WorldWideScience

Sample records for central serotonin release

  1. Enhanced central serotonin release from slices of rat hypothalamus following repeated nialamide administration: evidence supporting the overactive serotonin receptor theory of depression

    International Nuclear Information System (INIS)

    Researchers are suggesting unipolar affective disorders may be related to an abnormality in biogenic amine receptor-sensitivity. This abnormality may be a result of a dysfunction in central serotonin (5-HT) release mechanisms. 5-HT neurotransmission is modulated by presynaptic autoreceptors, which are members of the 5-HT1 receptor subtype. The autoreceptor is thought to play an important role in the homeostasis of the central 5-HT synapse and could be a site at which some antidepressants mediate their therapeutic effect. The number of 5-HT1 type receptor binding sites are reduced and behavior mediated by this receptor is abolished following repeated injections of monoamine oxidase inhibitor type antidepressants. These changes did not occur following a single injection. It was hypothesized that repeated treatment with a monoamine oxidase inhibitor would reduce the sensitivity of 5-HT autoreceptors and enhance 5-HT release. Rats were pretreated with single or repeated (twice daily for 7 days) intraperitoneal injections of nialamide (40 mg/kg) or chlorimipramine (10 mg/kg) and the ability of the autoreceptor agonist to inhibit potassium-induced 3H-5-HT release was evaluated using an in vitro superfusion system. These changes in 5-HT autoreceptor activity are consistent with other reports evaluating monoamine oxidase inhibitors on 5-HT1 type receptors. It is hypothesized that the changes in 5-HT neurotransmission are related to the antidepressant mechanism of monoamine oxidase inhibitors

  2. Nutrient-induced glucagon like peptide-1 release is modulated by serotonin

    OpenAIRE

    Ripken, Dina; Wielen, van der, F.W.M.; Wortelboer, Heleen M.; Meijerink, Jocelijn; Witkamp, Renger F.; Hendriks, Henk F. J.

    2016-01-01

    Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects...

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

    Directory of Open Access Journals (Sweden)

    Best Janet

    2010-08-01

    Full Text Available Abstract 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, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system. Methods We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data. Results We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct in silico experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to

  4. Determination of serotonin released from coffee wax by liquid chromatography.

    Science.gov (United States)

    Kele, M; Ohmacht, R

    1996-04-12

    A simple hydrolysis and extraction method was developed for the release of serotonin (5-hydroxytryptamine) from a coffee wax sample obtained from decaffeination of coffee beans. The recoverable amount of serotonin was determined by reversed-phase high-performance liquid chromatography with gradient elution and UV detection, using the standard addition method. Different type of basic deactivated chromatographic columns were used for the separation.

  5. Enhanced contextual fear memory in central serotonin-deficient mice

    OpenAIRE

    Dai, Jin-Xia; Han, Hui-Li; Tian, Meng; Cao, Jun; Xiu, Jian-Bo; Song, Ning-Ning; Huang, Ying; Xu, Tian-Le; Ding, Yu-Qiang; Xu, Lin

    2008-01-01

    Central serotonin (5-HT) dysregulation contributes to the susceptibility for mental disorders, including depression, anxiety, and posttraumatic stress disorder, and learning and memory deficits. We report that the formation of hippocampus-dependent spatial memory is compromised, but the acquisition and retrieval of contextual fear memory are enhanced, in central 5-HT-deficient mice. Genetic deletion of serotonin in the brain was achieved by inactivating Lmx1b selectively in the raphe nuclei o...

  6. Optogenetic control of serotonin and dopamine release in Drosophila larvae.

    Science.gov (United States)

    Xiao, Ning; Privman, Eve; Venton, B Jill

    2014-08-20

    Optogenetic control of neurotransmitter release is an elegant method to investigate neurobiological mechanisms with millisecond precision and cell type-specific resolution. Channelrhodopsin-2 (ChR2) can be expressed in specific neurons, and blue light used to activate those neurons. Previously, in Drosophila, neurotransmitter release and uptake have been studied after continuous optical illumination. In this study, we investigated the effects of pulsed optical stimulation trains on serotonin or dopamine release in larval ventral nerve cords. In larvae with ChR2 expressed in serotonergic neurons, low-frequency stimulations produced a distinct, steady-state response while high-frequency patterns were peak shaped. Evoked serotonin release increased with increasing stimulation frequency and then plateaued. The steady-state response and the frequency dependence disappeared after administering the uptake inhibitor fluoxetine, indicating that uptake plays a significant role in regulating the extracellular serotonin concentration. Pulsed stimulations were also used to evoke dopamine release in flies expressing ChR2 in dopaminergic neurons and similar frequency dependence was observed. Release due to pulsed optical stimulations was modeled to determine the uptake kinetics. For serotonin, Vmax was 0.54 ± 0.07 μM/s and Km was 0.61 ± 0.04 μM; and for dopamine, Vmax was 0.12 ± 0.03 μM/s and Km was 0.45 ± 0.13 μM. The amount of serotonin released per stimulation pulse was 4.4 ± 1.0 nM, and the amount of dopamine was 1.6 ± 0.3 nM. Thus, pulsed optical stimulations can be used to mimic neuronal firing patterns and will allow Drosophila to be used as a model system for studying mechanisms underlying neurotransmission.

  7. Reduced cocaine-induced serotonin, but not dopamine and noradrenaline, release in rats with a genetic deletion of serotonin transporters.

