drosophila melanogaster  

PubMed Central

Background In the fruit fly, Drosophila melanogaster, serotonin functions both as a neurotransmitter to regulate larval feeding, and in the development of the stomatogastric feeding circuit. There is an inverse relationship between neuronal serotonin levels during late embryogenesis and the complexity of the serotonergic fibers projecting from the larval brain to the foregut, which correlate with perturbations in feeding, the functional output of the circuit. Dopamine does not modulate larval feeding, and dopaminergic fibers do not innervate the larval foregut. Since dopamine can function in central nervous system development, separate from its role as a neurotransmitter, the role of neuronal dopamine was assessed on the development, and mature function, of the 5-HT larval feeding circuit. Results Both decreased and increased neuronal dopamine levels in late embryogenesis during development of this circuit result in depressed levels of larval feeding. Perturbations in neuronal dopamine during this developmental period also result in greater branch complexity of the serotonergic fibers innervating the gut, as well as increased size and number of the serotonin-containing vesicles along the neurite length. This neurotrophic action for dopamine is modulated by the D2 dopamine receptor expressed during late embryogenesis in central 5-HT neurons. Animals carrying transgenic RNAi constructs to knock down both dopamine and serotonin synthesis in the central nervous system display normal feeding and fiber architecture. However, disparate levels of neuronal dopamine and serotonin during development of the circuit result in abnormal gut fiber architecture and feeding behavior. Conclusions These results suggest that dopamine can exert a direct trophic influence on the development of a specific neural circuit, and that dopamine and serotonin may interact with each other to generate the neural architecture necessary for normal function of the circuit.

2012-01-01

110

Dopamine and serotonin receptors measured in vivo in Huntington's Disease with C-11 n-methylspiperone PET imaging  

SciTech Connect

Thirteen patients with the clinical diagnosis of Huntington's Disease (HD) and nine persons at risk to develop the disease were studied by positron emission tomography (PET) after administration of /sup 11/C-n-methylspiperone (NMSP), a tracer with a high affinity for D2 dopamine and, to a lesser degree, for S2 serotonin receptors. All subjects had an X-ray CT scan for positioning and to assess caudate size. Dopamine and serotonin receptor binding (D2 and S2) were estimated by the caudate/cerebellum activity ratio at 43 min. post injection (CA/CB), and frontal cortex/cerebellum (FR/CB), respectively. CA/CB's of HD pts. were lower than age and sex matched controls. However, when corrected by recovery coefficients (RC) for our PET using CT dimensions of the caudate, CA/CB's were higher than normal. The relative total number of D2 receptors (estimated by CA/CB x CT caudate volume) was lower than the controls without or with RC correction.

Wong, D.F.; Links, J.M.; Wanger, H.N. Jr.; Folstein, S.E.; Suneja, S.; Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Tune, L.E.; Pearlson, G.

1985-05-01

111

MPTP-induced hippocampal effects on serotonin, dopamine, neurotrophins, adult neurogenesis and depression-like behavior are partially influenced by fluoxetine in adult mice.  

PubMed

In Parkinson's disease the loss of dopamine induces motor impairment but also leads to non-motor symptoms such as cognitive impairment, anxiety and depression. Selective serotonine reuptake inhibitors (SSRI) are so far first line therapy for mood alterations in PD and have also been shown to influence cognition, however with often insufficient results due to yet not fully understood underlying pathomechanisms of the symptoms. Deficits in the generation and maturation of new neurons in the adult hippocampus seem to be key mechanisms of major depression and cognitive decline and are robustly influenced by serotonergic pharmacotherapy. In this study we analyzed the effects of a short- and long-term treatment with the SSRI fluoxetine on changes of hippocampal precursor maturation, neurotransmitter-receptor mRNA-expression, neurotrophin levels and clinical symptoms in the MPTP-mouse model for PD. The generation of neuronal precursors as well as the absolute numbers of endogenous immature neurons increased following MPTP and were further elevated by fluoxetine. Net neurogenesis however, impaired after MPTP, remained unchanged by fluoxetine treatment. Fluoxetine induced microenvironmental changes in the hippocampus that might be involved in enhanced precursor generation involved increased contents of the neurotrophins VEGF and BDNF and decreased hippocampal expression of the 5HT1a receptor mRNA and the D2 receptor mRNA. Clinically, we were not able to detect any differences in anxiety or depressive behavior in MPTP animals compared to controls which is in line with previous studies indicating that neuropsychiatric symptoms in PD are difficult to assess in rodents due to their clinical characteristics and involvement of several brain regions. Taken together, we show that fluoxetine partially enhances brain's capacity to counteract MPTP-induced neurodegeneration by increasing the endogenous pool of immature neurons and upregulating neural precursor cell generation. The mechanisms underlying this phenomenon and the link to the clinical use of fluoxetine in PD remain to be further elucidated. PMID:22520437

Lesemann, Anne; Reinel, Claudia; Hühnchen, Petra; Pilhatsch, Maximilian; Hellweg, Rainer; Klaissle, Philipp; Winter, Christine; Steiner, Barbara

2012-03-27

112

Effects of Perinatal Exposure to Bisphenol A on Brain Neurotransmitters in Female Rat Offspring  

Microsoft Academic Search

Pregnant Sprague-Dawley (CD IGS) rats were orally administered doses of bisphenol A (BPA) at 4, 40, and 400 mg\\/kg, from gestation days 6 to postnatal day 20. Neurotransmitters such as dopamine (DA) and serotonin (5HT) were extracted from the brains of dams and female offspring, and measured using liquid chromatography. BPA at 400 mg\\/kg was toxic and dosed rats died.

Takeshi HONMA; Muneyuki MIYAGAWA; Megumi SUDA; Rui-Sheng WANG; Kenichi KOBAYASHI; Soichiro SEKIGUCHI

2006-01-01

113

Serotonin (5HT), Fluoxetine, Imipramine and Dopamine Target Distinct 5HT Receptor Signaling to Modulate Caenorhabditis elegans Egg-Laying Behavior  

Microsoft Academic Search

Drugs that target the serotonergic system are the most commonly prescribed therapeutic agents and are used for treatment of a wide range of behavioral and neurological disorders. However, the mechanism of the drug action remain a conjecture. Here, we dissect the genetic targets of serotonin (5HT), the selective 5HT reuptake inhibitor (SSRI) fluoxetine (Prozac), the tricyclic antidepressant imipramine, and dopamine.

Catherine M. Dempsey; Scott M. Mackenzie; Andrew Gargus; Gabriela Blanco; Ji Ying Sze

2004-01-01

114

Radiotracers for PET and SPECT studies of neurotransmitter systems  

SciTech Connect

The study of neurotransmitter systems is one of the major thrusts in emission tomography today. The current generation of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) radiotracers examines neurotransmitter properties from a number of different perspectives including their pre and post synaptic sites and the activity of the enzymes which regulate their concentration. Although the dopamine system has been the most extensively investigated, other neurotransmitter systems including the acetylcholine muscarine, serotonin, benzodiazepine, opiate, NMDA and others are also under intensive development. Enzymes involved in the synthesis and regulation of neurotransmitter concentration, for example monoamine oxidase and amino acid decarboxylase has also been probed in vivo. Medical applications range from the study of normal function and the characterization of neurotransmitter activity in neurological and psychiatric diseases and in heart disease and cancer to the study of the binding of therapeutic drugs and substances of abuse. This chapter will provide an overview of the current generation of radiotracers for PET and SPECT studies of neurotransmitter systems including radiotracer design, synthesis localization mechanisms and applications in emission tomography. 60 refs., 1 tab.

Fowler, J.S.

1991-01-01

115

SLC6 neurotransmitter transporters: structure, function, and regulation.  

PubMed

The neurotransmitter transporters (NTTs) belonging to the solute carrier 6 (SLC6) gene family (also referred to as the neurotransmitter-sodium-symporter family or Na(+)/Cl(-)-dependent transporters) comprise a group of nine sodium- and chloride-dependent plasma membrane transporters for the monoamine neurotransmitters serotonin (5-hydroxytryptamine), dopamine, and norepinephrine, and the amino acid neurotransmitters GABA and glycine. The SLC6 NTTs are widely expressed in the mammalian brain and play an essential role in regulating neurotransmitter signaling and homeostasis by mediating uptake of released neurotransmitters from the extracellular space into neurons and glial cells. The transporters are targets for a wide range of therapeutic drugs used in treatment of psychiatric diseases, including major depression, anxiety disorders, attention deficit hyperactivity disorder and epilepsy. Furthermore, psychostimulants such as cocaine and amphetamines have the SLC6 NTTs as primary targets. Beginning with the determination of a high-resolution structure of a prokaryotic homolog of the mammalian SLC6 transporters in 2005, the understanding of the molecular structure, function, and pharmacology of these proteins has advanced rapidly. Furthermore, intensive efforts have been directed toward understanding the molecular and cellular mechanisms involved in regulation of the activity of this important class of transporters, leading to new methodological developments and important insights. This review provides an update of these advances and their implications for the current understanding of the SLC6 NTTs. PMID:21752877

Kristensen, Anders S; Andersen, Jacob; Jørgensen, Trine N; Sørensen, Lena; Eriksen, Jacob; Loland, Claus J; Strømgaard, Kristian; Gether, Ulrik

2011-07-13

116

Detection and Monitoring of Neurotransmitters - a Spectroscopic Analysis  

NASA Astrophysics Data System (ADS)

In this work we demonstrate the capability of confocal Raman mapping spectroscopy for simultaneously and locally detecting important compounds in neuroscience such as dopamine, serotonin, and adenosine. The Raman results show shifting of the characteristic vibrations of the compounds, observations consistent with previous spectroscopic studies. Although some vibrations are common in these neurotransmitters, Raman mapping was achieved by detecting non-overlapping characteristic spectral signatures of the compounds, as follows: for dopamine the vibration attributed to C-O stretching, for serotonin the indole ring stretching vibration, and for adenosine the adenine ring vibrations. Without damage, dyeing, or preferential sample preparation, confocal Raman mapping provided positive detection of each neurotransmitter, allowing association of the high-resolution spectra with specific micro-scale image regions. Such information is particularly important for complex, heterogeneous samples, where modification of the chemical or physical composition can influence the neurotransmission processes. We also report an estimated dopamine diffusion coefficient two orders of magnitude smaller than that calculated by the flow-injection method.

Manciu, Felicia; Lee, Kendall; Durrer, William; Bennet, Kevin

2012-10-01

117

Alterations in central fatigue by pharmacological manipulations of neurotransmitters in normal and high ambient temperature.  

PubMed

The scientific evidence is reviewed for the involvement of the brain monoamines serotonin, dopamine and noradrenaline (norepinephrine) in the onset of fatigue, in both normal and high ambient temperatures. The main focus is the pharmacological manipulations used to explore the central fatigue hypothesis. The original central fatigue hypothesis emphasizes that an exercise-induced increase in serotonin is responsible for the development of fatigue. However, several pharmacological studies attempted and failed to alter exercise capacity through changes in serotonergic neurotransmission in humans, indicating that the role of serotonin is often overrated. Recent studies, investigating the inhibition of the reuptake of both dopamine and noradrenaline, were capable of detecting changes in performance, specifically when ambient temperature was high. Dopamine and noradrenaline are prominent in innervated areas of the hypothalamus, therefore changes in the catecholaminergic concentrations may also be expected to be involved with the regulation of body core temperature during exercise in the heat. Evidence from different studies suggests that it is very unlikely that one neurotransmitter system is responsible for the appearance of central fatigue. The exact mechanism of fatigue is not known; presumably a complex interplay between both peripheral and central factors induces fatigue. Central fatigue will be determined by the collaboration of the different neurotransmitter systems, with the most important role possibly being for the catecholamines dopamine and noradrenaline. PMID:20199121

Roelands, Bart; Meeusen, Romain

2010-03-01

118

The role of endogenous serotonin in methamphetamine-induced neurotoxicity to dopamine nerve endings of the striatum.  

PubMed

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the striatum where long-term DA depletion and microglial activation are maximal. Endogenous DA has been implicated as a critical participant in METH-induced neurotoxicity, most likely as a substrate for non-enzymatic oxidation by METH-generated reactive oxygen species. The striatum is also extensively innervated by serotonin (5HT) nerve endings and this neurochemical system is modified by METH in much the same manner as seen in DA nerve endings (i.e., increased release of 5HT, loss of function in tryptophan hydroxylase and the serotonin transporter, long-term depletion of 5HT stores). 5HT can also be modified by reactive oxygen species to form highly reactive species that damage neurons but its role in METH neurotoxicity has not been assessed. Increases in 5HT levels with 5-hydroxytryptophan do not change METH-induced neurotoxicity to the DA nerve endings as revealed by reductions in DA, tyrosine hydroxylase and dopamine transporter levels. Partial reductions in 5HT with p-chlorophenylalanine are without effect on METH toxicity, despite the fact that p-chlorophenylalanine largely prevents METH-induced hyperthermia. Mice lacking the gene for brain tryptophan hydroxylase 2 are devoid of brain 5HT and respond to METH in the same manner as wild-type controls, despite showing enhanced drug-induced hyperthermia. Taken together, the present results indicate that endogenous 5HT does not appear to play a role in METH-induced damage to DA nerve endings of the striatum. PMID:20722968

Thomas, David M; Angoa Pérez, Mariana; Francescutti-Verbeem, Dina M; Shah, Mrudang M; Kuhn, Donald M

2010-09-06

119

Cholecystokinin combined with serotonin in the hypothalamus limits accumbens dopamine release while increasing acetylcholine: a possible satiation mechanism.  

PubMed

Serotonin (5-HT) or cholecystokinin (CCK) injected in the hypothalamic paraventricular nucleus (PVN) inhibits feeding, but the mechanism is unknown. Prior research suggests that dopamine (DA) input to the nucleus accumbens (NAc) motivates behavior, and a component of that motivation circuit includes hypothalamic feeding systems. Acetylcholine (ACh) in the NAc, on the other hand, may act in part to inhibit feeding and generate satiety. If so, 5-HT and/or CCK in the PVN should lower extracellular DA or release ACh in the NAc. Rats were prepared with microdialysis probes in the NAc and injectors in the PVN. Serotonin (7.75 microg) or CCK-8 (0.12 microg) injected in the PVN significantly decreased ipsilateral accumbens DA (63 and 73% of baseline, respectively, without effect on ACh). However, 5-HT plus CCK injected in combination decreased DA to 72% (P<0.001) and simultaneously increased extracellular ACh to 128% of baseline (P<0.001). In later tests with the same doses and the same animals, unilateral PVN injections of 5-HT, CCK, or both combined, significantly inhibited food intake in the early dark period. The results suggest that 5-HT in the PVN acts as a neural modulator that primes a hypothalamic satiation system to respond to CCK when the gastrointestinal tract contains food to be digested. The synergistic action of 5-HT plus phasic CCK may then activate a circuit that simultaneously limits DA and releases ACh in the accumbens as part of the satiation process. PMID:12560135

Helm, Katherine A; Rada, Pedro; Hoebel, Bartley G

2003-02-14

120

Variations of dopamine, serotonin, and amino acid concentrations in Noda epileptic rat (NER) retina  

Microsoft Academic Search

Noda epileptic rats (NER) exhibit frequent spontaneous tonic–clonic convulsions which represent a valuable model of human epilepsy. If implication of brain neurotransmitters was largely reported, little is known about retina. However, it has been reported that human epilepsy syndrome varies not only with the location of seizure foci but also according to rhythmic patterns, for which retina has a major

Evelyne Chanut; Benoît Labarthe; Brigitte Lacroix; Atsuhi Noda; Sylvie Gasdeblay; Jean-Robert Bondier; Claudine Versaux-Botteri

2006-01-01

121

Plasma neurotransmitters and cortisol in duodenal ulcer patients  

Microsoft Academic Search

Levels of noradrenaline, adrenaline, dopamine, free serotonin, platelet serotonin, and cortisol were measured in the plasma of duodenal ulcer patients and controls. All subjects received antacids, and these substances were also measured. During relapse, all patients showed raised noradrenaline, adrenaline, dopamine, free serotonin, and cortisol values. In contrast, platelet serotonin showed very low values, which correlated negatively with all the

Fuad Lechin; Bertha van der Dijs; Isaìs Rada; Hector Jara; Alex E. Lechin; Alejandra Cabrera; Marcel E. Lechin; Vladimir Jimènez; Francisco Gòmez; Simòn Villa; Emilio Acosta; Luis Arocha

1990-01-01

122

Polymorphisms of the dopamine D2 receptor, serotonin transporter, and GABA A receptor ? 3 subunit genes and alcoholism in Mexican-Americans  

Microsoft Academic Search

The etiology of alcohol dependence is a complex interaction of psychosocial and biologic factors. To study the impact of genetic factors that play an important role in an individual's vulnerability to alcohol abuse and dependence, we examined the genetic variations of the major neurotransmitter genes, including the dopamine D2 receptor (DRD2) TaqI A, B, and -141C insertion\\/deletion (Ins\\/Del) polymorphisms, the

Tamiko Konishi; Maria Calvillo; Ai-She Leng; Keh-Ming Lin; Yu-Jui Yvonne Wan

2004-01-01

123

USE OF SEROTONIN (5HT) AND OPIATE-BASED DRUGS IN THE PHARMACOTHERAPY OF ALCOHOL DEPENDENCE: AN OVERVIEW OF THE PRECLINICAL DATA  

Microsoft Academic Search

Numerous neurotransmitter systems (e.g. dopamine, y-aminobutyric acid (GABA), the endogenous opioids, and serotonin (5-hydroxytryptamine, 5-HT)) are involved in the regulation of alcohol consumption. Because 5-HT reuptalce inhibitors and opioid antagonists modify the activity of neurotransmitters, it has been hypothesized that they may also mediate the desire to drink alcohol by acting on specific receptors in the brain. Animal studies have

ANH DZUNG LE; DENISE M. TOMKINS; EDWARD M. SELLERS

1996-01-01

124

Neurotransmitter transporters: fruitful targets for CNS drug discovery  

Microsoft Academic Search

More than 20 members have been identified in the neurotransmitter transporter family. These include the cell surface re-uptake mechanisms for monoamine and amino acid neurotransmitters and vesicular transporter mechanisms involved in neurotransmitter storage. The norepinephrine and serotonin re-uptake transporters are key targets for antidepressant drugs. Clinically effective antidepressants include those with selectivity for either NE or serotonin uptake, and compounds

L Iversen

2000-01-01

125

Associations between Dopamine and Serotonin Genes and Job Satisfaction: Preliminary Evidence from the Add Health Study  

ERIC Educational Resources Information Center

|Previous behavioral genetic studies have found that job satisfaction is partially heritable. We went a step further to examine particular genetic markers that may be associated with job satisfaction. Using an oversample from the National Adolescent Longitudinal Study (Add Health Study), we found 2 genetic markers, dopamine receptor gene DRD4 VNTR…

Song, Zhaoli; Li, Wendong; Arvey, Richard D.

2011-01-01

126

Serotonin and Dopamine Play Complementary Roles in Gambling to Recover Losses  

Microsoft Academic Search

Continued gambling to recover losses—‘loss chasing’—is a prominent feature of social and pathological gambling. However, little is known about the neuromodulators that influence this behavior. In three separate experiments, we investigated the role of serotonin activity, D2\\/D3 receptor activity, and beta-adrenoceptor activity on the loss chasing of age and IQ-matched healthy adults randomized to treatment or an appropriate control\\/placebo. In

Daniel Campbell-Meiklejohn; Judi Wakeley; Vanessa Herbert; Jennifer Cook; Paolo Scollo; Manaan Kar Ray; Sudhakar Selvaraj; Richard E Passingham; Phillip Cowen; Robert D Rogers

2011-01-01

127

Effects of local and repeated systemic administration of (?)nicotine on extracellular levels of acetylcholine, norepinephrine, dopamine, and serotonin in rat cortex  

Microsoft Academic Search

Systemically administered (-)nicotine (0.2–1.2 mg\\/kg, s.c.) significantly increased the release of acetylcholine (ACh), norepinephrine (NE) and dopamine (DA) in rat cortex. The lowest dose of (-)nicotine examined (0.2 mg\\/kg, s.c) also significantly elevated extracellular serotonin (5-HT) levels, and the maximal increases of extracellular ACh (122% at 90 min post injection) and DA levels (249% at 120 min post-injection) were observed

K. L. Summers; E. Giacobini

1995-01-01

128

Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (±)3,4-methylenedioxymethamphetamine (“ecstasy”) users: relationship to cognitive performance  

Microsoft Academic Search

Background  (±)3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a recreational drug and brain serotonin (5-HT) neurotoxin. Under\\u000a certain conditions, MDMA can also damage brain dopamine (DA) neurons, at least in rodents. Human MDMA users have been found\\u000a to have reduced brain 5-HT transporter (SERT) density and cognitive deficits, although it is not known whether these are related.\\u000a This study sought to determine whether MDMA

Una D. McCann; Zsolt Szabo; Melin Vranesic; Michael Palermo; William B. Mathews; Hayden T. Ravert; Robert F. Dannals; George A. Ricaurte

2008-01-01

129

Behavioural and Biochemical Changes in the Feeding System of Lymnaea Induced by the Dopamine and Serotonin Neurotoxins 6-hydroxydopamine and 5,6-dihydroxytryptamine  

Microsoft Academic Search

The neurotoxins 5,6-dihydroxytryptamine (5,6-DHT) and 6-hydroxydopamine (6-OH-DA) were used to examine the role of monoamines in the feeding system of the snail Lymnaea stagnalis. Biting responses to sucrose were monitored up to 25 days after injection with drugs. Cerebral and buccal ganglia and cerebro-buccal connectives from the same groups of snails were examined for changes in serotonin and dopamine levels

G. Kemenes; L. Hiripi; P. R. Benjamin

1990-01-01

130

Neurotransmitters couple brain activity to subventricular zone neurogenesis  

PubMed Central

Adult neurogenesis occurs in two privileged microenvironments, the hippocampal subgranular zone of the dentate gyrus and the subventricular zone (SVZ) along the lateral ventricle. This review focuses on accumulating evidence suggesting that the activity of specific brain regions or bodily states influences SVZ cell proliferation and neurogenesis. Neuromodulators such as dopamine and serotonin have been shown to have long-range effects through neuronal projections into the SVZ. Local GABA and glutamate signaling have demonstrated effects on SVZ proliferation and neurogenesis, but an extra-niche source of these neurotransmitters remains to be explored and options will be discussed. There is also accumulating evidence that diseases and bodily states such as Alzheimer's disease, seizures, sleep, and pregnancy influence SVZ cell proliferation. With such complex behavior and environmentally-driven factors that control subregion-specific activity, it will become necessary to account for overlapping roles of multiple neurotransmitter systems on neurogenesis when developing cell therapies or drug treatments.

Young, Stephanie Z.; Taylor, M. Morgan; Bordey, Angelique

2011-01-01

131

MDMA-evoked changes in the binding of dopamine D(2) receptor ligands in striatum of rats with unilateral serotonin depletion.  

PubMed

We earlier reported an anomalous 50% decrease in [(11)C]N-methylspiperone ([(11)C]NMSP) binding to dopamine D(2)-like receptors in living pig striatum after challenge with 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), suggesting either (1) a species peculiarity in the vulnerability of butyrophenone binding to competition from dopamine or (2) a novel consequence of synergistic actions of serotonin and dopamine at dopamine receptors. To distinguish these possibilities, we used microPET to test the vulnerability of [(11)C]NMSP binding in striatum of rats with unilateral telencephalic serotonin lesions, later verified by [(125)I]RTI-55 autoradiography. Baseline [(11)C]NMSP microPET recordings were followed by either saline or MDMA-HCl (4 mg/kg) injections (i.v.), and a second [(11)C]NMSP recording, culminating with injection of [(3)H]raclopride for autoradiography ex vivo. Neither MDMA-challenge nor serotonin lesion had any detectable effect on [(11)C]NMSP binding. In contrast, MDMA challenge increased receptor occupancy by [(3)H]raclopride ex vivo (relative to the B(max) in vitro) from 8% to 12%, and doubled the free ligand concentration in cerebral cortex, apparently by blocking hepatic CYP2D6. Assuming a single binding-site model, the increased [(3)H]raclopride binding indicated doubling of the apparent equilibrium dissociation constant in vivo (K(app) (d)), revealing a 2-fold increase in competition from endogenous dopamine at [(3)H]raclopride binding sites. The results favor hypothesis (1) that the remarkable vulnerability of [(11)C]NMSP binding in pig striatum to MDMA challenge does not generalize to the rodent. PMID:19768811

Ostergaard, Søren Dinesen; Alstrup, Aage Kristian Olsen; Gramsbergen, Jan Bert; Minuzzi, Luciano; Pedersen, Kasper; Jensen, Svend Borup; Doudet, Doris; Cumming, Paul

2010-01-01

132

Brain serotonin and dopamine modulators, perceptual responses and endurance performance during exercise in the heat following creatine supplementation  

Microsoft Academic Search

BACKGROUND: The present experiment examined the responses of peripheral modulators and indices of brain serotonin (5-HT) and dopamine (DA) function and their association with perception of effort during prolonged exercise in the heat after creatine (Cr) supplementation. METHODS: Twenty one endurance-trained males performed, in a double-blind fashion, two constant-load exercise tests to exhaustion at 63 ± 5% V?\\u000a MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafeOvayLbaiaaaaa@2D11@O2 max

Marios Hadjicharalambous; Liam P Kilduff; Yannis P Pitsiladis

2008-01-01

133

Simultaneous determination of serotonin and dopamine at the PEDOP/MWCNTs-Pd nanoparticle modified glassy carbon electrode.  

PubMed

Electrochemical determination of dopamine (DA) and serotonin (5-HT) have been studied at a modified glassy carbon electrode (GCE) in 0.1 M phosphate buffer solution (PBS) using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) at pH 7.4, all over the interfering biomolecule ascorbic acid (AA). The GCE was modified by palladium-functionalized, multi-walled carbon nanotubes (MWCNTs-Pd) with electrochemical deposition of poly 3,4-ethylenedioxy pyrrole (PEDOP), denoted as PEDOP/MWCNTs-Pd/GCE, and investigated by SEM and EIS experiments. The highly electrocatalytic activity of the modified electrode toward 5-HT and DA was demonstrated from the sensitive and well-separated voltammetric experiment. The oxidation peaks found were 0.165 and 0.355 mV for DA and 5-HT, respectively. The composite film shows a significant accumulation effects on two species, as well as the mutual interference among the analytes. This biosensor was best in response compared to other modified electrodes made in the same lab. The lowest detection limits were found to be 5.0 x 10(-9) and 1.0 x 10(-8) for 5-HT and DA, respectively. The respective linear ranges were determined as 1.0 x 10(-7) to 2.0 x 10(-4) and 1.0 x 10(-7) to 2.0 x 10(-4) for 5-HT and DA. PMID:22754997

Kim, Seul Ki; Jeon, Seungwon

2012-03-01

134

Modulation of monoamine neurotransmitters in fighting fish Betta splendens exposed to waterborne phytoestrogens.  

PubMed

Endogenous estrogens are known to affect the activity of monoamine neurotransmitters in vertebrate animals, but the effects of exogenous estrogens on neurotransmitters are relatively poorly understood. We exposed sexually mature male fighting fish Betta splendens to environmentally relevant and pharmacological doses of three phytoestrogens that are potential endocrine disruptors in wild fish populations: genistein, equol, and ?-sitosterol. We also exposed fish to two doses of the endogenous estrogen 17?-estradiol, which we selected as a positive control because phytoestrogens are putative estrogen mimics. Our results were variable, but the effects were generally modest. Genistein increased dopamine levels in the forebrains of B. splendens at both environmentally relevant and pharmacological doses. The environmentally relevant dose of equol increased dopamine levels in B. splendens forebrains, and the pharmacological dose decreased norepinephrine (forebrain), dopamine (hindbrain), and serotonin (forebrain) levels. The environmentally relevant dose of ?-sitosterol decreased norepinephrine and dopamine in the forebrain and hindbrain, respectively. Our results suggest that sources of environmental phytoestrogens, such as runoff or effluent from agricultural fields, wood pulp mills, and sewage treatment plants, have the potential to modulate neurotransmitter activity in free-living fishes in a way that could interfere with normal behavioral processes. PMID:20012186

Clotfelter, Ethan D; McNitt, Meredith M; Carpenter, Russ E; Summers, Cliff H

2009-12-11

135

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

PubMed

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. PMID:19275596

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

136

In vitro and in vivo binding of (E)- and (Z)-N-(iodoallyl)spiperone to dopamine D sub 2 and serotonin 5-HT sub 2 neuroreceptors  

SciTech Connect

Apparent affinities (K{sub i}) of (E)- and (Z)-N-(iodoallyl)spiperone ((E)- and (Z)- NIASP) for dopamine D{sub 2} and serotonin 5-HT{sub 2} receptors were determined in competition binding assays. (Z)-NIASP (K{sub i} 0.35 nM, D{sub 2}; K{sub i} 1.75 nM, 5-HT{sub 2}) proved slightly more potent and selective for D{sub 2} sites in vitro than (E)-NIASP (K{sub i} 0.72 nM, D{sub 2}; K{sub i} 1.14 nM, 5-HT{sub 2}). In vivo, radioiodinated (E)- and (Z)-({sup 125}I)-NIASP showed regional distributions in mouse brain which are consonant with prolonged binding to dopamine D{sub 2} receptors accompanied by a minor serotonergic component of shorter duration. Stereoselective, dose-dependent blockade of (E)-({sup 125}I)-NIASP uptake was found for drugs binding to dopamine D{sub 2} sites, while drugs selective for serotonin 5-HT{sub 2}, {alpha}{sub 1}-adrenergic and dopamine D{sub 1} receptors did not inhibit radioligand binding 2 hr postinjection. Specific binding in striatal tissue was essentially irreversible over the time course of the study, and (E)-({sup 125}I)-NIASP gave a striatal to cerebellar tissue radioactivity concentration of 16.9 to 1 at 6 hr postinjection. Thus, (E)-({sup 125}I)-NIASP binds with high selectivity and specificity to dopamine D{sub 2} sites in vivo.

Lever, J.R.; Scheffel, U.A.; Stathis, M.; Musachio, J.L.; Wagner, H.N. Jr. (Johns Hopkins Univ., Baltimore, MD (USA))

1990-01-01

137

Analysis of urinary neurotransmitters by capillary electrophoresis: Sensitivity enhancement using field-amplified sample injection and molecular imprinted polymer solid phase extraction  

Microsoft Academic Search

Capillary electrophoresis (CE) has been investigated for the analysis of some neurotransmitters, dopamine (DA), 3-methoxytyramine (3-MT) and serotonin (5-hydroxytryptamine, 5-HT) at nanomolar concentrations in urine. Field-amplified sample injection (FASI) has been used to improve the sensitivity through the online pre-concentration samples. The cationic analytes were stacked at the capillary inlet between a zone of low conductivity - sample and pre-injection

Bérengère Claude; Reine Nehmé; Philippe Morin

2011-01-01

138

Electrophysiological effects of repeated administration of agomelatine on the dopamine, norepinephrine, and serotonin systems in the rat brain.  

PubMed

Agomelatine is a melatonergic MT1/MT2 agonist and a serotonin (5-HT) 5-HT(2C) antagonist. The effects of 2-day and 14-day administration of agomelatine were investigated on the activity of ventral tegmental area (VTA) dopamine (DA), locus coeruleus (LC) norepinephrine (NE), and dorsal raphe nucleus (DRN) 5-HT neurons using in vivo electrophysiology in rats. The 5-HT(1A) transmission was assessed at hippocampus CA3 pyramidal neurons. After a 2-day regimen of agomelatine (40?mg/kg/day, i.p.), an increase in the number of spontaneously active VTA-DA neurons (p<0.001) and in the firing rate of LC-NE neurons (p<0.001) was observed. After 14 days, the administration of agomelatine induced an increase in: (1) the number of spontaneously active DA neurons (p<0.05), (2) the bursting activity of DA neurons (bursts/min, p<0.01 and percentage of spikes occurring in bursts, p<0.05), (3) the firing rate of DRN-5-HT neurons (p<0.05), and (4) the tonic activation of postsynaptic 5-HT(1A) receptors located in the hippocampus. The increase in 5-HT firing rate was D2 dependent, as it was antagonized by the D2 receptor antagonist paliperidone. The enhancement of NE firing was restored by the 5-HT(2A) receptor antagonist MDL-100,907 after the 14-day regimen. All the effects of agomelatine were antagonized by a single administration of the melatonergic antagonist S22153 (except for the increase in the percentage of spikes occurring in burst for DA neurons). The present results suggest that (1) agomelatine exerts direct (2 days) and indirect (14 days) modulations of monoaminergic neuronal activity and (2) the melatonergic agonistic activity of agomelatine contributes to the enhancement of DA and 5-HT neurotransmission. PMID:22871919

Chenu, Franck; El Mansari, Mostafa; Blier, Pierre

2012-08-08

139

Regional and laminar distribution of the dopamine and serotonin innervation in the macaque cerebral cortex: a radioautographic study  

SciTech Connect

The regional density and laminar distribution of dopamine (DA) and serotonin (5-HT) afferents were investigated in the cerebral cortex of cynomolgus monkeys using a radioautographic technique that is based on the high affinity uptake capacity of these aminergic neurons. Large vibratome sections, 50 micron thick, were incubated with (3H) DA (0.2 microM) and desipramine (5 microM) or with unlabeled norepinephrine (5 microM) and (3H) 5-HT (0.6 microM), which allowed for the specific labeling of the DA and 5-HT innervations, respectively. After fixation, these sections were dried, defatted, and radioautographed by dipping. Semiquantitative data on the DA innervation also were provided by counting (3H) DA-labeled axonal varicosities in radioautographs from 4-micron-thick sections of the slices obtained after epon embedding. The DA innervation was widespread and differed in density and laminar distribution in the agranular and granular cortices. DA afferents were densest in the anterior cingulate (area 24) and the motor areas (areas 4, 6, and supplementary motor area (SMA)). In the latter they displayed a trilaminar pattern of distribution, predominating in layers I, IIIa, and V-VI, with characteristic cluster-like formations in layer IIIa, especially in the medial part of motor areas. In the granular prefrontal (areas 46, 9, 10, 11, 12), parietal (areas 1, 2, 3, 5, 7), temporal (areas 21, 22), and posterior cingulate (area 23) cortices, DA afferents were less dense and showed a bilaminar pattern of distribution, predominating in the depth of layer I and in layers V-VI; density in layers II, III, and IV was only 20% of that in layer I. The lowest density was in the visual cortex, particularly in area 17, where the DA afferents were almost restricted to layer I.

Berger, B.; Trottier, S.; Verney, C.; Gaspar, P.; Alvarez, C.

1988-07-01

140

Biosynthesis of dopamine and serotonin in the rat brain after repeated cocaine injections: a microdissection mapping study.  

PubMed

The purpose of the present study was to examine the effects of chronic cocaine on dopamine (DA) and serotonin (5-HT) synthesis in several rat brain regions implicated in drug reinforcement. Male rats were treated twice daily with cocaine (15 mg/kg, ip) or saline for 1 week. After 42 hr of abstinence, rats were challenged with either cocaine (15 mg/kg, ip) or saline, followed by the aromatic L-amino acid decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD-1015; 100 mg/kg, ip). Animals were decapitated 30 min after NSD-1015 and discrete brain regions were microdisected from 300 microns frozen sections. Postmortem tissue levels of 3,4-dihydroxyphenylalanine (DOPA) and 5-hyroxytryptophan (5-HTP) were quantified by HPLC with electrochemical detection and used to estimate biosynthesis of DA and 5-HT, respectively. In chronic saline-treated rats, cocaine dramatically suppressed DA and 5-HT synthesis in all forebrain regions examined, including: medial prefrontal cortex, nucleus accumbens, caudate nucleus, olfactory tubercle, and basolateral amygdala. The degree of inhibition ranged from 35-65% and was more pronounced in 5-HT neurons compared to DA neurons in the same tissue sample. In general, chronic cocaine did not significantly alter basal levels of DOPA or 5-HTP; a notable exception was lateral hypothalamus, where chronic cocaine reduced basal DA synthesis to 75% of control. After repeated cocaine injections, the synthesis-inhibiting effect of a challenge injection of cocaine was attenuated in many brain areas. These data suggest that whereas acute cocaine decreases DA and 5-HT synthesis in forebrain, chronic cocaine is not neurotoxic to DA and 5-HT neurons. In addition, the mechanism(s) mediating cocaine-induced suppression of monoamine synthesis may become desensitized by chronic exposure to the drug. PMID:8511717

Baumann, M H; Raley, T J; Partilla, J S; Rothman, R B

1993-05-01

141

Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine D3 and serotonin 5-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior.  

PubMed

Dopamine D(3) antagonism combined with serotonin 5-HT(1A) and 5-HT(2A) receptor occupancy may represent a novel paradigm for developing innovative antipsychotics. The unique pharmacological features of 5i are a high affinity for dopamine D(3), serotonin 5-HT(1A) and 5-HT(2A) receptors, together with a low affinity for dopamine D(2) receptors (to minimize extrapyramidal side effects), serotonin 5-HT(2C) receptors (to reduce the risk of obesity under chronic treatment), and for hERG channels (to reduce incidence of torsade des pointes). Pharmacological and biochemical data, including specific c-fos expression in mesocorticolimbic areas, confirmed an atypical antipsychotic profile of 5i in vivo, characterized by the absence of catalepsy at antipsychotic dose. PMID:19072656

Butini, Stefania; Gemma, Sandra; Campiani, Giuseppe; Franceschini, Silvia; Trotta, Francesco; Borriello, Marianna; Ceres, Nicoletta; Ros, Sindu; Coccone, Salvatore Sanna; Bernetti, Matteo; De Angelis, Meri; Brindisi, Margherita; Nacci, Vito; Fiorini, Isabella; Novellino, Ettore; Cagnotto, Alfredo; Mennini, Tiziana; Sandager-Nielsen, Karin; Andreasen, Jesper Tobias; Scheel-Kruger, Jorgen; Mikkelsen, Jens D; Fattorusso, Caterina

2009-01-01

142

Involvement of dopamine (DA)/serotonin (5-HT)/sigma (sigma) receptor modulation in mediating the antidepressant action of ropinirole hydrochloride, a D2/D3 dopamine receptor agonist.  

PubMed

Multiple lines of investigation have explored the role of dopaminergic systems in mental depression. Chronic treatment with antidepressant drugs has been reported to alter dopaminergic neurotransmission, most notably a sensitization of behavioural responses to agonists acting at D2/D3 dopamine receptors within the nucleus accumbens. Recent clinical evidences have shown that ropinirole, a D2/D3 dopamine receptor agonist, augments the action of various standard antidepressant drugs in treatment-resistant depression. The present study was undertaken to elucidate the possible mechanism of antidepressant action of ropinirole employing various behavioral paradigms of despair supported by the measurements of neurochemical changes in the tissue contents of dopamine (DA) and serotonin (5-HT) in the whole brain using high-performance-liquid chromatography (HPLC) with electrochemical detectors (ECD). In the mouse forced swim test (FST) or tail-suspension test (TST), ropinirole (1-10 mg/kg, i.p.) produced S-shaped dose-response curve in the percentage decrease in immobility period. Compared with vehicle, ropinirole (10 mg/kg., i.p.) had a significant anti-immobility effect without affecting locomotor activity. The reduction in the immobility period elicited by ropinirole (10 mg/kg, i.p.) in the FST was reversed by dopaminergic and sigma receptor antagonist, haloperidol (0.5 mg/kg, i.p.), and specific D2 dopamine receptor antagonist sulpiride (5 mg/kg i.p.), but not by SCH 23390 (0.5 mg/kg i.p), a D1 dopamine receptor antagonist. Rimcazole (5 mg/kg i.p.) (a sigma receptor antagonist), progesterone (10 mg/kg i.p.) (a sigma receptor antagonistic neurosteroid), BD 1047 (1 mg/kg i.p.) (a novel sigma receptor antagonist with preferential affinity for sigma-1 sites) also reversed the anti-immobility effect of ropinirole (10 mg/kg i.p.). The neurochemical studies of whole brain revealed that ropinirole at 10 mg/kg i.p. did not affect the tissue levels of dopamine but significantly increased serotonin levels. The study indicated that ropinirole possessed anti-immobility activity in FST by altering dopaminergic, serotonergic or sigma receptor function. PMID:17683790

Dhir, Ashish; Kulkarni, S K

2007-05-30

143

Memory, mood, dopamine, and serotonin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury.  

PubMed

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse serves as a model of basal ganglia injury and Parkinson's disease. The present study investigated the effects of MPTP-induced lesioning on associative memory, conditioned fear, and affective behavior. Male C57BL/6 mice were administered saline or MPTP and separate groups were evaluated at either 7 or 30 days post-lesioning. In the social transmission of food preference test, mice showed a significant decrease in preference for familiar food 30 days post-MPTP compared to controls. Mice at both 7 and 30 days post-MPTP lesioning had increased fear extinction compared to controls. High Performance Liquid Chromatography analysis of tissues homogenates showed dopamine and serotonin were depleted in the striatum, frontal cortex, and amygdala. No changes in anxiety or depression were detected by the tail suspension, sucrose preference, light-dark preference, or hole-board tests. In conclusion, acute MPTP lesioning regimen in mice causes impairments in associative memory and conditioned fear, no mood changes, and depletion of dopamine and serotonin throughout the brain. PMID:18718537

Vuckovi?, Marta G; Wood, Ruth I; Holschneider, Daniel P; Abernathy, Avery; Togasaki, Daniel M; Smith, Alexandra; Petzinger, Giselle M; Jakowec, Michael W

2008-08-05

144

Seasonal changes in circadian peripheral plasma concentrations of melatonin, serotonin, dopamine and cortisol in aged horses with Cushing's disease under natural photoperiod.  

PubMed

Equine pituitary pars intermedia dysfunction (PPID) is a common and serious condition that gives rise to Cushing's disease. In the older horse, it results in hyperadrenocorticism and disrupted energy metabolism, the severity of which varies with the time of year. To gain insight into the mechanism of its pathogenesis, 24-h profiles for peripheral plasma melatonin, serotonin, dopamine and cortisol concentrations were determined at the winter and summer solstices, and the autumn and spring equinoxes in six horses diagnosed with Cushing's disease and six matched controls. The nocturnal rises in plasma melatonin concentrations, although different across seasons, were broadly of the same duration and similar amplitude in both groups of animals (P > 0.05). The plasma concentrations of cortisol did not show seasonal variation and were different in diseased horses only in the summer when they were higher across the entire 24-h period (P < 0.05). Serotonin concentrations were not significantly affected by time of year but tended to be lower in Cushingoid horses (P = 0.07). By contrast, dopamine output showed seasonal variation and was significantly lower in the Cushing's group in the summer and autumn (P < 0.05). The finding that the profiles of circulating melatonin are similar in Cushingoid and control horses reveals that the inability to read time of year by animals suffering from Cushing's syndrome is an unlikely reason for the disease. In addition, the results provide evidence that alterations in the dopaminergic and serotoninergic systems may participate in the pathogenesis of PPID. PMID:18540997

Haritou, S J A; Zylstra, R; Ralli, C; Turner, S; Tortonese, D J

2008-06-06

145

Further SAR studies of piperidine-based analogues of cocaine. 2. Potent dopamine and serotonin reuptake inhibitors.  

PubMed

The synthesis and monoamine transporter activity of additional members of a series of 3,4-disubstituted piperidines (truncated analogues of the WIN series) are described. All members of this series were prepared from arecoline hydrobromide in optically pure form and were evaluated for their ability to inhibit high affinity uptake of dopamine (DA), serotonin (5-HT) and norepinephrine (NE) into rat brain nerve endings (synaptosomes). Most of the compounds prepared in this series are reasonably potent DAT inhibitors (K(i) values of 4-400 nM) and have selectivity for the 5-HT transporter relative to both the NE transporter (3-9-fold) and to the DAT ( approximately 25-fold). In the present series, (-)-methyl 1-methyl-4beta-(2-naphthyl)piperidine-3beta-carboxylate (6) was found to be the most potent piperidine-based ligand, exhibiting K(i)'s of 21 nM and 7.6 nM at the DAT and 5-HTT, respectively. While the 5-HTT activity of compound 6 is comparable to that of the antidepressant medication fluoxetine, it is less selective. As is apparent from the data presented, the naphthyl substituted piperidines 6-9, which differ in their stereochemistry, show different degrees of selectivity for the three transporters. Consistent with results reported in the literature for the tropane analogues, removal of the methyl group from the nitrogen atom of 9 leads to a further enhancement in 5-HTT activity. To examine the in vivo effects of these piperidines, preliminary behavioral screening was carried out on piperidine 14. Despite its 2.5-fold greater DAT activity compared to cocaine, piperidine 14 was found to be about 2. 5-fold less potent in increasing distance traveled in mice. However, consistent with its DAT activity, piperidine 14 was found to be about 2.5-fold more potent than cocaine in enhancing stereotypic movements. Further studies of these piperidine-based ligands may provide valuable insights into the pharmacological mechanisms underlying the enhancement in distance traveled versus stereotypic movements. The present results have important implications for better understanding the structural motifs required in the design of agents with specific potency and selectivity at monoamine transporters. PMID:10737754

Tamiz, A P; Zhang, J; Flippen-Anderson, J L; Zhang, M; Johnson, K M; Deschaux, O; Tella, S; Kozikowski, A P

2000-03-23

146

Neurotransmitter Transporters  

NSDL National Science Digital Library

Doctor Randy Blakely explains that all neurotransmitters have transporters supporting their activity, which are typically involved in assisting and modulating. Genetic changes in transporters can lead to psychiatric problems.

2009-12-26

147

Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats  

Microsoft Academic Search

Selective serotonin reuptake inhibitors (SSRIs) are a first-line treatment for depression. Recent reports in the literature describe differences in antidepressant effects among SSRIs. Although each SSRI apparently has different pharmacological actions aside from serotonin reuptake inhibition, the relations between antidepressant effects and unique pharmacological properties in respective SSRIs remain unclear. This study was designed to compare abilities of three systemically

Yuji Kitaichi; Takeshi Inoue; Shin Nakagawa; Shuken Boku; Aya Kakuta; Takeshi Izumi; Tsukasa Koyama

2010-01-01

148

Dopamine deficiency in mice  

Microsoft Academic Search

Dopamine is the principal neurotransmitter that mediates a wide range of brain functions, including locomotion, emotion, learning, and neuroendocrine modulation. To clarify the role of dopamine during postnatal development, it is useful to have mutant mice genetically deleting dopamine. In this paper, we describe the mice lacking expression of tyrosine hydroxylase (TH), the first and rate-limiting enzyme of catecholamine biosynthetic

Kazuto Kobayashi; Hiromi Sano

2000-01-01

149

An evaluation of l-ephedrine neurotoxicity with respect to hyperthermia and caudate/putamen microdialysate levels of ephedrine, dopamine, serotonin, and glutamate.  

PubMed

l-Ephedrine is an active ingredient in several herbal formulations with a mechanism of action similar to amphetamine and methamphetamine. However, its potential to damage dopaminergic terminals in the caudate/putamen (CPu) has yet to be fully evaluated. The studies here used in vivo brain microdialysis experiments to determine the systemic doses and extracellular brain levels of l-ephedrine necessary to produce similar increases in CPu extracellular dopamine and marked hyperthermia that were previously shown necessary for amphetamine-induced neurotoxicity in male Sprague-Dawley rats. At an environmental temperature of 23 degrees C, a single 40 mg/kg intraperitoneal (ip) dose of l-ephedrine produced marked hyperthermia (>/= 40 degrees C), peak microdialysate ephedrine levels of 7.3 +/- 1.2 microM, and a 20-fold increase in microdialysate dopamine levels. Twenty-five mg/kg produced a lesser degree of hyperthermia, peak microdialysate ephedrine levels of 2.6 +/- 0.4 microM, and a 10-fold increase in dopamine levels. Three doses of 40 mg/kg given at 3-h intervals or 4 doses of 25 mg/kg l-ephedrine given at 2-h intervals were compared with 4 doses of 5 mg/kg d-amphetamine given at 2-h intervals. Multiple doses of either ephedrine or amphetamine caused severe hyperthermia (>/= 41.3 degrees C) but striatal tissue levels of dopamine 7 days after dosing were reduced only 25% or less by ephedrine compared to the 75% reductions produced by amphetamine. The increases in CPu microdialysate levels of serotonin produced by either 4 x 25 mg/kg l-ephedrine or 4 x 5 mg/kg d-amphetamine did not significantly differ, but elevation of dopamine levels by d-amphetamine were over 2-fold times the level caused by l-ephedrine. Microdialysate glutamate levels were elevated to the same extent by either 25 mg/kg l-ephedrine or 4 x 5 mg/kg d-amphetamine. l-Ephedrine may not be as neurotoxic to dopaminergic terminals as d-amphetamine, because non-lethal doses of l-ephedrine do not sufficiently increase the CPu dopamine levels within nerve terminals or the extracellular space to those necessary for a more pronounced long-term dopamine depletion. PMID:10788568

Bowyer, J F; Newport, G D; Slikker, W; Gough, B; Ferguson, S A; Tor-Agbidye, J

2000-05-01

150

The Selective Serotonin2A Receptor Antagonist M100907 Reverses Behavioral Deficits in Dopamine Transporter Knockout Mice  

Microsoft Academic Search

A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for

Alasdair M Barr; Virginia Lehmann-Masten; Martin Paulus; Raul R Gainetdinov; Marc G Caron; Mark A Geyer

2004-01-01

151

Selective inhibitors of biosynthesis of aminergic neurotransmitters  

Microsoft Academic Search

ALTHOUGH the enzymatic decarboxylation of amino acids is of substantial importance to biochemistry1, there are few inhibitors of the decarboxylase enzymes which combine activity with selectivity. Several of the amines formed by in vivo decarboxylation of amino acids (biogenic amines) have key roles in physiology. The neurotransmitters dopamine, 5-hydroxytryptamine, histamine and gamma-aminobutyric acid result from such enzymatic decarboxylation; dopamine in

J. Kollonitsch; A. A. Patchett; S. Marburg; A. L. Maycock; L. M. Perkins; G. A. Doldouras; D. E. Duggan; S. D. Aster

1978-01-01

152

STRESS-INDUCED CHANGES IN EXTRACELLULAR DOPAMINE AND SEROTONIN IN THE MEDIAL PREFRONTAL CORTEX AND DORSAL HIPPOCAMPUS OF PRENATALLY MALNOURISHED RATS  

PubMed Central

Prenatal protein malnutrition continues to be a significant problem in the world today. Exposure to prenatal protein malnutrition increases the risk of a number of neuropsychiatric disorders in adulthood including depression, schizophrenia and attentional deficit disorder. In the present experiment we have examined the effects of stress on extracellular serotonin (5-HT) and dopamine in the medial prefrontal cortex and dorsal hippocampus of rats exposed in utero to protein malnutrition. The medial prefrontal cortex and dorsal hippocampus were chosen as two limbic forebrain regions involved in learning and memory, attention and the stress response. Extracellular 5-HT and dopamine were determined in the medial prefrontal cortex and dorsal hippocampus of adult male Sprague-Dawley rats using dual probe in vivo microdialysis. Basal extracellular 5-HT did not differ between malnourished and well-nourished controls in either the medial prefrontal cortex or the dorsal hippocampus. Basal extracellular dopamine was significantly decreased in the medial prefrontal cortex of malnourished animals. Restraint stress (20 m) produced a significant rise in extracellular dopamine in the medial prefrontal cortex of well-nourished rats but did not alter release in malnourished rats. In malnourished rats, stress produced an increase in 5-HT in the hippocampus, whereas stress produced a decrease in 5-HT in the hippocampus of well-nourished rats. These data demonstrate that prenatal protein malnutrition alters dopaminergic neurotransmission in the medial prefrontal cortex as well as altering the dopaminergic and serotonergic response to stress. These changes may provide part of the bases for alterations in malnourished animals’ response to stress.

Mokler, David J.; Torres, Olga I.; Galler, Janina R.; Morgane, Peter J.

2009-01-01

153

LeuT-desipramine structure suggests how antidepressants inhibit human neurotransmitter transporters  

PubMed Central

Tricyclic antidepressants exert their pharmacological effect - inhibiting the reuptake of serotonin, norepinephrine and dopamine - by directly blocking neurotransmitter transporters (SERT, NET and DAT, respectively) in the presynaptic membrane. The drug-binding site and the mechanism of this inhibition are poorly understood. We determined the crystal structure at 2.9 Å of the bacterial leucine transporter (LeuT), a homolog of SERT, NET and DAT, in complex with leucine and the antidepressant desipramine. Desipramine binds at the inner end of the extracellular cavity of the transporter and is held in place by a hairpin loop and by a salt bridge. This binding site is separated from the leucine-binding site by the extracellular gate of the transporter. By directly locking the gate, desipramine prevents conformational changes and blocks substrate transport. Mutagenesis experiments on human SERT and DAT indicate that both the desipramine-binding site and its inhibition mechanism are probably conserved in the human neurotransmitter transporters.

Zhou, Zheng; Zhen, Juan; Karpowich, Nathan K.; Goetz, Regina M.; Law, Christopher J.; Reith, Maarten E. A.; Wang, Da-Neng

2013-01-01

154

LeuT-Desipramine Structure Reveals How Antidepressants Block Neurotransmitter Reuptake  

SciTech Connect

Tricyclic antidepressants exert their pharmacological effect -- inhibiting the reuptake of serotonin, norepinephrine, and dopamine -- by directly blocking neurotransmitter transporters (SERT, NET, and DAT, respectively) in the presynaptic membrane. The drug-binding site and the mechanism of this inhibition are poorly understood. We determined the crystal structure at 2.9 angstroms of the bacterial leucine transporter (LeuT), a homolog of SERT, NET, and DAT, in complex with leucine and the antidepressant desipramine. Desipramine binds at the inner end of the extracellular cavity of the transporter and is held in place by a hairpin loop and by a salt bridge. This binding site is separated from the leucine-binding site by the extracellular gate of the transporter. By directly locking the gate, desipramine prevents conformational changes and blocks substrate transport. Mutagenesis experiments on human SERT and DAT indicate that both the desipramine-binding site and its inhibition mechanism are probably conserved in the human neurotransmitter transporters.

Zhou,Z.; Zhen, J.; Karpowich, N.; Goetz, R.; Law, C.; Reith, M.; Wang, D.

2007-01-01

155

Oxidatively generated DNA damage after Cu(II) catalysis of dopamine and related catecholamine neurotransmitters and neurotoxins: Role of reactive oxygen species  

Microsoft Academic Search

There is increasing evidence supporting a causal role for oxidatively damaged DNA in neurodegeneration during the natural aging process and in neurodegenerative diseases such as Parkinson and Alzheimer. The presence of redox-active catecholamine neurotransmitters coupled with the localization of catalytic copper to DNA suggests a plausible role for these agents in the induction of oxidatively generated DNA damage. In this

Wendy A. Spencer; Jeyaprakash Jeyabalan; Sunita Kichambre; Ramesh C. Gupta

2011-01-01

156

Neurotransmitter properties of the newborn human retina  

SciTech Connect

Human retinal tissue from a newborn was examined autoradiographically for the presence of high-affinity uptake and localization of the following putative neurotransmitters: dopamine, glycine, GABA, aspartate, and glutamate. In addition, the dopamine content of this newborn retina was measured by high pressure liquid chromatography. Our study reveals that specific uptake mechanisms for /sup 3/H-glycine, /sup 3/H-dopamine, and /sup 3/H-GABA are present at birth. However, the number and distribution of cells labeled with each of these /sup 3/H-transmitters are not identical to those observed in adult human retinas. Furthermore, the amount of endogenous dopamine in the newborn retina is approximately 1/20 the adult level. Photoreceptor-specific uptake of /sup 3/H-glutamate and /sup 3/H-aspartate are not observed. These findings indicate that, while some neurotransmitter-specific properties are present at birth, significant maturation of neurotransmitter systems occurs postnatally.

Hollyfield, J.G.; Frederick, J.M.; Rayborn, M.E.

1983-07-01

157

A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index  

Microsoft Academic Search

Variation in brain monoaminergic activity is heritable and modulates risk of alcoholism and other addictions, as well as food intake and energy expenditure. Monoamine oxidase A deaminates the monoamine neurotransmitters serotonin, dopamine (DA), and noradrenalin. The monoamine oxidase A (MAOA) gene (Xp11.5) contains a length polymorphism in its promoter region (MAOA-LPR) that putatively affects transcriptional efficiency. Our goals were to

F Ducci; T K Newman; S Funt; G L Brown; M Virkkunen; D Goldman

2006-01-01

158

New discoveries in the development of antipsychotics with novel mechanisms of action: beyond the atypical antipsychotics with serotonin dopamine antagonism  

Microsoft Academic Search

\\u000a Antipsychotic innovation can be divided into three eras. The first era began with the serendipitous discovery of the classical\\u000a antipsychotic neuroleptics, later found to mediate their therapeutic actions by blocking D2 dopamine receptors, particularly\\u000a in the mesolimbic dopamine pathway [1]. From the late 1950s through the 1980s, a large number of effective compounds sharing this mechanism of action were thus

Stephen M. Stahl; Darius K. Shayegan

159

Three-dimensional models of neurotransmitter transporters and their interactions with cocaine and S-citalopram.  

PubMed

Drugs that act on the human serotonin transporter (hSERT), human dopamine transporter (hDAT) and human noradrenaline transporter (hNET) are important in antidepressant treatment and well known in drug abuse. The investigation of their molecular mechanisms of action is very useful for designing new ligands with a therapeutic potential. The detailed three-dimensional molecular structure of any monoamine transporter is not known, but the three-dimensional electron density projection map of Escherichia coli Na+/H+ antiporter (NhaA) has provided structural basis for constructing models of such transporters using molecular modelling techniques. Three-dimensional models of these drug targets give insight into their structure, mechanisms and drug interactions. In these molecular modelling studies, an Escherichia coli NhaA model was first constructed based on its three-dimensional electron density projection map and experimental studies on NhaA and the Escherichia coli lactose permease symporter (Lac permease). Then three-dimensional models of the neurotransmitter transporters hDAT, hSERT and hNET were constructed based on the NhaA model and studies of ligand binding to mutated dopamine transporter (DAT) and serotonin transporter (SERT). The structural properties of these neurotransmitter transporter models have been examined, and their interactions with cocaine and S-citalopram have been investigated. PMID:16684682

Ravna, Aina Westrheim

2006-01-01

160

Regulation of embryonic neurotransmitter and tyrosine hydroxylase protein levels by ascorbic acid.  

PubMed

Scope: Ascorbic acid (ascorbate) is required to recycle tetrahydrobiopterin, which is necessary for neurotransmitter synthesis by the rate-limiting enzymes tyrosine and tryptophan hydroxylases. We sought to determine whether ascorbate might regulate embryonic brain cortex monoamine synthesis utilizing transgenic mouse models with varying intracellular ascorbate levels. Methods and results: In embryos lacking the sodium-dependent vitamin C transporter 2 (SVCT2), very low levels of brain ascorbate decreased cortex levels of norepinephrine and dopamine by approximately 33%, but had no effect on cortex serotonin or its metabolite, 5-hydroxyindole acetic acid. This decrease in ascorbate also led to a decrease in protein levels of tyrosine hydroxylase, but not of tryptophan hydroxylase. Increased cortex ascorbate in embryos carrying extra copies of the SVCT2 resulted in increased levels of dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), as well as serotonin and 5-hydroxyindole acetic acid. Conclusion: The dependence of embryonic brain cortex neurotransmitter synthesis and tyrosine hydroxylase expression on intracellular ascorbate emphasizes the importance of receiving adequate ascorbate during development. PMID:24095796

Meredith, M Elizabeth; May, James M

2013-10-01

161

Seasonal Changes in Circadian Peripheral Plasma Concentrations of Melatonin, Serotonin, Dopamine and Cortisol in Aged Horses with Cushing's Disease under Natural Photoperiod  

PubMed Central

Equine pituitary pars intermedia dysfunction (PPID) is a common and serious condition that gives rise to Cushing’s disease. In the older horse, it results in hyperadrenocorticism and disrupted energy metabolism, the severity of which varies with the time of year. To gain insight into the mechanism of its pathogenesis, 24-h profiles for peripheral plasma melatonin, serotonin, dopamine and cortisol concentrations were determined at the winter and summer solstices, and the autumn and spring equinoxes in six horses diagnosed with Cushing’s disease and six matched controls. The nocturnal rises in plasma melatonin concentrations, although different across seasons, were broadly of the same duration and similar amplitude in both groups of animals (P > 0.05). The plasma concentrations of cortisol did not show seasonal variation and were different in diseased horses only in the summer when they were higher across the entire 24-h period (P < 0.05). Serotonin concentrations were not significantly affected by time of year but tended to be lower in Cushingoid horses (P = 0.07). By contrast, dopamine output showed seasonal variation and was significantly lower in the Cushing’s group in the summer and autumn (P < 0.05). The finding that the profiles of circulating melatonin are similar in Cushingoid and control horses reveals that the inability to read time of year by animals suffering from Cushing’s syndrome is an unlikely reason for the disease. In addition, the results provide evidence that alterations in the dopaminergic and serotoninergic systems may participate in the pathogenesis of PPID.

Haritou, S J A; Zylstra, R; Ralli, C; Turner, S; Tortonese, D J

2008-01-01

162

SONU20176289, a compound combining partial dopamine D(2) receptor agonism with specific serotonin reuptake inhibitor activity, affects neuroplasticity in an animal model for depression.  

PubMed

We investigated the efficacy of SONU20176289, a member of a group of novel phenylpiperazine derivatives with a mixed dopamine D(2) receptor partial agonist and specific serotonin reuptake inhibitor (SSRI) activity, in a chronic stress model of depression in male tree shrews. Animals were subjected to a 7-day period of psychosocial stress before treatment for 28 days with SONU20176289 (6 mg/kg/day, p.o.), during which stress was maintained. Stress reduced the in vivo brain concentrations of N-acetyl-aspartate, total creatine, and choline-containing compounds, as measured by localized proton magnetic resonance spectroscopy. Post mortem analyses revealed a reduced adult dentate cell proliferation and a decreased GluR2 expression in the prefrontal cortex. All these alterations were prevented by concomitant administration of SONU20176289. The results provide further support to the concept that antidepressant treatments may act by normalizing disturbed neuroplasticity, and indicate that combining dopamine D(2) receptor agonism with SSRI activity may serve as an effective tool in the treatment of depressive/anxiety syndromes. PMID:18822282

Michael-Titus, Adina T; Albert, Monika; Michael, Gregory J; Michaelis, Thomas; Watanabe, Takashi; Frahm, Jens; Pudovkina, Olga; van der Hart, Marieke G C; Hesselink, Mayke B; Fuchs, Eberhard; Czéh, Boldizsár

2008-09-17

163

Neurotransmitter transporters in schistosomes: Structure, function and prospects for drug discovery.  

PubMed

Neurotransmitter transporters (NTTs) play a fundamental role in the control of neurotransmitter signaling and homeostasis. Sodium symporters of the plasma membrane mediate the cellular uptake of neurotransmitter from the synaptic cleft, whereas proton-driven vesicular transporters sequester the neurotransmitter into synaptic vesicles for subsequent release. Together these transporters control how much transmitter is released and how long it remains in the synaptic cleft, thereby regulating the intensity and duration of signaling. NTTs have been the subject of much research in mammals and there is growing interest in their activities among invertebrates as well. In this review we will focus our attention on NTTs of the parasitic flatworm Schistosoma mansoni. Bloodflukes of the genus Schistosoma are the causative agents of human schistosomiasis, a devastating disease that afflicts over 200million people worldwide. Schistosomes have a well-developed nervous system and a rich diversity of neurotransmitters, including many of the small-molecule ("classical") neurotransmitters that normally employ NTTs in their mechanism of signaling. Recent advances in schistosome genomics have unveiled numerous NTTs in this parasite, some of which have now been cloned and characterized in vitro. Moreover new genetic and pharmacological evidence suggests that NTTs are required for proper control of neuromuscular signaling and movement of the worm. Among these carriers are proteins that have been successfully targeted for drug discovery in other organisms, in particular sodium symporters for biogenic amine neurotransmitters such as serotonin and dopamine. Our goal in this chapter is to review the current status of research on schistosome NTTs, with emphasis on biogenic amine sodium symporters, and to evaluate their potential for anti-schistosomal drug targeting. Through this discussion we hope to draw attention to this important superfamily of parasite proteins and to identify new directions for future research. PMID:23800409

Ribeiro, Paula; Patocka, Nicholas

2013-06-22

164

Effect of antiparkinson drug HP-200 (Mucuna pruriens) on the central monoaminergic neurotransmitters.  

PubMed

HP-200, which contains Mucuna pruriens endocarp, has been shown to be effective in the treatment of Parkinson's disease. Mucuna pruriens endocarp has also been shown to be more effective compared to synthetic levodopa in an animal model of Parkinson's disease. The present study was designed to elucidate the long-term effect of Mucuna pruriens endocarp in HP-200 on monoaminergic neurotransmitters and its metabolite in various regions of the rat brain. HP-200 at a dose of 2.5, 5.0 or 10.0 g/kg/day was mixed with rat chow and fed daily ad lib to Sprague-Dawley rats (n = 6 for each group) for 52 weeks. Controls (n = 6) received no drug. Random assignment was made for doses and control. The rats were sacrificed at the end of 52 weeks and the neurotransmitters were analyzed in the cortex, hippocampus, substantia nigra and striatum. Oral administration of Mucuna pruriens endocarp in the form of HP-200 had a significant effect on dopamine content in the cortex with no significant effect on levodopa, norepinephrine or dopamine, serotonin, and their metabolites- HVA, DOPAC and 5-HIAA in the nigrostriatal tract. The failure of Mucuna pruriens endocarp to significantly affect dopamine metabolism in the striatonigral tract along with its ability to improve Parkinsonian symptoms in the 6-hydorxydopamine animal model and humans may suggest that its antiparkinson effect may be due to components other than levodopa or that it has an levodopa enhancing effect. PMID:15022157

Manyam, Bala V; Dhanasekaran, Muralikrishnan; Hare, Theodore A

2004-02-01

165

Clomipramine-induced serum prolactin as a marker for serotonin and dopamine turnover: results of an open label study  

Microsoft Academic Search

Central nervous system (CNS) monoamine deficits have been linked to a number of pathological conditions such as major depressive\\u000a disorder. Individual biological variations in 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol\\u000a (MHPG) might account for the variation in responses of neurotransmitter systems observed after the administration of clomipramine.\\u000a The prolactin response to clomipramine has been widely used to assess

Joachim Cordes; Kai G. Kahl; Christian Werner; Uwe Henning; Gunnar Regenbrecht; Rolf Larisch; Christian Schmidt-Kraepelin; Johanna Thünker; Marcus W. Agelink; Stefan Löffler; Thomas Hohlfeld; Wolfgang Gaebel; Ansgar Klimke

166

Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) for intraoperative neurochemical monitoring.  

PubMed

The Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) measures extracellular neurotransmitter concentration in vivo and displays the data graphically in nearly real time. WINCS implements two electroanalytical methods, fast-scan cyclic voltammetry (FSCV) and fixed-potential amperometry (FPA), to measure neurotransmitter concentrations at an electrochemical sensor, typically a carbon-fiber microelectrode. WINCS comprises a battery-powered patient module and a custom software application (WINCSware) running on a nearby personal computer. The patient module impresses upon the electrochemical sensor either a constant potential (for FPA) or a time-varying waveform (for FSCV). A transimpedance amplifier converts the resulting current to a signal that is digitized and transmitted to the base station via a Bluetooth radio link. WINCSware controls the operational parameters for FPA or FSCV, and records the transmitted data stream. Filtered data is displayed in various formats, including a background-subtracted plot of sequential FSCV scans - a representation that enables users to distinguish the signatures of various analytes with considerable specificity. Dopamine, glutamate, adenosine and serotonin were selected as analytes for test trials. Proof-of-principle tests included in vitro flow-injection measurements and in vivo measurements in rat and pig. Further testing demonstrated basic functionality in a 3-Tesla MRI unit. WINCS was designed in compliance with consensus standards for medical electrical device safety, and it is anticipated that its capability for real-time intraoperative monitoring of neurotransmitter release at an implanted sensor will prove useful for advancing functional neurosurgery. PMID:19963865

Kimble, Christopher J; Johnson, David M; Winter, Bruce A; Whitlock, Sidney V; Kressin, Kenneth R; Horne, April E; Robinson, Justin C; Bledsoe, Jonathan M; Tye, Susannah J; Chang, Su-Youne; Agnesi, Filippo; Griessenauer, Christoph J; Covey, Daniel; Shon, Young-Min; Bennet, Kevin E; Garris, Paul A; Lee, Kendall H

2009-01-01

167

Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) for Intraoperative Neurochemical Monitoring  

PubMed Central

The Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) measures extracellular neurotransmitter concentration in vivo and displays the data graphically in nearly real time. WINCS implements two electroanalytical methods, fast-scan cyclic voltammetry (FSCV) and fixed-potential amperometry (FPA), to measure neurotransmitter concentrations at an electrochemical sensor, typically a carbon-fiber microelectrode. WINCS comprises a battery-powered patient module and a custom software application (WINCSware) running on a nearby personal computer. The patient module impresses upon the electrochemical sensor either a constant potential (for FPA) or a time-varying waveform (for FSCV). A transimpedance amplifier converts the resulting current to a signal that is digitized and transmitted to the base station via a Bluetooth® radio link. WINCSware controls the operational parameters for FPA or FSCV, and records the transmitted data stream. Filtered data is displayed in various formats, including a background-subtracted plot of sequential FSCV scans—a representation that enables users to distinguish the signatures of various analytes with considerable specificity. Dopamine, glutamate, adenosine and serotonin were selected as analytes for test trials. Proof-of-principle tests included in vitro flow-injection measurements and in vivo measurements in rat and pig. Further testing demonstrated basic functionality in a 3-Tesla MRI unit. WINCS was designed in compliance with consensus standards for medical electrical device safety, and it is anticipated that its capability for real-time intraoperative monitoring of neurotransmitter release at an implanted sensor will prove useful for advancing functional neurosurgery.

Kimble, Christopher J.; Johnson, David M.; Winter, Bruce A.; Whitlock, Sidney V.; Kressin, Kenneth R.; Horne, April E.; Robinson, Justin C.; Bledsoe, Jonathan M.; Tye, Susannah J.; Chang, Su-Youne; Agnesi, Filippo; Griessenauer, Christoph J.; Covey, Daniel; Shon, Young-Min; Bennet, Kevin E.; Garris, Paul A.; Lee, Kendall H.

2010-01-01

168

Extracellular dopamine, norepinephrine, and serotonin in the ventral tegmental area and nucleus accumbens of freely moving rats during intracerebral dialysis following systemic administration of cocaine and other uptake blockers  

Microsoft Academic Search

Extracellular levels of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) were measured by microdialysis in conscious\\u000a rats equipped with dual probes, one in the ventral tegmental area (VTA) and another one in the contralateral nucleus accumbens\\u000a (NACC). Dialysate content of all amines in both regions was essentially abolished by local infusion of tetrodotoxin (1??M)\\u000a or Ca2+-free buffer. Injection of the

Maarten E. A. Reith; Ming-Ya Li; Qing-Shan Yan

1997-01-01

169

GABA Neurotransmitter  

NSDL National Science Digital Library

GABA occurs in 30-40% of all synapses-only glutamate is more widely distributed. Neurons in every region of the brain use GABA to fine-tune neurotransmission. Increasing GABA at the neuronal synapse inhibits the generation of the action potential of the neuron, thereby making it less likely to excite nearby neurons. A single neuron may have thousands of other neurons synapsing onto it. Some of these release activating (or depolarizing) neurotransmitters; others release inhibitory (or hyperpolarizing) neurotransmitters. GABA is the primary inhibitory neurotransmitter, which means it decreases the neuron's action potential. When the action potential drops below a certain level, known as the threshold potential, the neuron will not generate action potentials and thus not excite nearby neurons. The nucleus of a neuron is located in the cell body. Extending out from the cell body are dendrites and axons. Dendrites conduct impulses toward the cell body, Axons conducting impulses away from the cell body. A recording electrode has been attached to a voltmeter to record the charge across the cell membrane, the thin layer that controls movement in and out of the neuron. The resting potential in excitable neurons is usually around -65 to -70 millivolts (mV), which can be seen on the voltmeter. Excitatory synapses reduce the membrane potential: The synapses labeled A, B, and C are excitatory (e.g. glutamate ACH). These synapses release activating neurotransmitters, which reduce the resting potential of the neuron. If the voltage reaches the threshold potential, typically around -50 mv, an action potential is generated, which will travel down the axon, where it will communicate with a nearby cell. The strength of the stimuli that produce an action potential is important only insomuch as it reaches threshold potential. The resultant action potential is always the same, whether it was created by relatively strong or relatively weak stimuli. action potential is a constant. Decreasing the action potential: GABA is the primary inhibitory neurotransmitter, which means it decreases the neuronâÃÂÃÂs action potential. When the action potential drops below the threshold potential, the neuron will not excite nearby neurons. Exitatory PostSynaptic Potential (EPSP): The Exitatory PostSynaptic Potential (EPSP) of a single excitatory synapse is not sufficient to reach the threshold of the neuron. Rather, when a number of EPSPs are created in quick succession, their charges sum together. It is the combined sum of these EPSPs that creates an action potential Activation of inhibitory synapses such as GABA, on the other hand, makes resting potential more negative. This hyperpolarization is called an inhibitory postsynaptic potential (IPSP). Activation of inhibitory synapses (D and E) makes the resting potential of the neuron more negative. The resulting IPSP may also prevent what would otherwise have been effective EPSPs from triggering an action potential. It is the total summation of the EPSPs and IPSPs that determines whether a neuronâÃÂÃÂs charge is sufficient to cross the potential threshold.

2009-04-14

170

Serotonin Dysfunction in Autism  

Microsoft Academic Search

\\u000a This chapter reviews the evidence for the involvement of the neurotransmitter serotonin in the etiology of autism. Serotonin-containing\\u000a neurons in the raphe nuclei of the brainstem are among the first neurons to be generated, and their axonal projections extend\\u000a to widespread areas throughout the brain and spinal cord. Thus, the serotonergic system can influence early developmental\\u000a events throughout the brain.

Mary E. Blue; Michael V. Johnston; Carolyn B. Moloney; Christine F. Hohmann

171

Serotonin Receptors in Hippocampus  

PubMed Central

Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system.

Berumen, Laura Cristina; Rodriguez, Angelina; Miledi, Ricardo; Garcia-Alcocer, Guadalupe

2012-01-01

172

Reversal of dopamine D2 agonist-induced inhibition of ventral tegmental area neurons by Gq-linked neurotransmitters is dependent on protein kinase C, G protein-coupled receptor kinase, and dynamin.  

PubMed

Dopaminergic neurons of the ventral tegmental area are important components of brain pathways related to addiction. Prolonged exposure of these neurons to moderate concentrations of dopamine (DA) decreases their sensitivity to inhibition by DA, a process called DA-inhibition reversal (DIR). DIR is mediated by phospholipase C and conventional subtype of protein kinase C (cPKC) through concurrent stimulation of D2 and D1-like DA receptors, or by D2 stimulation concurrent with activation of 5-HT(2) or neurotensin receptors. In the present study, we further characterized this phenomenon by use of extracellular recordings in brain slices to examine whether DIR is linked to G protein-coupled receptor kinase-2 (GRK2) or dynamin by assessing DIR in the presence of antagonists of these enzymes. DIR was blocked by ?-ARK1 inhibitor, which inhibits GRK2, and by dynasore, which blocks dynamin. Reversal of inhibition by D2 agonist quinpirole was produced by serotonin (50 µM) and by neurotensin (5-10 nM). Serotonin-induced or neurotensin-induced reversal was blocked by ?-ARK1 inhibitor, dynasore, or cPKC antagonist 5,6,7,13-tetrahydro-13-methyl-5-oxo-12H-indolo[2,3-a]pyrrolo[3,4c]carbazole-12-propanenitrile (Gö6976). This further characterization of DIR indicates that cPKC, GRK2, and dynamin play important roles in the desensitization of D2 receptors. As drugs of abuse produce persistent increases in DA concentration in the ventral tegmental area, reduction of D2 receptor sensitivity as a result of drug abuse may be a critical factor in the processes of addiction. PMID:23019137

Nimitvilai, Sudarat; McElvain, Maureen A; Brodie, Mark S

2012-09-27

173

Inherited disorders of neurotransmitters in children and adults  

Microsoft Academic Search

Inherited disorders of neurotransmitters are a group of neurometabolic syndromes attributable to a primary disturbance of neurotransmitter metabolism or transport. This is an enlarging group of recognized disorders requiring specialized diagnostic procedures for detection. This review considers clinical disorders of biopterin, catecholamines, serotonin, glycine, pyridoxine, and GABA metabolism. Newly described syndromes such as cerebral folate deficiency and pyridoxal-5-phosphate dependency are

Phillip L. Pearl; Philip K. Capp; Edward J. Novotny; K. Michael Gibson

2005-01-01

174

Reserpine modulates neurotransmitter release to extend lifespan and alleviate age-dependent A? proteotoxicity in Caenorhabditis elegans.  

PubMed

Aging is a debilitating process often associated with chronic diseases such as diabetes, cardiovascular and neurodegenerative diseases like Alzheimer's disease (AD). AD occurs at a very high incidence posing a huge burden to the society. Model organisms such as C. elegans become essential to understand aging or lifespan extension - the etiology, molecular mechanism and identification of new drugs against age associated diseases. The AD model, manifesting A? proteotoxicity, in C. elegans is well established and has provided valuable insights. Earlier, we have reported that Reserpine, an FDA-approved antihypertensive drug, increases C. elegans lifespan with a high quality of life and ameliorates A? toxicity in C. elegans. But reserpine does not seem to act through the known lifespan extension pathways or inhibition of its known target, vesicular monoamine transporter, VMAT. Reserpine's mode of action and the pathways it activates are not known. Here, we have evaluated the presynaptic neurotransmitter(s) release pathway and identified acetylcholine (ACh) as the crucial player for reserpine's action. The corroborating evidences are: i) lack of lifespan extension in the ACh loss of function (hypomorphic) - synthesis (cha-1) and transport (unc-17) mutants; ii) mitigation of chronic aldicarb effect; iii) lifespan extension in dopamine (cat-2) and dopamine and serotonin (bas-1) biosynthetic mutants; iv) no rescue from exogenous serotonin induced paralysis in the AD model worms; upon reserpine treatment. Thus, modulation of acetylcholine is essential for reserpine's action. PMID:22212533

Saharia, Kopal; Arya, Upasna; Kumar, Ranjeet; Sahu, Rashmi; Das, Chinmaya Kumar; Gupta, Kuldeep; Dwivedi, Hemalata; Subramaniam, Jamuna R

2011-12-26

175

The phenotypic spectrum of paediatric neurotransmitter diseases and infantile parkinsonism  

Microsoft Academic Search

Summary  Paediatric neurotransmitter diseases are a group of inherited disorders attributable to a disturbance of neurotransmitter\\u000a metabolism. The monoamines, catecholamines and serotonin, also called biogenic amines, are neurotransmitters with multiple\\u000a roles including psychomotor function, hormone secretion, cardiovascular, respiratory and gastrointestinal control, sleep mechanisms,\\u000a body temperature and pain. Given the multiple functions of monoamines, disorders of their metabolism comprise a wide spectrum

R. Pons

2009-01-01

176

Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus  

PubMed Central

The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLU, Prozac®) is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured)) on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks) until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation) of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.

Berg, Cecilia; Backstrom, Tobias; Winberg, Svante; Lindberg, Richard; Brandt, Ingvar

2013-01-01

177

Changes in cerebral neurotransmitters and metabolites induced by acute donepezil and memantine administrations: a microdialysis study.  