    Science.gov (United States)

    Verheij, Michel M M; Karel, Peter; Cools, Alexander R; Homberg, Judith R

    2014-11-01

    It has recently been proposed that the increased reinforcing properties of cocaine and ecstasy observed in rats with a genetic deletion of serotonin transporters are the result of a reduction in the psychostimulant-induced release of serotonin. Here we provide the neurochemical evidence in favor of this hypothesis and show that changes in synaptic levels of dopamine or noradrenaline are not very likely to play an important role in the previously reported enhanced psychostimulant intake of these serotonin transporter knockout rats. The results may very well explain why human subjects displaying a reduced expression of serotonin transporters have an increased risk to develop addiction. PMID:25261262

  8. Impaired Brain Dopamine and Serotonin Release and Uptake in Wistar Rats Following Treatment with Carboplatin.

    Science.gov (United States)

    Kaplan, Sam V; Limbocker, Ryan A; Gehringer, Rachel C; Divis, Jenny L; Osterhaus, Gregory L; Newby, Maxwell D; Sofis, Michael J; Jarmolowicz, David P; Newman, Brooke D; Mathews, Tiffany A; Johnson, Michael A

    2016-06-15

    Chemotherapy-induced cognitive impairment, known also as "chemobrain", is a medical complication of cancer treatment that is characterized by a general decline in cognition affecting visual and verbal memory, attention, complex problem solving skills, and motor function. It is estimated that one-third of patients who undergo chemotherapy treatment will experience cognitive impairment. Alterations in the release and uptake of dopamine and serotonin, central nervous system neurotransmitters that play important roles in cognition, could potentially contribute to impaired intellectual performance in those impacted by chemobrain. To investigate how chemotherapy treatment affects these systems, fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes was used to measure dopamine and serotonin release and uptake in coronal brain slices containing the striatum and dorsal raphe nucleus, respectively. Measurements were taken from rats treated weekly with selected doses of carboplatin and from control rats treated with saline. Modeling the stimulated dopamine release plots revealed an impairment of dopamine release per stimulus pulse (80% of saline control at 5 mg/kg and 58% at 20 mg/kg) after 4 weeks of carboplatin treatment. Moreover, Vmax, the maximum uptake rate of dopamine, was also decreased (55% of saline control at 5 mg/kg and 57% at 20 mg/kg). Nevertheless, overall dopamine content, measured in striatal brain lysates by high performance liquid chromatography, and reserve pool dopamine, measured by FSCV after pharmacological manipulation, did not significantly change, suggesting that chemotherapy treatment selectively impairs the dopamine release and uptake processes. Similarly, serotonin release upon electrical stimulation was impaired (45% of saline control at 20 mg/kg). Measurements of spatial learning discrimination were taken throughout the treatment period and carboplatin was found to alter cognition. These studies support the need for additional

  9. Characterization and regulation of [3H]-serotonin uptake and release in rodent spinal

    International Nuclear Information System (INIS)

    The uptake and release of [3H]-serotonin were investigated in rat spinal cord synaptosomes. In the uptake experiments, sodium-dependent and sodium-independent [3H]-serotonin accumulation processes were found. Sodium-dependent [3H]-serotonin accumulation was: linear with sodium concentrations up to 180 mM; decreased by disruption of membrane integrity or ionic gradients; associated with purified synaptosomal fractions; and reduced after description of descending serotonergic neurons in the spinal cord. Of the uptake inhibitors tested, the most potent was fluoxetine (IC50 75 nM), followed by desipramine (IC50 430 nM) and nomifensine (IC50 950 nM). The sodium-independent [3H]-serotonin accumulation process was insensitive to most treatments and probably represents nonspecific membrane binding. Thus, only sodium-dependent [3H]-serotonin uptake represents the uptake process of serotonergic nerve terminals in rat spinal cord homogenates. In the release experiments, K+-induced release of previously accumulated [3H]-serotonin was Ca2+-dependent, and originated from serotonergic synaptosomes. Exogenous serotonin and 5-methyoxy-N,N-dimethyltryptamine inhibited [3H]-serotonin release in a concentration-dependent way. Of the antagonists tested, only methiothepin effectively blocked the effect of serotonin. These data support the existence of presynaptic serotonin autoreceptors on serotonergic nerve terminals in the rat spinal cord that act to inhibit a voltage and Ca2+-sensitive process linked to serotonin release. Alteration of spinai cord serotonergic function may therefore be possible by drugs acting on presynaptic serotonin autoreceptors in the spinal cord

  10. Characterization and regulation of (/sup 3/H)-serotonin uptake and release in rodent spinal

    Energy Technology Data Exchange (ETDEWEB)

    Stauderman, K.A.

    1986-01-01

    The uptake and release of (/sup 3/H)-serotonin were investigated in rat spinal cord synaptosomes. In the uptake experiments, sodium-dependent and sodium-independent (/sup 3/H)-serotonin accumulation processes were found. Sodium-dependent (/sup 3/H)-serotonin accumulation was: linear with sodium concentrations up to 180 mM; decreased by disruption of membrane integrity or ionic gradients; associated with purified synaptosomal fractions; and reduced after description of descending serotonergic neurons in the spinal cord. Of the uptake inhibitors tested, the most potent was fluoxetine (IC/sub 50/ 75 nM), followed by desipramine (IC/sub 50/ 430 nM) and nomifensine (IC/sub 50/ 950 nM). The sodium-independent (/sup 3/H)-serotonin accumulation process was insensitive to most treatments and probably represents nonspecific membrane binding. Thus, only sodium-dependent (/sup 3/H)-serotonin uptake represents the uptake process of serotonergic nerve terminals in rat spinal cord homogenates. In the release experiments, K/sup +/-induced release of previously accumulated (/sup 3/H)-serotonin was Ca/sup 2 +/-dependent, and originated from serotonergic synaptosomes. Exogenous serotonin and 5-methyoxy-N,N-dimethyltryptamine inhibited (/sup 3/H)-serotonin release in a concentration-dependent way. Of the antagonists tested, only methiothepin effectively blocked the effect of serotonin. These data support the existence of presynaptic serotonin autoreceptors on serotonergic nerve terminals in the rat spinal cord that act to inhibit a voltage and Ca/sup 2 +/-sensitive process linked to serotonin release. Alteration of spinai cord serotonergic function may therefore be possible by drugs acting on presynaptic serotonin autoreceptors in the spinal cord.

  11. Acute serotonin depletion releases motivated inhibition of response vigour

    NARCIS (Netherlands)

    Ouden, H.E.M. den; Swart, J.C.; Schmidt, K.; Fekkes, D.; Geurts, D.E.M.; Cools, R.