PubMed

Cholinesterase inhibitors including donepezil, rivastigmine, and galantamine and the N-methyl-D-aspartate (NMDA) antagonist, memantine are the medications currently approved for the treatment of Alzheimer's disease (AD). In addition to their beneficial effects on cognitive and functional domains typically disrupted in AD, these agents have also been shown to slow down the emergence of behavioral and psychotic symptoms associated with this disease. However, the underlying mechanisms for these therapeutic effects remain poorly understood and could involve effects of these medications on non-cholinergic or non-glutamatergic neurotransmitter systems respectively. These considerations prompted us to initiate a series of investigations to examine the acute and chronic effects of donepezil (Aricept (+/-)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-1 hydrochloride and memantine (1-amino-3,5-dimethyladamantane hydrochloride C12H21N.HCl)). The present study focuses on the acute effects of donepezil and memantine on brain extracellular levels of acetylcholine, dopamine, serotonin, norepinephrine and their metabolites. We assayed changes in the ventral and dorsal hippocampus and the prefrontal and medial temporal cortex by microdialysis. Memantine resulted in significant increases in extracellular dopamine (DA), norepinephrine (NE), and their metabolites, in the cortical regions, and in a reduction of DA in the hippocampus. Donepezil produced an increase in extracellular DA in the cortex and in the dorsal hippocampus. Norepinephrine increased in the cortex; with donepezil it increased in the dorsal hippocampus and the medial temporal cortex, and decreased in the ventral hippocampus. Interestingly both compounds decreased extracellular serotonin (5HT) levels. The metabolites of the neurotransmitters were increased in most areas. We also found an increase in extracellular acetylcholine (ACh) by memantine in the nucleus accumbens and the ventral tegmental area. Our results suggest both region and drug specific neurotransmitter effects of these agents as well as some similarities. We conclude that drugs influencing cognitive mechanisms induce changes in a number of neurotransmitters with the changes being both region and drug specific. Release and metabolism are altered and extracellular neurotransmitter levels can be increased or decreased by the drugs. Other studies are in progress to determine the pharmacological effects associated with chronic treatment with these compounds, which may be more pertinent to the clinical situation in which patients take these medications for months or years. PMID:16533671

Shearman, E; Rossi, S; Szasz, B; Juranyi, Z; Fallon, S; Pomara, N; Sershen, H; Lajtha, A

2005-12-21

178

Dopamine visualized in the basal ganglia of living man  

Microsoft Academic Search

The neurotransmitter dopamine has biological attributes that make it amenable to study by positron emission tomography, unlike many of the 40 or so neurotransmitters that have been identified in the brain. Dopamine deficiency in the nigrostriatal system is a characteristic of Parkinson's disease1, and a disturbance of dopamine metabolism is still widely held to be responsible for the syndrome of

E. S. Garnett; G. Firnau; C. Nahmias

1983-01-01

179

Prenatal Dopamine and Neonatal Behavior and Biochemistry  

PubMed Central

Depressed pregnant women (N=126) were divided into high and low prenatal maternal dopamine (HVA) groups based on a tertile split on their dopamine levels at 20 weeks gestation. The high versus the low dopamine group had lower CES-D scores, higher norepinephrine levels at the 20 week gestational age visit and higher dopamine and serotonin levels at both the 20 the 32 week gestational age visits. The neonates of the mothers with high versus low prenatal dopamine levels also had higher dopamine and serotonin levels as well as lower cortisol levels. Finally, the neonates in the high dopamine group had better autonomic stability and excitability scores on the Brazelton Neonatal Behavior Assessment Scale. Thus, prenatal maternal dopamine levels appear to be negatively related to prenatal depression scores and positively related to neonatal dopamine and behavioral regulation, although these effects are confounded by elevated serotonin levels.

Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Figueiredo, Barbara; Deeds, Osvelia; Ascencio, Angela; Schanberg, Saul; Kuhn, Cynthia

2008-01-01

180

Prenatal dopamine and neonatal behavior and biochemistry.  

PubMed

Depressed pregnant women (N=126) were divided into high and low prenatal maternal dopamine (HVA) groups based on a tertile split on their dopamine levels at 20 weeks gestation. The high versus the low dopamine group had lower Center for Epidemiological Studies-Depression Scale (CES-D) scores, higher norepinephrine levels at the 20-week gestational age visit and higher dopamine and serotonin levels at both the 20- and the 32-week gestational age visits. The neonates of the mothers with high versus low prenatal dopamine levels also had higher dopamine and serotonin levels as well as lower cortisol levels. Finally, the neonates in the high dopamine group had better autonomic stability and excitability scores on the Brazelton Neonatal Behavior Assessment Scale. Thus, prenatal maternal dopamine levels appear to be negatively related to prenatal depression scores and positively related to neonatal dopamine and behavioral regulation, although these effects are confounded by elevated serotonin levels. PMID:18774177

Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Figueiredo, Barbara; Deeds, Osvelia; Ascencio, Angela; Schanberg, Saul; Kuhn, Cynthia

2008-09-05

181

Interaction between serotonin transporter and dopamine D2/D3 receptor radioligand measures is associated with harm avoidant symptoms in anorexia and bulimia nervosa.  

PubMed

Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) have alterations of measures of serotonin (5-HT) and dopamine (DA) function, which persist after long-term recovery and are associated with elevated harm avoidance (HA), a measure of anxiety and behavioral inhibition. Based on theories that 5-HT is an aversive motivational system that may oppose a DA-related appetitive system, we explored interactions of positron emission tomography (PET) radioligand measures that reflect portions of these systems. Twenty-seven individuals recovered (REC) from eating disorders (EDs) (7 AN-BN, 11 AN, 9 BN) and nine control women (CW) were analyzed for correlations between [(11)C]McN5652 and [(11)C]raclopride binding. There was a significant positive correlation between [(11)C]McN5652 binding potential (BP(non displaceable(ND))) and [(11)C]Raclopride BP(ND) for the dorsal caudate, antero-ventral striatum (AVS), middle caudate, and ventral and dorsal putamen. No significant correlations were found in CW. [(11)C]Raclopride BP(ND), but not [(11)C]McN5652 BP(ND), was significantly related to HA in REC EDs. A linear regression analysis showed that the interaction between [(11)C]McN5652 BP(ND) and [(11)C]raclopride BP(ND) in the dorsal putamen significantly predicted HA. This is the first study using PET and the radioligands [(11)C]McN5652 and [(11)C]raclopride to show a direct relationship between 5-HT transporter and striatal DA D2/D3 receptor binding in humans, supporting the possibility that 5-HT and DA interactions contribute to HA behaviors in EDs. PMID:23154100

Bailer, Ursula F; Frank, Guido K; Price, Julie C; Meltzer, Carolyn C; Becker, Carl; Mathis, Chester A; Wagner, Angela; Barbarich-Marsteller, Nicole C; Bloss, Cinnamon S; Putnam, Karen; Schork, Nicholas J; Gamst, Anthony; Kaye, Walter H

2012-11-13

182

Dopamine D4 receptor (D4DR) and serotonin transporter promoter (5-HTTLPR) polymorphisms in the determination of temperament in 2-month-old infants.  

PubMed

We and others have previously shown that the dopamine D4 exon III repeat (D4DR) and the serotonin-transporter promoter region (5-HTTLPR) polymorphisms are not only associated with adult personality traits1-7 but also with temperament in 2-week-old neonates.8 We now report the results of a second study of these infants and their temperament at 2 months using Rothbart's Infant Behavior Questionnaire (IBQ).9 There were significant negative correlations between neonatal orientation and motor organization as measured by the Neonatal Behavioral Assessment Scale (NBAS)10 at 2 weeks and negative emotionality, especially distress in daily situations, at 2 months of age. There were significant main effects for negative emotionality and distress when the infants were grouped by the D4DR and the 5-HTTLPR polymorphisms. Infants with long D4DR alleles had significantly lower scores on Negative Emotionality (F[1, 72] = 8.50, P = 0.005) and Distress to Limitations (F[1,72] = 4.93, P = 0.03) than infants with short D4DR alleles. In contrast, infants with the short homozygous (s/s) 5-HTTLPR genotype had higher scores on Negative Emotionality (F[1,72] = 3.88, P = 0.053) and Distress to Limitations (F[1,72] = 4.94, P = 0.029) than infants with the I/s or I/I genotypes. The strongest effects occurred in those infants with the s/s 5-HTTLPR polymorphism who also were lacking long D4DR alleles which in some studies has been linked to adult novelty seeking.1,6 These infants showed most negative emotionality and most distress to daily situations, temperament traits that are perhaps the underpinning of adult neuroticism. PMID:10483054

Auerbach, J; Geller, V; Lezer, S; Shinwell, E; Belmaker, R H; Levine, J; Ebstein, R

1999-07-01

183

Cannabinoid-Induced Enhanced Interaction and Protein Levels of Serotonin 5-HT2A and Dopamine D2 Receptors in Rat Prefrontal Cortex  

PubMed Central

Recent evidence suggests that non-selective cannabinoid receptor agonists may regulate serotonin 2A (5-HT2A) receptor neurotransmission in brain. The molecular mechanisms of this regulation are unknown but could involve cannabinoid-induced enhanced interaction between 5-HT2A and dopamine D2 (D2) receptors. Here, we present experimental evidence that Sprague-Dawley rats treated with a non-selective cannabinoid receptor agonist (CP55,940, 50?g/kg, 7days, i.p.) showed enhanced co-immunoprecipitation of 5-HT2A and D2 receptors and enhanced membrane-associated expression of D2 and 5-HT2A receptors in prefrontal cortex (PFCx). Furthermore, 5-HT2A receptor mRNA levels were increased in PFCx suggesting a cannabinoid-induced upregulation of 5-HT2A receptors. To date, two cannabinoids receptors have been found in brain, CB1 and CB2 receptors. We used selective cannabinoid agonists in a neuronal cell line to study mechanisms that could mediate this 5-HT2A receptor upregulation. We found that selective CB2 receptor agonists upregulate 5-HT2A receptors by a mechanism that seems to involve activation of G?i G-proteins, ERK1/2, and AP-1 transcription factor. We hypothesize that the enhanced cannabinoid-induced interaction between 5-HT2A and D2 receptors and in 5-HT2A and D2 receptors protein levels in the PFCx might provide a molecular mechanism by which activation of cannabinoid receptors might be contribute to the pathophysiology of some cognitive and mood disorders.

Franklin, Jade M.; Carrasco, Gonzalo A.

2013-01-01

184

Increased accumbal dopamine during daily alcohol consumption and subsequent aggressive behavior in rats  

Microsoft Academic Search

Background  Alcohol drinking may lead to increased aggression in certain individuals, and both fighting and drinking increase levels of\\u000a dopamine and serotonin in mesocorticolimbic structures. Assessing the dynamic changes in these neurotransmitters during the\\u000a course of drinking and fighting has remained challenging.\\u000a \\u000a \\u000a \\u000a Objective  The objective of the study was to learn about ongoing monoaminergic activity in the nucleus accumbens of rats that

Annemoon M. M. van Erp; Klaus A. Miczek

2007-01-01

185

Role of Serotonin via 5HT2B Receptors in the Reinforcing Effects of MDMA in Mice  

Microsoft Academic Search

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) reverses dopamine and serotonin transporters to produce efflux of dopamine and serotonin, respectively, in regions of the brain that have been implicated in reward. However, the role of serotonin\\/dopamine interactions in the behavioral effects of MDMA remains unclear. We previously showed that MDMA-induced locomotion, serotonin and dopamine release are 5-HT2B receptor-dependent. The aim of

Stéphane Doly; Jesus Bertran-Gonzalez; Jacques Callebert; Alexandra Bruneau; Sophie Marie Banas; Arnauld Belmer; Katia Boutourlinsky; Denis Hervé; Jean-Marie Launay; Luc Maroteaux; Kenji Hashimoto

2009-01-01

186

The Sea Urchin Embryo, an Invertebrate Model for Mammalian Developmental Neurotoxicity, Reveals Multiple Neurotransmitter Mechanisms for Effects of Chlorpyrifos: Therapeutic Interventions and a Comparison with the Monoamine Depleter, Reserpine  

PubMed Central

Lower organisms show promise for the screening of neurotoxicants that might target mammalian brain development. Sea urchins use neurotransmitters as embryonic growth regulatory signals, so that adverse effects on neural substrates for mammalian brain development can be studied in this simple organism. We compared the effects of the organophosphate insecticide, chlorpyrifos in sea urchin embryos with those of the monoamine depleter, reserpine, so as to investigate multiple neurotransmitter mechanisms involved in developmental toxicity and to evaluate different therapeutic interventions corresponding to each neurotransmitter system. Whereas reserpine interfered with all stages of embryonic development, the effects of chlorpyrifos did not emerge until the mid-blastula stage. After that point, the effects of the two agents were similar. Treatment with membrane permeable analogs of the monoamine neurotransmitters, serotonin and dopamine, prevented the adverse effects of either chlorpyrifos or reserpine, despite the fact that chlorpyrifos works simultaneously through actions on acetylcholine, monoamines and other neurotransmitter pathways. This suggests that different neurotransmitters, converging on the same downstream signaling events, could work together or in parallel to offset the developmental disruption caused by exposure to disparate agents. We tested this hypothesis by evaluating membrane permeable analogs of acetylcholine and cannabinoids, both of which proved effective against chlorpyrifos- or reserpine-induced teratogenesis. Invertebrate test systems can provide both a screening procedure for mammalian neuroteratogenesis and may uncover novel mechanisms underlying developmental vulnerability as well as possible therapeutic approaches to prevent teratogenesis.

Buznikov, Gennady A.; Nikitina, Lyudmila A.; Rakic, Ljubisa M.; Milosevi, Ivan; Bezuglov, Vladimir V.; Lauder, Jean M.; Slotkin, Theodore A.

2007-01-01

187

Self-esteem in remitted patients with mood disorders is not associated with the dopamine receptor D4 and the serotonin transporter genes  

Microsoft Academic Search

Disturbances of the dopaminergic and serotoninergic neurotransmitter systems have been implicated in the pathogenesis of depressive symptoms. Associations have been reported between markers of the two neurotransmitter systems and the presence of illness or severity of depressive episodes, but no attention has been focused on the periods of remission. The present report focuses on a possible association of self-esteem in

Alessandro Serretti; Fabio Macciardi; Daniela Di Bella; Marco Catalano; Enrico Smeraldi

1998-01-01

188

[C-11]{beta}CNT: A new monoamine uptake ligand for studying serotonin and dopamine transporter sites in the living brain with PET  

SciTech Connect

There is considerable interest in measuring serotonin (5HT) and dopamine (DA) function in the human brain. Altered levels of 5HT and DA are recognized in drug abuse, neurotoxicities, psychiatric disorders, and neurodegenerative conditions including Alzheimer`s and Parkinson`s disease. Several phenyltropane analogs of cocaine bind tightly to both DA and 5HT uptake proteins. We have made a new agent from this class called {beta}CNT, 2{beta}-carboxymethyl-3{beta}-(2-naphthyl)-tropane, the isosteric O-for-CH{sub 2} analog of a compound reported to have among the highest measured affinities for DA and 5HT transporters and studied its in vivo brain distributions in animals for the first time. Optically pure {beta}CNT was made from cocaine, and labeled at the O-methyl position by esterification of {beta}CNT-acid with [C-11]CH{sub 3}OTfl under conditions similar to Wilson`s. HPLC-purified (99+%) final products (15-50% eob yield from CO{sub 2}, 40 min synth) had specific activities 0.1-1.2 Ci/{mu}mol at the time of injection. Preliminary [C-11]{beta}{beta}CNT rodent distribution showed very high brain uptake (3% ID at 60 min) and localization (striat: fr cort: hypo: cer: blood, 11: 5: 4: 1: 06). {beta}CNT-PET studies in juvenile pigs (5-20 mCi, 20-35 kg) found rapid brain uptake, and prominent retention (85 min) in midbrain, anterior brainstem and striatum, followed by cortex and olfactory bulb. Paroxetine pretreatment (5HT uptake blocker, 2mg/kg), diminished retention in most brain areas; nomifensine (DA/NE uptake blocker, 6 mg/kg) reduced striatum selectively. Direct comparisons of [C-11]{beta}CNT with other PET transporter radioligands {beta}CFT, {beta}CIT, and {beta}CTT (RTI-32) in the same pig found {beta}CNT had highest overall brain uptake among the agents. These initial results suggest {beta}CNT has favorable properties for imaging both 5HT and DA transporters in vivo, and further evaluation of its potential as a human PET agent is warranted.

Mulholland, G.K.; Zheng, Q.H.; Zhou, F.C. [Indiana Univ. Medical Center, Indianapolis, IN (United States)] [and others

1996-05-01

189

The influence of microinjections of serotonin and dopamine into the dorsal raphé nucleus on the extinction of a conditioned reflex in rats  

Microsoft Academic Search

There is notion extant in the contemporary literature that the serotoninergic (5-HT) system of the brain effects inhibitory control of behavior: pharmacological stimulation of this system reduces the motor activity of animals, attenuates emotional stress reactions, increases the duration of sleep [2], while the systemic administration of the serotonin precursor, 5-hydroxytryptophan [3] or the local injection of serotonin into the

N. P. Shugalev; G. Hartman

1993-01-01

190

Molecular determinants of ligand interaction with serotonin transporters  

Microsoft Academic Search

The serotonin transporter (SERT) is a protein responsible for limiting the spatial and temporal actions of the neurotransmitter serotonin (5-HT) by regulating the concentration of 5-HT in the synapse through a reuptake mechanism. SERT is a target for a variety of drugs, including tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and the abused drugs cocaine and amphetamine. The two aims

David Lance Roman

2004-01-01

191

Optimization of Molecularly Imprinted Polymers of Serotonin for Biomaterial Applications  

Microsoft Academic Search

We prepared molecularly imprinted polymers (MIPs) of serotonin (5-hydroxytryptamine or 5-HT), a neurotransmitter and mood modulator, using a combination of neutral (methacrylamide or acrylamide) and positively charged (methacrylic acid) functional monomers. Water, PBS, acidified methanol and sodium dodecyl sulfate were compared as rinsing solvents for the removal of serotonin from the MIPs. Methacrylamide MIPs rinsed in acidified methanol (92% serotonin

Shahana S. Khurshid; Christine E. Schmidt; Nicholas A. Peppas

2011-01-01

192

Neonatal +-methamphetamine exposure in rats alters adult locomotor responses to dopamine D1 and D2 agonists and to a glutamate NMDA receptor antagonist, but not to serotonin agonists.  

PubMed

Neonatal exposure to (+)-methamphetamine (Meth) results in long-term behavioural abnormalities but its developmental mechanisms are unknown. In a series of experiments, rats were treated from post-natal days (PD) 11-20 (stage that approximates human development from the second to third trimester) with Meth or saline and assessed using locomotor activity as the readout following pharmacological challenge doses with dopamine, serotonin and glutamate agonists or antagonists during adulthood. Exposure to Meth early in life resulted in an exaggerated adult locomotor hyperactivity response to the dopamine D1 agonist SKF-82958 at multiple doses, a high dose only under-response activating effect of the D2 agonist quinpirole, and an exaggerated under-response to the activating effect of the N-methyl-d-aspartic acid (NMDA) receptor antagonist, MK-801. No change in locomotor response was seen following challenge with the 5-HT releaser p-chloroamphetamine or the 5-HT2/3 receptor agonist, quipazine. These are the first data to show that PD 11-20 Meth exposure induces long-lasting alterations to dopamine D1, D2 and glutamate NMDA receptor function and may suggest how developmental Meth exposure leads to many of its long-term adverse effects. PMID:22391043

Graham, Devon L; Amos-Kroohs, Robyn M; Braun, Amanda A; Grace, Curtis E; Schaefer, Tori L; Skelton, Matthew R; Williams, Michael T; Vorhees, Charles V

2012-03-06

193

Pediatric neurotransmitter diseases  

Microsoft Academic Search

The pediatric neurotransmitter disorders represent a challenging group of rare neurometabolic disorders classified on the\\u000a basis of alterations in neurotransmitter metabolic pathways. The disorders are currently classified into disturbances of monoamine\\u000a and gamma-aminobutyric acid (GABA) metabolism, although disorders of other neurotransmitters, such as glutamate and melatonin,\\u000a may well be recognized in future investigations. This review summarizes the clinical and laboratory

Phillip L. Pearl; Denise D. Wallis; K. Michael Gibson

2004-01-01

194

Classical neurotransmitters and neuropeptides involved in generalized epilepsy: a focus on antiepileptic drugs.  

PubMed

We describe the alterations of classical neurotransmitters and neuropeptides in generalized epilepsy. A neuronal network in this disease is developed. Gamma aminobutyric acid (GABA) hypoactivity induces dopamine hyperactivity because dopaminergic neurons are affected by the inhibitory influence of the GABAergic system through GABA(A) receptors. Glutamate hyperactivity is exerted via presynaptic N-methyl-D-aspartate (NMDA) receptors, which strongly inhibit serotoninergic neurons, and via postsynaptic ionotropic glutaminergic receptors, which can induce epileptic seizures. A collection of specific subreceptors of classical neurotransmitters and neuropeptides involved in epileptogenesis is reported. The question arises whether agonists/antagonists of neuropeptides (neuropeptide Y, galanin…) could have additional antiepileptic properties. The effect of conventional and newer antiepileptic drugs interfering with these subreceptors is discussed on the basis of the neuronal network suggested. From these data, it is concluded that new antiepileptic drugs interfering with other specific subreceptors (GABA(B) antagonists, metabotropic glutaminergic receptors subtype 5 (mGlu5R) antagonists, mGlu2/3R agonists, 5-serotonin (5-HT(7)) agonists) could further stabilize the neuronal network in generalized epilepsy. PMID:22050744

Werner, F-M; Coveñas, R

2011-01-01

195

Neurotransmitter regulation of somatostatin secretion by fetal rat cerebral cortical cells in culture.  

PubMed

Extensive studies exploring the regulation of hypothalamic somatostatin GHRIH release have been reported, but the factors regulating GHRIH release in the cerebral cortex have not been well defined. We have studied the effects of central neurotransmitters on GHRIH secretion by cultured fetal rat cerebral cortical cells and on intracellular GHRIH levels. Cells maintained in vitro for 15-20 days were incubated with dopamine (DA), acetylcholine (ACh), gamma-aminobutyric acid (GABA), norepinephrine (NE), serotonin (SE) or histamine (His) (10(-11) M to 10(3) M) for 30 minutes. Following incubation, immunoreactive GHRIH was measured by RIA in cell extracts and incubation media. DA increased intracellular GHRIH content but have no effect on GHRIH in the media. Both media and intracellular GHRIH content were significantly reduced by GABA and SE. The effect of NE was stimulatory at low (10(-9) M) and inhibitory at high (10(-5) M to 10(-3) M) concentrations. ACh was found to increase media GHRIH and to decrease intracellular GHRIH content; 30 min exposure to His did not significantly modify either media or intracellular GHRH. Our findings with fetal rat cerebral cortical cells in culture demonstrate that endogenous neurotransmitters do have the capacity to directly influence GHRIH regulation. PMID:7904279

de los Frailes, M T; Cacicedo, L; Lorenzo, M J; Tolón, R M; Fernández, G; Sánchez Franco, F

1993-10-01

196

Serotonin syndrome  

MedlinePLUS

US Food and Drug Administration. FDA Public Health Advisory: Combined Use of 5-Hydroxytryptamine Receptor Agonists (Triptans), Selective Serotonin Reuptake Inhibitors (SSRIs) or Selective Serotonin/Norepinephrine Reuptake ...

197

Detection of neurotransmitters by a light scattering technique based on seed-mediated growth of gold nanoparticles  

Microsoft Academic Search

A simple light scattering detection method for neurotransmitters has been developed, based on the growth of gold nanoparticles. Neurotransmitters (dopamine, L-dopa, noradrenaline and adrenaline) can effectively function as active reducing agents for generating gold nanoparticles, which result in enhanced light scattering signals. The strong light scattering of gold nanoparticles then allows the quantitative detection of the neurotransmitters simply by using

Li Shang; Shaojun Dong

2008-01-01

198

Alcohol and Neurotransmitter Interactions  

Microsoft Academic Search

Evidence suggests that alcohol affects brain function by interacting with multiple neurotransmitter systems, thereby disrupting the delicate balance between inhibitory and excitatory neurotransmitters. Short-term alcohol exposure tilts this balance in favor of inhibitory influences. After long-term alcohol exposure, however, the brain attempts to compensate by tilting the balance back toward equilibrium. These neurological changes occur as the development of tolerance

C. FERNANDO VALENZUELA

199

Effects of subchronic exposure to styrene on the extracellular and tissue levels of dopamine, serotonin and their metabolites in rat brain  

Microsoft Academic Search

At present, there is controversy over the neurotoxic potential of styrene. Several epidemiological and clinical studies have shown that styrene exposure causes alterations of central nervous system functions in humans. Neurotransmitters have been implicated in the pathogenesis of styrene neurotoxicity in rodents. Several studies carried out on postmortem brain tissue suggest that styrene may alter dopaminergic neurotransmission in rabbit or

F. Gagnaire; M. Chalansonnet; N. Carabin; J.-C. Micillino

2006-01-01

200

In vivo assessment of dopamine D-2 and serotonin S-2 receptors measured by C-11 N-methylspiperone (NMSP) in manic-depressive illness  

Microsoft Academic Search

The hypothesis has been suggested that either the dopaminergic or serotonergic neurotransmitter systems may be involved in manic-depressive illness (MD). The authors have studied 16 subjects with C-11 NMSP PET imaging. Two had never received neuroleptics; 4 were drug free for 1 month at the time of scanning; of these 3 were acutely manic; the rest were on stable lithium

D. F. Wong; G. Pearlson; H. N. Jr. Wagner; R. F. Dannals; S. Suneja; E. Bjorgvinsson; J. M. Links; H. T. Ravert; A. A. Wilson; F. Schaerf

1985-01-01

201

Effects of neurotransmitters and guidance cues on neuronal growth cone guidance via receptor-mediated pathways  

Microsoft Academic Search

Growth cones are motile structures located at the tips of axons and guide axons to their proper target locations during development. Soluble and membrane-bound cues induce growth cone guidance by changing the dynamics of the actin and microtubule cytoskeleton. Neurotransmitters, including serotonin (5-HT) have been established as soluble guidance cues. This project has focused on determining the effects neurotransmitters and

Elisabeth E Garland

2010-01-01

202

Treatment with Tyrosine, a Neurotransmitter Precursor, Reduces Environmental Stress in Humans,  

National Technical Information Service (NTIS)

Acutely stressful situations can disrupt behavior and deplete brain norepinephrine and dopamine, catecholaminergic neurotransmitters. In animals, administration of tyrosine, a food constituent and precursor of the catecholamines, reduces these behavioral ...

H. R. Lieberman L. E. Banderet

1988-01-01

203

Effects of amantadine on circulating neurotransmitters in healthy subjects  

Microsoft Academic Search

Considering that glutamatergic axons innervate the C1(Ad) medullary nuclei, which are responsible for the excitation of the\\u000a peripheral adrenal glands, we decided to investigate catecholamines (noradrenaline, adrenaline and dopamine) plus indolamines\\u000a (plasma serotonin and platelet serotonin) at the blood level, before and after a small oral dose of amantadine, a selective\\u000a NMDA antagonist. We found that the drug provoked a

Fuad Lechin; Bertha van der Dijs; Betty Pardey-Maldonado; Jairo E. Rivera; Scarlet Baez; Marcel E. Lechin

2010-01-01

204

Neurotransmitter imaging in living cells based on native fluorescence detection  

SciTech Connect

A UV laser-based optical microscope and CCD detection system with high sensitivity has been developed to image neurotransmitters in living cells. We demonstrate the detection of serotonin that has been taken up into individual living glial cells (astrocytes) based on its native fluorescence. We found that the fluorescence intensity of astrocytes increased by up to 10 times after serotonin uptake. The temporal resolution of this detection system at 10{sup -4} M serotonin is as fast as 50 ms, and the spatial resolution is diffraction limited. This UV laser microscope imaging system shows promise for studies of spatial-temporal dynamics of neurotransmitter levels in living neurons and glia. 19 refs., 5 figs., 1 tab.

Tan, W.; Yeung, E.S. [Ames Lab., IA (United States)]|[Iowa State Univ., Ames, IA (United States); Parpura, V.; Haydon, P.G. [Iowa State Univ., Ames, IA (United States)

1995-08-01

205

Serotonin 2A receptors differentially contribute to abuse-related effects of cocaine and cocaine-induced nigrostriatal and mesolimbic dopamine overflow in nonhuman primates.  

PubMed

Two of the most commonly used procedures to study the abuse-related effects of drugs in laboratory animals are intravenous drug self-administration and reinstatement of extinguished behavior previously maintained by drug delivery. Intravenous self-administration is widely accepted to model ongoing drug-taking behavior, whereas reinstatement procedures are accepted to model relapse to drug taking following abstinence. Previous studies indicate that 5-HT2A receptor antagonists attenuate the reinstatement of cocaine-maintained behavior but not cocaine self-administration in rodents. Although the abuse-related effects of cocaine have been closely linked to brain dopamine systems, no previous study has determined whether this dissociation is related to differential regulation of dopamine neurotransmission. To elucidate the neuropharmacological and neuroanatomical mechanisms underlying this phenomenon, we evaluated the effects of the selective 5-HT2A receptor antagonist M100907 on intravenous cocaine self-administration and drug- and cue-primed reinstatement in rhesus macaques (Macaca mulatta). In separate subjects, we evaluated the role of 5-HT2A receptors in cocaine-induced dopamine overflow in the nucleus accumbens (n = 4) and the caudate nucleus (n = 5) using in vivo microdialysis. Consistent with previous studies, M100907 (0.3 mg/kg, i.m.) significantly attenuated drug- and cue-induced reinstatement but had no significant effects on cocaine self-administration across a range of maintenance doses. Importantly, M100907 (0.3 mg/kg, i.m.) attenuated cocaine-induced (1.0 mg/kg, i.v.) dopamine overflow in the caudate nucleus but not in the nucleus accumbens. These data suggest that important abuse-related effects of cocaine are mediated by distinct striatal dopamine projection pathways. PMID:23946394

Murnane, Kevin S; Winschel, Jake; Schmidt, Karl T; Stewart, LaShaya M; Rose, Samuel J; Cheng, Kejun; Rice, Kenner C; Howell, Leonard L

2013-08-14

206

Neurotransmitters and Synaptic Transmission  

Microsoft Academic Search

\\u000a The hair cell transmits information about an acoustic signal by releasing a neurotransmitter to excite afferent nerve fibers.\\u000a This results in discharge of the auditory nerve. The release of neurotransmitter by the hair cell is triggered by the entry\\u000a of calcium into the hair cell through voltage-dependent calcium (Vca) channels. Even in the absence of acoustic stimulation, the small resting

William F. Sewell

207

Central serotonin 4 receptors selectively regulate the impulse-dependent exocytosis of dopamine in the rat striatum: in vivo studies with morphine, amphetamine and cocaine  

Microsoft Academic Search

In vivo microdialysis and single-cell extracellular recordings were used to assess the involvement of serotonin4 (5-HT4) receptors in the effects induced by morphine, amphetamine and cocaine on nigrostriatal and mesoaccumbal dopaminergic (DA) pathway activity.The increase in striatal DA release induced by morphine (2.5 mg\\/kg, s.c.) was significantly reduced by the selective 5-HT4 antagonists GR 125487 (0.1 and 1 mg\\/kg, i.p.)

Grégory Porras; Vincenzo Di Matteo; Philippe De Deurwaerdère; Ennio Esposito; Umberto Spampinato

2002-01-01

208

Serotonin: multiphoton imaging and relevant spectral data  

NASA Astrophysics Data System (ADS)

Coupling three-photon microscopy with automated stage movement can now produce a live high resolution map of the neurotransmitter serotonin in a single cross section of the whole rat brain. Accurate quantification of these serotonin images demands appropriate spectral filtering. This requires one to consider that the spectral characteristics of serotonin show a remarkable variation as it non-covalently associates with different molecules, as we discuss here. Also it is known that serotonin emission changes when it forms a covalent adduct with para-formaldehyde. This provides a potential route for producing a whole brain serotonin map using multiphoton microscopy in a fixed rat brain. Here we take the initial step showing that multiphoton microscopy of this adduct can quantitatively image chemically induced changes in serotonin distribution.

Kaushalya, S. K.; Nag, Suman; Balaji, J.; Maiti, S.

2008-03-01

209

Dopamine may be ‘hyper’ with respect to noradrenaline metabolism, but ‘hypo’ with respect to serotonin metabolism in children with attention-deficit hyperactivity disorder  

Microsoft Academic Search

Noradrenaline: Hechtman (J Psychiat Neurosci 1994;19:193) argued for a role for frontal dopamine (DA) and noradrenaline (NA) in ADHD, where Oades (Prog Neurobiol 1987;29:365) has described lateralised functional impairments. Mechanisms (e.g. via alpha-2 sites) for stimulating low NA activity in ADHD children (J Am Acad Child Adolesc Psychiatry 1997;36:1688) in order to promote interactions with mesocortical DA have been discussed

Robert D Oades

2002-01-01

210

THE ROLE OF NEUROTRANSMITTERS IN ALCOHOL DEPENDENCE: ANIMAL RESEARCH  

Microsoft Academic Search

Abstract — Animal studies have demonstrated,that alcohol changes neurotransrrutter concentrations in the brain. These changes in levels of dopamine, serotonin, ^aminobutync acid (GABA), endogenous opioid peptides, and noradrcnaline are associated with activation of reward centres in the brain. It is this property of alcohol that is believed to be responsible for the reinforcing effect of alcohol consumption in rats. One

Philippe De Witte

211

Serotonin and brain development: role in human developmental diseases  

Microsoft Academic Search

Serotonin is known to play a role in brain development prior to the time it assumes its role as a neurotransmitter in the mature brain. Serotonin regulates both the development of serotonergic neurons (termed autoregulation of development) and the development of target tissues. In both cases, the astroglial-derived protein, S-100? plays a role. Disruption of serotonergic development can leave permanent

Patricia M. Whitaker-Azmitia

2001-01-01

212

Drosophila 5HT_2 Serotonin Receptor: Coexpression with Fushi-Tarazu During Segmentation  

Microsoft Academic Search

Serotonin, first described as a neurotransmitter in invertebrates, has been investigated mostly for its functions in the mature central nervous system of higher vertebrates. Serotonin receptor diversity has been described in the mammalian brain and in insects. We report the isolation of a cDNA coding for a Drosophila melanogaster serotonin receptor that displays a sequence, a gene organization, and pharmacological

Jean-Francois Colas; Jean-Marie Launay; Odile Kellermann; Philippe Rosay; Luc Maroteaux

1995-01-01

213

Is serotonin hyperalgesic or analgesic?  

Microsoft Academic Search

Serotonin (5-hydroxtryptamine, 5-HT) is an important molecule in pain processing and modulation. Whether 5-HT has an analgesic\\u000a or hyperalgesic action depends on the cell type and type of receptor it acts on. In the periphery, 5-HT sensitizes afferent\\u000a nerve fibers, thus contributing to hyperalgesia in infiammation and nerve injury. In the trigeminal system, agonism at 5-HT1B\\/D receptors reduces neurotransmitter release,

Claudia Sommer

2006-01-01

214

Neurotransmitter-related features of the retinal pigment epithelium.  

PubMed

Various neurotransmitter-related biochemical features of the separated pigment epithelium and neural retina of the cow have been examined. The pigment epithelium contains high affinity binding sites for several pharmacological agents thought to attach to neurotransmitter receptor sites with a high degree of specificity. Thus, serotonergic, adrenergic and opiate receptors appear to be present in the pigment epithelium. Serotonin has also been detected in this region. Several neuropeptides were found in the pigment epithelium. Relatively large amounts of neurotensin and met-enkephalin were present, but substance P was not detected. PMID:20487951

Bondy, S C; Ali, S F; Hong, J S; Wilson, W E; Fletcher, T; Chader, G

1983-01-01

215

Automated mass spectrometric analysis of urinary and plasma serotonin  

Microsoft Academic Search

Serotonin emerges as crucial neurotransmitter and hormone in a growing number of different physiologic processes. Besides\\u000a extensive serotonin production previously noted in patients with metastatic carcinoid tumors, serotonin now is implicated\\u000a in liver cell regeneration and bone formation. The aim was to develop a rapid, sensitive, and highly selective automated on-line\\u000a solid-phase extraction method coupled to high-performance liquid chromatography–tandem mass

Wilhelmina H. A. de Jong; Marianne H. L. I. Wilkens; Elisabeth G. E. de Vries; Ido P. Kema

2010-01-01

216

The genetics of schizophrenia: glutamate not dopamine?  

PubMed

The major targets of current drugs used in mental health, such as neurotransmitter receptors and transporters, are based on serendipitous findings from several decades ago, and there is currently a severe drought of new drug targets. There is a pressing need for novel drugs, and much hope has been placed on the use of molecular genetics to help define them. However, despite evidence for a genetic basis to schizophrenia stretching back for over a century, and a heritability of about 80%, the identification of susceptibility genes has been an uphill struggle. Candidate gene studies, which have generally focussed on obvious candidates from the dopamine and serotonin systems, as well as genes involved in brain development, have not generally been successful, although meta-analysis indicates that the dopamine D3 receptor gene (DRD3) and the serotonin receptor gene type 2A (HTR2A) may have a very small influence on risk. Linkage analysis has provided robust evidence of genetic loci, for example, on chromosomes 8p, 13q and 22q, and also implies shared genetic aetiology with bipolar disorder. The identification of these loci together with advances in genetic technology, especially the characterisation of polymorphisms, the understanding of haplotypes and the development of statistical methods, has lead to the identification of several plausible susceptibility genes, including neuregulin 1, proline dehydrogenase and dysbindin. Interestingly, these genes point more towards a role for the glutamate pathway rather than the dopamine pathway in schizophrenia. We have attempted to replicate some of these findings in schizophrenic patients from SW China, and we find significant association with a novel neuregulin 1 haplotype, with proline dehydrogenase polymorphisms, but not with catechol-O-methyltransferase (COMT). The replication of neuregulin 1 association on chromosome 8p by several investigators is the most convincing to date, and the presence of a syndrome similar to dementia praecox of 8p linked families, and the lack of linkage of bipolar disorder to this region is a testament to the ideas of Kraepelin more than 100 years ago. PMID:14623361

Collier, David A; Li, Tao

2003-11-01

217

Cortical serotonin and norepinephrine denervation in parkinsonism: Preferential loss of the beaded serotonin innervation  

PubMed Central

Parkinson’s Disease (PD) is marked by prominent motor symptoms that reflect striatal dopamine insufficiency. However, non-motor symptoms, including depression, are common in PD. These changes have been suggested to reflect pathological involvement of non-dopaminergic systems. We examined regional changes in serotonin and norepinephrine systems in mice treated with two different 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment paradigms and that survived for 3 or 16 weeks after the last MPTP injection. MPTP caused a decrease in striatal dopamine concentration, the magnitude of which depended on the treatment regimen and survival interval after MPTP treatment. There was significant involvement of other subcortical areas receiving a dopamine innervation, but no consistent changes in serotonin or norepinephrine levels in subcortical sites. In contrast, we observed an enduring decrease in serotonin and norepinephrine concentrations in both the somatosensory and medial prefrontal (PFC) cortex. Immunohistochemical studies also revealed a decrease in the density of PFC norepinephrine and serotonin axons. The decrease in the cortical serotonergic innervation preferentially involved the thick beaded but not smooth fine serotonin axons. Similar changes in the serotonin innervation of postmortem samples of the prefrontal cortex from idiopathic PD cases were seen. Our findings point to a major loss of the serotonin and norepinephrine innervations of the cortex in MPTP-induced parkinsonism, and suggest that loss of the beaded cortical serotonin innervation is associated with a predisposition to the development of depression in PD.

Nayyar, Tultul; Bubser, Michael; Ferguson, Marcus C.; Neely, M. Diana; Goodwin, J. Shawn; Montine, Thomas J.; Deutch, Ariel Y.; Ansah, Twum A.

2009-01-01

218

Analysis of drug effects on neurotransmitter release  

SciTech Connect

The release of neurotransmitter is routinely studied in a superfusion system in which serial samples are collected and the effects of drugs or other treatments on the amount of material in the superfusate is determined. With frequent sampling interval, this procedure provides a mechanism for dynamically characterizing the release process itself. Using automated data collection in conjunction with polyexponential computer analysis, the equation which describes the release process in each experiment is determined. Analysis of the data during the nontreated phase of the experiment allows an internal control to be used for accurately assessing any changes in neurotransmitter release which may occur during a subsequent treatment phase. The use of internal controls greatly improves the signal to noise ratio and allows determinations of very low concentrations of drugs on small amounts of tissue to be made. In this presentation, the effects of 10 ..mu..M nicotine on /sup 3/H-dopamine release in rat nucleus accumbens is described. The time course, potency and efficacy of the drug treatment is characterized using this system. Determinations of the exponential order of the release as well as the rate constants allow one to study the mechanism of the release process. A description of /sup 3/H-dopamine release in normal as well as Ca/sup + +/-free medium is presented.

Rowell, P.; Garner, A.

1986-03-05

219

Schizophrenia and dopamine receptors.  

PubMed

Schizophrenia patients are behaviorally supersensitive to dopamine-like drugs such as amphetamine or methylphenidate, meaning that patients respond to such drugs with increased psychotic symptoms, as compared to control subjects. A basis of such supersensitivity may be an increased pre-synaptic release of dopamine or a post-synaptic elevation of D2 receptors or of D2High receptors in active stages of schizophrenia. While the pre-synaptic release of dopamine is normal in stable patients with schizophrenia, brain imaging studies find that D2 receptors are increased by an average of 5.8% in antipsychotic-free schizophrenia patients. It is possible that the behavioral supersensitivity may stem from more D2High receptors in schizophrenia. Although the antipsychotic/dopamine D2 receptor can exist in vitro in a state of high affinity for dopamine (as D2High), or in a state of low affinity for dopamine (as D2Low), there is no clear evidence that D2High states can be selectively labeled or stably exist in vivo. Nevertheless, two studies revealed an 80% increase in apparent D2High receptors in schizophrenia patients after reducing endogenous dopamine. The elevation in apparent D2High receptors in vivo in schizophrenia matches the elevation in D2High receptors in vitro in animal models of psychosis, including dopamine-supersensitive animals pretreated with amphetamine, marijuana, or phencyclidine, or animals with gene knockouts in various neurotransmitter pathways, including those for glutamate receptors. The elevation of D2High receptors in vitro and the increased apparent D2High receptors in vivo is consistent with behavioral dopamine supersensitivity in schizophrenia patients. PMID:23860356

Seeman, Philip

2013-07-13

220

Transport of biogenic amine neurotransmitters at the mouse blood-retina and blood-brain barriers by uptake1 and uptake2.  

PubMed

Uptake1 and uptake2 transporters are involved in the extracellular clearance of biogenic amine neurotransmitters at synaptic clefts. We looked for them at the blood-brain barrier (BBB) and blood-retina barriers (BRB), where they could be involved in regulating the neurotransmitter concentration and modulate/terminate receptor-mediated effects within the neurovascular unit (NVU). Uptake2 (Oct1-3/Slc22a1-3, Pmat/Slc29a4) and Mate1/Slc47a1 transporters are also involved in the transport of xenobiotics. We used in situ carotid perfusion of prototypic substrates like [(3)H]-1-methyl-4-phenylpyridinium ([(3)H]-MPP(+)), [(3)H]-histamine, [(3)H]-serotonin, and [(3)H]-dopamine, changes in ionic composition and genetic deletion of Oct1-3 carriers to detect uptake1 and uptake2 at the BBB and BRB. We showed that uptake1 and uptake2 are involved in the transport of [(3)H]-dopamine and [(3)H]-MPP(+) at the blood luminal BRB, but not at the BBB. These functional studies, together with quantitative RT-PCR and confocal imaging, suggest that the mouse BBB lacks uptake1 (Net/Slc6a2, Dat/Slc6a3, Sert/Slc6a4), uptake2, and Mate1 on both the luminal and abluminal sides. However, we found evidence for functional Net and Oct1 transporters at the luminal BRB. These heterogeneous transport properties of the brain and retina NVUs suggest that the BBB helps protect the brain against biogenic amine neurotransmitters in the plasma while the BRB has more of a metabolic/endocrine role. PMID:22850405

André, Pascal; Saubaméa, Bruno; Cochois-Guégan, Véronique; Marie-Claire, Cynthia; Cattelotte, Julie; Smirnova, Maria; Schinkel, Alfred H; Scherrmann, Jean-Michel; Cisternino, Salvatore

2012-08-01

221

Protective effect of taurine on the decreased biogenic amine neurotransmitter levels in the brain of mice exposed to arsenic.  

PubMed

Arsenic (As) exposure has a toxic effect on the central nervous system, especially on learning and memory. Norepinephrine (NE), dopamine (DA), and serotonin (5-HT) play an important role in learning and memory function of the brain. In the present study, the protective effect of taurine on the disturbed biogenic amine neurotransmitter levels in the mouse brain induced by arsenic was examined. Sixty SPF mice were divided into three groups. The As exposure group was administered with 4 ppm As(2)O(3) through drinking water for 60 days. The protective group was treated with both 4 ppm As(2)O(3) and 150 mg/kg taurine. The control group was given drinking water alone. The levels of NE, DA, and 5-HT were determined by HPLC in the cerebrum and cerebellum of mice. Ultrastructure of synapses in brain tissue of mice was observed in these groups by transmission electron microscopy. The mRNA expressions of dopamine beta hydroxylase (DBH), tyrosine hydroxylase (TH), and tryptophan hydroxylase (TPH) as NE, DA, and 5-HT synzymes were also analyzed by real-time RT-PCR. The results showed that the concentrations of NE, DA, and 5-HT; the number of synaptic vesicles; and the expressions of TH, TPH, and DBH genes in the brains of mice exposed to As alone were significantly decreased. However, administration of taurine significantly alleviated the toxic effect on biochemicals detected in the experiment, compared with that in the brain of mice exposed to As alone. These results indicated that taurine was effective in counteracting the decreased biogenic amine neurotransmitter level and the mRNA expressions of their synzymes induced by arsenic. PMID:23392890

Liu, Xiaohui; Piao, Fengyuan; Li, Yachen

2013-01-01

222

Disturbances in the Secretion of Neurotransmitters in IA-2/IA-2? Null Mice: Changes in Behavior, Learning and Life Span  

PubMed Central

Islet-associated protein 2 (IA-2) and IA-2? are major autoantigens in type 1 diabetes and transmembrane proteins in dense core secretory vesicles (DCV) of neuroendocrine cells. The deletion of these genes results in a decrease in insulin secretion. The present study was initiated to test the hypothesis that this deletion not only affects the secretion of insulin, but has a more global effect on neuroendocrine secretion that leads to disturbances in behavior and learning. Measurement of neurotransmitters showed that norepinephrine, dopamine and serotonin were significantly decreased in the brain of double knockout (DKO) mice (P< 0.05 to <0.001). In tests evaluating anxiety-like behavior and conditioned-learning, the DKO mice showed a highly significant increase in anxiety-like behavior (P<0.01 to <0.001) and impairment of conditioned learning (P<0.01) as compared to WT mice. The DKO mice also displayed an increase in spontaneous and induced seizures (P<0.01) and age-related death. Contrary to the generally held view that IA-2 and IA-2? are expressed exclusively in DCV, subcellular fractionation studies revealed that IA-2?, but not IA-2, co-purifies with fractions rich in synaptic vesicles (SV), and that the secretion of dopamine, GABA and glutamate from the synaptosomes of the DKO mice was significantly decreased as was the number of SV (P<0.01). Taken together, these findings show that IA-2? is present in both DCV and SV, and that the deletion of IA-2/IA-2? has a global effect on the secretion of neurotransmitters. The impairment of secretion leads to behavioral and learning disturbances, seizures and reduced life span.

Nishimura, Takuya; Kubosaki, Atsutaka; Ito, Yoichiro; Notkins, Abner L.

2009-01-01

223

Serotonin: good or bad for bone  

PubMed Central

Besides its action as a neurotransmitter, serotonin has multiple physiological functions in several peripheral organs. Recently, Yadav et al. suggested that peripheral serotonin produced in the gut was a major negative regulator of osteoblast proliferation. These data were challenged by Cui et al. that showed no change in bone density in mature mice with a global invalidation of tryptophan hydroxylase 1, the enzyme responsible of serotonin synthesis in the periphery. In this context, we showed that osteoclasts are able to synthetize serotonin that acts locally to induce osteoclast precursors differentiation. Our data and previous results from others suggest that rather than acting as a hormone, serotonin produced in the bone could act locally on osteoclast and osteoblast realizing in the bone a complete micro-serotoninergic system.

de Vernejoul, Marie-Christine; Collet, Corinne; Chabbi-Achengli, Yasmine

2012-01-01

224

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain  

PubMed Central

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn2+ into the prefrontal cortex indicated that DAT KO mice have a truncated Mn2+ distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn2+ transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here.

Zhang, Xiaowei; Bearer, Elaine L.; Boulat, Benoit; Hall, F. Scott; Uhl, George R.; Jacobs, Russell E.

2010-01-01

225

Measuring the serotonin uptake site using (/sup 3/H)paroxetine--a new serotonin uptake inhibitor  

SciTech Connect

Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand.

Gleiter, C.H.; Nutt, D.J.

1988-01-01

226

Regulation of vesicular neurotransmitter transporters  

Microsoft Academic Search

Neurotransmitters are key molecules of neurotransmission. They are concentrated first in the cytosol and then in small synaptic vesicles of presynaptic terminals by the activity of specific neurotransmitter transporters of the plasma and the vesicular membrane, respectively. It has been shown that postsynaptic responses to single neurotransmitter packets vary over a wide range, which may be due to a regulation

G. Ahnert-Hilger; M. Höltje; I. Pahner; S. Winter; I. Brunk

2003-01-01

227

A short update on the structure of drug binding sites on neurotransmitter transporters  

PubMed Central

Background The dopamine (DAT), noradrenalin (NET) and serotonin (SERT) transporters are molecular targets for different classes of psychotropic drugs. Cocaine and the SSRI (S)-citalopram block neurotransmitter reuptake competitively, but while cocaine is a non-selective reuptake inhibitor, (S)-citalopram is a selective SERT inhibitor. Findings Here we present comparisons of the binding sites and the electrostatic potential surfaces (EPS) of DAT, NET and SERT homology models based on two different LeuTAa templates; with a substrate (leucine) in an occluded conformation (PDB id 2a65), and with an inhibitor (tryptophan) in an open-to-out conformation (PDB id 3f3a). In the occluded homology models, two conserved aromatic amino acids (tyrosine and phenylalanine) formed a gate between the putative binding pockets, and this contact was interrupted in the open to out conformation. The EPS of DAT and NET were generally negative in the vestibular area, whereas the EPS of the vestibular area of SERT was more neutral. Conclusions The findings presented here contribute as an update on the structure of the binding sites of DAT, NET and SERT. The updated models, which have larger ligand binding site areas than models based on other templates, may serve as improved tools for virtual ligand screening.

2011-01-01

228

Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6.  

PubMed

The SLC6 family is a diverse set of transporters that mediate solute translocation across cell plasma membranes by coupling solute transport to the cotransport of sodium and chloride down their electrochemical gradients. These transporters probably have 12 transmembrane domains, with cytoplasmic N- and C-terminal tails, and at least some may function as homo-oligomers. Family members include the transporters for the inhibitory neurotransmitters GABA and glycine, the aminergic transmitters norepinephrine, serotonin, and dopamine, the osmolytes betaine and taurine, the amino acid proline, and the metabolic compound creatine. In addition, this family includes a system B(0+) cationic and neutral amino acid transporter, and two transporters for which the solutes are unknown. In general, SLC6 transporters act to regulate the level of extracellular solute concentrations. In the central and the peripheral nervous system, these transporters can regulate signaling among neurons, are the sites of action of various drugs of abuse, and naturally occurring mutations in several of these proteins are associated with a variety of neurological disorders. For example, transgenic animals lacking specific aminergic transporters show profoundly disturbed behavioral phenotypes and probably represent excellent systems for investigating psychiatric disease. SLC6 transporters are also found in many non-neural tissues, including kidney, intestine, and testis, consistent with their diverse physiological roles. Transporters in this family represent attractive therapeutic targets because they are subject to multiple forms of regulation by many different signaling cascades, and because a number of pharmacological agents have been identified that act specifically on these proteins. PMID:12719981

Chen, Nian-Hang; Reith, Maarten E A; Quick, Michael W

2003-04-29

229

Estradiol modulates neurotransmitter concentrations in the developing zebra finch song system.  

PubMed

The neural song system in zebra finches is highly sexually dimorphic; only males sing and the brain regions controlling song are far larger in males than females. Estradiol (E2) administered during development can partially masculinize both structure and function. However, additional mechanisms, including those through which E2 may act, remain unclear. Male and female zebra finches were treated with E2 or control vehicle from post-hatching days 3 through 25, at which time norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were measured in individual nuclei of the song system. Main effects of sex were not detected. However, E2 increased NE in the robust nucleus of the arcopallium (RA). In HVC (proper name), the hormone decreased 5-HT across the two sexes and increased DA in females only. These effects suggest that, while baseline levels of these neurotransmitters may not contribute to sexually dimorphic development of the song system, they could play specific roles in functions common to both sexes and/or in modification of the song system by exogenous E2. PMID:23628476

Wade, Juli; Peabody, Camilla; Tang, Yu Ping; Qi, Linda; Burnett, Robert

2013-04-27

230

Development of the Wireless Instantaneous Neurotransmitter Concentration System for intraoperative neurochemical monitoring using fast-scan cyclic voltammetry  

PubMed Central

Object Emerging evidence supports the hypothesis that modulation of specific central neuronal systems contributes to the clinical efficacy of deep brain stimulation (DBS) and motor cortex stimulation (MCS). Real-time monitoring of the neurochemical output of targeted regions may therefore advance functional neurosurgery by, among other goals, providing a strategy for investigation of mechanisms, identification of new candidate neurotransmitters, and chemically guided placement of the stimulating electrode. The authors report the development of a device called the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for intraoperative neurochemical monitoring during functional neurosurgery. This device supports fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode (CFM) for real-time, spatially and chemically resolved neurotransmitter measurements in the brain. Methods The FSCV study consisted of a triangle wave scanned between ?0.4 and 1 V at a rate of 300 V/second and applied at 10 Hz. All voltages were compared with an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single carbon fiber (r = 2.5 ?m) into a glass capillary and pulling the capillary to a microscopic tip by using a pipette puller. The exposed carbon fiber (that is, the sensing region) extended beyond the glass insulation by ~ 100 ?m. The neurotransmitter dopamine was selected as the analyte for most trials. Proof-of-principle tests included in vitro flow injection and noise analysis, and in vivo measurements in urethane-anesthetized rats by monitoring dopamine release in the striatum following high-frequency electrical stimulation of the medial forebrain bundle. Direct comparisons were made to a conventional hardwired system. Results The WINCS, designed in compliance with FDA-recognized consensus standards for medical electrical device safety, consisted of 4 modules: 1) front-end analog circuit for FSCV (that is, current-to-voltage transducer); 2) Bluetooth transceiver; 3) microprocessor; and 4) direct-current battery. A Windows-XP laptop computer running custom software and equipped with a Universal Serial Bus–connected Bluetooth transceiver served as the base station. Computer software directed wireless data acquisition at 100 kilosamples/second and remote control of FSCV operation and adjustable waveform parameters. The WINCS provided reliable, high-fidelity measurements of dopamine and other neurochemicals such as serotonin, norepinephrine, and ascorbic acid by using FSCV at CFM and by flow injection analysis. In rats, the WINCS detected subsecond striatal dopamine release at the implanted sensor during high-frequency stimulation of ascending dopaminergic fibers. Overall, in vitro and in vivo testing demonstrated comparable signals to a conventional hardwired electrochemical system for FSCV. Importantly, the WINCS reduced susceptibility to electromagnetic noise typically found in an operating room setting. Conclusions Taken together, these results demonstrate that the WINCS is well suited for intraoperative neurochemical monitoring. It is anticipated that neurotransmitter measurements at an implanted chemical sensor will prove useful for advancing functional neurosurgery.

Bledsoe, Jonathan M.; Kimble, Christopher J.; Covey, Daniel P.; Blaha, Charles D.; Agnesi, Filippo; Mohseni, Pedram; Whitlock, Sidney; Johnson, David M.; Horne, April; Bennet, Kevin E.; Lee, Kendall H.; Garris, Paul A.

2009-01-01

231

Boolean network analysis of a neurotransmitter signaling pathway  

Microsoft Academic Search

BackgroundA Boolean network is a simple computational model that may provide insight into the overall behavior of genetic networks and is represented by variables with two possible states (on\\/off), of the individual nodes\\/genes of the network. In this study, a Boolean network model has been used to simulate a molecular pathway between two neurotransmitter receptor, dopamine and glutamate receptor, systems

Simone Gupta; Siddharth S. Bisht; Ritushree Kukreti; Sanjeev Jain; Samir K. Brahmachari

2007-01-01

232

Action of Androgenic Steroids on Brain Neurotransmitters in Rats  

Microsoft Academic Search

The effects of androgenic steroids on the dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) contents of different brain regions have been studied in order to elucidate the possible involvement of neurotransmitters in the negative feedback action of androgens. Administration of testosterone propionate (TP); (100 ?g\\/kg or 5 mg\\/kg, i.p.) increased plasma testosterones, which reached a maximum at about 30 min

I. Vermes; M. Várszegi; É. K. Tóth; G. Telegdy

1979-01-01

233

Tritium-3-N-methylspiperone labels D2 dopamine receptors in basal ganglia and S2 serotonin receptors in cerebral cortex  

SciTech Connect

Detailed studies of the properties of /sup 3/H-3-N-methylspiperone (NMSP) binding in rat and human brain homogenates were performed at 37/sup 0/C. In homogenates of rat striatum and frontal cortex and human caudate and frontal cortex tissues, the specific binding was found to be saturable. Rat caudate contained 33.2 pmol/gm wet-weight tissue and displayed an equilibrium dissociation constant (Kd) of 8.7 X 10(-11) M; rat frontal cortex contained 18.5 pmol/gm wet-weight tissue and displayed a Kd of 1.5 X 10(-10) M. Human caudate contained 8.96 pmol/gm wet-weight tissue and displayed a Kd of 1.1 X 10(-10) M; human frontal cortex possessed 9.8 pmol/gm wet-weight tissue and a Kd of 4.4 X 10(-10) M. Kinetic studies revealed a very rapid rate of association in all the tissues studied. The rate of dissociation was relatively slow in all 4 tissue preparations; the dissociation rate was somewhat slower in rat striatum and human caudate relative to rat and human frontal cortex. This was consistent with the somewhat higher affinity, relative to frontal cortex, displayed by /sup 3/H-NMSP in rat striatal and human caudate tissue. The pharmacological properties of the specific binding in rat striatal and human caudate tissues were very similar and indicated the presence of brain D2 dopamine receptors. In rat and human frontal cortex tissue homogenates, the pharmacological characteristics of the specific binding indicated the presence of 5-HT2 receptors.

Lyon, R.A.; Titeler, M.; Frost, J.J.; Whitehouse, P.J.; Wong, D.F.; Wagner, H.N. Jr.; Dannals, R.F.; Links, J.M.; Kuhar, M.J.

1986-10-01

234

Development of neurotransmitter metabolism in embryos of the leech Haementeria ghilianii.  

PubMed

We have investigated the development of neurotransmitter metabolism in embryos of the glossiphoniid leech Haementeria ghilianii. The neurotransmitter content of dissected embryonic tissues was measured by means of radioenzymatic assays, while the presence of neurotransmitters in individual identified neurons was detected by means of immunocytochemical and monoamine histofluorescence techniques. The capacity for synthesis of neurotransmitters was measured by incubating dissected embryonic tissues in radiolabeled neurotransmitter precursors. A specific neurotransmitter uptake system present in some neurons was detected by means of an autoradiographic technique. At an early stage of development of the nervous system, when most neurons are just beginning process outgrowth, the nerve cord acquires the capacity to synthesize ACh, 5-HT, and GABA from their immediate precursors, and contains ACh. Moreover, 5-HT-immunoreactive neurons and neurons that are capable of GABA uptake can be identified. Dopamine-containing neurons are first detected by their histofluorescence at a slightly later stage, after process outgrowth is under way. As development continues, the content of and capacity for synthesis of these neurotransmitters increase, as does the number of neurons capable of GABA uptake. During the earlier stages of development, ACh content exceeds 5-HT content, which in turn exceeds dopamine content. By the end of embryogenesis, however, 5-HT and dopamine contents have greatly increased relative to ACh content, with 5-HT content exceeding ACh content by a factor of 2. Of the neurotransmitters thus far studied, 5-HT is present in the highest amount in the juvenile and adult nerve cord. Our results indicate that in the development of the leech nervous system neurotransmitter metabolism is one of the first neuronal characters to differentiate and that the subsequent levels of the different neurotransmitters are differentially regulated. PMID:2880941

Glover, J C; Stuart, D K; Cline, H T; McCaman, R E; Magill, C; Stent, G S

1987-02-01

235

cDNA Encoding the Rat D, Dopamine Receptor Linked to Adenylyl Cyclase Activation and Expression of the Receptor Protein in Plasmid-Transfected Cell Lines.  

National Technical Information Service (NTIS)

Dopamine receptors belong to a large class of neurotransmitter and hormone receptors which are linked to their signal transduction pathways via guanine nucleotide binding regulatory (G) proteins, and are amongst the most intensively studied neurotransmitt...

D. Sibley F. Monsma L. Mahan L. McVitte

1990-01-01

236

Chromosome 11: gene for dopamine receptors, Matt RidleySite: DNA Interactive (www.dnai.org)  

NSDL National Science Digital Library

Interviewee: Matt Ridley DNAi Location:Genome>tour>genome spots>Dopamine receptor Location: chromosome 11 gene name: D4DR (dopamine receptor) This gene on chromosome 11 appears to influence personality. The protein produced from this gene is a receptor for the neurotransmitter dopamine. Dopamine pathways control many aspects of the brain, including blood flow. If this gene contains many repeated sequences the person is less responsive to dopamine and more likely to seek external "thrills" in their lives.

2008-10-06

237

Serotonin syndrome.  

PubMed

Serotonin syndrome is a preventable, drug-related complication that results from increased brainstem serotonin activity, usually precipitated by the use of one or more serotonergic drugs. Its clinical presentation consists of autonomic dysfunction, alteration in mental status, and neuromuscular disorder. Early recognition and treatment is important, because this condition is potentially fatal. Management includes withdrawal of causative agents and supportive measures such as hemodynamic stabilization, sedation, temperature control, hydration, and monitoring for complications. Serotonin antagonists, specifically cyproheptadine, have been used, but the documented benefits are purely anecdotal. PMID:16681290

Prator, Bettina C

2006-04-01

238

Glutamate–dopamine–GABA interactions in the aging basal ganglia  

Microsoft Academic Search

The study of neurotransmitter interactions gives a better understanding of the physiology of specific circuits in the brain. In this review we focus mostly on our own results on the interaction of the neurotransmitters glutamate, dopamine and GABA in the basal ganglia during the normal process of aging. We review first the studies on the action of endogenous glutamate on

Francisco Mora; Gregorio Segovia; Alberto del Arco

2008-01-01

239

Serotonin Syndrome  

MedlinePLUS

... 2008;33:29. Boyer EW, et al. Current concepts: The serotonin syndrome. The New England Journal of ... conditions of use policy (Updated July 13, 2013) LEGAL CONDITIONS AND TERMS OF USE APPLICABLE TO ALL ...

240

Serotonin-Labeled CdSe Nanocrystals: Applications for Neuroscience  

NASA Astrophysics Data System (ADS)

Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter which has been linked to the regulation of critical behaviors including sleep, appetite, and mood. The serotonin transporter (SERT) is a 12-transmembrane domain protein responsible for clearance of serotonin from extracellular spaces following release. In order to assess the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters we have measured the ability of serotonin-labeled CdSe nanocrystals (SNACs) to block the uptake of tritiated serotonin by the human and Drosophila serotonin transporters (hSERT and dSERT). Estimated Ki values, the SNAC concentration at which half of the serotonin transport activity is blocked, were determined by nonlinear regression to be Ki (hSERT ) = 74uM and Ki (dSERT ) = 29uM. These values and our inability to detect free serotonin indicate that SNACs selectively interact with the serotonin recognition site of the transporter. We have also exposed the SNACs to cells containing ionotropic serotonin receptors and have measured the electrical response of the cell using a two microelectrode voltage clamp. We find that serotonin receptors do respond to the SNACs and we measure currents similar to the free serotonin response. These results indicate that ligand-conjugated nanocrystals can be used to label both receptor and transporter proteins. Initial fluorescence labeling experiments will be discussed.

Kippeny, Tadd; Adkins, Erika; Adams, Scott; Thomlinson, Ian; Schroeter, Sally; Defelice, Louis; Blakely, Randy; Rosenthal, Sandra

2000-03-01

241

A standardized chinese herbal decoction, kai-xin-san, restores decreased levels of neurotransmitters and neurotrophic factors in the brain of chronic stress-induced depressive rats.  

PubMed

Kai-xin-san (KXS), a Chinese herbal decoction being prescribed by Sun Simiao in Beiji Qianjin Yaofang about 1400 years ago, contains Ginseng Radix et Rhizoma, Polygalae Radix, Acori tatarinowii Rhizoma, and Poria. KXS has been used to treat stress-related psychiatric disease with the symptoms of depression and forgetfulness in ancient China until today. However, the mechanism of its antidepression action is still unknown. Here, the chronic mild-stress-(CMS-) induced depressive rats were applied in exploring the action mechanisms of KXS treatment. Daily intragastric administration of KXS for four weeks significantly alleviated the CMS-induced depressive symptoms displayed by enhanced sucrose consumption. In addition, the expressions of those molecular bio-markers relating to depression in rat brains were altered by the treatment of KXS. These KXS-regulated brain biomarkers included: (i) the levels of dopamine, norepinephrine, and serotonin (ii) the transcript levels of proteins relating to neurotransmitter metabolism; (iii) the transcript levels of neurotrophic factors and their receptors. The results suggested that the anti-depressant-like action of KXS might be mediated by an increase of neurotransmitters and expression of neurotrophic factors and its corresponding receptors in the brain. Thus, KXS could serve as alternative medicine, or health food supplement, for patients suffering from depression. PMID:22973399

Zhu, Kevin Yue; Mao, Qing-Qiu; Ip, Siu-Po; Choi, Roy Chi-Yan; Dong, Tina Ting-Xia; Lau, David Tai-Wai; Tsim, Karl Wah-Keung

2012-08-29

242

Neurosteroid and neurotransmitter alterations in Parkinson's disease.  

PubMed

Parkinson's disease (PD) is associated with a massive loss of dopaminergic cells in the substantia nigra leading to dopamine hypofunction and alteration of the basal ganglia circuitry. These neurons, are under the control, among others, of the excitatory glutamatergic and inhibitory ?-aminobutyric acid (GABA) systems. An imbalance between these systems may contribute to excitotoxicity and dopaminergic cell death. Neurosteroids, a group of steroid hormones synthesized in the brain, modulate the function of several neurotransmitter systems. The substantia nigra of the human brain expresses high concentrations of allopregnanolone (3?, 5?tetrahydroprogesterone), a neurosteroid that positively modulates the action of GABA at GABAA receptors and of 5?-dihydroprogesterone, a neurosteroid acting at the genomic level. This article reviews the roles of NS acting as neuroprotectants and as GABAA receptor agonists in the physiology and pathophysiology of the basal ganglia, their impact on dopaminergic cell activity and survival, and potential therapeutic application in PD. PMID:23563222

di Michele, Flavia; Luchetti, Sabina; Bernardi, Giorgio; Romeo, Elena; Longone, Patrizia

2013-04-04

243

Sensing small neurotransmitter-enzyme interaction with nanoporous gated ion-sensitive field effect transistors.  

PubMed

Ion-sensitive field effect transistors with gates having a high density of nanopores were fabricated and employed to sense the neurotransmitter dopamine with high selectivity and detectability at micromolar range. The nanoporous structure of the gates was produced by applying a relatively simple anodizing process, which yielded a porous alumina layer with pores exhibiting a mean diameter ranging from 20 to 35 nm. Gate-source voltages of the transistors demonstrated a pH-dependence that was linear over a wide range and could be understood as changes in surface charges during protonation and deprotonation. The large surface area provided by the pores allowed the physical immobilization of tyrosinase, which is an enzyme that oxidizes dopamine, on the gates of the transistors, and thus, changes the acid-base behavior on their surfaces. Concentration-dependent dopamine interacting with immobilized tyrosinase showed a linear dependence into a physiological range of interest for dopamine concentration in the changes of gate-source voltages. In comparison with previous approaches, a response time relatively fast for detecting dopamine was obtained. Additionally, selectivity assays for other neurotransmitters that are abundantly found in the brain were examined. These results demonstrate that the nanoporous structure of ion-sensitive field effect transistors can easily be used to immobilize specific enzyme that can readily and selectively detect small neurotransmitter molecule based on its acid-base interaction with the receptor. Therefore, it could serve as a technology platform for molecular studies of neurotransmitter-enzyme binding and drugs screening. PMID:22040747

Kisner, Alexandre; Stockmann, Regina; Jansen, Michael; Yegin, Ugur; Offenhäusser, Andreas; Kubota, Lauro Tatsuo; Mourzina, Yulia

2011-10-17

244

Na+/K(+)-ATPase regulation by neurotransmitters.  

PubMed

A long period of experimental work has led to the conclusion that Na+/K(+)-ATPase is the enzymatic version of the Na+/K+ pump. This enzymatic system is in charge of various important cell functions. Among them cationic equilibrium and recovering of resting membrane potential in neurons is relevant. A tetrameric ensemble of peptides conform the system known as alpha and beta subunits. The alpha subunit is subdivided in alpha 1, alpha 2 and alpha 3, according to different location and properties. Regulatory factors intrinsic to the Na+/K(+)-ATPase system are: ATP, Na+ and Mg2+ concentrations inside the cell, and K+ outside. The enzyme activity is also regulated by extrinsic factors like some hormones (insulin and thyroxine). Induction of gene expression or post-translational modifications of the preexisting pool of the enzyme are the basic mechanisms of regulation proposed. Other extrinsic factors that seem to regulate the enzyme activity are some neurotransmitters. Among them the most extensively studied are catecholamines, mainly norepinephrine (NE) and lately serotonin (5-HT). The mechanism suggested for NE activation of the enzyme seems to involve specific receptors or a non-specific chelating action related to the catechol group that would relieve the inhibition by divalent cations. Another possibility is that NE removes an endogenous inhibitory factor present in the cytoplasm. The Na+/K(+)-ATPase is activated also by 5-HT. In vivo pharmacological and nutriological manipulations of brain 5-HT are accompanied by parallel responses of Na+/K(+)-ATPase activity. Serotonin agonists do activate the enzyme and antagonists neutralize the activation. In vitro there is a different dose dependent activation, according to the brain region. The mechanism involved seems to implicate a specific receptor system. Serotonin-Na+/K(+)-ATPase interaction in the rat brain is probably of functional relevance because it disappears in amygdaloid kindling. Also it seems to influence the ionic regulation of the pigment transport mechanism in crayfish photoreceptors. In relation to other neurotransmitters, a weak response to histamine was observed with acetylcholine, GABA and glutamic acid, the results were negative. PMID:1363908

Hernández-R, J

1992-01-01

245

Infantile parkinsonism-dystonia: a dopamine "transportopathy"  

PubMed Central

The dopamine transporter (DAT) retrieves the neurotransmitter dopamine from the synaptic cleft at dopaminergic synapses. Variations in solute carrier family 6A, member 3 (SLC6A3/DAT1), the human gene encoding DAT, have been implicated in attention deficit hyperactivity and bipolar disorders, and DAT is a prominent site of action for drugs such as amphetamines and cocaine. In this issue of the JCI, Kurian et al. report that an autosomal recessive infantile parkinsonism-dystonia is caused by loss-of-function mutations in DAT that impair dopamine reuptake (see the related article beginning on page 1595). Though this might be predicted to result in dopamine excess in the synaptic cleft, it likely also causes depletion of presynaptic dopamine stores and possibly downregulation of postsynaptic dopamine receptor function, resulting in impairments in dopaminergic neurotransmission consistent with the clinical presentation. This is the first report of a genetic alteration in DAT function underlying a parkinsonian disorder.

Blackstone, Craig

2009-01-01

246

Homeostatic mechanisms in dopamine synthesis and release: a mathematical model  

Microsoft Academic Search

BACKGROUND: Dopamine is a catecholamine that is used as a neurotransmitter both in the periphery and in the central nervous system. Dysfunction in various dopaminergic systems is known to be associated with various disorders, including schizophrenia, Parkinson's disease, and Tourette's syndrome. Furthermore, microdialysis studies have shown that addictive drugs increase extracellular dopamine and brain imaging has shown a correlation between

Janet A. Best; H. FREDERIK Nijhout; Michael C. Reed

2009-01-01

247

Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux  

Microsoft Academic Search

BACKGROUND: Neurological diseases and neuropsychiatric disorders that vary depending on female life stages suggest that sex hormones may influence the function of neurotransmitter regulatory machinery such as the dopamine transporter (DAT). RESULTS: In this study we tested the rapid nongenomic effects of several physiological estrogens [estradiol (E2), estrone (E1), and estriol (E3)] on dopamine efflux via the DAT in a

Rebecca A Alyea; Cheryl S Watson

2009-01-01

248

Inborn errors of neurotransmitter receptors.  

PubMed

Inborn errors of neurotransmitter receptors are recently described gene mutations that directly affect receptor function. Currently three conditions are known to be caused by this mechanism: hyperekplexia; two forms of congenital inherited myasthenic syndromes; and autosomal dominant nocturnal frontal lobe epilepsy. Here, neurotransmitters, their receptors and known inborn errors of receptor function are reviewed. PMID:10407774

Surtees, R

1999-06-01

249

Chapter III The use of dopamine receptor knockout mice in understanding brain dopamine neurotransmission and sprouting in the nigrostriatal pathway  

Microsoft Academic Search

The neurotransmitter dopamine is thought to play a major role in a number of physiological processes and pathological conditions including schizophrenia, Parkinson's disease, Huntington's disease and drug addiction. Dopamine elicits its effects by interacting with a number of receptors, each with specific binding profiles, signaling cascades and expression profile. However, because of the structural similarity of these receptors, specific ligands

Malcolm K. Horne; John Drago; Janelle Nunan

2005-01-01

250

Androgens coordinate neurotransmitter-related gene expression in male whiptail lizards  

PubMed Central

Sex steroid hormones coordinate neurotransmitter systems in the male brain to facilitate sexual behavior. Although neurotransmitter release in the male brain has been well documented, little is known about how androgens orchestrate changes in gene expression of neurotransmitter receptors. We used male whiptail lizards (Cnemidophorus inornatus) to investigate how androgens alter neurotransmitter-related gene expression in brain regions involved in social decision-making. We focused on three neurotransmitter systems involved in male-typical sexual behavior, including the NMDA glutamate receptor, nitric oxide, and dopamine receptors. Here we show that in androgen-treated males, there are coordinated changes in neurotransmitter-related gene expression. In androgen-implanted castrates compared to blank-implanted castrates (control group), we found associated increases in neuronal nitric oxide synthase (nNOS) gene expression in the nucleus accumbens, preoptic area and ventromedial hypothalamus, a decrease of NR1 gene expression (obligate subunit of NMDA receptors) in the medial amygdaloid area and nucleus accumbens, and a decrease in D1 and D2 dopamine receptor gene expression in the nucleus accumbens. Our results support and expand the current model of androgen-mediated gene expression changes of neurotransmitter-related systems that facilitate sexual behavior in males. This also suggests that the proposed evolutionarily ancient reward system that reinforces sexual behavior in amniote vertebrates extends to reptiles.

O'Connell, Lauren A.; Mitchell, Maggie M.; Hofmann, Hans A.; Crews, David

2012-01-01

251

Dopamine transporter (DAT1) VNTR polymorphism in 12 Indian populations  

Microsoft Academic Search

The dopamine transporter (DAT1) is a membrane spanning protein that binds the neurotransmitter dopamine and performs re-uptake\\u000a of dopamine from the synapse into a neuron. The gene encoding DAT1 consists of 15 exons spanning 60 kb on chromosome 5p15.32.\\u000a Several studies have investigated the possible associations between variants in DAT1 gene and psychiatric disorders. The present\\u000a study aimed to determine the

L. V. K. S. Bhaskar; Kumarasamy Thangaraj; Connie J. Mulligan; Samiksha Wasnik; Amrita Nandan; Varun Kumar Sharma; Vishwas Sharma; Alla Govardhana Reddy; Lalji Singh; Vadlamudi Raghavendra Rao

2009-01-01

252

Moderate exercise and chronic stress produce counteractive effects on different areas of the brain by acting through various neurotransmitter receptor subtypes: A hypothesis  

PubMed Central

Background Regular, "moderate", physical exercise is an established non-pharmacological form of treatment for depressive disorders. Brain lateralization has a significant role in the progress of depression. External stimuli such as various stressors or exercise influence the higher functions of the brain (cognition and affect). These effects often do not follow a linear course. Therefore, nonlinear dynamics seem best suited for modeling many of the phenomena, and putative global pathways in the brain, attributable to such external influences. Hypothesis The general hypothesis presented here considers only the nonlinear aspects of the effects produced by "moderate" exercise and "chronic" stressors, but does not preclude the possibility of linear responses. In reality, both linear and nonlinear mechanisms may be involved in the final outcomes. The well-known neurotransmitters serotonin (5-HT), dopamine (D) and norepinephrine (NE) all have various receptor subtypes. The article hypothesizes that 'Stress' increases the activity/concentration of some particular subtypes of receptors (designated nts) for each of the known (and unknown) neurotransmitters in the right anterior (RA) and left posterior (LP) regions (cortical and subcortical) of the brain, and has the converse effects on a different set of receptor subtypes (designated nth). In contrast, 'Exercise' increases nth activity/concentration and/or reduces nts activity/concentration in the LA and RP areas of the brain. These effects may be initiated by the activation of Brain Derived Neurotrophic Factor (BDNF) (among others) in exercise and its suppression in stress. Conclusion On the basis of this hypothesis, a better understanding of brain neurodynamics might be achieved by considering the oscillations caused by single neurotransmitters acting on their different receptor subtypes, and the temporal pattern of recruitment of these subtypes. Further, appropriately designed and planned experiments will not only corroborate such theoretical models, but also shed more light on the underlying brain dynamics.

Sarbadhikari, Suptendra N; Saha, Asit K

2006-01-01

253

Comparison of phenelzine and geometric isomers of its active metabolite, ?-phenylethylidenehydrazine, on rat brain levels of amino acids, biogenic amine neurotransmitters and methylamine.  

PubMed

Phenelzine is a monoamine oxidase (MAO) inhibitor used in treatment of depression and anxiety disorders. It also elevates brain levels of ?-aminobutyric acid (GABA) and inhibits primary amine oxidase (PrAO), an enzyme whose activity and/or expression has been reported to be increased in diabetes mellitus, Alzheimer's disease and cardiovascular disorders. Phenelzine is not only an inhibitor of, but also a substrate for, MAO and it has been suggested that an active metabolite, namely ?-phenylethylidenehydrazine (PEH), is responsible for phenelzine's effects on amino acids. PEH is also a strong inhibitor of PrAO but has weak effects on MAO. PEH has a double bond and can thus exist as (E)- and (Z)-geometric isomers, but to date the two isomers have not been compared with regard to their neurochemical effects. We have investigated the effects of phenelzine, (E)- and (Z)-PEH on rat whole brain levels of amino acids, biogenic amine neurotransmitters and methylamine (an endogenous substrate of PrAO). Under the conditions used in the study, (E)- and (Z)-PEH appear to be equivalent in their neurochemical properties. Both PEH isomers and phenelzine produced marked increases in rat brain levels of GABA and alanine while decreasing brain levels of glutamine. Phenelzine increased brain levels of biogenic amine neurotransmitters (noradrenaline, dopamine and serotonin), whereas neither PEH isomer altered levels of these neurotransmitters to a considerable extent. All three drugs significantly increased rat brain levels of methylamine, with (E)- and (Z)-PEH causing a greater increase than phenelzine. These results are discussed in relation to the possible therapeutic applications of these drugs. PMID:23392617

Matveychuk, Dmitriy; Nunes, Emerson; Ullah, Nasir; Velázquez-Martinez, Carlos A; MacKenzie, Erin M; Baker, Glen B

2013-02-08

254

The Influence of Serotonin on Fear Learning  

PubMed Central

Learning of associations between aversive stimuli and predictive cues is the basis of Pavlovian fear conditioning and is driven by a mismatch between expectation and outcome. To investigate whether serotonin modulates the formation of such aversive cue-outcome associations, we used functional magnetic resonance imaging (fMRI) and dietary tryptophan depletion to reduce brain serotonin (5-HT) levels in healthy human subjects. In a Pavlovian fear conditioning paradigm, 5-HT depleted subjects compared to a non-depleted control group exhibited attenuated autonomic responses to cues indicating the upcoming of an aversive event. These results were closely paralleled by reduced aversive learning signals in the amygdala and the orbitofrontal cortex, two prominent structures of the neural fear circuit. In agreement with current theories of serotonin as a motivational opponent system to dopamine in fear learning, our data provide first empirical evidence for a role of serotonin in representing formally derived learning signals for aversive events.