    2015-01-01

    Rationale The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas,

  12. Acute serotonin depletion releases motivated inhibition of response vigour

    NARCIS (Netherlands)

    Ouden, H.E.M. den; Swart, J.C.; Schmidt, K.; Fekkes, D.; Geurts, D.E.M.; Cools, R.

    2015-01-01

    RATIONALE: The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas,

  13. alpha 1-Adrenoceptors modulate citalopram-induced serotonin release

    NARCIS (Netherlands)

    Rea, Kieran; Folgering, Joost; Westerink, Ben H. C.; Cremers, Thomas I. F. H.

    2010-01-01

    Previous studies suggest that noradrenaline may regulate serotonergic (5-HT) neurotransmission at the serotonin cell body and noradrenaline nerve terminal. Using microdialysis coupled to HPLC, we investigated the effects of alpha 1-adrenoceptor manipulation on extracellular serotonin levels in the v

  14. Studies on central nervous system serotonin receptors in mood disorders.

    Science.gov (United States)

    Young, A; Goodwin, G M

    1991-01-01

    The evidence from studies of central nervous system serotonin (5-HT) receptors is reviewed and the role of these in the pathogenesis of mood disorders is discussed. Clinical evidence indicates that 5-HT function is abnormal in mood disorders. 5-HT precursors and selective inhibitors of 5-HT uptake are effective antidepressives and inhibition of 5-HT synthesis can block the action of antidepressives. Studies of 5-HT in experimental animals after chronic administration of antidepressive treatments suggest that intact 5-HT neurons are necessary for the action of these treatments. Multiple 5-HT receptor subtypes have recently been identified and the effects of chronic antidepressive treatment on some receptor subtypes function in experimental animals have been established. The increasing availability of powerful new in vivo imaging techniques like single photon emission tomography (SPET), and positron emission tomography (PET) may make possible a more direct examination of 5-HT receptor function in patients suffering from mood disorders. PMID:2029163

  15. Serotonin released from amacrine neurons is scavenged and degraded in bipolar neurons in the retina

    OpenAIRE

    Ghai, Kanika; Zelinka, Christopher; Fischer, Andy J.

    2009-01-01

    The neurotransmitter serotonin is synthesized in the retina by one type of amacrine neuron but accumulates in bipolar neurons in many vertebrates. The mechanisms, functions and purpose underlying of serotonin in bipolar cells remain unknown. Here, we demonstrate that exogenous serotonin transiently accumulates in a distinct type of bipolar neuron. KCl-mediated depolarization causes the depletion of serotonin from amacrine neurons and, subsequently, serotonin is taken-up by bipolar neurons. Th...

  16. L-DOPA elicits non-vesicular releases of serotonin and dopamine in hemiparkinsonian rats in vivo.

    Science.gov (United States)

    Miguelez, Cristina; Navailles, Sylvia; Delaville, Claire; Marquis, Loïse; Lagière, Mélanie; Benazzouz, Abdelhamid; Ugedo, Luisa; De Deurwaerdère, Philippe

    2016-08-01

    The control of the secretory activity of serotonergic neurons has been pointed out to reduce motor and non-motor side effects of the antiparkinsonian drug L-DOPA. This strategy deserves further investigation because it is presently unclear whether L-DOPA promotes a non-vesicular release of dopamine and serotonin from serotonergic neurons. To get a full neurochemical picture compatible with the existence of such a mechanism, we combined multisite intracerebral microdialysis, post mortem tissue measurement and single unit extracellular recordings in the dorsal raphe nucleus from hemiparkinsonian rats. L-DOPA (3-100mg/kg, ip.) non-homogeneously decreased extracellular serotonin levels in the striatum, substantia nigra pars reticulata, hippocampus and prefrontal cortex and homogenously serotonin tissue content in the striatum, cortex and cerebellum. L-DOPA (12mg/kg) did not modify the firing rate or pattern of serotonergic-like neurons recorded in the dorsal raphe nucleus. When focusing on serotonin release in the prefrontal cortex and the hippocampus, we found that L-DOPA (12 or 100mg/kg) enhanced serotonin extracellular levels in both regions upon Ca(2+) removal. Concomitantly, L-DOPA-stimulated dopamine release partly persisted in the absence of Ca(2+) in a region-dependent manner. Local application of the serotonin reuptake inhibitor citalopram (1µM) blunted the responses to L-DOPA (3-12mg/kg), measured as extracellular dopamine levels, most prominently in the hippocampus. These data stress that L-DOPA, already at low to moderate doses, promotes non-vesicular releases of serotonin and dopamine in a region-dependent manner. PMID:27234917

  17. Inhibition of serotonin release by bombesin-like peptides in rat hypothalamus in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Saporito, M.S.; Warwick, R.O. Jr.

    1989-01-01

    We investigated the activity of bombesin (BN), neuromedin-C (NM-C) and neuromedin-B (NM-B) on serotonin (5-HT) release and reuptake in rat hypothalamus (HYP) in vitro. BN and NM-C but not NM-B decreased K/sup +/ evoked /sup 3/H-5-HT release from superfused HYP slices by 25%. Bacitracin, a nonspecific peptidase inhibitor, reversed the inhibitory effect of BN on K/sup +/ evoked /sup 3/H-5-HT release. Phosphoramidon (PAN, 10 /mu/M) an endopeptidase 24.11 inhibitor, abolished the inhibitory effect of BN, but not NM-C, on K/sup +/ evoked /sup 3/H-5-HT release. The peptidyl dipeptidase A inhibitor enalaprilat (ENP, 10 /mu/M), enhanced both BN and NM-C inhibition of /sup 3/H-5-HT release. Bestatin (BST, 10 /mu/M) had no effect on BN or NM-C inhibitory activity on /sup 3/H-5-HT release. Neither BN, NM-C nor NM-B affected reuptake of /sup 3/H-5-HT into HYP synaptosomes alone or in combination with any of the peptidase inhibitors, nor did these peptides alter the ability of fluoxetine to inhibit /sup 3/H-5-HT uptake.