Hindi Attar, Catherine; Finckh, Barbara; Buchel, Christian

2012-01-01

255

Head-to-Head Comparisons of Carbon Fiber Microelectrode Coatings for Sensitive and Selective Neurotransmitter Detection by Voltammetry  

PubMed Central

Voltammetry is widely used to investigate neurotransmission and other biological processes but is limited by poor chemical selectivity and fouling of commonly used carbon fiber microelectrodes (CFMs). We performed direct comparisons of three key coating materials purported to impart selectivity and fouling resistance to electrodes: Nafion, base-hydrolyzed cellulose acetate (BCA), and fibronectin. We systematically evaluated the impact on a range of electrode parameters. Fouling due to exposure to brain tissue was investigated using an approach that minimizes the use of animals while enabling evaluation of statistically significant populations of electrodes. We find that BCA is relatively fouling resistant. Moreover, detection at BCA-coated CFMs can be tuned by altering hydrolysis times to minimize the impact on sensitivity losses while maintaining fouling resistance. Fibronectin coating is associated with moderate losses in sensitivity after coating and fouling. Nafion imparts increased sensitivity for dopamine and norepinephrine but not serotonin, as well as the anticipated selectivity for cationic neurotransmitters over anionic metabolites. However, while Nafion has been suggested to resist fouling, both dip-coating and electro-deposition of Nafion are associated with substantial fouling, similar to levels observed at bare electrodes after exposure to brain tissue. Direct comparisons of these coatings identified unique electroanalytical properties of each that can be used to guide selection tailored to the goals and environment of specific studies.

Singh, Yogesh S.; Sawarynski, Lauren E.; Dabiri, Pasha D.; Choi, Wonwoo R.; Andrews, Anne M.

2011-01-01

256

Boosting serotonin in the brain: is it time to revamp the treatment of depression?  

Microsoft Academic Search

Abnormalities in serotonin systems are presumably linked to various psychiatric disorders including schizophrenia and depression. Medications intended for these disorders aim to either block the reuptake or the degradation of this neurotransmitter. In an alternative approach, efforts have been made to enhance serotonin levels through dietary manipulation of precursor levels with modest clinical success. In the last 30 years, there

Mariana P Torrente; Alan J Gelenberg; Kent E Vrana

2012-01-01

257

Fluoxetine at anorectic doses does not have properties of a dopamine uptake inhibitor  

Microsoft Academic Search

Summary Although fluoxetine is a highly selective inhibitor of serotonin uptake in vitro and in vivo, some investigators have suggested that dopamine uptake inhibition may contribute to anorectic actions of fluoxetine. The present experiments were done to determine fluoxetine's effects in some animal protocols in which dopamine uptake inhibitors have characteristic actions. Mazindol prevented the depletion of striatal dopamine and

R. W. Fuller; S. K. Hemrick-Luecke; H. D. Snoddy

1994-01-01

258

Dopamine and the Origins of Human Intelligence  

Microsoft Academic Search

A general theory is proposed that attributes the origins of human intelligence to an expansion of dopaminergic systems in human cognition. Dopamine is postulated to be the key neurotransmitter regulating six predominantly left-hemispheric cognitive skills critical to human language and thought: motor planning, working memory, cognitive flexibility, abstract reasoning, temporal analysis\\/sequencing, and generativity. A dopaminergic expansion during early hominid evolution

Fred H. Previc

1999-01-01

259

Dopamine covalently modifies and functionally inactivates parkin  

Microsoft Academic Search

Inherited mutations in PARK2, the gene encoding parkin, cause selective degeneration of catecholaminergic neurons in the substantia nigra and locus coeruleus of the brainstem, resulting in early-onset parkinsonism. But the role of parkin in common, sporadic forms of Parkinson disease remains unclear. Here we report that the neurotransmitter dopamine covalently modifies parkin in living dopaminergic cells, a process that increases

Beth L Ostaszewski; Andreas Weihofen; Michael G Schlossmacher; Dennis J Selkoe; Matthew J LaVoie

2005-01-01

260

Serotonin-2 receptor stimulation normalizes striatal preprotachykinin messenger RNA in an animal model of Parkinson's disease.  

PubMed

Dopamine and serotonin neurotransmission regulate striatal preprotachykinin messenger RNA levels. In the present study, we investigated serotonin 2A/2C receptor-mediated regulation of preprotachykinin messenger RNA expression in the rat striatum after adult dopamine depletion produced with 6-hydroxydopamine. Significant reductions (46-61% of control values) in preprotachykinin messenger RNA levels were detected by in situ hybridization in rostral, central and caudal regions of the striatum after >85% dopamine depletion. Repeated administration of the specific serotonin2A/2C receptor agonist, (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrobromide, to dopamine-depleted rats completely reversed the reduction in preprotachykinin messenger RNA levels in rostral, central and dorsal-caudal striatal regions. In unlesioned (vehicle-injected) control animals, repeated administration of (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrobromide did not affect preprotachykinin messenger RNA expression in rostral, central and ventral-caudal striatal regions, but decreased preprotachykinin messenger RNA levels in the dorsal-caudal striatal subregion. In addition, serotonin turnover in the dopamine-depleted rostral striatum was significantly increased by 35-45% which is consistent with serotonin hyperinnervation after 6-hydroxydopamine lesions. These data show that the decrease in striatal preprotachykinin messenger RNA after dopamine depletion can be normalized with repeated serotonin2A/2C receptor stimulation. We hypothesize that this serotonin2A/2C receptor regulation of preprotachykinin messenger RNA expression after 6-hydroxydopamine is a consequence of serotonin hyperinnervation, which may include increased striatal serotonin2A/2C receptors, induced by dopamine depletion. We also propose that the serotonin system could be pharmacologically targeted to restore the direct striatal tachykinin pathway in Parkinson's disease. PMID:10473249

Gresch, P J; Walker, P D

1999-01-01

261

Serotonin Transporter and Receptor Expression in Osteocytic MLO-Y4 Cells  

PubMed Central

Neurotransmitter regulation of bone metabolism has been a subject of increasing interest and investigation. We reported previously that osteoblastic cells express a functional serotonin (5-HT) signal transduction system, with mechanisms for responding to and regulating uptake of 5-HT. The clonal murine osteocytic cell line, MLO-Y4, demonstrates expression of the serotonin transporter (5-HTT), and the 5-HT1A, and 5-HT2A receptors by real-time RT-PCR and immunoblot analysis. Immunohistochemistry using antibodies for the 5-HTT, and the 5-HT1A and 5-HT2A receptors reveals expression of all three proteins in both osteoblasts and osteocytes in rat tibia. 5-HTT binding sites were demonstrated in the MLO-Y4 cells with nanomolar affinity for the stable cocaine analog [125I]RTI-55. Imipramine and fluoxetine, antagonists with specificity for 5-HTT, show the highest potency to antagonize [125I]RTI-55 binding in the MLO-Y4 cells. GBR-12935, a relatively selective dopamine transporter antagonist, had a much lower potency, as did desipramine, a selective norepinephrine transporter antagonist. The maximal [3H]5-HT uptake rate in MLO-Y4 cells was 2.85 pmol/15 min/well, with a Km value of 290 nM. Imipramine and fluoxetine inhibited specific [3H]5-HT uptake with IC50 values in the nanomolar range. 5-HT rapidly stimulated PGE2 release from MLO-Y4 cells; the EC50 for 5-HT was 0.1 ?M, with a 3-fold increase seen at 60 min. The rate limiting enzyme for serotonin synthesis, tryptophan hydroxylase, is expressed in MLO-Y4 cells as well as osteoblastic MC3T3-E1 cells. Thus, osteocytes, as well as osteoblasts, are capable of 5-HT synthesis, and express functional receptor and transporter components of the 5-HT signal transduction system.

BLIZIOTES, M.; ESHLEMAN, A.; BURT-PICHAT, B.; ZHANG, X.-W.; HASHIMOTO, J.; WIREN, K.; CHENU, C.

2006-01-01

262

Neurotransmitter transporters: structure meets function.  

PubMed

At synapses, sodium-coupled transporters remove released neurotransmitters, thereby recycling them and maintaining a low extracellular concentration of the neurotransmitter. The molecular mechanism underlying sodium-coupled neurotransmitter uptake is not completely understood. Several structures of homologs of human neurotransmitter transporters have been solved with X-ray crystallography. These crystal structures have spurred a plethora of computational and experimental work to elucidate the molecular mechanism underlying sodium-coupled transport. Here, we compare the structures of GltPh, a glutamate transporter homolog, and LeuT, a homolog of neurotransmitter transporters for the biogenic amines and inhibitory molecules GABA and glycine. We relate these structures to data obtained from experiments and computational simulations, to draw conclusions about the mechanism of uptake by sodium-coupled neurotransmitter transporters. Here, we propose how sodium and substrate binding is coupled and how binding of sodium and substrate opens and closes the gates in these transporters, thereby leading to an efficient coupled transport. PMID:23664361

Focke, Paul J; Wang, Xiaoyu; Larsson, H Peter

2013-05-01

263

Serotonin enhances solitariness in phase transition of the migratory locust.  

PubMed

The behavioral plasticity of locusts is a striking trait presented during the reversible phase transition between solitary and gregarious individuals. However, the results of serotonin as a neurotransmitter from the migratory locust Locusta migratoria in phase transition showed an alternative profile compared to the results from the desert locust Schistocerca gregaria. In this study, we investigated the roles of serotonin in the brain during the phase change of the migratory locust. During the isolation of gregarious nymphs, the concentration of serotonin in the brain increased significantly, whereas serotonin receptors (i.e., 5-HT 1 , 5-HT 2 , and 5-HT 7 ) we identified here showed invariable expression patterns. Pharmacological intervention showed that serotonin injection in the brain of gregarious nymphs did not induced the behavioral change toward solitariness, but injection of this chemical in isolated gregarious nymphs accelerated the behavioral change from gregarious to solitary phase. During the crowding of solitary nymphs, the concentration of serotonin in the brain remained unchanged, whereas 5-HT 2 increased after 1 h of crowding and maintained stable expression level thereafter. Activation of serotonin-5-HT2 signaling with a pharmaceutical agonist inhibited the gregariousness of solitary nymphs in crowding treatment. These results indicate that the fluctuations of serotonin content and 5-HT 2 expression are results of locust phase change. Overall, this study demonstrates that serotonin enhances the solitariness of the gregarious locusts. Serotonin may regulate the withdrawal-like behavioral pattern displayed during locust phase change and this mechanism is conserved in different locust species. PMID:24109441

Guo, Xiaojiao; Ma, Zongyuan; Kang, Le

2013-10-07

264

Serotonin enhances solitariness in phase transition of the migratory locust  

PubMed Central

The behavioral plasticity of locusts is a striking trait presented during the reversible phase transition between solitary and gregarious individuals. However, the results of serotonin as a neurotransmitter from the migratory locust Locusta migratoria in phase transition showed an alternative profile compared to the results from the desert locust Schistocerca gregaria. In this study, we investigated the roles of serotonin in the brain during the phase change of the migratory locust. During the isolation of gregarious nymphs, the concentration of serotonin in the brain increased significantly, whereas serotonin receptors (i.e., 5-HT1, 5-HT2, and 5-HT7) we identified here showed invariable expression patterns. Pharmacological intervention showed that serotonin injection in the brain of gregarious nymphs did not induced the behavioral change toward solitariness, but injection of this chemical in isolated gregarious nymphs accelerated the behavioral change from gregarious to solitary phase. During the crowding of solitary nymphs, the concentration of serotonin in the brain remained unchanged, whereas 5-HT2 increased after 1 h of crowding and maintained stable expression level thereafter. Activation of serotonin-5-HT2 signaling with a pharmaceutical agonist inhibited the gregariousness of solitary nymphs in crowding treatment. These results indicate that the fluctuations of serotonin content and 5-HT2 expression are results of locust phase change. Overall, this study demonstrates that serotonin enhances the solitariness of the gregarious locusts. Serotonin may regulate the withdrawal-like behavioral pattern displayed during locust phase change and this mechanism is conserved in different locust species.

Guo, Xiaojiao; Ma, Zongyuan; Kang, Le

2013-01-01

265

Convergent Pathways for Steroid Hormone-and Neurotransmitter-Induced Rat Sexual Behavior  

NASA Astrophysics Data System (ADS)

Estrogen and progesterone modulate gene expression in rodents by activation of intracellular receptors in the hypothalamus, which regulate neuronal networks that control female sexual behavior. However, the neurotransmitter dopamine has been shown to activate certain steroid receptors in a ligand-independent manner. A dopamine receptor stimulant and a D_1 receptor agonist, but not a D_2 receptor agonist, mimicked the effects of progesterone in facilitating sexual behavior in female rats. The facilitatory effect of the neurotransmitter was blocked by progesterone receptor antagonists, a D_1 receptor antagonist, or antisense oligonucleotides to the progesterone receptor. The results suggest that in rodents neurotransmitters may regulate in vivo gene expression and behavior by means of cross-talk with steroid receptors in the brain.

Mani, S. K.; Allen, J. M. C.; Clark, J. H.; Blaustein, J. D.; O'Malley, B. W.

1994-08-01

266

Brain neurotransmitters in fatigue and overtraining.  

PubMed

Since the publication of the serotonin hypothesis, numerous theories involving the accumulation or depletion of different substances in the brain have been proposed to explain central fatigue. Although the theoretical rationale for the "serotonin-fatigue hypothesis" is clear, several seemingly well-conducted studies have failed to support a significant role for 5-hydroxytryptamine in the development of fatigue. As brain function appears to be dependent upon the interaction of a number of systems, it is unlikely that a single neurotransmitter system is responsible for central fatigue. Several other mechanisms are involved, with evidence supporting a role for the brain catecholamines. Fatigue is therefore probably an integrated phenomenon, with complex interaction among central and peripheral factors. When prolonged and excessive training happens, concurrent with other stressors and insufficient recovery, performance decrements can result in chronic maladaptations that can lead to the overtraining syndrome (OTS). The mechanism of the OTS could be difficult to examine in detail, perhaps because the stress caused by excessive training load, in combination with other stressors, might trigger different "defence mechanisms" such as the immunological, neuroendocrine, and other physiological systems that all interact and probably therefore cannot be pinpointed as the "sole" cause of the OTS. It might be that, as in other syndromes, the psychoneuroimmunology (study of brain-behavior-immune interrelationships) might shed a light on the possible mechanisms of the OTS, but until there is a definite diagnostic tool, it is of utmost importance to standardize measures that are now thought to provide a good inventory of the training status of the athlete. It is very important to emphasize the need to distinguish the OTS from overreaching and other potential causes of temporary underperformance such as anemia, acute infection, muscle damage, and insufficient carbohydrate intake. PMID:18059610

Meeusen, Romain; Watson, Philip; Hasegawa, Hiroshi; Roelands, Bart; Piacentini, Maria F

2007-10-01

267

Changes in neurotransmitter receptor expression levels in rat brain after 4-week exposure to 1-bromopropane.  

PubMed

1-Bromopropane (1-BP), an alternative to ozone-depleting solvents, exhibits neurotoxicity and reproductive toxicity in animals and humans. The present study investigated the effects of exposure to 1-BP on expression of neurotransmitter receptor genes in the rat brain to explore possible biomarkers for central neurotoxicity and find brain regions sensitive for microarray analysis. Thirty-six F344 rats were divided at random into four equal groups of nine and exposed to 1-BP at 0, 400, 800 and 1000 ppm for 8 h/day; 7 days/week for 4 weeks. Total RNA from different brain regions was extracted and real-time PCR was conducted to quantify the mRNA levels of serotonin, dopamine and GABA receptors. Western blot analysis for specific regions of interest was also carried out to determine the protein levels. The mRNAs of 5HTr2a, D2R and GABAa1 were down regulated in a 1-BP dose-dependent manner in the hippocampus. The mRNA levels of 5HTr1a, 5HTr2a, D1R and GABAa1 were significantly decreased in the cortex of rats exposed to 800 ppm, but not to 1000 ppm. The mRNAs of 5HTr1a and 5HTr3a in the pons-medulla were decreased in rats exposed to 400 ppm or higher concentrations. The mRNA expression of D2R in the hippocampus and 5HTr1a and 5HTr3a in the pons-medulla oblongata were the most sensitive indicators of 1-BP neurotoxicity. The results suggest that mRNA expression analysis is useful in identifying brain regions susceptible to 1-BP, as well as providing potential biomarkers for central nervous system toxicity. PMID:19576243

Mohideen, Sahabudeen Sheik; Ichihara, Sahoko; Banu, Shameema; Liu, Fang; Kitoh, Junzoh; Ichihara, Gaku

2009-07-01

268

Effects of cognitive-behavioral therapy on Eating Disorders: neurotransmitter secretory response to treatment.  

PubMed

The effects of cognitive-behavioral therapy (CBT) on central dopamine (DA), noradrenaline (NE) and serotonin (5-HT) secretion were studied in a group of 50 female inpatients, of which 14 suffered from anorexia nervosa restricted type (AN-R), 14 from anorexia nervosa bingeing-purging type (AN-BP), and 22 from bulimia nervosa (BN). The aim of the study was to see whether or not CBT modifies the secretion of central DA (blood homovanillic acid=HVA), NE (blood 3-methoxy-4-hydroxy-phenylglycol=MHPG) and the 5-HT transporter (as evaluated by the platelet paroxetine binding=[(3)H]-Par-binding), if the physical and psychological effects of CBT correlate with changes of the neurotransmitter secretion; and if the biological effects of CBT are linked to specific psychopathological aspect of the disorders. The treatment lasted 20 weeks. Body-mass Index, bingeing and purging, specific AN-BN psychopathological (EDE 12-OD), depression (Beck Inventory), anxiety (STAY Form-Y-1), impulsiveness (Barratt Impulsiveness Scale), self-esteem (Rosenberg Self-Biochemical Scale) and temperament (Temperament and Character Inventory, Cloninger Scale) were assessed at baseline and at the end of the treatment. CBT significantly improved the psychophysical aspects of the diseases. HVA and MHPG concentrations did not change. The [(3)H]-Par-binding parameters, the maximum binding capacity (B(max)) and dissociation constant (K(d)) values did not change in either AN-R or AN-BP patients, while the [(3)H]-Par B(max) (and not the K(d)) increased significantly in BN patients. Correlations emerged between basal and final [(3)H]-Par B(max) values and psychopathological scores, but not between CBT-induced differences between basal and final values. Our data suggest that only in BN CBT may act through changes in 5-HT system function. PMID:19962832

Brambilla, F; Dalle Grave, R; Calugi, S; Marchesini, G; Baroni, S; Marazziti, D

2009-12-04

269

Receptors and other signaling proteins required for serotonin control of locomotion in Caenorhabditis elegans.  

PubMed

A better understanding of the molecular mechanisms of signaling by the neurotransmitter serotonin is required to assess the hypothesis that defects in serotonin signaling underlie depression in humans. Caenorhabditis elegans uses serotonin as a neurotransmitter to regulate locomotion, providing a genetic system to analyze serotonin signaling. From large-scale genetic screens we identified 36 mutants of C. elegans in which serotonin fails to have its normal effect of slowing locomotion, and we molecularly identified eight genes affected by 19 of the mutations. Two of the genes encode the serotonin-gated ion channel MOD-1 and the G-protein-coupled serotonin receptor SER-4. mod-1 is expressed in the neurons and muscles that directly control locomotion, while ser-4 is expressed in an almost entirely non-overlapping set of sensory and interneurons. The cells expressing the two receptors are largely not direct postsynaptic targets of serotonergic neurons. We analyzed animals lacking or overexpressing the receptors in various combinations using several assays for serotonin response. We found that the two receptors act in parallel to affect locomotion. Our results show that serotonin functions as an extrasynaptic signal that independently activates multiple receptors at a distance from its release sites and identify at least six additional proteins that appear to act with serotonin receptors to mediate serotonin response. PMID:23023001

Gürel, Güliz; Gustafson, Megan A; Pepper, Judy S; Horvitz, H Robert; Koelle, Michael R

2012-09-28

270

Serotonin synthesis, release and reuptake in terminals: a mathematical model  

Microsoft Academic Search

BACKGROUND: Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels,

Janet Best; H. Frederik Nijhout; Michael Reed

2010-01-01

271

Neuroimaging of the Serotonin Transporter: Possibilities and Pitfalls  

Microsoft Academic Search

Nuclear medicine imaging techniques like positron emission tomography (PET) and single-photon emission computed tomography (SPECT) apply radiolabeled drugs that bind selectively to specific neurotransmitter receptors and transporters such as the serotonin transporter (SERT) in the living human brain. They can help overcome certain limitations of postmortem, platelet and genetic studies of the SERT. This review compares the outcome of those

Peter Brust; Swen Hesse; Ulrich Muller; Zsolt Szabo

2006-01-01

272

Effects of Postnatal Serotonin Agonism on Fear Response and Memory  

Technology Transfer Automated Retrieval System (TEKTRAN)

The neurotransmitter serotonin (5-HT) also acts as a neurogenic compound in the developing brain. Early administration of a 5-HT agonist could alter the development of the serotonergic circuitry, altering behaviors mediated by 5-HT signaling, such as memory, fear and aggression. White leghorn chicks...

273

Investigation of serotonin-1A receptor function in the human psychopharmacology of MDMA  

Microsoft Academic Search

Serotonin (5-HT) release is the primary pharmacological mechanism of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) action in the primate brain. Dopamine release and direct stimulation of dopamine D2 and serotonin 5-HT2A receptors also contributes to the overall action of MDMA. The role of 5-HT1A receptors in the human psychopharmacology of MDMA, however, has not yet been elucidated. In order to reveal the consequences

F. Hasler; E. Studerus; K. Lindner; S. Ludewig; FX Vollenweider

2009-01-01

274

Serotonin2 receptor stimulation normalizes striatal preprotachykinin messenger RNA in an animal model of Parkinson's disease  

Microsoft Academic Search

Dopamine and serotonin neurotransmission regulate striatal preprotachykinin messenger RNA levels. In the present study, we investigated serotonin2A\\/2C receptor-mediated regulation of preprotachykinin messenger RNA expression in the rat striatum after adult dopamine depletion produced with 6-hydroxydopamine. Significant reductions (46–61% of control values) in preprotachykinin messenger RNA levels were detected by in situ hybridization in rostral, central and caudal regions of the

P. J. Gresch; P. D. Walker

1999-01-01

275

The Cytoplasmic Permeation Pathway of Neurotransmitter Transporters†  

PubMed Central

Ion-coupled solute transporters are responsible for transporting nutrients, ions and signaling molecules across a variety of biological membranes. Recent high-resolution crystal structures of several transporters from protein families that were previously thought to be unrelated show common structural features indicating a large structural family representing transporters from all kingdoms of life. This review describes studies that led to an understanding of the conformational changes required for solute transport in this family. The first structure in this family showed the bacterial amino acid transporter LeuT, which is homologous to neurotransmitter transporters, in an extracellularly-oriented conformation with a molecule of leucine occluded at the substrate site. Studies with the mammalian serotonin transporter identified positions, buried in the LeuT structure, that defined a potential pathway leading from the cytoplasm to the substrate binding site. Modeling studies utilized an inverted structural repeat within the LeuT crystal structure to predict the conformation of LeuT in which the cytoplasmic permeation pathway, consisting of positions identified in SERT, was open for substrate diffusion to the cytoplasm. From the difference between the model and the crystal structures, a simple “rocking bundle” mechanism was proposed, in which a 4-helix bundle changed its orientation with respect to the rest of the protein to close the extracellular pathway and open the cytoplasmic one. Subsequent crystal structures from structurally related proteins provide evidence supporting this model for transport.

Rudnick, Gary

2011-01-01

276

Cytoplasmic permeation pathway of neurotransmitter transporters.  

PubMed

Ion-coupled solute transporters are responsible for transporting nutrients, ions, and signaling molecules across a variety of biological membranes. Recent high-resolution crystal structures of several transporters from protein families that were previously thought to be unrelated show common structural features indicating a large structural family representing transporters from all kingdoms of life. This review describes studies that led to an understanding of the conformational changes required for solute transport in this family. The first structure in this family showed the bacterial amino acid transporter LeuT, which is homologous to neurotransmitter transporters, in an extracellularly oriented conformation with a molecule of leucine occluded at the substrate site. Studies with the mammalian serotonin transporter identified positions, buried in the LeuT structure, that defined a potential pathway leading from the cytoplasm to the substrate binding site. Modeling studies utilized an inverted structural repeat within the LeuT crystal structure to predict the conformation of LeuT in which the cytoplasmic permeation pathway, consisting of positions identified in SERT, was open for diffusion of the substrate to the cytoplasm. From the difference between the model and the crystal structures, a simple "rocking bundle" mechanism was proposed, in which a four-helix bundle changed its orientation with respect to the rest of the protein to close the extracellular pathway and open the cytoplasmic one. Subsequent crystal structures from structurally related proteins provide evidence supporting this model for transport. PMID:21774491

Rudnick, Gary

2011-08-10

277

Pyrethroid insecticides evoke neurotransmitter release from rabbit striatal slices  

SciTech Connect

The effects of the synthetic pyrethroid insecticide fenvalerate ((R,S)-alpha-cyano-3-phenoxybenzyl(R,S)-2-(4-chlorophenyl)-3- methylbutyrate) on neurotransmitter release in rabbit brain slices were investigated. Fenvalerate evoked a calcium-dependent release of (/sup 3/H)dopamine and (/sup 3/H)acetylcholine from rabbit striatal slices that was concentration-dependent and specific for the toxic stereoisomer of the insecticide. The release of (/sup 3/H)dopamine and (/sup 3/H)acetylcholine by fenvalerate was modulated by D2 dopamine receptor activation and antagonized completely by the sodium channel blocker, tetrodotoxin. These findings are consistent with an action of fenvalerate on the voltage-dependent sodium channels of the presynaptic membrane resulting in membrane depolarization, and the release of dopamine and acetylcholine by a calcium-dependent exocytotic process. In contrast to results obtained in striatal slices, fenvalerate did not elicit the release of (/sup 3/H)norepinephrine or (/sup 3/H)acetylcholine from rabbit hippocampal slices indicative of regional differences in sensitivity to type II pyrethroid actions.

Eells, J.T.; Dubocovich, M.L.

1988-08-01

278

Serotonin modulation of cortical neurons and networks  

PubMed Central

The serotonergic pathways originating in the dorsal and median raphe nuclei (DR and MnR, respectively) are critically involved in cortical function. Serotonin (5-HT), acting on postsynaptic and presynaptic receptors, is involved in cognition, mood, impulse control and motor functions by (1) modulating the activity of different neuronal types, and (2) varying the release of other neurotransmitters, such as glutamate, GABA, acetylcholine and dopamine. Also, 5-HT seems to play an important role in cortical development. Of all cortical regions, the frontal lobe is the area most enriched in serotonergic axons and 5-HT receptors. 5-HT and selective receptor agonists modulate the excitability of cortical neurons and their discharge rate through the activation of several receptor subtypes, of which the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT3 subtypes play a major role. Little is known, however, on the role of other excitatory receptors moderately expressed in cortical areas, such as 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro and in vivo studies suggest that 5-HT1A and 5-HT2A receptors are key players and exert opposite effects on the activity of pyramidal neurons in the medial prefrontal cortex (mPFC). The activation of 5-HT1A receptors in mPFC hyperpolarizes pyramidal neurons whereas that of 5-HT2A receptors results in neuronal depolarization, reduction of the afterhyperpolarization and increase of excitatory postsynaptic currents (EPSCs) and of discharge rate. 5-HT can also stimulate excitatory (5-HT2A and 5-HT3) and inhibitory (5-HT1A) receptors in GABA interneurons to modulate synaptic GABA inputs onto pyramidal neurons. Likewise, the pharmacological manipulation of various 5-HT receptors alters oscillatory activity in PFC, suggesting that 5-HT is also involved in the control of cortical network activity. A better understanding of the actions of 5-HT in PFC may help to develop treatments for mood and cognitive disorders associated with an abnormal function of the frontal lobe.

Celada, Pau; Puig, M. Victoria; Artigas, Francesc

2013-01-01

279

Functional consequences of homo- but not hetero-oligomerization between transporters for the biogenic amine neurotransmitters.  

PubMed

Before this study, the human norepinephrine transporter (hNET) was the only member of the biogenic amine neurotransmitter transporter family that had not been demonstrated to be a functional homo-oligomer. Here, using two forms of the transporter, I155C and hNET-myc, with distinct antigenicity and inhibitor sensitivity, we demonstrated that hNET exists as a homo-oligomer. hNET I155C is a functional mutant and is sensitive to inactivation by the sulfhydryl reagent [2-(trimethylammonium)ethyl]methanethiosulfonate, while hNET-myc is resistant to inactivation by this reagent. Coimmunoprecipitation of these two forms demonstrated that a physical interaction exists between norepinephrine transporter monomers. Further characterization of this physical interaction has revealed that the activity of norepinephrine transporters depends on interactions between monomers. Because norepinephrine transporters and serotonin transporters are the only two members of the neurotransmitter transporter family endogenously expressed in the cell membrane of the same cells, placental syncytiotrophoblasts, we tested the ability of norepinephrine transporters and serotonin transporters to associate and function in a hetero-oligomeric form. Similarly, coexpression of hNET-myc with serotonin transporter-FLAG showed a physical interaction in coimmunoprecipitation assays. However, coexpression of serotonin and norepinephrine transporters did not sensitize norepinephrine transporter activity to inhibition by citalopram, a selective serotonin transport inhibitor. Thus, the norepinephrine transporter-serotonin transporter physical association did not produce functional consequences. Based on this, we propose that the transporters for biogenic amine neurotransmitters interact functionally in homo- but not hetero-oligomeric forms. PMID:12787070

Kocabas, A M; Rudnick, G; Kilic, F

2003-06-01

280

Serotonin Regulates Mammary Gland Development via an Autocrine-Paracrine Loop  

Microsoft Academic Search

Mammary gland development is controlled by a dynamic interplay between endocrine hormones and locally produced factors. Biogenic monoamines (serotonin, dopamine, norepinephrine, and others) are an important class of bioregulatory molecules that have not been shown to participate in mammary development. Here we show that mammary glands stimulated by prolactin (PRL) express genes essential for serotonin biosynthesis (tryptophan hydroxylase [TPH] and

Manabu Matsuda; Tatsuhiko Imaoka; Archie J Vomachka; Gary A Gudelsky; Zhaoyuan Hou; Meenakshi Mistry; Jason P Bailey; Kathryn M Nieport; Diego J Walther; Michael Bader; Nelson D Horseman

2004-01-01

281

Contributions to the field of neurotransmitters by Japanese scientists, and reflections on my own research  

PubMed Central

Part I describes important contributions made by some Japanese pioneers in the field of neurotransmitters: (their achievements in parentheses) J. Takamine (isolation and crystallization of adrenaline); K. Shimidzu (early hint for acetylcholine as a neurotransmitter); F. Kanematsu (donation of the Kanematsu Memorial Institute in Sydney); T. Hayashi (discovery of the excitatory action of glutamate and the inhibitory action of GABA); and I. Sano (discovery of a high concentration of dopamine in striatum, its reduction in a patient with Parkinson’s disease and the treatment with DOPA). In Part II, I present some of my reflections on my research on neurotransmitters. The work of my colleagues and myself has made some significant contributions to the establishment of neurotransmitter roles played by GABA and substance P, the first amino acid and the first peptide neurotransmitters, respectively. By the early 1960s, 3 substances, i.e., acetylcholine, noradrenaline, and adrenaline, had been established as neurotransmitters. Now the number of neurotransmitters is believed to be as many as 50 or even more mainly due to the inclusion of several amino acids and a large number of peptide transmitters.

Otsuka, Masanori

2007-01-01

282

Glycogen Synthase Kinase-3 is an Intermediate Modulator of Serotonin Neurotransmission  

PubMed Central

Serotonin is a neurotransmitter with broad functions in brain development, neuronal activity, and behaviors; and serotonin is the prominent drug target in several major neuropsychiatric diseases. The multiple actions of serotonin are mediated by diverse serotonin receptor subtypes and associated signaling pathways. However, the key signaling components that mediate specific function of serotonin neurotransmission have not been fully identified. This review will provide evidence from biochemical, pharmacological, and animal behavioral studies showing that serotonin regulates the activation states of brain glycogen synthase kinase-3 (GSK3) via type 1 and type 2 serotonin receptors. In return, GSK3 directly interacts with serotonin receptors in a highly selective manner, with a prominent effect on modulating serotonin 1B receptor activity. Therefore, GSK3 acts as an intermediate modulator in the serotonin neurotransmission system, and balanced GSK3 activity is essential for serotonin-regulated brain function and behaviors. Particularly important, several classes of serotonin-modulating drugs, such as antidepressants and atypical antipsychotics, regulate GSK3 by inhibiting its activity in brain, which reinforces the importance of GSK3 as a potential therapeutic target in neuropsychiatric diseases associated with abnormal serotonin function.

Polter, Abigail M.; Li, Xiaohua

2011-01-01

283

Dopamine Transporter Blockade Increases LTP in the CA1 Region of the Rat Hippocampus via Activation of the D3 Dopamine Receptor  

ERIC Educational Resources Information Center

Dopamine has been demonstrated to be involved in the modulation of long-term potentiation (LTP) in the CA1 region of the hippocampus. As monoamine transporter blockade will increase the actions of endogenous monoamine neurotransmitters, the effect of a dopamine transporter (DAT) antagonist on LTP was assessed using field excitatory postsynaptic…

Swant, Jarod; Wagner, John J.

2006-01-01

284

Dopamine Transporter Blockade Increases LTP in the CA1 Region of the Rat Hippocampus via Activation of the D3 Dopamine Receptor  

ERIC Educational Resources Information Center

|Dopamine has been demonstrated to be involved in the modulation of long-term potentiation (LTP) in the CA1 region of the hippocampus. As monoamine transporter blockade will increase the actions of endogenous monoamine neurotransmitters, the effect of a dopamine transporter (DAT) antagonist on LTP was assessed using field excitatory postsynaptic…

Swant, Jarod; Wagner, John J.

2006-01-01

285

Imaging of endogenous neurotransmitter release  

Microsoft Academic Search

A method for imaging endogenous release of two common neurotransmitters from tissue slices is described. This detection employs fluorometric, enzymatic assays for glutamate and for GABA, the progress of which is directly monitored by a cooled CCD camera. The assays are highly specific for their substrate, allowing accurate determination of either glutamate or GABA release by tissues. The images captured

G. S Ayoub; S Grutsis; H Simko

1998-01-01

286

Effects of serotonin on induced epileptiform activity in CA1 pyramidal neurons of genetically epilepsy prone rats  

Microsoft Academic Search

The seizure susceptibility in genetically epilepsy prone rats (GEPRs) is reported to be caused by abnormalities in several neurotransmitter systems including the serotonergic system. Among the reported abnormalities is a decrease in brain serotonin content. Therefore, we examined the effects of exogenous serotonin on brain slices from the severe seizure strain of GEPRs (GEPR-9s). We employed conventional electrophysiological techniques to

Delanthi Salgado-Commissariat; Karim A Alkadhi

1996-01-01

287

A Preliminary Study of Gene Polymorphisms Involved in the Neurotransmitters Metabolism of a Homogeneous Spanish Autistic Group  

ERIC Educational Resources Information Center

|Twin studies have shown a strong genetic component for autism. Neurotransmitters, such as serotonin and catecholamines, have been suggested to play a role in the disease since they have an essential function in synaptogenesis and brain development. In this preliminary study, polymorphism of genes implicated in the serotonergic and dopaminergic…

Calahorro, Fernando; Alejandre, Encarna; Anaya, Nuria; Guijarro, Teresa; Sanz, Yolanza; Romero, Auxiliadora; Tienda, Pilar; Burgos, Rafael; Gay, Eudoxia; Sanchez, Vicente; Ruiz-Rubio, Manuel

2009-01-01

288

A Preliminary Study of Gene Polymorphisms Involved in the Neurotransmitters Metabolism of a Homogeneous Spanish Autistic Group  

ERIC Educational Resources Information Center

Twin studies have shown a strong genetic component for autism. Neurotransmitters, such as serotonin and catecholamines, have been suggested to play a role in the disease since they have an essential function in synaptogenesis and brain development. In this preliminary study, polymorphism of genes implicated in the serotonergic and dopaminergic…

Calahorro, Fernando; Alejandre, Encarna; Anaya, Nuria; Guijarro, Teresa; Sanz, Yolanza; Romero, Auxiliadora; Tienda, Pilar; Burgos, Rafael; Gay, Eudoxia; Sanchez, Vicente; Ruiz-Rubio, Manuel

2009-01-01

289

Alterations in cholinergic and non-cholinergic neurotransmitter receptor densities in transgenic Tg2576 mouse brain with ?-amyloid plaque pathology  

Microsoft Academic Search

Cholinergic deficits in Alzheimer’s disease are accompanied by a number of alterations in other transmitter systems including glutamate, noradrenaline and serotonin, suggesting the involvement also of other neurotransmitter systems in the pathogenesis of the disease. To address the question whether ?-amyloid may contribute to these deficits, brain tissue from transgenic Tg2576 mice with Alzheimer plaque pathology at ages of 5

Margrit Klingner; Jenny Apelt; Ashok Kumar; Dietlind Sorger; Osama Sabri; Jörg Steinbach; Matthias Scheunemann; Reinhard Schliebs

2003-01-01

290

Dopamine release from serotonergic nerve fibers is reduced in L-DOPA-induced dyskinesia  

PubMed Central

L-DOPA (3,4-dihydroxyphenyl-L-alanine) is the most commonly used treatment for symptomatic control in patients with Parkinson’s disease. Unfortunately, most patients develop severe side effects, such as dyskinesia, upon chronic L-DOPA treatment. The patophysiology of dyskinesia is unclear, however, involvement of serotonergic nerve fibers in converting L-DOPA to dopamine has been suggested. Therefore, potassium-evoked dopamine release was studied after local application of L-DOPA in the striata of normal, dopamine- and dopamine/serotonin-lesioned L-DOPA naïve, and dopamine-denervated chronically L-DOPA-treated dyskinetic rats using in vivo chronoamperometry. The results revealed that local L-DOPA administration into normal and intact hemisphere of dopamine-lesioned L-DOPA naïve animals significantly increased the potassium-evoked dopamine release. L-DOPA application also increased the dopamine peak amplitude in the dopamine-depleted L-DOPA naïve striatum, although these dopamine levels were several-folds lower than in the normal striatum, while no increased dopamine release was found in the dopamine/serotonin-denervated striatum. In dyskinetic animals, local L-DOPA application did not affect the dopamine release, resulting in significantly attenuated dopamine levels compared to those measured in L-DOPA naïve dopamine-denervated striatum. To conclude, L-DOPA is most likely converted to dopamine in serotonergic nerve fibers in the dopamine-depleted striatum, but the dopamine release is several-fold lower than in normal striatum. Furthermore, L-DOPA loading does not increase the dopamine release in dyskinetic animals as found in L-DOPA naïve animals, despite similar density of serotonergic innervation. Thus, the dopamine overflow produced from the serotonergic nerve fibers appears not to be the major cause of dyskinetic behavior.

Nevalainen, Nina; af Bjerken, Sara; Lundblad, Martin; Gerhardt, Greg A.; Stromberg, Ingrid

2011-01-01

291

CMOS neurotransmitter microarray: 96-channel integrated potentiostat with on-die microsensors.  

PubMed

A 8 × 12 array of integrated potentiostats for on-CMOS neurotransmitter imaging is presented. Each potentiostat channel measures bidirectional redox currents proportional to the concentration of a neurochemical. By combining the current-to-frequency and the single-slope analog-to-digital converter (ADC) architectures a total linear dynamic range of 95 dB is achieved. A 3.8 mm × 3.1 mm prototype fabricated in a 0.35 ?m standard CMOS technology was integrated with flat and 3D on-die gold microelectrodes and an on-chip microfluidic network. It is experimentally validated in in-situ recording of neurotransmitter dopamine. PMID:23853333

Nazari, Meisam Honarvar; Mazhab-Jafari, Hamed; Leng, Lian; Guenther, Axel; Genov, Roman

2013-06-01

292

Neurotensin and dopamine interactions.  