  18. Effects of their nutrient precursors on the synthesis and release of serotonin, the catecholamines, and acetylcholine - Implications for behavioral disorders

    Science.gov (United States)

    Wurtman, Richard J.

    1988-01-01

    Authentic foods affect brain serotonin synthesis by modifying brain tryptophan levels, carbohydrates increasing and proteins decreasing these levels. The carbohydrate-induced rise in brain serotonin tends to diminish the likelihood that one carbohydrate-rich, protein-poor meal or snack will be followed by another. This mechanism is apparently disturbed in carbohydrate-craving obesity, which may explain why this syndrome responds well to d-fenfluramine, a serotoninergic drug. Pure nutrients like tyrosine or choline can also affect the rates at which their neurotransmitter products, the catecholamines and acetylcholine, are synthesized in and released from nerve terminals, suggesting that these compounds may find uses as drugs.

  19. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

    Science.gov (United States)

    Cotel, Florence; Exley, Richard; Cragg, Stephanie J.; Perrier, Jean-François

    2013-01-01

    Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle adequately independently of the muscle physiology. Indirect evidence indicates that central fatigue is caused by serotonin (5-HT), but the cellular mechanisms are unknown. In a slice preparation from the spinal cord of the adult turtle, we found that prolonged stimulation of the raphe-spinal pathway—as during motor exercise—activated 5-HT1A receptors that decreased motoneuronal excitability. Electrophysiological tests combined with pharmacology showed that focal activation of 5-HT1A receptors at the axon initial segment (AIS), but not on other motoneuronal compartments, inhibited the action potential initiation by modulating a Na+ current. Immunohistochemical staining against 5-HT revealed a high-density innervation of 5-HT terminals on the somatodendritic membrane and a complete absence on the AIS. This observation raised the hypothesis that a 5-HT spillover activates receptors at this latter compartment. We tested it by measuring the level of extracellular 5-HT with cyclic voltammetry and found that prolonged stimulations of the raphe-spinal pathway increased the level of 5-HT to a concentration sufficient to activate 5-HT1A receptors. Together our results demonstrate that prolonged release of 5-HT during motor activity spills over from its release sites to the AIS of motoneurons. Here, activated 5-HT1A receptors inhibit firing and, thereby, muscle contraction. Hence, this is a cellular mechanism for central fatigue. PMID:23487756

  20. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

    OpenAIRE

    Cotel, Florence; Exley, Richard; Cragg, Stephanie J.; Perrier, Jean-François

    2013-01-01

    Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle adequately independently of the muscle physiology. Indirect evidence indicates that central fatigue is caused by serotonin (5-HT), but the cellular mechanisms are unknown. In a slice preparation from the spi...

  1. Location and function of serotonin in the central and peripheral nervous system of the Colorado potato beetle.

    NARCIS (Netherlands)

    Haeften, van T.

    1993-01-01

    In this thesis we have localized serotoninergic neurons in the central and peripheral nervous system of the Colorado potato beetle, Leptinotarsa decemlineata by means of immunohistochemistry with a specific antiserurn to serotonin and assessed the possible role of these neurons in feeding physiology

  2. Serotonin 5-HT(2A) receptor activation induces 2-arachidonoylglycerol release through a phospholipase c-dependent mechanism.

    Science.gov (United States)

    Parrish, Jason C; Nichols, David E

    2006-11-01

    To date, several studies have demonstrated that phospholipase C-coupled receptors stimulate the production of endocannabinoids, particularly 2-arachidonoylglycerol. There is now evidence that endocannabinoids are involved in phospholipase C-coupled serotonin 5-HT(2A) receptor-mediated behavioral effects in both rats and mice. The main objective of this study was to determine whether activation of the 5-HT(2A) receptor leads to the production and release of the endocannabinoid 2-arachidonoylglycerol. NIH3T3 cells stably expressing the rat 5-HT(2A) receptor were first incubated with [(3)H]-arachidonic acid for 24 h. Following stimulation with 10 mum serotonin, lipids were extracted from the assay medium, separated by thin layer chromatography, and analyzed by liquid scintillation counting. Our results indicate that 5-HT(2A) receptor activation stimulates the formation and release of 2-arachidonoylglycerol. The 5-HT(2A) receptor-dependent release of 2-arachidonoylglycerol was partially dependent on phosphatidylinositol-specific phospholipase C activation. Diacylglycerol produced downstream of 5-HT(2A) receptor-mediated phospholipase D or phosphatidylcholine-specific phospholipase C activation did not appear to contribute to 2-arachidonoylglycerol formation in NIH3T3-5HT(2A) cells. In conclusion, our results support a functional model where neuromodulatory neurotransmitters such as serotonin may act as regulators of endocannabinoid tone at excitatory synapses through the activation of phospholipase C-coupled G-protein coupled receptors. PMID:17010161

  3. Central serotonin depletion modulates the behavioural, endocrine and physiological responses to repeated social stress and subsequent c-fos expression in the brains of male rats.

    Science.gov (United States)

    Chung, K K; Martinez, M; Herbert, J

    1999-01-01

    Intraspecific confrontation has been used to study effect of depleting central serotonin on the adaptation of male rats to repeated social stress (social defeat). Four groups of adult male rats were used (serotonin depletion/sham: stressed; serotonin depletion/sham: non-stressed). Central serotonin was reduced (by 59-97%) by a single infusion of the neurotoxin 5,7-dihydroxtryptamine (150 microg) into the cerebral ventricles; levels of dopamine and noradrenaline were unaltered (rats received appropriate uptake blockers prior to neurotoxic infusions). Sham-operated animals received solute only. Rats were then either exposed daily for 10 days to a second larger aggressive male in the latter's home cage, or simply transferred to an empty cage (control procedure). Rats with reduced serotonin failed to show the increased freezing behaviour during the pre-defeat phase of the social interaction test characteristic of sham animals. There was no change in the residents' behaviour. Core temperature increased during aggressive interaction in sham rats, and this did not adapt with repeated stress. By contrast, stress-induced hyperthermia was accentuated in serotonin-reduced rats as the number of defeat sessions increased. Basal core temperature was unaffected by serotonin depletion. Heart rate increased during social defeat, but this did not adapt with repeated stress; serotonin depletion had no effect on this cardiovascular response. Basal corticosterone was increased in serotonin-depleted rats, but the progressive reduction in stress response over days was not altered. C-fos expression in the brain was not altered in control (non-stressed) rats by serotonin reduction in the areas examined, but there was increased expression after repeated social stress in the medial amygdala of 5-HT depleted rats. These experiments show that reduction of serotonin alters responses to repeated social stress in male rats, and suggests a role for serotonin in the adaptive process.