PubMed

Interactions between the classical monoamine neurotransmitter dopamine (DA) and the peptide neurotransmitter neurotensin (NT) in the central nervous system (CNS) have now been investigated for over two decades. Interest in this topic has been sustained, primarily because of the potential clinical relevance of these interactions to schizophrenia and drug abuse. In the past five years, important new discoveries in the NT field have markedly expanded our previous database. Additional NT receptors have been cloned, and novel and refined techniques have contributed to a more detailed description of the anatomy of the CNS NT system. Additionally, lipophilic NT receptor antagonists, active in the CNS after peripheral administration, have rendered more facile the investigation of the physiologic importance of endogenous NT at electrophysiologic, neurochemical, and behavioral levels. In the present review, the discussion of NT/DA interactions will progress from a discussion of the anatomical interactions between these two systems, to electrophysiologic and neurochemical interactions, and finally to behavioral implications-always with focus toward the potential clinical relevance of the data. The discussion of interactions between NT and DA systems will be limited to those occurring within the CNS. Moreover, because the DA projections from the midbrain to the striatum account for the bulk of the DA innervation in the CNS, we will focus on NT/DA interactions within these brain regions. Last, because of the extensive literature on NT/DA interactions available in the rat, our discussion will be based primarily on studies using this species. PMID:11734615

Binder, E B; Kinkead, B; Owens, M J; Nemeroff, C B

2001-12-01

293

Dopamine as a prolactin (PRL) inhibitor.  

PubMed

Dopamine is a small and relatively simple molecule that fulfills diverse functions. Within the brain, it acts as a classical neurotransmitter whose attenuation or overactivity can result in disorders such as Parkinson's disease and schizophrenia. Major advances in the cloning and characterization of biosynthetic enzymes, transporters, and receptors have increased our knowledge regarding the metabolism, release, reuptake, and mechanism of action of dopamine. Dopamine reaches the pituitary via hypophysial portal blood from several hypothalamic nerve tracts that are regulated by PRL itself, estrogens, and several neuropeptides and neurotransmitters. Dopamine binds to type-2 dopamine receptors that are functionally linked to membrane channels and G proteins and suppresses the high intrinsic secretory activity of the pituitary lactotrophs. In addition to inhibiting PRL release by controlling calcium fluxes, dopamine activates several interacting intracellular signaling pathways and suppresses PRL gene expression and lactotroph proliferation. Thus, PRL homeostasis should be viewed in the context of a fine balance between the action of dopamine as an inhibitor and the many hypothalamic, systemic, and local factors acting as stimulators, none of which has yet emerged as a primary PRL releasing factor. The generation of transgenic animals with overexpressed or mutated genes expanded our understanding of dopamine-PRL interactions and the physiological consequences of their perturbations. PRL release in humans, which differs in many respects from that in laboratory animals, is affected by several drugs used in clinical practice. Hyperprolactinemia is a major neuroendocrine-related cause of reproductive disturbances in both men and women. The treatment of hyperprolactinemia has greatly benefited from the generation of progressively more effective and selective dopaminergic drugs. PMID:11739329

Ben-Jonathan, N; Hnasko, R

2001-12-01

294

Neurobehavioral toxic effects of perinatal oral exposure to aluminum on the developmental motor reflexes, learning, memory and brain neurotransmitters of mice offspring.  

PubMed

Aluminum (Al) is a known neurotoxicant and circumstantial evidence has linked this metal with several neurodegenerative disorders like Alzheimer's disease, but no causal relationship has yet been proved. Al-induced behavioral alterations as well as cognitive deficits and rodent brain neurotransmitter level, are well known in adults but the exact mechanism in the offspring of perinatally Al exposed dams is not yet understood properly and needs more attention. In the present study, the perinatal oral exposure of the dams to 300 and 600mg/kg/day Al (aluminum chloride) resulted in significant and deleterious effects in the offspring inflicting a dose-dependent reduction in postnatal body weight gain, delays in opening of the eyes and appearance of body hair fuzz, and deficits in the sensory motor reflexes of the mice pups during weaning period (from the day of birth to postnatal day 21). During adolescent ages of the male offspring, a significant and dose-dependent deficit was also observed in their locomotor activity at postnatal day 22 (PD 22), learning capability (at PD 25), and cognitive behavior (at PD 30-36). Furthermore, a significant and dose-dependent disturbance in the levels of neurotransmitters like dopamine (DA) and serotonin (5-HT) was also observed in the forebrain region of the offspring at PD 7, PD 14, PD 21, PD 30, and PD 36. Thus, perinatal Al exposure, particularly during pregnancy and lactation period, can affect the in utero developing fetus and postnatal developing sucklings, raising the concerns that during a critical perinatal period of brain development, Al exposure has potential and long lasting neurotoxic hazards and might modify the properties of the dopaminergic system and thus can change the threshold of that system or other related systems at later ages. A reduced use of Al during pregnancy is of crucial importance in preventing Al-induced delayed neurotoxicity in the offspring. PMID:22115621

Abu-Taweel, Gasem M; Ajarem, Jamaan S; Ahmad, Mohammad

2011-11-13

295

Comparative Developmental Neurotoxicity of Organophosphates In Vivo: Transcriptional Responses of Pathways for Brain Cell Development, Cell Signaling, Cytotoxicity and Neurotransmitter Systems  

PubMed Central

Organophosphates affect mammalian brain development through a variety of mechanisms beyond their shared property of cholinesterase inhibition. We used microarrays to characterize similarities and differences in transcriptional responses to chlorpyrifos and diazinon, assessing defined gene groupings for the pathways known to be associated with the mechanisms and/or outcomes of chlorpyrifos-induced developmental neurotoxicity. We exposed neonatal rats to daily doses of chlorpyrifos (1 mg/kg) or diazinon (1 or 2 mg/kg) on postnatal days 1-4 and evaluated gene expression profiles in brainstem and forebrain on day 5; these doses produce little or no cholinesterase inhibition. We evaluated pathways for general neural cell development, cell signaling, cytotoxicity and neurotransmitter systems, and identified significant differences for >60% of 252 genes. Chlorpyrifos elicited major transcriptional changes in genes involved in neural cell growth, development of glia and myelin, transcriptional factors involved in neural cell differentiation, cAMP-related cell signaling, apoptosis, oxidative stress, excitotoxicity, and development of neurotransmitter synthesis, storage and receptors for acetylcholine, serotonin, norepinephrine and dopamine. Diazinon had similar effects on many of the same processes but also showed major differences from chlorpyrifos. Our results buttress the idea that different organophosphates target multiple pathways involved in neural cell development but also that they deviate in key aspects that may contribute to disparate neurodevelopmental outcomes. Equally important, these pathways are compromised at exposures that are unrelated to biologically significant cholinesterase inhibition and its associated signs of systemic toxicity. The approach used here demonstrates how planned comparisons with microarrays can be used to screen for developmental neurotoxicity.

Slotkin, Theodore A.; Seidler, Frederic J.

2007-01-01

296

Surface-relevant regulable DNA toroids induced by dopamine.  

PubMed

Dopamine (2-(3,4-dihydroxyphenyl)ethylamine) is known as a natural chemical neurotransmitter and is also a cytotoxic and genotoxic molecule for cell apoptosis. In this work, the interaction of DNA with dopamine was investigated. Though the electrostatic interaction of DNA and dopamine was weak in aqueous solution, dopamine condensed circular pBR322 DNA into toroids on the mica surface cooperatively with ethanol. The formed DNA toroids came from the shrinking of DNA that was driven by ethanol-enhanced DNA-dopamine electrostatic interaction. The size of the DNA toroids could be modulated by varying the concentration of dopamine. This study offers useful information about the DNA condensation induced by monovalent cations and the sample preparation for AFM measurement and application. On the other hand, this work provides the potential strategies to prepare morphology and size controllable DNA condensates, which have valuable applications in gene transfection and nanotechnology. PMID:19344139

Guo, Cunlan; Liu, Zhelin; Xu, Fugang; Sun, Lanlan; Sun, Yujing; Yang, Tao; Li, Zhuang

2009-04-30

297

Neurotransmitter Synthesis by Neuroblastoma Clones  

Microsoft Academic Search

Neuroblastoma clones were examined for choline acetyltransferase (EC 2.3.1.6), tyrosine hydroxylase (EC 1.14.3.a), acetylcholinesterase (EC 3.1.1.7), and also for neurite formation. One clone does not form axons or dendrites. Three types of clones were found with respect to neurotransmitter synthesis: cholinergic, adrenergic, and clones that do not synthesize acetylcholine or catechols. All clones contain acetylcholinesterase. These results show that genes

Takehiko Amano; Elliott Richelson; Marshall Nirenberg

1972-01-01

298

Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease  

Microsoft Academic Search

Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, embryonic stem (ES) cells proliferate extensively and can generate

Jong-Hoon Kim; Jonathan M. Auerbach; José A. Rodríguez-Gómez; Iván Velasco; Denise Gavin; Nadya Lumelsky; Sang-Hun Lee; John Nguyen; Rosario Sánchez-Pernaute; Krys Bankiewicz; Ron McKay

2002-01-01

299

Human genetics of plasma dopamine ß-hydroxylase activity: applications to research in psychiatry and neurology  

Microsoft Academic Search

Rationale Norepinephrine (NE) is a key neurotransmitter in the central and peripheral nervous systems. Dopamine ?-hydroxylase (D?H) catalyzes the synthesis of NE from dopamine (DA) and occurs in the plasma as a stable heritable trait. Studies of this trait have been useful in psychiatric and neurological research. Objective To selectively and critically review the literature on plasma D?H, and on

J. F. Cubells; C. P. Zabetian

2004-01-01

300

Carbon nanofiber electrode array for electrochemical detection of dopamine using fast scan cyclic voltammetry  

PubMed Central

A carbon nanofiber (CNF) electrode array was integrated with the Wireless Instantaneous Neurotransmitter Sensor System (WINCS) for detection of dopamine using fast scan cyclic voltammetry (FSCV). Dopamine detection performance by CNF arrays was comparable to that of traditional carbon fiber microelectrodes (CFMs), demonstrating that CNF arrays can be utilized as an alternative carbon electrodes for neurochemical monitoring.

Koehne, Jessica E.; Marsh, Michael; Boakye, Adwoa; Douglas, Brandon; Kim, In Yong; Chang, Su-Youne; Jang, Dong-Pyo; Bennet, Kevin E.; Kimble, Christopher; Andrews, Russell; Meyyappan, M.; Lee, Kendall H.

2012-01-01

301

Excess nicotinamide increases plasma serotonin and histamine levels.  

PubMed

Methylation, a methyl group-consuming reaction, plays a key role in the degradation (i.e., inactivation) of monoamine neurotransmitters, including catecholamines, serotonin and histamine. Without labile methyl groups, the methylation-mediated degradation cannot take place. Although high niacin (nicotinic acid and nicotinamide) intake, which is very common nowadays, is known to deplete the body's methyl-group pool, its effect on monoamine-neurotransmitter degradation is not well understood. The aim of this article was to investigate the effect of excess nicotinamide on the levels of plasma serotonin and histamine in healthy subjects. Urine and venous blood samples were collected from nine healthy male volunteers before and after oral loading with 100 mg nicotinamide. Plasma N(1)-methylnicotinamide, urinary N(1)-methyl-2-pyridone-5-carboxamide (2-Py), and plasma betaine levels were measured by using high-performance liquid chromatography (HPLC). Plasma concentrations of choline, serotonin and histamine were measured using commercial kits. The results showed that the plasma N(1)-methylnicotinamide level and the urinary excretion of 2-Py significantly increased after oral loading with 100 mg nicotinamide, which was accompanied with a decrease in the methyl-group donor betaine. Compared with those before nicotinamide load, five-hour postload plasma serotonin and histamine levels significantly increased. These results suggest that excess nicotinamide can disturb monoamine-neurotransmitter metabolism. These findings may be of significance in understanding the etiology of monoamine-related mental diseases, such as schizophrenia and autism (a neurodevelopmental disorder). PMID:23426511

Tian, Yan-Jie; Li, Da; Ma, Qiang; Gu, Xin-Yi; Guo, Ming; Lun, Yong-Zhi; Sun, Wu-Ping; Wang, Xin-Yuan; Cao, Yu; Zhou, Shi-Sheng

2013-02-25

302

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions  

Microsoft Academic Search

The widespread use of the selective serotonin reuptake inhibitors (SSRIs) has been accompanied by numerous reports describing a potential association with hyperprolactinemia. Antipsychotics are commonly known to elevate serum prolactin (PRL) through blockade of dopamine receptors in the pituitary. However, there is little awareness of the mechanisms by which SSRIs stimulate PRL release. Hyperprolactinemia may result in overt symptoms such

Ana B F Emiliano; Julie L Fudge; ABF Emiliano

2004-01-01

303

Circulating serotonin in vertebrates.  

PubMed

The role of circulating serotonin is unclear and whether or not serotonin is present in the blood of non-mammalian species is not known. This study provides the first evidence for the presence of serotonin in thrombocytes of birds and three reptilian species, the endothermic leatherback sea turtle, the green sea turtle and the partially endothermic American alligator. Thrombocytes from a fresh water turtle, American bullfrog, Yellowfin tuna, and Chinook salmon did not contain serotonin. Serotonin is a vasoactive substance that regulates skin blood flow, a major mechanism for endothermic body temperature regulation, which could explain why circulating serotonin is present in warm-blooded species. The temperature sensitivity of human blood platelets with concomitant changes in serotonin content further supports a link between circulating serotonin and thermoregulation. Phylogenetic comparison of the presence of circulating serotonin indicated an evolutionary divergence within reptilian species that might coincide with the emergence of endothermy. PMID:16041566

Maurer-Spurej, E

2005-08-01

304

Differential modulation of the default mode network via serotonin-1A receptors.  

PubMed

Reflecting one's mental self is a fundamental process for evaluating the personal relevance of life events and for moral decision making and future envisioning. Although the corresponding network has been receiving growing attention, the driving neurochemical mechanisms of the default mode network (DMN) remain unknown. Here we combined positron emission tomography and functional magnetic resonance imaging to investigate modulations of the DMN via serotonin-1A receptors (5-HT(1A)), separated for 5-HT autoinhibition (dorsal raphe nucleus) and local inhibition (heteroreceptors in projection areas). Using two independent approaches, regional 5-HT(1A) binding consistently predicted DMN activity in the retrosplenial cortex for resting-state functional magnetic resonance imaging and the Tower of London task. On the other hand, both local and autoinhibitory 5-HT(1A) binding inversely modulated the posterior cingulate cortex, the strongest hub in the resting human brain. In the frontal part of the DMN, a negative association was found between the dorsal medial prefrontal cortex and local 5-HT(1A) inhibition. Our results indicate a modulation of key areas involved in self-referential processing by serotonergic neurotransmission, whereas variations in 5-HT(1A) binding explained a considerable amount of the individual variability in the DMN. Moreover, the brain regions associated with distinct introspective functions seem to be specifically regulated by the different 5-HT(1A) binding sites. Together with previously reported modulations of dopamine and GABA, this regional specialization suggests complex interactions of several neurotransmitters driving the default mode network. PMID:22308408

Hahn, Andreas; Wadsak, Wolfgang; Windischberger, Christian; Baldinger, Pia; Höflich, Anna S; Losak, Jan; Nics, Lukas; Philippe, Cécile; Kranz, Georg S; Kraus, Christoph; Mitterhauser, Markus; Karanikas, Georgios; Kasper, Siegfried; Lanzenberger, Rupert

2012-01-30

305

Dopamine receptors in human gastrointestinal mucosa  

SciTech Connect

Dopamine is a putative enteric neurotransmitter that has been implicated in exocrine secretory and motility functions of the gastrointestinal tract of several mammalian species including man. This study was designed to determine the presence of dopamine binding sites in human gastric and duodenal mucosa and to describe certain biochemical characteristics of these enteric receptor sites. The binding assay was performed in triplicate with tissue homogenates obtained from healthy volunteers of both sexes using /sup 3/H-dopamine as a ligand. The extent of nonspecific binding was determined in the presence of a 100-fold excess of unlabeled dopamine. Scatchard analysis performed with increasing concentrations of /sup 3/H-dopamine (20-500 nM) revealed a single class of saturable dopamine binding sites in gastric and duodenal mucosa. The results of this report demonstrate the presence of specific dopamine receptors in human gastric and duodenal mucosa. These biochemical data suggest that molecular abnormalities of these receptor sites may be operative in the pathogenesis of important gastrointestinal disorders. 33 references, 2 figures.

Hernandez, D.E.; Mason, G.A.; Walker, C.H.; Valenzuela, J.E.

1987-12-21

306

Functional activation by central monoamines of human dopamine D 4 receptor polymorphic variants coupled to GIRK channels in Xenopus oocytes  

Microsoft Academic Search

We studied the functional activation of different polymorphic variants of the human dopamine D4 receptors by the three major central monoamines, dopamine, noradrenaline and serotonin. Dopamine D4 receptors carrying two (D4.2), four (D4.4) or seven (D4.7) repeats within the third intracellular domain were co-expressed with G protein-regulated inwardly rectifying potassium channels (GIRK1) in frog oocytes. All the dopamine D4 receptor

Carolina Wedemeyer; Juan D. Goutman; María E. Avale; Lucía F. Franchini; Marcelo Rubinstein; Daniel J. Calvo

2007-01-01

307

Serotonin and amino acids: partners in delirium pathophysiology?  

PubMed

Delirium may be the result of dysfunction of multiple interacting neurotransmitter systems. Changes in the levels of various amino acids being precursors of cerebral neurotransmitters may affect their function and, thus, contribute to the development of delirium. Serotonin is one of the neurotransmitters that may play an important role in medical and surgical delirium. Normal serotonin synthesis and release in the human brain is, among others, dependent on the availability of its precursor tryptophan (Trp) from blood. The essential amino acid Trp competes with the other large neutral amino acids (LNAA) tyrosine, phenylalanine, valine, leucine, and isoleucine for transport across the blood-brain barrier. This competition determines its uptake into the brain, represented by the ratio of the plasma level of Trp to the sum of the other LNAA. The plasma ratio of Trp/LNAA, plasma level of Trp, and serotonin in plasma and platelets have been used as indirect peripheral measures for central serotonergic functioning. Both increased and decreased serotonergic activity have been associated with delirium. Serotonin agonists can induce psychosis, both elevated Trp availability and increased cerebral serotonin have been associated with hepatic encephalopathy, and excess serotonergic brain activity has been related to the development of the serotonin syndrome of which delirium is a main symptom. On the other hand, alcohol withdrawal delirium, delirium in levodopa-treated Parkinson patients, and postoperative delirium have been related to reduce cerebral Trp availability from plasma suggesting diminished serotonergic function. Rick factors for delirium such as severe illness, surgery, and trauma can induce immune activation and a physical stress response comprising increased activity of the limbic-hypothalamic-pituitary-adrenocortical axis, the occurrence of a low T3 syndrome, and, possibly, changes in the permeability of the blood-brain barrier. There are indications that these changes have their effect on plasma amino acid concentrations, e.g., Trp, and multiple cerebral neurotransmitters, including serotonin. This stress response may be different depending on the stage of illness being acute or chronic. It will require further study to determine the complex influence of the stress response and immune activation on plasma amino acids, neurotransmitter function and the development of delirium, especially in the more vulnerable older patients. PMID:10837101

van der Mast, R C; Fekkes, D

2000-04-01

308

Specification of Neurotransmitter Identity by Phox2 Proteins in Neural Crest Stem Cells  

Microsoft Academic Search

We have investigated the specification of noradrenergic neurotransmitter identity in neural crest stem cells (NCSCs). Retroviral expression of both wild-type and dominant-negative forms of the paired homeodomain transcription factor Phox2a indicates a crucial and direct role for this protein (and\\/or the closely related Phox2b) in the regulation of endogenous tyrosine hydroxylase (TH) and dopamine-? hydroxylase (DBH) gene expression in these

Liching Lo; Xavier Morin; Jean-François Brunet; David J. Anderson

1999-01-01

309

Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling  

Microsoft Academic Search

Catecholamines are important regulators of homeostasis, yet their functions in hematopoiesis are poorly understood. Here we report that immature human CD34+ cells dynamically expressed dopamine and ?2-adrenergic receptors, with higher expression in the primitive CD34+CD38lo population. The myeloid cytokines G-CSF and GM-CSF upregulated neuronal receptor expression on immature CD34+ cells. Treatment with neurotransmitters increased the motility, proliferation and colony formation

Asaf Spiegel; Shoham Shivtiel; Alexander Kalinkovich; Aya Ludin; Neta Netzer; Polina Goichberg; Yaara Azaria; Igor Resnick; Izhar Hardan; Herzel Ben-Hur; Arnon Nagler; Menachem Rubinstein; Tsvee Lapidot

2007-01-01

310

Effects Of Novel Monoamine Oxidases And Cholinesterases Targeting Compounds On Brain Neurotransmitters And Behavior In Rat Model Of Vascular Dementia.  

PubMed

Neurodegenerative disorders are associated with different neurochemical and morphological alterations in the brain leading to cognitive and behavioural impairments. New therapeutic strategies comprise multifunctional drugs. The aim of the presented studies is to evaluate in vivo the novel compounds - ASS188 and ASS234-which combine the benzylpiperidine moiety of the acetylcholinesteras (AChE) inhibitor donepezil and the indolyl propargylamino moiety of the monoaminooxidase (MAO) inhibitor, N-[(5-benzyloxy-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine, with respect to their influence on cerebral amine neurotransmitters systems and neuroprotective activity. The presumed therapeutic potential of these compounds has been evaluated following their administration to rats with experimental vascular dementia. A rat model of the permanent bilateral occlusion of the common carotid arteries (BCCAO) and the holeboard memory test were employed for this purpose. Wistar rats were used, either intact or 1 day after BCCAO. ASS188 (1 mg/kg) and ASS234 (5 mg/kg) were given s.c. for 5 consecutive days. Working and reference memory in rats was evaluated by holeboard tests before- and 7 and 12 days after BCCAO. The activities of MAOs, AChE and histamine N-methyltransferase (HMT), as well as cerebral amines concentrations were assayed. A significant inhibition of brain MAO A (>95%) and weaker MAO B (ca 60%) and HMT (<30%) and reduced AChE activities was recorded with a pronounced (2 - 10 fold) increase in the cerebral concentrations of serotonin, dopamine, and noradrenaline and smaller rises (up to 30%) of histamine. The BCCAO rats treated with ASS188 or ASS234 tended to perform holeboard tests better than the BCCAO untreated group, indicating a beneficial effect of the administered therapeutics. PMID:23701539

Stasiak, Anna; Mussur, Miros?aw; Unzeta, Mercedes; Samadi, Abdelouahid; Marco-Contelles, José L; Fogel, W Agnieszka

2013-05-16

311

Application of carboxymethyl-beta-cyclodextrin as a chiral selector in capillary electrophoresis for enantiomer separation of selected neurotransmitters.  

PubMed

The aim of this work was to optimize conditions for capillary electrophoresis separation of different neurotransmitters (serotonin, phenylalanine, dopamine, adrenaline, ephedrine, propranolol and DOPA) in a single run, including separation of existing enantiomers. As chiral selectors added to the borate background, electrolyte unsubstituted alpha-, beta- and -gamma-cyclodextrins (CDs), methyl-, dimethyl-, and trimethyl-substituted beta-CDs, and hydroxypropyl-substituted alpha-, beta- and gamma-CDs were examined. Also carboxymethyl-beta-CD and succinyl-beta-CD were used for this purpose. In addition to the kind and concentration of chiral selector, some other experimental factors also have been optimized, such as concentration of borate buffer, content of methanol, pH of electrolyte, method of sample introduction into the capillary and washing procedure between consecutive runs. The best results were obtained using 20 mM carboxymethyl-beta-CD in borate buffer of pH 7.5 as running electrolyte and hydrostatic injection. The obtained sensitivity of response (peak height) varied from 0.4 for adrenalines to 2.3 mAU mM(-1) for propranolols. The concentration detection limits (S/N=3) were in the range from 0.04 mM for propranolols to 0.2 mM for adrenalines. The resolution obtained in optimized conditions in a single run was from 0.75 for adrenalins and 1.0 for propranolols up to 2.0 for ephedrines. The developed method was employed for determination of these analytes in brain tissue extracts. PMID:11556337

Marusza, W; Trojanowicz, M; Margasi?ska, M; Engelhardt, H

2001-08-17

312

Expression of serotonin (5HT) during CNS development of the cephalopod mollusk, Idiosepius notoides  

Microsoft Academic Search

Cephalopods are unique among mollusks in exhibiting an elaborate central nervous system (CNS) and remarkable cognitive abilities.\\u000a Despite a profound knowledge of the neuroanatomy and neurotransmitter distribution in their adult CNS, little is known about\\u000a the expression of neurotransmitters during cephalopod development. Here, we identify the first serotonin-immunoreactive (5-HT-ir)\\u000a neurons during ontogeny and describe the establishment of the 5-HT system

Tim Wollesen; Bernard M. Degnan; Andreas Wanninger

2010-01-01

313

Membrane Glycoprotein M6B Interacts with the Human Serotonin Transporter  

Microsoft Academic Search

The serotonin transporter (SERT) belongs to a family of sodium- and chloride-dependent neurotransmitter transporters that\\u000a are responsible for the active re-uptake of the neurotransmitter serotonin from the synapse. In the present study, using the\\u000a yeast two-hybrid system, we identified the membrane glycoprotein M6B as a binding partner of SERT. This interaction was further\\u000a verified by co-immunoprecipitation and glutathione-S-transferase pull-down assays.

Anja Winther Fjorback; Heidi Kaastrup Müller; Ove Wiborg

2009-01-01

314

Long-term administration of m-chlorophenylpiperazine (mCPP) to rats induces changes in serotonin receptor binding, dopamine levels and locomotor activity without altering prolactin and corticosterone secretion  

Microsoft Academic Search

Meta-chlorophenylpiperazine (mCPP) is a serotonin (5-HT) agonist with antidepressant actions. In order to investigate the effects of chronic mCPP treatment the drug was administered to rats for 15 days (5 mg\\/kg twice daily). Controls were administered saline. Long-term mCPP treatment led to a 36% increase in [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) binding to 5-HT1a receptors in hippocampus and a 74% decrease in [3H]ketanserin

Jakob Ulrichsen; John S. Partilla; Elizabeth M. Dax

1992-01-01

315

Electrochemical quantification of serotonin in the live embryonic zebrafish intestine  

PubMed Central

We monitored real-time in vivo levels of serotonin release in the digestive system of intact zebrafish embryos during early development (5 dpf) using differential pulse voltammetry with implanted carbon fiber microelectrodes modified with carbon nanotubes dispersed in nafion. A detection limit of 1 nM, a linear range between 5 to 200 nM and a sensitivity of 83.65 nA·?M?1 were recorded. The microelectrodes were implanted at various locations in the intestine of zebrafish embryos. Serotonin levels of up to 29.9(±1.13) nM were measured in vivo in normal physiological conditions. Measurements were performed in intact live embryos without additional perturbation beyond electrode insertion. The sensor was able to quantify pharmacological alterations in serotonin release and provide the longitudinal distribution of this neurotransmitter along the intestine with high spatial resolution. In the presence of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), concentrations of 54.1(±1.05) nM were recorded while in the presence of p-chloro-phenylalanine (PCPA), a tryptophan hydroxylase inhibitor, the serotonin levels decreased to 7.2(±0.45) nM. The variation of serotonin levels was correlated with immunohistochemical analysis. We have demonstrated the first use of electrochemical microsensors for in vivo monitoring of intestinal serotonin levels in intact zebrafish embryos.

Njagi, John; Ball, Michael; Best, Marc; Wallace, Kenneth N.; Andreescu, Silvana

2010-01-01

316

Automated mass spectrometric analysis of urinary and plasma serotonin.  

PubMed

Serotonin emerges as crucial neurotransmitter and hormone in a growing number of different physiologic processes. Besides extensive serotonin production previously noted in patients with metastatic carcinoid tumors, serotonin now is implicated in liver cell regeneration and bone formation. The aim was to develop a rapid, sensitive, and highly selective automated on-line solid-phase extraction method coupled to high-performance liquid chromatography-tandem mass spectrometry (XLC-MS/MS) to quantify low serotonin concentrations in matrices such as platelet-poor plasma and urine. Fifty microliters plasma or 2.5 microL urine equivalent were pre-purified by automated on-line solid-phase extraction, using weak cation exchange. Chromatography of serotonin and its deuterated internal standard was performed with hydrophilic interaction chromatography. Mass spectrometric detection was operated in multiple reaction monitoring mode using a quadrupole tandem mass spectrometer with positive electrospray ionization. Serotonin concentrations were determined in platelet-poor plasma of metastatic carcinoid patients (n = 23) and healthy controls (n = 22). Urinary reference intervals were set by analyzing 24-h urine collections of 120 healthy subjects. Total run-time was 6 min. Intra- and inter-assay analytical variation were <10%. Linearity in the 0-7300 micromol/L calibration range was excellent (R(2) > 0.99). Quantification limits were 30 and 0.9 nmol/L in urine and plasma, respectively. Platelet-poor serotonin concentrations in metastatic carcinoid patients were significantly higher than in controls. The urinary reference interval was 10-78 micromol/mol creatinine. Serotonin analysis with sensitive and specific XLC-MS/MS overcomes limitations of conventional HPLC. This enables accurate quantification of serotonin for both routine diagnostic procedures and research in serotonin-related disorders. PMID:20140664

de Jong, Wilhelmina H A; Wilkens, Marianne H L I; de Vries, Elisabeth G E; Kema, Ido P

2010-02-07

317

Growth-Inhibitory Effects of Serotonin Uptake Inhibitors on Human Prostate Carcinoma Cell Lines  

Microsoft Academic Search

Growth stimulation of a variety of cell types by the neurotransmitter serotonin has been reported. We have examined the effects of three serotonin-uptake inhibitors, 6-nitroquipazine, zimelidine and fluoxetine (Prozac, Eli Lilly Co., Indianapolis, Indiana) on human prostate carcinoma cell lines. In vitro, all 3 of these compounds inhibited the proliferation of PC-3, DU-145 and LNCaP cells in a dose-dependent manner.

Mansoor Abdul; Christopher J. Logothetis; Naseema M. Hoosein

1995-01-01

318

Octopamine and Serotonin-Stimulated Phosphorylation of Specific Protein in the Abdominal Ganglion of Aplysia californica  

Microsoft Academic Search

Phosphorylation of a protein (or proteins) of molecular weight 120,000 in the Aplysia abdominal ganglion, as measured by incorporation of [32P] or [33P]sodium phosphate in vitro followed by separation of the phospho-proteins on sodium dodecyl sulfate-polyacrylamide gels, was specifically stimulated by incubation in the presence of the putative neurotransmitters octopamine or serotonin. The stimulatory effect of octopamine and serotonin was

Irwin B. Levitan; Samuel H. Barondes

1974-01-01

319

Increased dopamine tone during meditation-induced change of consciousness  

Microsoft Academic Search

This is the first in vivo demonstration of an association between endogenous neurotransmitter release and conscious experience. Using 11C-raclopride PET we demonstrated increased endogenous dopamine release in the ventral striatum during Yoga Nidra meditation. Yoga Nidra is characterized by a depressed level of desire for action, associated with decreased blood flow in prefrontal, cerebellar and subcortical regions, structures thought to

Troels W Kjaer; Camilla Bertelsen; Paola Piccini; David Brooks; Jørgen Alving; Hans C Lou

2002-01-01

320

Neural Circuits, Neurotransmitters, and Behavior  

Microsoft Academic Search

\\u000a In bulimia nervosa (BN), and in related binge–purge syndromes, factors affecting central serotonin (5-hydroxytryptamine, 5-HT)\\u000a function appear to contribute not only to appetitive dysregulation but also to temperamental and personality manifestations.\\u000a Drawing upon findings from neurobiological, molecular-genetic, and brain-imaging studies, we present an integrative model\\u000a of the role of 5-HT function in bulimic syndromes. At the core of our model

Howard Steiger; Kenneth R. Bruce; Patricia Groleau

321

Alteration in the neurotransmitter levels in the brain of the freshwater snakehead fish (Channa punctatus) exposed to carbofuran  

Microsoft Academic Search

Channa punctatus a freshwater fish exposed to carbofuran (0.6 mg l-1) for 15 days exhibited alterations in norepinephrine (NE), dopamine (DA) and serotonin (5-HT) levels. NE levels increased in the cerebellum and decreased in the medulla and cerebral cortex relative to the controls. Increased DA levels were observed in the cerebellum and medulla whereas DA levels decreased in the cerebral

Krishna Gopal; Muralidhar Ram

1995-01-01

322

Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves.  

PubMed

Heart valve disease and pulmonary hypertension, in patients with carcinoid tumors and people who used the fenfluramine-phentermine combination for weight control, have been associated with high levels of serotonin in blood. The mechanism by which serotonin induces valvular changes is not well understood. We recently reported that increased oxidative stress is associated with valvular changes in aortic valve stenosis in humans and mice. In this study, we tested the hypothesis that serotonin induces oxidative stress in human heart valves, and examined mechanisms by which serotonin may increase reactive oxygen species. Superoxide (O2*.-) was measured in heart valves from explanted human hearts that were not used for transplantation. (O2*.-) levels (lucigenin-enhanced chemoluminescence) were increased in homogenates of cardiac valves and blood vessels after incubation with serotonin. A nonspecific inhibitor of flavin-oxidases (diphenyliodonium), or inhibitors of monoamine oxidase [MAO (tranylcypromine and clorgyline)], prevented the serotonin-induced increase in (O2*.-). Dopamine, another MAO substrate that is increased in patients with carcinoid syndrome, also increased (O2*.-) levels in heart valves, and this effect was attenuated by clorgyline. Apocynin [an inhibitor of NAD(P)H oxidase] did not prevent increases in (O2*.-) during serotonin treatment. Addition of serotonin to recombinant human MAO-A generated (O2*.-), and this effect was prevented by an MAO inhibitor. In conclusion, we have identified a novel mechanism whereby MAO-A can contribute to increased oxidative stress in human heart valves and pulmonary artery exposed to serotonin and dopamine. PMID:19666839

Peña-Silva, Ricardo A; Miller, Jordan D; Chu, Yi; Heistad, Donald D

2009-08-07

323

Uptake inhibition of biogenic amines by newer antidepressant drugs: Relevance to the dopamine hypothesis of depression  

Microsoft Academic Search

The dopamine theory of depression was studied by assessing the effect of antidepressant drugs on uptake of dopamine, noradrenaline, and serotonin in synaptosomes from rat brain. Five newer drugs—butriptyline, maprotiline, trimipramine, iprindole, and mianserine—exhibited rather potent inhibition of 3H-dopamine uptake in corpus striatum, as their IC50 values, which were in the order of 10-6–10-5 M, were only about 50 times

A. Randrup; C. BRiESTRUP

1977-01-01

324

Neurotransmitter CART as a New Therapeutic Candidate for Parkinson's Disease  

PubMed Central

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. To date, there is no effective treatment that halts its progression. Increasing evidence indicates that mitochondria play an important role in the development of PD. Hence mitochondria-targeted approaches or agents may have therapeutic promise for treatment of the disease. Neuropeptide CART (cocaine-amphetamine-regulated transcript), a hypothalamus and midbrain enriched neurotransmitter with an antioxidant property, can be found in mitochondria, which is the main source of reactive oxygen species. Systemic administration of CART has been found to ameliorate dopaminergic neuronal loss and improve motor functions in a mouse model of PD. In this article, we summarize recent progress in studies investigating the relationship between CART, dopamine, and the pathophysiology of PD, with a focus on mitochondria-related topics.

Mao, Peizhong; Meshul, Charles K.; Thuillier, Philippe; Reddy, P. Hemachandra

2013-01-01

325

Neurotransmitter CART as a New Therapeutic Candidate for Parkinson's Disease.  

PubMed

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. To date, there is no effective treatment that halts its progression. Increasing evidence indicates that mitochondria play an important role in the development of PD. Hence mitochondria-targeted approaches or agents may have therapeutic promise for treatment of the disease. Neuropeptide CART (cocaine-amphetamine-regulated transcript), a hypothalamus and midbrain enriched neurotransmitter with an antioxidant property, can be found in mitochondria, which is the main source of reactive oxygen species. Systemic administration of CART has been found to ameliorate dopaminergic neuronal loss and improve motor functions in a mouse model of PD. In this article, we summarize recent progress in studies investigating the relationship between CART, dopamine, and the pathophysiology of PD, with a focus on mitochondria-related topics. PMID:23543038

Mao, Peizhong; Meshul, Charles K; Thuillier, Philippe; Reddy, P Hemachandra

2013-01-18

326

Chemical stimulants of leaf-trenching by cabbage loopers: natural products, neurotransmitters, insecticides, and drugs.  

PubMed

Larvae of the cabbage looper, Trichoplusia ni (Lepidoptera: Noctuidae), often transect leaves with a narrow trench before eating the distal section. The trench reduces larval exposure to exudates, such as latex, during feeding. Plant species that do not emit exudate, such as Plantago lanceolata, are not trenched. However, if exudate is applied to a looper's mouth during feeding on P. lanceolata, the larva will often stop and cut a trench. Dissolved chemicals can be similarly applied and tested for effectiveness at triggering trenching. With this assay, I have documented that lactucin from lettuce latex (Lactuca sativa), myristicin from parsley oil (Petroselinum crispum), and lobeline from cardinal flower (Lobelia cardinalis) elicit trenching. These compounds are the first trenching stimulants reported. Several other constituents of lettuce and parsley, including some phenylpropanoids, monoterpenes, and furanocoumarins had little or no activity. Cucurbitacin E glycoside found in cucurbits, another plant family trenched by cabbage loopers, also was inactive. Lactucin, myristicin, and lobeline all affect the nervous system of mammals, with lobeline acting specifically as an antagonist of nicotinic acetylcholine receptors. To determine if cabbage loopers respond selectively to compounds active at acetylcholine synapses, I tested several neurotransmitters, insecticides, and drugs with known neurological activity, many of which triggered trenching. Active compounds included dopamine, serotonin, the insecticide imidacloprid, and various drugs such as ipratropium, apomorphine, buspirone, and metoclopramide. These results document that noxious plant chemicals trigger trenching, that loopers respond to different trenching stimulants in different plants, that diverse neuroactive chemicals elicit the behavior, and that feeding deterrents are not all trenching stimulants. The trenching assay offers a novel approach for identifying defensive plant compounds with potential uses in agriculture or medicine. Cabbage loopers in the lab and field routinely trench and feed on plants in the Asteraceae and Apiaceae. However, first and third instar larvae enclosed on Lobelia cardinalis (Campanulaceae) failed to develop, even though the third instar larvae attempted to trench. Trenching ability does not guarantee effective feeding on plants with canal-borne exudates. Cabbage loopers must not only recognize and respond to trenching stimulants, they must also tolerate exudates during the trenching procedure to disable canalicular defenses. PMID:14584674

Dussourd, David E

2003-09-01

327

Salvinorin A exerts opposite presynaptic controls on neurotransmitter exocytosis from mouse brain nerve terminals.  

PubMed

We investigated the effects of salvinorin A on the basal and the 12 mM K(+)-evoked release of preloaded [(3)H]noradenaline ([(3)H]NA) and [(3)H]serotonin ([(3)H]5-HT) from mouse hippocampal nerve terminals (synaptosomes), as well as on the basal and 12mM K(+)-evoked release of preloaded [(3)H]dopamine ([(3)H]DA) from mouse striatal and prefrontal cortex (PFc) synaptosomes. Salvinorin A (0.1-1000 nM) failed to affect the basal release of amines, but inhibited the 12 mM K(+)-evoked, Ca(2+)-dependent, exocytotic-like release of [(3)H]5-HT and [(3)H]DA. At the same concentration, salvinorin A facilitated the 12 mM K(+)-evoked, Ca(2+)-dependent, exocytotic-like release of [(3)H]NA. These effects could not be observed in pertussis toxin (PTx) entrapped synaptosomes. The broad spectrum kappa-opioid receptor (KOR) antagonist norbinaltorphimine (norBNI, 1-100 nM) antagonized the inhibition of [(3)H]5-HT and [(3)H]DA exocytosis as well as the facilitation of [(3)H]NA overflow induced by 100 nM salvinorin A. The KOR agonist U69593 (1-100 nM) mimicked salvinorin A in inhibiting [(3)H]5-HT and of [(3)H]DA exocytosis, its effect being prevented by norBNI, but leaving unchanged the K(+)-evoked release of [(3)H]NA. The effects of Salvinorin A on neurotransmitter exocytosis were not prevented by the selective mu opioid (MOR) receptor antagonist CTAP (10-100 nM), whereas facilitation of [(3)H]NA exocytosis, but not inhibition of [(3)H]5-HT and [(3)H]DA K(+)-evoked release, was counteracted by the delta opioid receptor (DOR) antagonist naltrindole (1-100 nM). We conclude that salvinorin A presynaptically modulates central NA, 5-HT, and DA exocytosis evoked by a mild depolarizing stimulus by acting at presynaptic opioid receptors having different pharmacological profiles. PMID:19628000

Grilli, Massimo; Neri, Elisa; Zappettini, Stefania; Massa, Francesca; Bisio, Angela; Romussi, Giovanni; Marchi, Mario; Pittaluga, Anna

2009-07-21

328

How Addictive Drugs Disrupt Presynaptic Dopamine Neurotransmission  

PubMed Central

The fundamental principle that unites addictive drugs appears to be that each enhances synaptic dopamine by means that dissociate it from normal behavioral control, so that they act to reinforce their own acquisition. This occurs via the modulation of synaptic mechanisms involved in learning, including enhanced excitation or disinhibition of dopamine neuron activity, blockade of dopamine reuptake, and altering the state of the presynaptic terminal to enhance evoked over basal transmission. Amphetamines offer an exception to such modulation in that they combine multiple effects to produce non-exocytic stimulation-independent release of neurotransmitter via reverse transport independent from normal presynaptic function. Questions on the molecular actions of addictive drugs, prominently including the actions of alcohol and solvents, remain unresolved, but their ability to co-opt normal presynaptic functions helps to explain why treatment for addiction has been challenging.

Sulzer, David

2011-01-01

329

Dopamine receptor sensitivity after chronic dopamine agonists  

Microsoft Academic Search

Several previous reports have demonstrated that chronic administration of both directly and indirectly acting dopamine agonists produces a supersensitive behavioral response to challenge doses of dopamine agonists when compared to the responses induced by acute administration of these drugs. That is, a given dose of a dopamine agonist will produce a greater response after chronic dopamine agonist treatment than is

William H. Riffee; Richard E. Wilcox; Dana M. Vaughn; Robert V. Smith

1982-01-01

330

The discovery of chemical neurotransmitters.  

PubMed

Neurotransmitters have become such an intrinsic part of our theories about brain function that many today are unaware of how difficult it was to prove their existence or the protracted dispute over the nature of synaptic transmission. The story is important not only because it is fascinating science history, but also because it exemplifies much of what is best in science and deserving to be emulated. The friendships formed among such major figures in this history as Henry Dale, Otto Loewi, Wilhelm Feldberg, Walter Cannon, and others extended over two world wars, enriching their lives and facilitating their research. Even the dispute-the "war of the sparks and the soups"--between neurophysiologists and pharmacologists over whether synaptic transmission is electrical or chemical played a positive role in stimulating the research needed to provide convincing proof. PMID:12027394

Valenstein, Elliot S

2002-06-01

331

Stress, neurotransmitters, corticosterone and body-brain integration.  

PubMed

Stress can be defined as a brain-body reaction towards stimuli arising from the environment or from internal cues that are interpreted as a disruption of homeostasis. The organization of the response to a stressful situation involves not only the activity of different types of neurotransmitter systems in several areas of the limbic system, but also the response of neurons in these areas to several other chemicals and hormones, chiefly glucocorticoids, released from peripheral organs and glands. Thus, stress is probably the process through which body-brain integration plays a major role. Here we review first the responses to an acute stress in terms of neurotransmitters such as dopamine, acetylcholine, glutamate and GABA in areas of the brain involved in the regulation of stress responses. These areas include the prefrontal cortex, amygdala, hippocampus and nucleus accumbens and the interaction among those areas. Then, we consider the role of glucocorticoids and review some recent data about the interaction of these steroids with several neurotransmitters in those same areas of the brain. Also the actions of other substances (neuromodulators) released from peripheral organs such as the pancreas, liver or gonads (insulin, IGF-1, estrogens) are reviewed. The role of an environmental enrichment on these same responses is also discussed. Finally a section is devoted to put into perspective all these environmental-brain-body-brain interactions during stress and their consequences on aging. It is concluded that the integrative perspective framed in this review is relevant for better understanding of how the organism responds to stressful challenges and how this can be modified through different environmental conditions during the process of aging. This article is part of a Special Issue entitled: Brain Integration. PMID:22285436

Mora, Francisco; Segovia, Gregorio; Del Arco, Alberto; de Blas, Marta; Garrido, Pedro

2012-01-03

332

meso-Transdiene analogs inhibit vesicular monoamine transporter-2 function and methamphetamine-evoked dopamine release.  

PubMed

Lobeline, a nicotinic receptor antagonist and neurotransmitter transporter inhibitor, is a candidate pharmacotherapy for methamphetamine abuse. meso-Transdiene (MTD), a lobeline analog, lacks nicotinic receptor affinity, retains affinity for vesicular monoamine transporter 2 (VMAT2), and, surprisingly, has enhanced affinity for dopamine (DA) and serotonin transporters [DA transporter (DAT) and serotonin transporter (SERT), respectively]. In the current study, MTD was evaluated for its ability to decrease methamphetamine self-administration in rats relative to food-maintained responding. MTD specifically decreased methamphetamine self-administration, extending our previous work. Classical structure-activity relationships revealed that more conformationally restricted MTD analogs enhanced VMAT2 selectivity and drug likeness, whereas affinity at the dihydrotetrabenazine binding and DA uptake sites on VMAT2 was not altered. Generally, MTD analogs exhibited 50- to 1000-fold lower affinity for DAT and were equipotent or had 10-fold higher affinity for SERT, compared with MTD. Representative analogs from the series potently and competitively inhibited [(3)H]DA uptake at VMAT2. (3Z,5Z)-3,5-bis(2,4-dichlorobenzylidene)-1-methylpiperidine (UKMH-106), the 3Z,5Z-2,4-dichlorophenyl MTD analog, had improved selectivity for VMAT2 over DAT and importantly inhibited methamphetamine-evoked DA release from striatal slices. In contrast, (3Z,5E)-3,5-bis(2,4-dichlorobenzylidene)-1-methylpiperidine (UKMH-105), the 3Z,5E-geometrical isomer, inhibited DA uptake at VMAT2, but did not inhibit methamphetamine-evoked DA release. Taken together, these results suggest that these geometrical isomers interact at alternate sites on VMAT2, which are associated with distinct pharmacophores. Thus, structural modification of the MTD molecule resulted in analogs exhibiting improved drug likeness and improved selectivity for VMAT2, as well as the ability to decrease methamphetamine-evoked DA release, supporting the further evaluation of these analogs as treatments for methamphetamine abuse. PMID:21177475

Horton, David B; Siripurapu, Kiran B; Norrholm, Seth D; Culver, John P; Hojahmat, Marhaba; Beckmann, Joshua S; Harrod, Steven B; Deaciuc, Agripina G; Bardo, Michael T; Crooks, Peter A; Dwoskin, Linda P

2010-12-21

333

Plasma HVA in Adults with Mental Retardation and Stereotyped Behavior: Biochemical Evidence for a Dopamine Deficiency Model.  

ERIC Educational Resources Information Center

Assessment of the neurotransmitter dopamine through measurement of the dopamine metabolite homovanillic acid (HVA) in adult subjects with mental retardation and with high rates of body stereotypy (n=12), compulsive behaviors (n=9), or neither (n=12) found lowest HVA concentrations in the stereotypy group and highest in the compulsive group. (DB)

Lewis, Mark H.; And Others

1996-01-01

334

Biosensors for Brain Trauma and Dual Laser Doppler Flowmetry: Enoxaparin Simultaneously Reduces Stroke-Induced Dopamine and Blood Flow while Enhancing Serotonin and Blood Flow in Motor Neurons of Brain, In Vivo  

PubMed Central

Neuromolecular Imaging (NMI) based on adsorptive electrochemistry, combined with Dual Laser Doppler Flowmetry (LDF) is presented herein to investigate the brain neurochemistry affected by enoxaparin (Lovenox®), an antiplatelet/antithrombotic medication for stroke victims. NMI with miniature biosensors enables neurotransmitter and neuropeptide (NT) imaging; each NT is imaged with a response time in milliseconds. A semiderivative electronic reduction circuit images several NT’s selectively and separately within a response time of minutes. Spatial resolution of NMI biosensors is in the range of nanomicrons and electrochemically-induced current ranges are in pico- and nano-amperes. Simultaneously with NMI, the LDF technology presented herein operates on line by illuminating the living brain, in this example, in dorso-striatal neuroanatomic substrates via a laser sensor with low power laser light containing optical fiber light guides. NMI biotechnology with BRODERICK PROBE® biosensors has a distinct advantage over conventional electrochemical methodologies both in novelty of biosensor formulations and on-line imaging capabilities in the biosensor field. NMI with unique biocompatible biosensors precisely images NT in the body, blood and brain of animals and humans using characteristic experimentally derived half-wave potentials driven by oxidative electron transfer. Enoxaparin is a first line clinical treatment prescribed to halt the progression of acute ischemic stroke (AIS). In the present studies, BRODERICK PROBE® laurate biosensors and LDF laser sensors are placed in dorsal striatum (DStr) dopaminergic motor neurons in basal ganglia of brain in living animals; basal ganglia influence movement disorders such as those correlated with AIS. The purpose of these studies is to understand what is happening in brain neurochemistry and cerebral blood perfusion after causal AIS by middle cerebral artery occlusion in vivo as well as to understand consequent enoxaparin and reperfusion effects actually while enoxaparin is inhibiting blood clots to alleviate AIS symptomatology. This research is directly correlated with the medical and clinical needs of stroke victims. The data are clinically relevant, not only to movement dysfunction but also to the depressive mood that stroke patients often endure. These are the first studies to image brain neurotransmitters while any stroke medications, such as anti-platelet/anti-thrombotic and/or anti-glycoprotein are working in organ systems to alleviate the debilitating consequences of brain trauma and stroke/brain attacks.

Broderick, Patricia A.; Kolodny, Edwin H.

2011-01-01

335

Nutritional tryptophan restriction and the role of serotonin in development and plasticity of central visual connections.  

PubMed

Tryptophan is an essential amino acid and metabolic precursor of serotonin. Serotonin is both a classical neurotransmitter and a signaling molecule that plays crucial roles in the development of neural circuits and plasticity. The specification of neural circuits in rodents occurs during the postnatal period with conspicuous influence of environmental factors including the nutritional status. Sensory, motor and cognitive systems develop during a critical period, a time window that is crucial to the use-dependent organization of neuronal circuits. This review presents recent experimental findings that disclose some mechanism of tryptophan- and serotonin-dependent plasticity in the developing and adult brain. PMID:18781081

Serfaty, Claudio A; Oliveira-Silva, Priscilla; Faria Melibeu, Adriana da Cunha; Campello-Costa, Paula

2008-09-09

336

Signaling Pathways Take Aim at Neurotransmitter Transporters  

NSDL National Science Digital Library

Neurotransmitter transporters are the target of various pharmacological agents used to treat psychological or cognitive conditions, such as depression and attention-deficit disorder. In addition, some of the effects of stimulant-type drugs of abuse result from inhibition of neurotransmitter transporters. Robinson describes the intersection between neurotransmitter transporters and signaling pathways. Neurotransmitter transporters can be regulated by altering the rate of internalization and insertion into the plasma membrane to control cell surface expression or by altering the activity of the transporters within the membrane. As the mechanisms governing regulation of these transporters become elucidated, new potential therapeutic targets may be revealed, given the many processes affected by the activity of neurotransmitter transporters.

Michael B. Robinson (University of Pennsylvania;Departments of Pediatrics and Pharmacology, Children's Hospital of Philadelphia REV)

2003-11-04

337

Hypoxia. 3. Hypoxia and neurotransmitter synthesis  

PubMed Central

Central and peripheral neurons as well as neuroendocrine cells express a variety of neurotransmitters/modulators that play critical roles in regulation of physiological systems. The synthesis of several neurotransmitters/modulators is regulated by O2-requiring rate-limiting enzymes. Consequently, hypoxia resulting from perturbations in O2 homeostasis can affect neuronal functions by altering neurotransmitter synthesis. Two broad categories of hypoxia are frequently encountered: continuous hypoxia (CH) and intermittent hypoxia (IH). CH is often seen during high altitude sojourns, whereas IH is experienced in sleep-disordered breathing with recurrent apneas (i.e., brief, repetitive cessations of breathing). This article presents what is currently known on the effects of both forms of hypoxia on neurotransmitter levels and neurotransmitter synthesizing enzymes in the central and peripheral nervous systems.

2011-01-01

338

Serotonin Modulates Olfactory Processing in the Antennal Lobe of Drosophila  

PubMed Central

Sensory systems must be able to extract features of environmental cues within the context of the different physiological states of the organism and often temper their activity in a state-dependent manner via the process of neuromodulation. We examined the effects of the neuromodulator serotonin on a well-characterized sensory circuit, the antennal lobe of Drosophila melanogaster, using two-photon microscopy and the genetically expressed calcium indicator, G-CaMP. Serotonin enhances sensitivity of the antennal lobe output projection neurons in an odor-specific manner. For odorants that sparsely activate the antennal lobe, serotonin enhances projection neuron responses and causes an offset of the projection neuron tuning curve, most likely by increasing projection neuron sensitivity. However, for an odorant that evokes a broad activation pattern, serotonin enhances projection neuron responses in some, but not all, glomeruli. Further, serotonin enhances the responses of inhibitory local interneurons, resulting in a reduction of neurotransmitter release from the olfactory sensory neurons via GABAB receptor-dependent presynaptic inhibition, which may be a mechanism underlying the odorant-specific modulation of projection neuron responses. Our data suggest that the complexity of serotonin modulation in the antennal lobe accommodates coding stability in a glomerular pattern and flexible projection neuron sensitivity under different physiological conditions.

Dacks, Andrew M.; Green, David S.; Root, Cory M.; Nighorn, Alan J.; Wang, Jing W.

2010-01-01

339

(/sup 3/H)Spiroxatrine labels a serotonin/sub 1A/-like site in the rat hippocampus  

SciTech Connect

(/sup 3/H)Spiroxatrine was examined as a potential ligand for the labeling of 5-HT/sub 1A/ sites in the rat hippocampus. Analysis o the binding of (/sup 3/H)spiroxatrine in the absence and presence of varying concentrations of three monoamine neurotransmitters revealed that serotonin (5-HT) had high affinity for the (/sup 3/H)spiroxatrine binding sites, consistent with the labeling of 5-HT/sub 1/ sites, while dopamine and norepinephrine had very low affinity. Saturation studies of the binding of (/sup 3/H)spiroxatrine revealed a single population of sites with a K/sub d/ = 2.21 nM. Further pharmacologic characterization with the 5-HT/sub 1A/ ligands 8-hydroxy-2-(di-ni-propylamino)tetralin, ipsapirone, and WB4101 and the butyrophenone compounds spiperone and haloperidol gave results that were consistent with (/sup 3/H)spiroxatrine labeling 5-HT/sub 1A/ sites. This ligand produced stable, reproducible binding with a good ratio of specific to nonspecific binding. The binding of (/sup 3/H)spiroxatrine was sensitive to GTP, suggesting that this ligand may act as an agonist. 21 references, 5 figures, 2 tables.

Nelson, D.L.; Monroe, P.J.; Lambert, G.; Yamamura, H.I.

1987-09-28

340

The Dopamine Augmenter L-DOPA Does Not Affect Positive Mood in Healthy Human Volunteers  

PubMed Central

Dopamine neurotransmission influences approach toward rewards and reward-related cues. The best cited interpretation of this effect proposes that dopamine mediates the pleasure that commonly accompanies reward. This hypothesis has received support in some animal models and a few studies in humans. However, direct assessments of the effect of transiently increasing dopamine neurotransmission have been largely limited to the use of psychostimulant drugs, which elevate brain levels of multiple neurotransmitters in addition to dopamine. In the present study we tested the effect of more selectively elevating dopamine neurotransmission, as produced by administration of the immediate dopamine precursor, L-DOPA (0, 100/25, 200/50 mg, Sinemet), in healthy human volunteers. Neither dose altered positive mood. The results suggest that dopamine neurotransmission does not directly influence positive mood in humans.

Liggins, John; Pihl, Robert O.; Benkelfat, Chawki; Leyton, Marco

2012-01-01

341

Serotonin transporter (SERT) and translocator protein (TSPO) expression in the obese ob\\/ob mouse  

Microsoft Academic Search

BACKGROUND: An ever growing body of evidences is emerging concerning metabolism hormones, neurotransmitters or stress-related biomarkers as effective modulators of eating behavior and body weight in mammals. The present study sought at examining the density and affinity of two proteins related to neurotransmission and cell metabolism, the serotonin transporter SERT and the cholesterol import-benzodiazepine site TSPO (translocator protein), in a

Gino Giannaccini; Laura Betti; Lionella Palego; Andrea Pirone; Lara Schmid; Mario Lanza; Laura Fabbrini; Caterina Pelosini; Margherita Maffei; Ferruccio Santini; Aldo Pinchera; Antonio Lucacchini

2011-01-01

342

Serotonin decreases aggression via 5HT 1A receptors in the fighting fish Betta splendens  

Microsoft Academic Search

The role of the monoamine neurotransmitter serotonin (5-HT) in the modulation of conspecific aggression in the fighting fish (Betta splendens) was investigated using pharmacological manipulations. We used a fish's response to its mirror image as our index of aggressive behavior. We also investigated the effects of some manipulations on monoamine levels in the B. splendens brain. Acute treatment with 5-HT

Ethan D. Clotfelter; Erin P. O'Hare; Meredith M. McNitt; Russ E. Carpenter; Cliff H. Summers

2007-01-01

343

Role of Serotonin in the Immune System and in Neuroimmune Interactions  

Microsoft Academic Search

Serotonin (5-HT) is one of the most extensively studied neurotransmitters of the central nervous system. 5-HT is, however, also present in a variety of peripheral tissues including in constituents of the immune system. The function of 5-HT in the immune system has received increasing attention since about 1984, but has been reviewed only once, in 1985. In recent years, modern

Rainald Mössner; Klaus-Peter Lesch

1998-01-01

344

Cognitive dysfunction in neuropsychiatric disorders: Selected serotonin receptor subtypes as therapeutic targets  

Microsoft Academic Search

The indolamine, serotonin (5-hydroxytryptamine-5-HT) was identified and initially characterized around the middle of the twentieth century and it is now known to participate in multiple physiologic processes in mammalians. As a neurotransmitter, 5-HT is well documented to play a significant role in the pathophysiology and treatment of a variety of psychiatric disorders including anxiety, depression, and schizophrenia. In addition, there

Alvin V. Terry Jr.; Jerry J. Buccafusco; Christina Wilson

2008-01-01

345

Serotonin in Aging, Late-Life Depression, and Alzheimer's Disease: The Emerging Role of Functional Imaging  

Microsoft Academic Search

Serotonin (5-HT) neuron and neurotransmitter loss in normal aging and neuropsychiatric diseases of late life may contribute to behavioral changes commonly observed in the elderly population. Extensive evidence implicates a deficit in serotonergic neurotransmission in the development of major depression. It has been further suggested that the age-related changes in 5-HT neurons may predispose the elderly to develop depression. There

Carolyn Cidis Meltzer; Gwenn Smith; Steven T DeKosky; Bruce G Pollock; Chester A Mathis; Robert Y Moore; David J Kupfer; Charles F Reynolds

1998-01-01

346

A Murine Dopamine Neuron-Specific cDNA Library and Microarray: Increased COXI Expression during Methamphetamine Neurotoxicity  

Microsoft Academic Search

Due to brain tissue heterogeneity, the molecular genetic profile of any neurotransmitter-specific neuronal subtype is unknown. The purpose of this study was to purify a population of dopamine neurons, construct a cDNA library, and generate an initial gene expression profile and a microarray representative of dopamine neuron transcripts. Ventral mesencephalic dopamine neurons were purified by fluorescent-activated cell sorting from embryonic

Tanya Barrett; Tao Xie; Yulan Piao; Ora Dillon-Carter; George J. Kargul; Meng K. Lim; Francis J. Chrest; Robert Wersto; Daniel L. Rowley; Magdalena Juhaszova; Li Zhou; Marquis P. Vawter; Kevin G. Becker; Christopher Cheadle; William H. Wood III; Una D. McCann; William J. Freed; Minoru S. Ko; George A. Ricaurte; David M. Donovan

2001-01-01

347

Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology  

PubMed Central

The neurotransmitter serotonin (5-HT), widely distributed in the central nervous system (CNS), is involved in a large variety of physiological functions. In several brain regions 5-HT is diffusely released by volume transmission and behaves as a neuromodulator rather than as a “classical” neurotransmitter. In some cases 5-HT is co-localized in the same nerve terminal with other neurotransmitters and reciprocal interactions take place. This review will focus on the modulatory action of 5-HT on the effects of glutamate and ?-amino-butyric acid (GABA), which are the principal neurotransmitters mediating respectively excitatory and inhibitory signals in the CNS. Examples of interaction at pre-and/or post-synaptic levels will be illustrated, as well as the receptors involved and their mechanisms of action. Finally, the physiological meaning of neuromodulatory effects of 5-HT will be briefly discussed with respect to pathologies deriving from malfunctioning of serotonin system.

Ciranna, L

2006-01-01

348

Release of Neurotransmitters in the CNS by Spinal Cord Stimulation: Survey of Present State of Knowledge and Recent Experimental Studies  

Microsoft Academic Search

Electric Stimulation applied to the posterior surface of the spinal cord (SCS) is an established treatment in certain chronic pain syndromes resistant to con-ventional therapeutic procedures. Despite the clinical value of SCS, the mechanisms behind the efficacy of the method are largely unknown. Several neurotransmitters in the CNS (e.g. Opioids, serotonin, noradrenaline, substance P, GABA), have been pro-posed to be

B. Linderoth; C. O. Stiller; L. Gunasekera; W. T. OConnor; J. Franck; B. Gazelius; E. Brodin

1993-01-01

349

The Dopamine D2 Receptor Gene, Perceived Parental Support, and Adolescent Loneliness: Longitudinal Evidence for Gene-Environment Interactions  

ERIC Educational Resources Information Center

|Background: Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine-related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Methods: Associations among the DRD2, sex, parental…

van Roekel, Eeske; Goossens, Luc; Scholte, Ron H. J.; Engels, Rutger C. M. E.; Verhagen, Maaike

2011-01-01

350

Noninvasive Visualization of Human Dopamine Dynamics from PET Images  

PubMed Central

We recently introduced strategies for extracting temporal patterns of brain dopamine fluctuations from dynamic positron emission tomography (PET) data using the tracer, [11C]-raclopride. Each of our methods yields a collection of time-concentration curves for endogenous dopamine. Given a spatially dense collection of curves (i.e., one at every voxel in a region of interest), we produce image volumes of dopamine (DA) concentration, DA(X?, t), at multiple voxel locations and each time-frame. The volume over time-frames constitutes a 4D dataset that can be thought of as a DA “movie”. There are a number of ways to visualize such data. Viewing cine loops of a slice through the DA volume is one way. Creating images of dopamine peak-time, Tpeak(X?), derived from a movie, is another. Each visualization may reveal spatio-temporal patterns of neurotransmitter activity heretofore unobservable. We conducted an initial validation experiment in which identical DA responses were induced by an identical task, initiated at different times by the same subject, in two separate PET scans. A comparison of the resulting Tpeak(X?) images revealed a large contiguous cluster of striatal voxels, on each side, whose DA timing was consistent with the relative timing of the tasks. Hence, the DA movies and their respective peak-time images were shown to be new types of functional image that contain bonafide timing information about a neurotransmitter’s response to a stimulus.

Morris, E.D.; Constantinescu, C.C.; Sullivan, J.M.; Normandin, M.D.; Christopher, L.A.

2013-01-01

351

Inhibitory effect of selective serotonin reuptake inhibitors on the vesicular monoamine transporter 2  

Microsoft Academic Search

The neuronal vesicular monoamine transporter (VMAT2) is the target molecule of action of some psychostimulants, such as methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). The present study examined the effect of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), on VMAT2 activity by measuring adenosine triphosphate-dependent [3H]dopamine uptake into synaptic vesicles prepared from rat striatum. SSRIs, fluoxetine, paroxetine, and fluvoxamine, inhibited vesicular [3H]dopamine

Satoshi Yasumoto; Kohei Tamura; Junichi Karasawa; Ryota Hasegawa; Kazutaka Ikeda; Toshifumi Yamamoto; Hideko Yamamoto

2009-01-01

352

The Association between Dopamine DRD2 Polymorphisms and Working Memory Capacity Is Modulated by a Functional Polymorphism on the Nicotinic Receptor Gene CHRNA4  

Microsoft Academic Search

Working memory capacity is extremely limited and individual differences are heritable to a considerable extent. In the search for a better understanding of the exact genetic underpinnings of working memory, most research has focused on functional gene variants involved in the metabolism of the neurotransmitter dopamine. Recently, there has been investigation of genes related to other neurotransmitter systems such as

Sebastian A. Markett; Christian Montag; Martin Reuter

2010-01-01

353

Neurotransmitter and Peptide Localization in Human Brain.  

National Technical Information Service (NTIS)

Studies utilizing human brain tissue examined the colocalozation of neurotransmitters using immunocytochemical and in vitro hybridization techniques. Results have shown the coexistance of somatostatin and neuropeptide Y in the hippocampus, and galanin and...

V. Chan-Palay

1990-01-01

354

Waterborne lead affects circadian variations of brain neurotransmitters in fathead minnows  

SciTech Connect

Lead is a potent neurotoxin affecting brain levels of a number of vertebrate neurotransmitters. Reports on these effects are, however, not consistent either among or within species. For example, with lead-intoxicated rats there are reports of decreased acetylcholine (ACh) release and decreased ACh brain levels as well as reports of increased levels or no change in levels. Also, with rats there are reports of increased levels, decreased levels, or no change in brain catecholamines, with lead producing similar changes in both norephinephrine (NE) and dopamine (DA) in some cases and differences in response between the two in others. Although most early reports dealt with whole brain levels, reports on neurotransmitter levels in specific brain regions can be equally conflicting. Similar sorts of discrepancies exist among studies with fishes. Much of the variation among studies on lead effects on neurotransmitters is, no doubt, due to differences among the studies in variables such as: species, age, dosage and duration, route of administration. However, lead can apparently affect circadian locomotor rhythms of both rats and fishes. Therefore, another possible cause for the variation among studies is that there is an interaction among dosage, sampling time and endogenous rhythms. A lead-produced phase shift or disruption in endogenous neurotransmitter rhythms could in turn elicit a host of varying results and interpretations depending on the circadian time of sampling. We elected to examine this possibility in the fathead minnow, Pimephales promelas, a freshwater species widely used for toxicity studies. 15 refs., 3 figs.

Spieler, R.E. [Nova Southeastern Univ., Dania, FL (United States); Russo, A.C. [California State Univ., Long Beach, CA (United States); Weber, D.N. [Univ. of Wisconsin, Milwaukee, WI (United States)

1995-09-01

355

Calmodulin-dependent regulation of neurotransmitter release differs in subsets of neuronal cells.  

PubMed

The purpose of this study was to determine whether calmodulin (CaM) plays a role in neurotransmitter release by examining the effect that ophiobolin A (OBA), a CaM antagonist, on neurotransmitter release from clonal rat pheochromocytoma PC12 cells, primary cortical neurons, and primary cerebellar granule cells. OBA inhibited Ca(2+)/CaM-dependent phosphorylation of cAMP response element binding protein in all cell types tested. Moreover, Ca(2+)-dependent release of dopamine and acetylcholine from PC12 cells were remarkably reduced by OBA in a dose-dependent and temporal manner, but neurotransmitter release partially recovered with the addition of CaM in membrane permeabilized PC12 cells. OBA and several synthetic CaM antagonists suppressed Ca(2+)-dependent glutamate release from cerebral cortical neurons, but not from cerebellar granule cells. Myosin Va, a CaM binding protein, localized to synaptic vesicles of PC12 cells and cerebral cortical neurons, but not in cerebellar granule cells. OBA suppressed Ca(2+)-induced myosin Va dissociation from secretory vesicles, and inhibited secretory vesicle motility in PC12 cells. These results suggest that CaM, although not essential, regulates neurotransmitter release in a subset of neurons and secretory cells, and myosin Va is a possible target of OBA in this process. PMID:23973605

Ando, Kosuke; Kudo, Yoshihisa; Aoyagi, Kyota; Ishikawa, Ryoki; Igarashi, Michihiro; Takahashi, Masami

2013-08-23

356

Central actions of a novel and selective dopamine antagonist  

SciTech Connect

Receptors for the neurotransmitter dopamine traditionally have been divided into two subgroups: the D/sub 1/ class, which is linked to the stimulation of adenylate cyclase-activity, and the D/sub 2/ class which is not. There is much evidence suggesting that it is the D/sub 2/ class which is not. There is much evidence suggesting that it is the D/sub 2/ dopamine receptor that mediates the physiological and behavioral actions of dopamine in the intact animal. However, the benzazepine SCH23390 is a dopamine antagonist which has potent behavioral actions while displaying apparent neurochemical selectivity for the D/sub 1/ class of dopamine receptors. The purpose of this dissertation was to (1) confirm and characterize this selectivity, and (2) test certain hypothesis related to possible modes of action of SCH233390. The inhibition of adenylate cyclase by SCH23390 occurred via an action at the dopamine receptor only. A radiolabeled analog of SCH23390 displayed the receptor binding properties of a specific high-affinity ligand, and regional receptor densities were highly correlated with dopamine levels. The subcellular distribution of (/sup 3/H)-SCH23390 binding did not correspond completely with that of dopamine-stimulated adenylate cyclase. The neurochemical potency of SCH23390 as a D/sub 1/ receptor antagonist was preserved following parental administration. A variety of dopamine agonists and antagonists displayed a high correlation between their abilities to compete for (/sup 3/H)-SCH23390 binding in vitro and to act at an adenylate cyclase-linked receptor. Finally, the relative affinities of dopamine and SCH23390 for both D/sub 1/ receptors and (/sup 3/H)-SCH23390 binding sites were comparable. It is concluded that the behavioral effects of SCH23390 are mediated by actions at D/sub 1/ dopamine receptors only, and that the physiological importance of this class of receptors should be reevaluated.

Schulz, D.W.

1985-01-01

357

The neurobiology of tetrahydrobiopterin biosynthesis: a model for regulation of GTP cyclohydrolase I gene transcription within nigrostriatal dopamine neurons.  

PubMed

Within the brain, the reduced pteridine cofactor 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) is absolutely required for the synthesis of the monoamine (MA) neurotransmitters dopamine (DA), norepinephrine, epinephrine (E), and serotonin (5-HT), the novel gaseous neurotransmitter nitric oxide and the production of yet to be identified 1-O-alkylglycerol-derived lipids. GTP cyclohydrolase I (GTPCH) catalyzes the first and limiting step in the BH4 biosynthetic pathway, which is now thought to involve up to eight different proteins supporting six alternate de novo and two alternate salvage pathways. Gene expression analysis across different regions of the human brain shows the abundance of transcripts coding for all eight of these proteins to be highly correlated with each other and to be enriched within human MA neurons. The potential for multiple routes for BH4 synthesis therefore exists within the human brain. GTPCH expression is particularly heterogeneous across different populations of human and rodent MA-containing neurons, with low expression levels and therefore BH4 being a characteristic of nigrostriatal DA (NSDA) neurons. Basic knowledge of how GCH1 gene transcription is controlled within NSDA neurons may explain the distinctive susceptibility of these neurons to human genetic mutations that result in BH4 deficiency. A model for cyclic adenosine monophosphate-dependent GCH1 transcription is described that involves a unique combination of DNA regulatory sequences and transcription factors. This model proposes that low levels of GCH1 transcription within NSDA neurons are driven by their distinctive physiology, suggesting that pharmacological manipulation of GCH1 gene transcription can be used to modify BH4 levels and therefore DA synthesis in the basal ganglia. PMID:23457032

Kapatos, Gregory

2013-03-04

358

Role of Serotonin 5-HT3 Receptors in Intestinal Inflammation.  

PubMed

Serotonin (5-hydroxytryptamine; 5-HT), a well-characterized neurotransmitter in the central nervous system, plays a crucial role in regulating mood, body temperature, sleep, appetite, and metabolism. Serotonin is synthesized in the serotonergic neuron of the central nervous system; however, approximately 90% of serotonin is synthesized and localized in the gastrointestinal (GI) tract, especially in the enterochromaffin (EC) cells. In the GI tract, serotonin mediates control over a variety of physiological functions such as contraction/relaxation of smooth muscle, and peristaltic and secretory reflexes, directly or indirectly through intrinsic primary afferent neurons. The receptors mediating the action of serotonin are mainly classified into 7 major groups known as the 5-HT1 to 5-HT7 receptors. The 5-HT3 receptor is distinguished from among the other 5-HT receptor subtypes because it is only a ligand-gated ion channel, whereas the other subtypes serve as G protein-coupled receptors. The 5-HT3 receptor, which is generally considered to be localized in the central and peripheral nervous systems, is involved in processes associated with emotion, cognition, memory, pain perception, and GI functions including secretion and motility. Recently, an increasing number of findings have provided evidence of the important role of the 5-HT3 receptor in the regulation of inflammatory and immune responses. In fact, several 5-HT3 receptor antagonists have been reported to ameliorate intestinal inflammation. Therefore, this review focuses on the role of 5-HT3 receptors in the pathogenesis of intestinal inflammation. PMID:23995650

Kato, Shinichi

2013-01-01

359

The serotonin 5-HT7 receptors: two decades of research.  

PubMed

Like most neurotransmitters, serotonin possesses a simple structure. However, the pharmacological consequences are more complex and diverse. Serotonin is involved in numerous functions in the human body including the control of appetite, sleep, memory and learning, temperature regulation, mood, behavior, cardiovascular function, muscle contraction, endocrine regulation, and depression. Low levels of serotonin may be associated with several disorders, namely increase in aggressive and angry behaviors, clinical depression, Parkinson's disease, obsessive-compulsive disorder, eating disorders, migraine, irritable bowel syndrome, tinnitus, and bipolar disease. These effects are mediated via different serotonin (5-HT) receptors. In this review, we will focus on the last discovered member of this serotonin receptor family, the 5-HT7 receptor. This receptor belongs to the G protein-coupled receptor superfamily and was cloned two decades ago. Later, different splice variants were described but no major functional differences have been described so far. All 5-HT7 receptor variants are coupled to G?s proteins and stimulate cAMP formation. Recently, several interacting proteins have been reported, which can influence receptor signaling and trafficking. PMID:24042216

Gellynck, Evelien; Heyninck, Karen; Andressen, Kjetil W; Haegeman, Guy; Levy, Finn Olav; Vanhoenacker, Peter; Van Craenenbroeck, Kathleen

2013-09-17

360

Serotonin of mast cell origin contributes to hippocampal function  

PubMed Central

In the CNS, serotonin, an important neurotransmitter and trophic factor, is synthesized by both mast cells and neurons. Mast cells, like other immune cells, are born in the bone marrow and migrate to many tissues. We show that they are resident in the mouse brain throughout development and adulthood. Measurements based on capillary electrophoresis with native fluorescence detection indicate that a significant contribution of serotonin to the hippocampal milieu is associated with mast cell activation. Compared to their littermates, mast cell deficient C57BL/6 KitW-sh/W-sh mice have profound deficits in hippocampus-dependent spatial learning and memory and in hippocampal neurogenesis. These deficits are associated with a reduction in cell proliferation and in immature neurons in the dentate gyrus, but not in the subventricular zone – a neurogenic niche lacking mast cells. Chronic treatment with fluoxetine, a selective serotonin reuptake inhibitor, reverses the deficit in hippocampal neurogenesis in mast cell deficient mice. In summary, the present studies demonstrate that mast cells are a source of serotonin, that mast cell deficient C57BL/6 KitW-sh/W-sh mice have disrupted hippocampus-dependent behavior and neurogenesis, and that elevating serotonin in these mice, by treatment with fluoxetine, reverses these deficits. We conclude that mast cells contribute to behavioral and physiological functions of the hippocampus and note that they play a physiological role in neuroimmune interactions, even in the absence of inflammatory responses.

Nautiyal, Katherine M.; Dailey, Christopher A.; Jahn, Jaquelyn L.; Rodriquez, Elizabeth; Son, Nguyen Hong; Sweedler, Jonathan V.; Silver, Rae

2012-01-01

361

Antidepressant treatment and emotional processing: can we dissociate the roles of serotonin and noradrenaline?  

PubMed

The ability to match individual patients to tailored treatments has the potential to greatly improve outcomes for individuals suffering from major depression. In particular, while the vast majority of antidepressant treatments affect either serotonin or noradrenaline or a combination of these two neurotransmitters, it is not known whether there are particular patients or symptom profiles which respond preferentially to the potentiation of serotonin over noradrenaline or vice versa. Experimental medicine models suggest that the primary mode of action of these treatments may be to remediate negative biases in emotional processing. Such models may provide a useful framework for interrogating the specific actions of antidepressants. Here, we therefore review evidence from studies examining the effects of drugs which potentiate serotonin, noradrenaline or a combination of both neurotransmitters on emotional processing. These results suggest that antidepressants targeting serotonin and noradrenaline may have some specific actions on emotion and reward processing which could be used to improve tailoring of treatment or to understand the effects of dual-reuptake inhibition. Specifically, serotonin may be particularly important in alleviating distress symptoms, while noradrenaline may be especially relevant to anhedonia. The data reviewed here also suggest that noradrenergic-based treatments may have earlier effects on emotional memory that those which affect serotonin. PMID:23392757

Pringle, A; McCabe, C; Cowen, P J; Harmer, C J

2013-02-07

362

Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review.  

PubMed

The US Food and Drug Administration (FDA) have suggested that fatal serotonin syndrome (SS) is possible with selective serotonin reuptake inhibitors (SSRIs) and triptans: this warning affects millions of patients as these drugs are frequently given simultaneously. SS is a complex topic about which there is much misinformation. The misconception that 5-HT1A receptors can cause serious SS is still widely perpetuated, despite quality evidence that it is activation of the 5-HT2A receptor that is required for serious SS. This review considers SS involving serotonin agonists: ergotamine, lysergic acid diethylamide, bromocriptine, and buspirone, as well as triptans, and reviews the experimental foundation underpinning the latest understanding of SS. It is concluded that there is neither significant clinical evidence, nor theoretical reason, to entertain speculation about serious SS from triptans and SSRIs. The misunderstandings about SS exhibited by the FDA, and shared by the UK Medicines and Healthcare products Regulatory Agency (in relation to methylene blue), are an important issue with wide ramifications. PMID:19925619

Gillman, P Ken

2009-11-17

363

meso-Transdiene Analogs Inhibit Vesicular Monoamine Transporter-2 Function and Methamphetamine-Evoked Dopamine ReleaseS?  

PubMed Central

Lobeline, a nicotinic receptor antagonist and neurotransmitter transporter inhibitor, is a candidate pharmacotherapy for methamphetamine abuse. meso-Transdiene (MTD), a lobeline analog, lacks nicotinic receptor affinity, retains affinity for vesicular monoamine transporter 2 (VMAT2), and, surprisingly, has enhanced affinity for dopamine (DA) and serotonin transporters [DA transporter (DAT) and serotonin transporter (SERT), respectively]. In the current study, MTD was evaluated for its ability to decrease methamphetamine self-administration in rats relative to food-maintained responding. MTD specifically decreased methamphetamine self-administration, extending our previous work. Classical structure-activity relationships revealed that more conformationally restricted MTD analogs enhanced VMAT2 selectivity and drug likeness, whereas affinity at the dihydrotetrabenazine binding and DA uptake sites on VMAT2 was not altered. Generally, MTD analogs exhibited 50- to 1000-fold lower affinity for DAT and were equipotent or had 10-fold higher affinity for SERT, compared with MTD. Representative analogs from the series potently and competitively inhibited [3H]DA uptake at VMAT2. (3Z,5Z)-3,5-bis(2,4-dichlorobenzylidene)-1-methylpiperidine (UKMH-106), the 3Z,5Z-2,4-dichlorophenyl MTD analog, had improved selectivity for VMAT2 over DAT and importantly inhibited methamphetamine-evoked DA release from striatal slices. In contrast, (3Z,5E)-3,5-bis(2,4-dichlorobenzylidene)-1-methylpiperidine (UKMH-105), the 3Z,5E-geometrical isomer, inhibited DA uptake at VMAT2, but did not inhibit methamphetamine-evoked DA release. Taken together, these results suggest that these geometrical isomers interact at alternate sites on VMAT2, which are associated with distinct pharmacophores. Thus, structural modification of the MTD molecule resulted in analogs exhibiting improved drug likeness and improved selectivity for VMAT2, as well as the ability to decrease methamphetamine-evoked DA release, supporting the further evaluation of these analogs as treatments for methamphetamine abuse.