  4. Association of central serotonin transporter availability and body mass index in healthy Europeans

    DEFF Research Database (Denmark)

    Hesse, Swen; van de Giessen, Elsmarieke; Zientek, Franziska;

    2014-01-01

    UNLABELLED: Serotonin-mediated mechanisms, in particular via the serotonin transporter (SERT), are thought to have an effect on food intake and play an important role in the pathophysiology of obesity. However, imaging studies that examined the correlation between body mass index (BMI) and SERT...

  5. Serotonin immunoreactivity in the central nervous system of the marine molluscs Pleurobranchaea californica and Tritonia diomedea.

    Science.gov (United States)

    Sudlow, L C; Jing, J; Moroz, L L; Gillette, R

    1998-06-15

    The central nervous systems of the marine molluscs Pleurobranchaea californica (Opisthobranchia: Notaspidea) and Tritonia diomedea (Opisthobranchia: Nudibranchia) were examined for serotonin-immunoreactive (5-HT-IR) neurons and processes. Bilaterally paired clusters of 5-HT-IR neuron somata were distributed similarly in ganglia of the two species. In the cerebropleural ganglion complex, these were the metacerebral giant neurons (both species), a dorsal anterior cluster (Pleurobranchaea only), a dorsal medial cluster including identified neurons of the escape swimming network (both species), and a dorsal lateral cluster in the cerebropleural ganglion (Pleurobranchaea only). A ventral anterior cluster (both species) adjoined the metacerebral giant somata at the anterior ganglion edge. Pedal ganglia had the greatest number of 5-HT-IR somata, the majority located near the roots of the pedal commissure in both species. Most 5-HT-IR neurons were on the dorsal surface of the pedal ganglia in Pleurobranchaea and were ventral in Tritonia. Neither the buccal ganglion of both species nor the visceral ganglion of Pleurobranchaea had 5-HT-IR somata. Afew asymmetrical 5-HT-IR somata were found in cerebropleural and pedal ganglia in both species, always on the left side. The clustering of 5-HT-IR neurons, their diverse axon pathways, and the known physiologic properties of their identified members are consistent with a loosely organized arousal system of serotonergic neurons whose components can be generally or differentially active in expression of diverse behaviors. PMID:9619500

  6. Human fear acquisition deficits in relation to genetic variants of the corticotropin releasing hormone receptor 1 and the serotonin transporter.

    Directory of Open Access Journals (Sweden)

    Ivo Heitland

    Full Text Available The ability to identify predictors of aversive events allows organisms to appropriately respond to these events, and failure to acquire these fear contingencies can lead to maladaptive contextual anxiety. Recently, preclinical studies demonstrated that the corticotropin-releasing factor and serotonin systems are interactively involved in adaptive fear acquisition. Here, 150 healthy medication-free human subjects completed a cue and context fear conditioning procedure in a virtual reality environment. Fear potentiation of the eyeblink startle reflex (FPS was measured to assess both uninstructed fear acquisition and instructed fear expression. All participants were genotyped for polymorphisms located within regulatory regions of the corticotropin releasing hormone receptor 1 (CRHR1 - rs878886 and the serotonin transporter (5HTTLPR. These polymorphisms have previously been linked to panic disorder and anxious symptomology and personality, respectively. G-allele carriers of CRHR1 (rs878886 showed no acquisition of fear conditioned responses (FPS to the threat cue in the uninstructed phase, whereas fear acquisition was present in C/C homozygotes. Moreover, carrying the risk alleles of both rs878886 (G-allele and 5HTTLPR (short allele was associated with increased FPS to the threat context during this phase. After explicit instructions regarding the threat contingency were given, the cue FPS and context FPS normalized in all genotype groups. The present results indicate that genetic variability in the corticotropin-releasing hormone receptor 1, especially in interaction with the 5HTTLPR, is involved in the acquisition of fear in humans. This translates prior animal findings to the human realm.

  7. Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system

    NARCIS (Netherlands)

    Passchier, Jan; van Waarde, A

    2001-01-01

    The 5-HT1A subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain and is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT1A receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic beha

  8. Central serotonin and dopamine transporters in overeating, obesity and insulin resistance

    NARCIS (Netherlands)

    K.E.M. Koopman

    2014-01-01

    The objectives of this thesis were to study cerebral serotonin transporters (SERT) in the diencephalon and striatal dopamine transporters (DAT) in humans in different metabolic conditions (i.e. lean, obese and insulin resistant state) in relation to feeding behavior and to investigate the early cons

  9. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P;

    1988-01-01

    Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

  10. Serotonin-like immunoreactivity in the central and peripheral nervous systems of the interstitial acochlidean Asperspina sp. (Opisthobranchia).