Horton, David B.; Siripurapu, Kiran B.; Norrholm, Seth D.; Culver, John P.; Hojahmat, Marhaba; Beckmann, Joshua S.; Harrod, Steven B.; Deaciuc, Agripina G.; Bardo, Michael T.; Crooks, Peter A.

2011-01-01

364

Tyrosine Hydroxylase and Regulation of Dopamine Synthesis  

PubMed Central

Tyrosine hydroxylase is the rate-limiting enzyme of catecholamine biosynthesis; it uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to DOPA. Its amino terminal 150 amino acids comprise a domain whose structure is involved in regulating the enzyme’s activity. Modes of regulation include phosphorylation by multiple kinases at 4 different serine residues, and dephosphorylation by 2 phosphatases. The enzyme is inhibited in feedback fashion by the catecholamine neurotransmitters. Dopamine binds to TyrH competitively with tetrahydrobiopterin, and interacts with the R domain. TyrH activity is modulated by protein-protein interactions with enzymes in the same pathway or the tetrahydrobiopterin pathway, structural proteins considered to be chaperones that mediate the neuron’s oxidative state, and the protein that transfers dopamine into secretory vesicles. TyrH is modified in the presence of NO, resulting in nitration of tyrosine residues and the glutathionylation of cysteine residues.

Daubner, S. Colette; Le, Tiffany; Wang, Shanzhi

2011-01-01

365

Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system  

Microsoft Academic Search

Summary The reason for the high frequency of depression and anxiety in Parkinson's disease is poorly understood. Degeneration of neurotransmitter systems other than dopamine might play a specific role in the occurrence of these affective disorders. We used (11C)RTI-32 PET, an in vivo marker of both dopamine and noradrenaline trans- porter binding, to localize differences between depressed and non-depressed patients.

Philippe Remy; Miroslava Doder; Andrew Lees; Nora Turjanski; David Brooks

2005-01-01

366

Dopamine D2 receptor polymorphisms and susceptibility to alcohol dependence in Indian males: a preliminary study  

Microsoft Academic Search

BACKGROUND: Dopamine is an important neurotransmitter involved in reward mechanism in the brain and thereby influences development and relapse of alcohol dependence. The dopamine D2 receptor (DRD2) gene on chromosome 11 (q22-q23) has been found to be associated with increased alcohol consumption through mechanisms involving incentive salience attributions and craving in alcoholic patients. Therefore, we investigated the association of three

Pushplata Prasad; Atul Ambekar; Meera Vaswani

2010-01-01

367

Serotonin: a novel bone mass controller may have implications for alveolar bone  

PubMed Central

As recent studies highlight the importance of alternative mechanisms in the control of bone turnover, new therapeutic approaches can be envisaged for bone diseases and periodontitis-induced bone loss. Recently, it has been shown that Fluoxetine and Venlafaxine, serotonin re-uptake inhibitors commonly used as antidepressants, can positively or negatively affect bone loss in rat models of induced periodontitis. Serotonin is a neurotransmitter that can be found within specific nuclei of the central nervous system, but can also be produced in the gut and be sequestered inside platelet granules. Although it is known to be mainly involved in the control of mood, sleep, and intestinal physiology, recent evidence has pointed at far reaching effects on bone metabolism, as a mediator of the effects of Lrp5, a membrane receptor commonly associated with Wnt canonical signaling and osteoblast differentiation. Deletion of Lrp5 in mice lead to increased expression of Tryptophan Hydroxylase 1, the gut isoform of the enzyme required for serotonin synthesis, thus increasing serum levels of serotonin. Serotonin, in turn, could bind to HTR1B receptors on osteoblasts and stop their proliferation by activating PKA and CREB. Although different groups have reported controversial results on the existence of an Lrp5-serotonin axis and the action of serotonin in bone remodeling, there is convincing evidence that serotonin modulators such as SSRIs can affect bone turnover. Consequently, the effects of this drug family on periodontal physiology should be thoroughly explored.

2013-01-01

368

Activation of serotonin receptors promotes microglial injury-induced motility but attenuates phagocytic activity.  

PubMed

Microglia, the brain immune cell, express several neurotransmitter receptors which modulate microglial functions. In this project we studied the impact of serotonin receptor activation on distinct microglial properties as serotonin deficiency not only has been linked to a number of psychiatric disease like depression and anxiety but may also permeate from the periphery through blood-brain barrier openings seen in neurodegenerative disease. First, we tested the impact of serotonin on the microglial response to an insult caused by a laser lesion in the cortex of acute slices from Cx3Cr1-GFP-/+ mice. In the presence of serotonin the microglial processes moved more rapidly towards the laser lesion which is considered to be a chemotactic response to ATP. Similarly, the chemotactic response of cultured microglia to ATP was also enhanced by serotonin. Quantification of phagocytic activity by determining the uptake of microspheres showed that the amoeboid microglia in slices from early postnatal animals or microglia in culture respond to serotonin application with a decreased phagocytic activity whereas we could not detect any significant change in ramified microglia in situ. The presence of microglial serotonin receptors was confirmed by patch-clamp experiments in culture and amoeboid microglia and by qPCR analysis of RNA isolated from primary cultured and acutely isolated adult microglia. These data suggest that microglia express functional serotonin receptors linked to distinct microglial properties. PMID:22198120

Krabbe, Grietje; Matyash, Vitali; Pannasch, Ulrike; Mamer, Lauren; Boddeke, Hendrikus W G M; Kettenmann, Helmut

2011-12-17

369

The Neurotropic Parasite Toxoplasma Gondii Increases Dopamine Metabolism  

PubMed Central

The highly prevalent parasite Toxoplasma gondii manipulates its host's behavior. In infected rodents, the behavioral changes increase the likelihood that the parasite will be transmitted back to its definitive cat host, an essential step in completion of the parasite's life cycle. The mechanism(s) responsible for behavioral changes in the host is unknown but two lines of published evidence suggest that the parasite alters neurotransmitter signal transduction: the disruption of the parasite-induced behavioral changes with medications used to treat psychiatric disease (specifically dopamine antagonists) and identification of a tyrosine hydroxylase encoded in the parasite genome. In this study, infection of mammalian dopaminergic cells with T. gondii enhanced the levels of K+-induced release of dopamine several-fold, with a direct correlation between the number of infected cells and the quantity of dopamine released. Immunostaining brain sections of infected mice with dopamine antibody showed intense staining of encysted parasites. Based on these analyses, T. gondii orchestrates a significant increase in dopamine metabolism in neural cells. Tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, was also found in intracellular tissue cysts in brain tissue with antibodies specific for the parasite-encoded tyrosine hydroxylase. These observations provide a mechanism for parasite-induced behavioral changes. The observed effects on dopamine metabolism could also be relevant in interpreting reports of psychobehavioral changes in toxoplasmosis-infected humans.

Prandovszky, Emese; Gaskell, Elizabeth; Martin, Heather; Dubey, J. P.; Webster, Joanne P.; McConkey, Glenn A.

2011-01-01

370

Recognition of Psychostimulants, Antidepressants, and Other Inhibitors of Synaptic Neurotransmitter Uptake by the Plasma Membrane Monoamine Transporters  

Microsoft Academic Search

The plasma membrane monoamine transporters terminate neurotransmission by removing dopamine, norepinephrine, or serotonin\\u000a from the synaptic cleft between neurons. Specific inhibitors for these transporters, including the abused psychostimulants\\u000a cocaine and amphetamine and the tricyclic and SSRI classes of antidepressants, exert their physiological effects by interfering\\u000a with synaptic uptake and thus prolonging the actions of the monoamine. Pharmacological, biochemical, and immunological

Christopher K. Surratt; Okechukwu T. Ukairo; Suneetha Ramanujapuram

371

Recognition of psychostimulants, antidepressants, and other inhibitors of synaptic neurotransmitter uptake by the plasma membrane monoamine transporters  

Microsoft Academic Search

The plasma membrane monoamine transporters terminate neurotransmission by removing dopamine, norepinephrine, or serotonin\\u000a from the synaptic cleft between neurons. Specific inhibitors for these transporters, including the abused psychostimulants\\u000a cocaine and amphetamine and the tricyclic and SSRI classes of antidepressants, exert their physiological effects by interfering\\u000a with synaptic uptake and thus prolonging the actions of the monoamine. Pharmacological, biochemical, and immunological

Christopher K. Surratt; Okechukwu T. Ukairo; Suneetha Ramanujapuram

2005-01-01

372

Differentiated properties of identified serotonin neurons in dissociated cultures of embryonic rat brain stem  

PubMed Central

Serotonin neurons in 14-d embryonic rat brain stem were identified by peroxidase-antiperoxidase immunocytochemistry with an affinity-purified antiserotonin antibody. Brain-stem tissue was dissected from 14- or 15- d embryonic rats, dissociated and grown in cell culture for up to 5 wk, and serotonin neurons were identified by immunocytochemistry. Within 24 h of plating, serotonin immunoreactivity was present in 3.3% of neurons. Immunoreactivity in neuronal cell bodies decreased with time, whereas staining of processes increased. The number of serotonin- immunoreactive neurons remained constant at 3-5% over the first 14 d in culture. From 14 to 28 d, the total number of neurons decreased with little change in the number of serotonin neurons, such that, by day 28 in culture, up to 36% of surviving neurons exhibited serotonin immunoreactivity. Similar percentages of cultured brain stem neurons accumulating 3H-serotonin were identified by autoradiography. Uptake was abolished by the serotonin-uptake inhibitor, clomipramine, but was unaffected by excess norepinephrine, or by the norepinephrine-uptake inhibitor, maprotiline. Synthesis of 3H-serotonin was detected after incubation of cultures with 3H-tryptophan, and newly synthesized serotonin was released by potassium depolarization in a calcium- dependent manner. More than 95% of serotonin neurons were destroyed after incubation of cultures with 5,6-dihydroxytryptamine. Brain-stem cultures contained virtually no neurons with the ability to accumulate 3H-norepinephrine or 3H-dopamine. Approximately 40% of brain-stem neurons were labeled with gamma-aminobutyric acid (3H-GABA). However, there was almost no overlap in the surface area of neurons accumulating 3H-serotonin or 3H-GABA.

1981-01-01

373

Molecular cloning of genomic DNA and chromosomal assignment of the gene for human aromatic L-amino acid decarboxylase, the enzyme for catecholamine and serotonin biosynthesis  

SciTech Connect

Aromatic L-amino acid decarboxylase (AADC) catalyzes the decarboxylation of both L-3,4-dihydroxyphenylalanine and L-5-hydroxytryptophan to dopamine and serotonin, respectively, which are major mammalian neurotransmitters and hormones belonging to catecholamines and indoleamines. This report describes the organization of the human AADC gene. The authors proved that the gene of human AADC consists of 15 exons spanning more than 85 kilobases and exists as a single copy in the haploid genome. The boundaries between exon and intron followed the AG/GT rule. The sizes of exons and introns ranged from 20 to 400 bp and from 1.0 to 17.7 kb, respectively, while the sizes of four introns were not determined. Untranslated regions located in the 5{prime} region of mRNA were encoded by two exons, exons 1 and 2. The transcriptional starting point was determined around G at position {minus}111 by primer extension and S1 mapping. There were no typical TATA box' and CAAT box' within 540 bp from the transcriptional starting point. The human AADC gene was mapped to chromosome band 7p12.1-p12.3 by fluorescence in situ hybridization. This is the first report on the genomic structure and chromosomal localization of the AADC gene in mammals.

Sumi-Ichinose, Chiho (Nagoya Univ. (Japan)); Ichinose, Hiroshi; Nagatsu, Toshiharu (Fujita Health Univ., Aichi (Japan)); Takahashi, Eiichi; Hori, Tadaaki (National Inst. of Radiological Sciences, Chiba (Japan))

1992-03-03

374

1 PRECISE REPORTING, LLC WWW.PRECISE-REPORTING. ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... of the neurotransmitters on the left and low 7 levels of norepinephrine, serotonin, and dopamine. Of 8 note, the only neurotransmitter system that's ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials

375

Effect of manganese treatment on the levels of neurotransmitters, hormones, and neuropeptides: modulation by stress  

SciTech Connect

Six weeks of daily intraperitoneal injection with manganese chloride (15 mg/kg body wt) reduced the normal weight gain of male Fischer-344 rats. This treatment depressed plasma testosterone and corticosterone levels, but prolactin levels were unaffected. The only significant changes in the levels of a variety of neuropeptides assayed in several regions were increases in the levels of hypothalamic substance P and pituitary neurotensin. Striatal serotonin, dopamine, and their metabolites were unchanged in manganese-exposed rats relative to saline-injected controls. However, the stress of injection combined with the effect of manganese appeared to significantly increase concentrations of striatal monoamines relative to uninjected controls.

Hong, J.S.; Jung, C.R.; Seth, P.K.; Mason, G.; Bondy, S.C.

1984-08-01

376

In vivo measurement of somatodendritic release of dopamine in the ventral tegmental area  

PubMed Central

The ventral tegmental area (VTA), the locus of mesolimbic dopamine cell bodies, contains dopamine. Experiments in brain slices have demonstrated that VTA dopamine can be released by local electrical stimulation. Measurements with both push-pull cannula and microdialysis in intact animals have also obtained evidence for releasable dopamine. Here we demonstrate that dopamine release in the VTA can be evoked by remote stimulations of the medial forebrain bundle (MFB) in the anesthetized rat. In initial experiments, the MFB was electrically stimulated while a carbon-fiber electrode was lowered to the VTA, with recording by fast-scan cyclic voltammetry. While release was not observed with the carbon fiber 4 to 6 mm below dura, a voltammetric response was observed a t 6-8 mm below dura, but the voltammogram was poorly defined. At lower depths, in the VTA, dopamine release was evoked. Immunohistochemistry experiments with antibodies for tyrosine hydroxylase (TH) confirmed that dopamine processes were primarily found below 8 mm. Similarly, tissue content determined by liquid chromatography revealed serotonin but not dopamine dorsal to 8 mm with both dopamine and serotonin at lower depths. Evaluation of the VTA signal by pharmacological means showed that it increased with inhibitors of dopamine uptake, but release was not altered by D2 agents. Dopamine release in the VTA was frequency dependent and could be exhausted by stimulations longer than 5 s. Thus, VTA dopamine release can be evoked in vivo by remote stimulations and it resembles release in terminal regions, possessing a similar uptake mechanism and a finite releasable storage pool.

Kita, Justin M.; Kile, Brian M.; Parker, Lauren E.; Wightman', R. Mark

2009-01-01

377

(+)-AJ 76 and (+)UH 232: Central stimulants acting as preferential dopamine autoreceptor antagonists  

Microsoft Academic Search

The biochemical and behavioral effects of the putative dopamine autoreceptor antagonists cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76 and cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, were evaluated in various in vivo models in rats. Both compounds produced a marked elevation in brain dopamine synthesis and turnover with only slight effects on the synthesis and turnover of serotonin (5-HT) and noradrenaline being noted. (+)-AJ 76 and (+)-UH 232

Kjell Svensson; Anette M. Johansson; Tor Magnusson; Arvid Carlsson

1986-01-01

378

Role of Dopamine Transporter in Methamphetamine-Induced Neurotoxicity: Evidence from Mice Lacking the Transporter  

Microsoft Academic Search

The role of the dopamine transporter (DAT) in mediating the neurotoxic effects of methamphetamine (METH) was tested in mice lacking DAT. Dopamine (DA) and serotonin (5-HT) content, glial fibrillary acidic protein (GFAP) expression, and free radical formation were assessed as markers of METH neurotoxicity in the striatum and\\/or hippocampus of wild-type, heterozygote, and homozygote (DAT 2\\/2) mice. Four injections of

Fabio Fumagalli; Raul R. Gainetdinov; Kenneth J. Valenzano; Marc G. Caron

1998-01-01

379

Neuronal cell lines transfected with the dopamine D 2 receptor gene promoter as a model for studying the effects of antidepressant drugs  

Microsoft Academic Search

The present study investigated the effect of three antidepressant drugs (ADs), desipramine (DMI, a noradrenaline reuptake inhibitor), citalopram (CIT, a selective serotonin reuptake inhibitor) and mianserin (MIA, thought to act as an antagonist of pre-synaptic ?2 adrenoceptor) on the transcriptional activity of the dopamine D2 receptor gene promoter. The fragment of dopamine D2 receptor gene promoter (?850 to +133) was

Marta Dziedzicka-Wasylewska; Joanna Solich

2004-01-01

380

Clozapine and other neuroleptic drugs antagonize the light-evoked suppression of melatonin biosynthesis in chick retina: involvement of the D 4 -like dopamine receptor  

Microsoft Academic Search

Summary The subtype of dopamine receptor mediating the suppressive effect of light on melatonin biosynthesis in chick retina was characterized pharmacologically. Acute exposure of animals to light during the dark phase of the light-dark cycle dramatically decreased melatonin levels and activity of serotonin N-acetyltransferase (NAT; a key regulatory enzyme in melatonin biosynthetic pathway). Various antagonists of dopamine receptors were tested

J. B. Zawilska; T. Derbiszewska; J. Z. Nowak

1994-01-01

381

Detection and Quantification of Neurotransmitters in Dialysates  

PubMed Central

Sensitive analytical methods are needed for the separation and quantification of neurotransmitters obtained in microdialysate studies. This unit describes methods that permit quantification of nanomolar concentrations of monoamines and their metabolites (high-pressure liquid chromatography electrochemical detection), acetylcholine (HPLC-coupled to an enzyme reactor), and amino acids (HPLC-fluorescence detection; capillary electrophoresis with laser-induced fluorescence detection).

Zapata, Agustin; Chefer, Vladimir I.; Shippenberg, Toni S.; Denoroy, Luc

2010-01-01

382

Presynaptic inhibition of elicited neurotransmitter release  

Microsoft Academic Search

Activation of presynaptic receptors for a variety of neurotransmitters and neuromodulators inhibits transmitter release at many synapses. Such presynaptic inhibition might serve as a means of adjusting synaptic strength or preventing excessive transmitter release, or both. Previous evidence showed that presynaptic modulators inhibit Ca2+ channels and activate K+ channels at neuronal somata. These modulators also inhibit spontaneous transmitter release by

Ling-Gang Wu; Peter Saggau

1997-01-01

383

RESPONSES OF NEUROTRANSMITTER SYSTEMS TO TOXICANT EXPOSURE  

EPA Science Inventory

As technology has become more refined and available in recent years, a major focus for neurotoxicologists has been the evaluation of toxicant effects on neuronal function. This interest will probably increase as the number of new chemical messengers (i.e., neurotransmitters and n...

384

Synthesis of Fluorescent Analogs of Neurotransmitters  

Microsoft Academic Search

Fluorescent analogs of biomolecules have been known as useful probes to study the structure, conformations and dynamics of cellular processes. These probes are more ideal than fluorescent labeled probes, as fluorescent analog probes retain the shape, size, conformation, and recognition element of the natural substrate, while giving useful intracellular information about detection and dynamics of biomolecules. The monoamine neurotransmitters control

Sharanappa Maduraya Bagale

2011-01-01

385

Detection and quantification of neurotransmitters in dialysates.  

PubMed

Sensitive analytical methods are needed for the separation and quantification of neurotransmitters obtained in microdialysate studies. This unit describes methods that permit quantification of nanomolar concentrations of monoamines and their metabolites (high-performance liquid chromatography [HPLC] electrochemical detection), acetylcholine (HPLC-coupled to an enzyme reactor), and amino acids (HPLC-fluorescence detection, capillary electrophoresis with laser-induced fluorescence detection). PMID:23559307

Zapata, Agustin; Chefer, Vladimir I; Parrot, Sandrine; Denoroy, Luc

2013-04-01

386

Physiological Mechanisms of Sexual Dysfunction Side Effects Associated With Antidepressant Medication  

Microsoft Academic Search

Sexual dysfunction side effects have been associated with antidepressant medication, especially with serotonin reuptake inhibitors. Neurotransmitters appear to be involved, especially dopamine and serotonin, but the processes by which they influence sexual dysfunction are not clear.

John B. Murray

1998-01-01

387

Low Extracellular Dopamine Levels Are Maintained in the Anoxic Turtle (Trachemys scripta) Striatum  

Microsoft Academic Search

The uncontrolled increase of extracellular dopamine (DA) has been implicated in the pathogenesis of hypoxic\\/ischemic damage in the mammalian brain. But unlike the harmful release of excitatory neurotransmitters such as glutamate and aspartate, which occurs on brain depolarization, excessive extracellular DA levels occur even with mild hypoxia in the mammalian brain. The purpose of this study was to determine whether

Sarah L. Milton; Peter L. Lutz

1998-01-01

388

Developmental Changes in Dopamine Neurotransmission in Adolescence: Behavioral Implications and Issues in Assessment  

ERIC Educational Resources Information Center

|Adolescence is characterized by increased risk-taking, novelty-seeking, and locomotor activity, all of which suggest a heightened appetitive drive. The neurotransmitter dopamine is typically associated with behavioral activation and heightened forms of appetitive behavior in mammalian species, and this pattern of activation has been described in…

Wahlstrom, Dustin; Collins, Paul; White, Tonya; Luciana, Monica

2010-01-01

389

Blink Rate in Boys with Fragile X Syndrome: Preliminary Evidence for Altered Dopamine Function  

ERIC Educational Resources Information Center

|Background: Dopamine, a neurotransmitter involved in motor and cognitive functioning, can be non-invasively measured via observation of spontaneous blink rates. Blink rates have been studied in a number of clinical conditions including schizophrenia, autism, Parkinsons, and attention deficit/hyperactivity disorder with results implicating either…

Roberts, J. E.; Symons, F. J.; Johnson, A.-M.; Hatton, D. D.; Boccia, M. L.

2005-01-01

390

Dopamine Regulation of Human Speech and Bird Song: A Critical Review  

ERIC Educational Resources Information Center

|To understand the neural basis of human speech control, extensive research has been done using a variety of methodologies in a range of experimental models. Nevertheless, several critical questions about learned vocal motor control still remain open. One of them is the mechanism(s) by which neurotransmitters, such as dopamine, modulate speech and…

Simonyan, Kristina; Horwitz, Barry; Jarvis, Erich D.

2012-01-01

391

Developmental Changes in Dopamine Neurotransmission in Adolescence: Behavioral Implications and Issues in Assessment  

ERIC Educational Resources Information Center

Adolescence is characterized by increased risk-taking, novelty-seeking, and locomotor activity, all of which suggest a heightened appetitive drive. The neurotransmitter dopamine is typically associated with behavioral activation and heightened forms of appetitive behavior in mammalian species, and this pattern of activation has been described in…

Wahlstrom, Dustin; Collins, Paul; White, Tonya; Luciana, Monica

2010-01-01

392

Functional imaging studies of dopamine system and cognition in normal aging and Parkinson's disease  

Microsoft Academic Search

Modern functional imaging methods, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), provide non-invasive, quantitative tools for the direct measurement of neurotransmitter function in the living human brain. The dopamine system has been of key interest; first, because it has a prominant role in several cognitive and motor processes, and secondly because the tracers currently

Valtteri Kaasinen; Juha O Rinne

2002-01-01

393

An 8×8 CMOS microelectrode array for electrochemical dopamine detection  

Microsoft Academic Search

This work presents the design and characterization of an integrated CMOS (complementary metal oxide semiconductor) electrochemical sensor array for dopamine (DA) detection. The chip is intended to provide as a platform for high- throughput measurement of neurotransmitter release during exocytosis. Interdigitated gold microelectrodes with a 5-Pm gap are fabricated on CMOS chips by a post-CMOS lithographic process. A buffer with

Po-Hung Yang; Michael S.-C. Lu

2011-01-01

394

DAMB, a Novel Dopamine Receptor Expressed Specifically in Drosophila Mushroom Bodies  

Microsoft Academic Search

The modulatory neurotransmitters that trigger biochemical cascades underlying olfactory learning in Drosophila mushroom bodies have remained unknown. To identify molecules that may perform this role, putative biogenic amine receptors were cloned using the polymerase chain reaction (PCR) and single-strand conformation polymorphism analysis. One new receptor, DAMB, was identified as a dopamine D1 receptor by sequence analysis and pharmacological characterization. In

Kyung-An Han; Neil S Millar; Michael S Grotewiel; Ronald L Davis

1996-01-01

395

Dual dopamine–5HT releasers: potential treatment agents for cocaine addiction  

Microsoft Academic Search

Biogenic amine transporters (BATs) are integral membrane proteins that translocate biogenic amine neurotransmitters (norepinephrine, dopamine (DA) and 5-hydroxytryptamine (5-HT)) across cell mem- branes. BATs are the principal sites of action for many psychotropic drugs, including abused stimulants such as cocaine and methamphetamine. Preclinical and human data demonstrate that withdrawal from long-term cocaine administration produces a dual deficit of synap- tic

Richard B. Rothman; Bruce E. Blough; Michael H. Baumann

2006-01-01

396

Neurotransmitter receptor heteromers and their integrative role in 'local modules': The striatal spine module  

PubMed Central

‘Local module’ is a fundamental functional unit of the central nervous system that can be defined as the minimal portion of one or more neurons and-or one or more glial cells that operates as an independent integrative unit. This review focuses on the importance of neurotransmitter receptor heteromers for the operation of local modules. To illustrate this, we use the striatal spine module (SSM), comprised of the dendritic spine of the medium spiny neuron (MSN), its glutamatergic and dopaminergic terminals and astroglial processes. The SSM is found in the striatum, and although aspects such as neurotransmitters and receptors will be specific to the SSM, some general principles should apply to any local module in the brain. The analysis of some of the receptor heteromers in the SSM shows that receptor heteromerization is associated with particular elaborated functions in this local module. Adenosine A2A receptor-dopamine D2 receptor-glutamate metabotropic mGlu5 receptor heteromers are located adjacent to the glutamatergic synapse of the dendritic spine of the enkephalin MSN, and their cross-talk within the receptor heteromers helps to modulate postsynaptic plastic changes at the glutamatergic synapse. A1 receptor-A2A receptor heteromers are found in the glutamatergic terminals and the molecular cross-talk between the two receptors in the heteromer helps to modulate glutamate release. Finally, dopamine D2 receptor-non-?7 nicotinic acetylcholine receptor heteromers, which are located in dopaminergic terminals, introduce the new concept of autoreceptor heteromer.

Ferre, Sergi; Agnati, Luigi F.; Ciruela, Francisco; Lluis, Carme; Woods, Amina S.; Fuxe, Kjell; Franco, Rafael

2007-01-01

397

Permselectivity of neurotransmitters at overoxidized polypyrrole-film-coated glassy carbon electrodes.  

PubMed

The permselectivity of neurotransmitters such as dopamine, epinephrine, and norepinephrine at overoxidized polypyrrole (OPPY)-film-coated glassy carbon electrodes has been investigated. The chemically-modified electrodes exhibit attractive permselectivity and antifouling properties of rejecting anionic species, e.g. ascorbate, etc. Compared with the response of neurotransmitters at modified electrodes overoxidized in phosphate buffer solution (pH 7.4), higher sensitivity and reversibility response can be obtained at modified electrodes overoxidized in sodium hydroxide solution. The effect of film thickness on the permselective response was tested. Rotating disk electrode experiments were used to determine the apparent diffusion coefficients of several electroactive solutes in the OPPY films. The influence of the hydrophobicity of the organic ions on the permeability within the polymer films was discussed. Dopamine and epinephrine were determined at the 1 x 10(-6)-1 x 10(-4) M level by means of voltammetry after an exposure period of 2 min in 0.1 M phosphate buffer (pH 7.4) with detection limits of 8 x 10(-7) M and 6 x 10(-7) M respectively. PMID:18966692

Kang, T F; Shen, G L; Yu, R Q

1996-11-01

398

Synthesis on accumulation of putative neurotransmitters by cultured neural crest cells  

SciTech Connect

The events mediating the differentiation of embryonic neural crest cells into several types of neurons are incompletely understood. In order to probe one aspect of this differentiation, we have examined the capacity of cultured quail trunk neural crest cells to synthesize, from radioactive precursors, and store several putative neurotransmitter compounds. These neural crest cultures develop the capacity to synthesize and accumulate acetylcholine and the catecholamines norepinephrine and dopamine. In contrast, detectable but relatively little synthesis and accumulation of 5-hydroxytryptamine gamma-aminobutyric acid, or octopamine from the appropriate radiolabeled precursors were observed. The capacity for synthesis and accumulation of radiolabeled acetylcholine and catecholamines is very low or absent at 2 days in vitro. Between 3 and 7 days in vitro, there is a marked rise in both catecholamine and acetylcholine accumulation in the cultures. These findings suggest that, under the particular conditions used in these experiments, the development of neurotransmitter biosynthesis in trunk neural crest cells ijs restricted and resembles, at least partially, the pattern observed in vivo. The development of this capacity to synthesize and store radiolabeled acetylcholine and catecholamines from the appropriate radioactive precursors coincides closely with the development of the activities of the synthetic enzymes choline acetyltransferase and dopamine beta-hydroxylase reported by others.

Maxwell, G.D.; Sietz, P.D.; Rafford, C.E.

1982-07-01

399

Dopamine, learning and motivation  

Microsoft Academic Search

The hypothesis that dopamine is important for reward has been proposed in a number of forms, each of which has been challenged. Normally, rewarding stimuli such as food, water, lateral hypothalamic brain stimulation and several drugs of abuse become ineffective as rewards in animals given performance-sparing doses of dopamine antagonists. Dopamine release in the nucleus accumbens has been linked to

Roy A. Wise

2004-01-01

400

Distinct modes of dopamine and GABA release in a dual transmitter neuron  

PubMed Central

We now know of a surprising number of cases where single neurons contain multiple neurotransmitters. Neurons that contain a fast-acting neurotransmitter such as glutamate or GABA, and a modulatory transmitter such as dopamine are a particularly interesting case because they presumably serve dual signaling functions. The olfactory bulb contains a large population of GABA and dopamine-containing neurons, which have been implicated in normal olfaction as well as in Parkinson’s disease. Yet, they have been classified as non-exocytotic catecholamine neurons because of the apparent lack of vesicular monoamine transporters. Thus we examined how dopamine is stored and released from tyrosine-hydroxylase-positive-GFP (TH+-GFP) mouse periglomerular neurons in vitro. TH+ cells expressed both VMAT2 and VGAT, consistent with vesicular storage of both dopamine and GABA. Carbon fiber amperometry revealed that release of dopamine was quantal and calcium-dependent, but quantal size was much less than expected for large dense core vesicles, suggesting that release originated from EM-identified small clear vesicles. A single action potential in a TH+ neuron evoked a brief GABA synaptic current whereas evoked dopamine release was asynchronous, lasting for tens of seconds. Our data suggests that dopamine and GABA serve temporally distinct roles in these dual transmitter neurons.

Borisovska, Maria; Bensen, AeSoon; Chong, Gene; Westbrook, Gary L.

2013-01-01

401

Radiotracers for PET and SPECT studies of neurotransmitter systems.  

National Technical Information Service (NTIS)

The study of neurotransmitter systems is one of the major thrusts in emission tomography today. The current generation of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) radiotracers examines neurotransmitter prop...

J. S. Fowler

1991-01-01

402

Imaging neurotransmitter uptake and depletion in astrocytes  

SciTech Connect

An ultraviolet (UV) laser-based optical microscope and charge-coupled device (CCD) detection system was used to obtain chemical images of biological cells. Subcellular structures can be easily seen in both optical and fluorescence images. Laser-induced native fluorescence detection provides high sensitivity and low limits of detection, and it does not require coupling to fluorescent dyes. We were able to quantitatively monitor serotonin that has been taken up into and released from individual astrocytes on the basis of its native fluorescence. Different regions of the cells took up different amounts of serotonin with a variety of uptake kinetics. Similarly, we observed different serotonin depletion dynamics in different astrocyte regions. There were also some astrocyte areas where no serotonin uptake or depletion was observed. Potential applications include the mapping of other biogenic species in cells as well as the ability to image their release from specific regions of cells in response to external stimuli. {copyright} {ital 1997} {ital Society for Applied Spectroscopy}

Tan, W. [Ames Laboratory-USDOE and Department of Chemistry, Iowa State University, Ames, Iowa 50011 (United States)]|[Department of Chemistry, University of Florida, Gainesville, Florida 32611-7200 (United States); Haydon, P.G. [Department of Zoology and Genetics, Laboratory of Cellular Signaling, Iowa State University, Ames, Iowa 50011 (United States); Yeung, E.S. [Ames Laboratory-USDOE and Department of Chemistry, Iowa State University, Ames, Iowa 50011 (United States)

1997-08-01

403

Interplay between glutamate and serotonin within the dorsal periaqueductal gray modulates anxiety-related behavior of rats exposed to the elevated plus-maze  

Microsoft Academic Search

Several neurotransmitters, including glutamate and serotonin, modulate defensive behaviors related to anxiety in the rat dorsal periaqueductal gray (PAG). Although both glutamate N-methyl-d-aspartic acid (NMDA) and serotonin type 1-A (5-HT1A) receptors have been shown to interfere with these subtle responses, such as inhibitory avoidance, a possible interaction between them remains to be examined. To address this issue, the present study

Cladis L. K. Moraes; Leandro J. Bertoglio; Antonio P. Carobrez

2008-01-01

404

Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD)  

Microsoft Academic Search

A recent study demonstrated that treatment of hyperactive mice with psychostimulants and serotonergic agents produced a calming effect that was dependent on serotonergic neurotransmission and was not associated with any changes in extracellular dopamine levels.1 The complex interaction between the serotonergic and dopaminergic neurotransmitter systems suggests that a balance between the two systems may be necessary for mediating hyperactive behaviour.

J F Quist; C L Barr; R Schachar; W Roberts; M Malone; R Tannock; V S Basile; J Beitchman; J L Kennedy

2000-01-01

405

ASTROCYTIC NEUROTRANSMITTER RECEPTORS IN SITU AND IN VIVO  

Microsoft Academic Search

In the brain, astrocytes are associated intimately with neurons and surround synapses. Due to their close proximity to synaptic clefts, astrocytes are in a prime location for receiving synaptic information from released neurotransmitters. Cultured astrocytes express a wide range of neurotransmitter receptors, but do astrocytes in vivo also express neurotransmitter receptors and, if so, are the receptors activated by synaptically

JAMES T PORTER; KEN D MCCARTHY

1997-01-01

406

Discovery of Novel Selective Serotonin Reuptake Inhibitors Through Development of a Protein-Based Pharmacophore  

PubMed Central

The serotonin transporter (SERT), a member of the neurotransmitter sodium symporter (NSS) family, is responsible for the reuptake of serotonin from the synaptic cleft to maintain neurotransmitter homeostasis. SERT is established as an important target in the treatment of anxiety and depression. Because a high-resolution crystal structure is not available, a computational model of SERT was built based upon the x-ray coordinates of the leucine transporter LeuT, a bacterial NSS homolog. The model was used to develop the first SERT structure-based pharmacophore. Virtual screening (VS) of a small molecule structural library using the generated SERT computational model yielded candidate ligands of diverse scaffolds. Pharmacological analysis of the VS hits identified two SERT-selective compounds, potential lead compounds for further SERT-related medication development.

Manepalli, Sankar; Geffert, Laura M.; Surratt, Christopher K.

2011-01-01

407

Serotonin and beyond: therapeutics for major depression.  

PubMed

The serotonin (5-HT, 5-hydroxytryptamine) system has been implicated in the pathogenesis of major depressive disorder (MDD). The case for its contribution to the therapeutic efficacy of a wide variety of antidepressant treatments is, however, much stronger. All antidepressant strategies have been shown to enhance 5-HT transmission in the brain of laboratory animals. Catecholamines, norepinephrine (NE) and dopamine (DA) can also play a pivotal role in the mechanism of action of certain antidepressant strategies. The enhancement of 5-HT transmission by selective serotonin reuptake inhibitors, which leads to a dampening of the activity of NE and DA neurons, may account in part for the low remission rate achieved with these medications and/or the residuals symptoms after remission is achieved. The functional connectivity between the 5-HT, NE and DA systems can be used to understand the mechanism of action of a wide variety of augmentation strategies in treatment-resistant MDD. Proof-of-concept studies have shown that antidepressant medications with complementary mechanisms of action on monoaminergic systems can double the remission rate achieved in a trial of standard duration. Novel approaches are also being used to treat MDD, which also appear to involve the monoaminergic system(s) to a varying extent. PMID:23440470

Blier, Pierre; El Mansari, Mostafa

2013-02-25

408

Rapid, sensitive detection of neurotransmitters at microelectrodes modified with self-assembled SWCNT forests.  

PubMed

Carbon nanotube (CNT) modification of microelectrodes can result in increased sensitivity without compromising time response. However, dip coating CNTs is not very reproducible and the CNTs tend to lay flat on the electrode surface which limits access to the electroactive sites on the ends. In this study, aligned CNT forests were formed using a chemical self-assembly method, which resulted in more exposed CNT ends to the analyte. Shortened, carboxylic acid functionalized single-walled CNTs were assembled from a dimethylformamide (DMF) suspension onto a carbon-fiber disk microelectrode modified with a thin iron hydroxide-decorated Nafion film. The modified electrodes were highly sensitive, with 36-fold higher oxidation currents for dopamine using fast-scan cyclic voltammetry than bare electrodes and 34-fold more current than electrodes dipped in CNTs. The limit of detection (LOD) for dopamine was 17 ± 3 nM at a 10 Hz repetition rate and 65 ± 7 nM at 90 Hz. The LOD at 90 Hz was the same as a bare electrode at 10 Hz, allowing a 9-fold increase in temporal resolution without a decrease in sensitivity. Similar increases were observed for other cationic catecholamine neurotransmitters, and the increases in current were greater than for anionic interferents such as ascorbic acid and 3,4-dihydroxyphenylacetic acid (DOPAC). The CNT forest electrodes had high sensitivity at 90 Hz repetition rate when stimulated dopamine release was measured in Drosophila . The sensitivity, temporal resolution, and spatial resolution of these CNT forest modified disk electrodes facilitate enhanced electrochemical measurements of neurotransmitter release in vivo. PMID:22823497

Xiao, Ning; Venton, B Jill

2012-08-24

409

Rapid, sensitive detection of neurotransmitters at microelectrodes modified with self-assembled SWCNT forests  

PubMed Central

Carbon nanotube (CNT) modification of microelectrodes can result in increased sensitivity without compromising time response. However, dip coating CNTs is not very reproducible and the CNTs tend to lay flat on the electrode surface which limits access to the electroactive sites on the ends. In this study, aligned CNT forests were formed using a chemical self-assembly method, which resulted in more exposed CNT ends to the analyte. Shortened, carboxylic acid functionalized single-walled CNTs were assembled from a DMF suspension onto a carbon-fiber disk microelectrode modified with a thin iron hydroxide-decorated Nafion film. The modified electrodes were highly sensitive, with 36-fold higher oxidation currents for dopamine using fast-scan cyclic voltammetry than bare electrodes and 34-fold more current than electrodes dipped in CNTs. The limit of detection for dopamine was 17 ± 3 nM at a 10 Hz repetition rate and 65 ± 7 nM at 90 Hz. The LOD at 90 Hz was the same as a bare electrode at 10 Hz, allowing a 9-fold increase in temporal resolution without a decrease in sensitivity. Similar increases were observed for other cationic catecholamine neurotransmitters and the increases in current were greater than for anionic interferents such as ascorbic acid and 3,4-dihydroxyphenylacetic acid (DOPAC). The CNT forest electrodes had high sensitivity at 90 Hz repetition rate when stimulated dopamine release was measured in Drosophila. The sensitivity, temporal resolution, and spatial resolution of these CNT forest modified disk electrodes facilitate enhanced electrochemical measurements of neurotransmitters release in vivo.

Xiao, Ning; Venton, B. Jill

2012-01-01

410

Membrane receptors for hormones and neurotransmitters  

PubMed Central

Receptors for peptide hormones and neurotransmitters are integral components of the plasma membrane of cells which serve to couple the external milieu to the intracellular regulators of metabolism. These macromolecules are usually high molecular weight glycoproteins, and in many cases appear to have more than one subunit capable of binding the hormone. The interaction of the hormone or neurotransmitter with its receptor is rapid, reversible, and of high affinity and specificity. Many receptors exhibit cooperative properties in hormone binding or biological function. The concentration of receptors on the membrane is a function of continued synthesis and degradation, and may be altered by a variety of factors including the hormone itself. The fluid mosaic nature of the membrane may allow hormone receptors and effectors to exist in free floating states. Further investigations of the hormone- receptor interaction will no doubt yield new insights into both the mechanism of hormone action and membrane structure and function.