    Science.gov (United States)

    Hochberg, Rick

    2007-08-01

    Species of Acochlidea are common members of the marine interstitial environment and defined in part by their minuscule size and highly divergent morphology relative to other benthic opisthobranchs. Despite these differences, acochlideans such as species of Asperspina display many plesiomorphic characteristics, including an unfused condition of their neural ganglia. To gain insight into the distribution of specific neural subsets within acochlidean ganglia, a species of Asperspina was studied by using anti-serotonin immunohistochemistry and epifluorescence and confocal laser scanning microscopy. Results reveal similarities between Asperspina and larger opisthobranchs in the general distribution of serotonergic perikarya in the central nervous system. Specifically, the arrangement of perikarya into regional clusters within the cerebral and pedal ganglia and the absence of immunoreactive perikarya in the pleural ganglia are similar to the model species of Aplysia californica, Pleurobranchaea californica, and Tritonia diomedea. Moreover, serotonergic innervation of the rhinophores in all opisthobranchs, including Asperspina sp., originates from the cerebral ganglion instead of directly from the rhinophoral ganglion. Serotonergic innervation of the body wall, including the epithelium, muscles, and pedal sole, appears to arise exclusively from pedal and accessory ganglia. These observations indicate a general conservation of serotonin-like immunoreactivity in the central and peripheral nervous systems of acochlidean and other benthic opisthobranchs. PMID:17679719

  11. Anabolic androgenic steroids and central monoaminergic systems : Supratherapeutic doses of nandrolone decanoate affect dopamine and serotonin

    OpenAIRE

    Birgner, Carolina

    2008-01-01

    Supratherapeutic doses of anabolic androgenic steroids (AASs) are administered, not only as performance-enhancing drugs in the world of sports, but also in order to modify behaviour. AAS abusers are at risk of developing serious physical and psychological side effects such as dependence and aggressive behaviour. The aim of this thesis was to investigate the impact of supratherapeutic doses of nandrolone decanoate after subchronic administration on dopamine and serotonin pathways involved in d...

  12. DO OPIOIDS EVOKE THE RELEASE OF SEROTONIN IN THE SPINAL-CORD - AN INVIVO MICRODIALYSIS STUDY OF THE REGULATION OF EXTRACELLULAR SEROTONIN IN THE RAT

    NARCIS (Netherlands)

    MATOS, FF; ROLLEMA, H; BROWN, JL; BASBAUM, AI

    1992-01-01

    This study investigated the regulation of serotonin (5-HT) and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal spinal cord of awake, freely moving rats, using microdialysis coupled to HPLC with electrochemical detection and tested the hypothesis that opioids exert their analge

  13. Serotonin-mediated central fatigue underlies increased endurance capacity in mice from lines selectively bred for high voluntary wheel running.

    Science.gov (United States)

    Claghorn, Gerald C; Fonseca, Ivana A T; Thompson, Zoe; Barber, Curtis; Garland, Theodore

    2016-07-01

    Serotonin (5-hydroxytryptamine; 5-HT) is implicated in central fatigue, and 5-HT1A pharmaceuticals are known to influence locomotor endurance in both rodents and humans. We studied the effects of a 5-HT1A agonist and antagonist on both forced and voluntary exercise in the same set of mice. This cohort of mice was taken from 4 replicate lines of mice that have been selectively bred for high levels of voluntary wheel running (HR) as compared with 4 non-selected control (C) lines. HR mice run voluntarily on wheels about 3× as many revolutions per day as compared with C, and have greater endurance during forced treadmill exercise. We hypothesized that drugs targeting serotonin receptors would have differential effects on locomotor behavior of HR and C mice. Subcutaneous injections of a 5-HT1A antagonist (WAY-100,635), a combination of 5-HT1A agonist and a 5-HT1A/1B partial agonist (8-OH-DPAT+pindolol), or physiological saline were given to separate groups of male mice before the start of each of three treadmill trials. The same manipulations were used later during voluntary wheel running on three separate nights. WAY-100,635 decreased treadmill endurance in HR but not C mice (dose by linetype interaction, P=0.0014). 8-OH-DPAT+pindolol affected treadmill endurance (P<0.0001) in a dose-dependent manner, with no dose by linetype interaction. Wheel running was reduced in HR but not C mice at the highest dose of 8-OH-DPAT+pindolol (dose by linetype, P=0.0221), but was not affected by WAY-100,635 treatment. These results provide further evidence that serotonin signaling is an important determinant of performance during both forced and voluntary exercise. Although the elevated wheel running of HR mice does not appear related to alterations in serotonin signaling, their enhanced endurance capacity does. More generally, our results indicate that both forced and voluntary exercise can be affected by an intervention that acts (primarily) centrally. PMID:27106566

  14. Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system

    International Nuclear Information System (INIS)

    The 5-HT1A subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain and is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT1A receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic behaviour, motion sickness and eating disorders, they are an important target for drug therapy. Here, we review the radioligands which are available for visualisation and quantification of this important neuroreceptor in the human brain, using positron emission tomography (PET) or single-photon emission tomography (SPET). More than 20 compounds have been labelled with carbon-11 (half-life 20 min), fluorine-18 (half-life 109.8 min) or iodine-123 (half-life 13.2 h): structural analogues of the agonist, 8-OH-DPAT, structural analogues of the antagonist, WAY 100635, and apomorphines. The most successful radioligands thus far are [carbonyl-11C] WAY-100635 (WAY), [carbonyl-11C]desmethyl-WAY-100635 (DWAY), p-[18F]MPPF and [11C]robalzotan (NAD-299). The high-affinity ligands WAY and DWAY produce excellent images of 5-HT1A receptor distribution in the brain (even the raphe nuclei are visualised), but they cannot be distributed to remote facilities and they probably cannot be used to measure changes in endogenous serotonin. Binding of the moderate-affinity ligands MPPF and NAD-299 may be more sensitive to serotonin competition and MPPF can be distributed to PET centres within a flying distance of a few hours. Future research should be directed towards: (a) improvement of the metabolic stability in primates; (b) development of a fluorinated radioligand which can be produced in large quantities and (c) production of a radioiodinated or technetium-labelled ligand for SPET. (orig.)

  15. Role for Na/sup +/, H/sup +/, and Ca/sup 2 +/ during (/sup 3/H)-serotonin release from rat basophilic leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Stump, R.F.; Oliver, J.M.; Deanin, G.G.

    1986-03-05

    The authors have investigated the roles of Na/sup +/, pH, and Ca/sup 2 +/ in the release of (/sup 3/H)-serotonin from RBL-2H3 cells. The importance of extracellular Ca/sup 2 +/ for antigen-induced mediator release is well known. The authors report that mediator release also depends on extracellular Na/sup +/ and that the Na/sup +/ ionophore, monensin, like the Ca/sup 2 +/ ionophores A23187 and ionomycin, mimics antigen in causing release. Amiloride suppresses serotonin release, indicating that antigen activates the Na/sup +//H/sup +/ antiport. Antigen-stimulated Na/sup +//H/sup +/ exchange (and/or the resulting cytoplasmic alkalinization) may affect mediator release in part by controlling cytoplasmic free Ca/sup 2 +/ levels. The authors report that antigen normally causes a spike followed by a plateau of Ca/sup 2 +/-Quin 2 fluorescence. Only the spike occurs when cells are incubated with antigen in low Na/sup +/ medium. Conversely, monensin produces a Ca/sup 2 +/ plateau without a spike phase. In addition, cytoplasmic alkalinization due to increased Na/sup +//H/sup +/ exchange may directly cause secretion. Both NH/sub 4/Cl and monensin cause mediator release in Ca/sup 2 +/-free medium: these reagents increase pH by about 0.1 units as measured by the fluorescent dye, BCECF. TPA that stimulates Na/sup +//H/sup +/ exchange in other cells does not cause release directly but it potentiates both antigen and Ca/sup 2 +/ ionophore-induced release in RBL-2h3 cells. This further suggests synergistic roles for Na/sup +//H/sup +/ exchange and Ca/sup 2 +/ mobilization in the control of mediator release.

  16. Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

    Science.gov (United States)

    Atzori, Marco; Cuevas-Olguin, Roberto; Esquivel-Rendon, Eric; Garcia-Oscos, Francisco; Salgado-Delgado, Roberto C; Saderi, Nadia; Miranda-Morales, Marcela; Treviño, Mario; Pineda, Juan C; Salgado, Humberto

    2016-01-01

    number of experimental and clinical findings, a major challenge will be to adapt this hypothesis to integrate the role of other neurotransmitters released during stress in a centralized fashion, like serotonin, acetylcholine, and histamine, as well as those released in a non-centralized fashion, like purines and cytokines. PMID:27616990

  17. Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

    Science.gov (United States)

    Atzori, Marco; Cuevas-Olguin, Roberto; Esquivel-Rendon, Eric; Garcia-Oscos, Francisco; Salgado-Delgado, Roberto C.; Saderi, Nadia; Miranda-Morales, Marcela; Treviño, Mario; Pineda, Juan C.; Salgado, Humberto

    2016-01-01

    large number of experimental and clinical findings, a major challenge will be to adapt this hypothesis to integrate the role of other neurotransmitters released during stress in a centralized fashion, like serotonin, acetylcholine, and histamine, as well as those released in a non-centralized fashion, like purines and cytokines. PMID:27616990

  18. In vivo release of serotonin in cat dorsal vagal complex and cervical ventral horn induced by electrical stimulation of the medullary raphe nuclei.

    Science.gov (United States)

    Brodin, E; Linderoth, B; Goiny, M; Yamamoto, Y; Gazelius, B; Millhorn, D E; Hökfelt, T; Ungerstedt, U

    1990-12-10

    Extracellular levels of serotonin (5-hydroxytryptamine; 5-HT) were monitored by microdialysis in the dorsal vagal complex (DVC) and the ventral horn of the spinal cord at the level of the phrenic motor nucleus in decerebrated cats. A selective serotonin uptake inhibitor, alaproclate (10(-4) M) was included in the dialysis probe perfusion fluid to increase basal and stimulated levels of 5-HT. Electrical stimulation (30 Hz, 10 V, 0.5 ms) in the nucleus raphe obscurus, containing neurons projecting to the DVC and to the ventral horn, induced a 2-3-fold increase of the 5-HT release in both these regions. After termination of the stimulation, the release gradually decreased during the following 60 min. Substance P, which coexists with 5-HT in descending neurons, did not significantly affect the 5-HT release when it was added (100 microM) to the probe perfusion fluid. The present findings are in accordance with the hypothesis that prolonged release of 5-HT is responsible for the previously demonstrated long-lasting facilitation of phrenic activity following raphe obscurus stimulation. PMID:1705856

  19. Role of Central Serotonin in Anticipation of Rewarding and Punishing Outcomes: Effects of Selective Amygdala or Orbitofrontal 5-HT Depletion.

    Science.gov (United States)

    Rygula, Rafal; Clarke, Hannah F; Cardinal, Rudolf N; Cockcroft, Gemma J; Xia, Jing; Dalley, Jeff W; Robbins, Trevor W; Roberts, Angela C

    2015-09-01

    Understanding the role of serotonin (or 5-hydroxytryptamine, 5-HT) in aversive processing has been hampered by the contradictory findings, across studies, of increased sensitivity to punishment in terms of subsequent response choice but decreased sensitivity to punishment-induced response suppression following gross depletion of central 5-HT. To address this apparent discrepancy, the present study determined whether both effects could be found in the same animals by performing localized 5-HT depletions in the amygdala or orbitofrontal cortex (OFC) of a New World monkey, the common marmoset. 5-HT depletion in the amygdala impaired response choice on a probabilistic visual discrimination task by increasing the effectiveness of misleading, or false, punishment and reward, and decreased response suppression in a variable interval test of punishment sensitivity that employed the same reward and punisher. 5-HT depletion in the OFC also disrupted probabilistic discrimination learning and decreased response suppression. Computational modeling of behavior on the discrimination task showed that the lesions reduced reinforcement sensitivity. A novel, unitary account of the findings in terms of the causal role of 5-HT in the anticipation of both negative and positive motivational outcomes is proposed and discussed in relation to current theories of 5-HT function and our understanding of mood and anxiety disorders. PMID:24879752

  20. Hypothalamic neuropeptide Y (NPY) gene expression is not affected by central serotonin in the rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Mancebo, María J; Ceballos, Francisco C; Pérez-Maceira, Jorge; Aldegunde, Manuel

    2013-09-01

    Mammalian studies have shown a link between serotonin (5-HT) and neuropeptide Y (NPY) in the acute regulation of feeding and energy homeostasis. Taking into account that the actions of 5-HT and NPY on food intake in fish are similar to those observed in mammals, the objective of this study was to characterize a possible short-term interaction between hypothalamic 5-HT and NPY, by examining whether 5-HT regulates NPY gene expression, to help clarify the mechanism underlying the observed anorexigenic action of central 5-HT in the rainbow trout. We used qRT-PCR to determine the levels of NPY mRNA in the hypothalamus-preoptic area (HPA) of rainbow trout after intraperitoneal (i.p.) injection of a single dose of dexfenfluramine (dFF, 3mgkg(-1); 24h-fasted and fed fish) or intracerebroventricular (i.c.v.) administration of 5-HT (100μgkg(-1); 24h-fasted fish). Significant suppression of food intake was observed after administration of 5-HT and dFF. No significant changes in NPY gene expression were obtained 150min after administration of 5-HT or dFF. However, administration of the 5HT1B receptor agonist anpirtoline did not have any significant effect on food intake in rainbow trout. The results suggest that in fish, unlike in mammals, neither the NPY neurons of the HPA nor the 5-HT1B receptor subtype participate in the neural circuitry involved in the inhibition of food intake induced by central serotoninergic activation.

  1. Central serotonin(2B) receptor blockade inhibits cocaine-induced hyperlocomotion independently of changes of subcortical dopamine outflow.

    Science.gov (United States)

    Devroye, Céline; Cathala, Adeline; Di Marco, Barbara; Caraci, Filippo; Drago, Filippo; Piazza, Pier Vincenzo; Spampinato, Umberto

    2015-10-01

    The central serotonin2B receptor (5-HT2BR) is currently considered as an interesting pharmacological target for improved treatment of drug addiction. In the present study, we assessed the effect of two selective 5-HT2BR antagonists, RS 127445 and LY 266097, on cocaine-induced hyperlocomotion and dopamine (DA) outflow in the nucleus accumbens (NAc) and the dorsal striatum of freely moving rats. The peripheral administration of RS 127445 (0.16 mg/kg, i.p.) or LY 266097 (0.63 mg/kg, i.p.) significantly reduced basal DA outflow in the NAc shell, but had no effect on cocaine (10 mg/kg, i.p.)-induced DA outflow in this brain region. Also, RS 127445 failed to modify both basal and cocaine-induced DA outflow in the NAc core and the dorsal striatum. Conversely, both 5-HT2BR antagonists reduced cocaine-induced hyperlocomotion. Furthermore, RS 127445 as well as the DA-R antagonist haloperidol (0.1 mg/kg, i.p.) reduced significantly the late-onset hyperlocomotion induced by the DA-R agonist quinpirole (0.5 mg/kg, s.c.). Altogether, these results demonstrate that 5-HT2BR blockade inhibits cocaine-induced hyperlocomotion independently of changes of subcortical DA outflow. This interaction takes place downstream to DA neurons and could involve an action at the level of dorsostriatal and/or NAc DA transmission, in keeping with the importance of these brain regions in the behavioural responses of cocaine. Overall, this study affords additional knowledge into the regulatory control exerted by the 5-HT2BR on ascending DA pathways, and provides additional support to the proposed role of 5-HT2BRs as a new pharmacological target in drug addiction. PMID:26116760

  2. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

    DEFF Research Database (Denmark)

    Cotel, Florence; Exley, Richard; Cragg, Stephanie;

    2013-01-01

    Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle adequat......-HT during motor activity spills over from its release sites to the AIS of motoneurons. Here, activated 5-HT1A receptors inhibit firing and, thereby, muscle contraction. Hence, this is a cellular mechanism for central fatigue......Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle......--as during motor exercise--activated 5-HT1A receptors that decreased motoneuronal excitability. Electrophysiological tests combined with pharmacology showed that focal activation of 5-HT1A receptors at the axon initial segment (AIS), but not on other motoneuronal compartments, inhibited the action potential...

  3. Serotonin and noradrenaline reuptake inhibitors improve micturition control in mice.

    Directory of Open Access Journals (Sweden)

    Marco Redaelli

    Full Text Available Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothesis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overactive bladder. Mice were injected with cyclophosphamide (40 mg/kg, to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipramine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and noradrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory effect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition.

  4. Effect of U and {sup 137}Cs chronic contamination on dopamine and serotonin metabolism in the central nervous system of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Houpert, P.; Lestaevel, P. [Inst. de Radioprotection et de Surete Nucleaire (IRSN), Inst. de Radioprotection et de Surete Nucleaire, Dept. de la RadioProtection de l' Homme, Service de RadioBiologie et d' Epidemiologie, Lab. RadioToxicologie experimentale, Pierrelatte (France)]. E-mail: philippe.lestaevel@irsn.fr; Amourette, C. [Centre de Recherches du Service de Sante des Armees Emile Parde, Dept. de Radiobiologie et Radiopathologie, La Tronche (France); Dhieux, B.; Bussy, C.; Paquet, F. [Inst. de Radioprotection et de Surete Nucleaire (IRSN), Inst. de Radioprotection et de Surete Nucleaire, Dept. de la RadioProtection de l' Homme, Service de RadioBiologie et d' Epidemiologie, Lab. RadioToxicologie experimentale, Pierrelatte (France)

    2004-02-01

    Following the Chernobyl accident, the most significant problem for the population of the former Soviet Union for the next 50-70 years will be chronic internal contamination by radionuclides. One of the few experiments carried out in this field reported that neurotransmitter metabolism in the central nervous system of the rat was disturbed after feeding with oats contaminated by {sup 137}Cs for 1 month. The present study assessed the effect of chronic contamination by depleted U or {sup 137}Cs on the metabolism of two neurotransmitters in cerebral areas of rats. Dopamine and serotonin were chosen because their metabolism has been shown to be disturbed after external irradiation, even at moderate doses. Dopamine, serotonin, and some of their catabolites were measured by high-pressure liquid chromatography coupled with an electrochemical detector in five cerebral structures of rats contaminated over a 1-month period by drinking water (40 mg U{center_dot}L{sup -1} or 6500 Bq {sup 137}Cs{center_dot}L{sup -1}). In the striatum, hippocampus, cerebral cortex, thalamus, and cerebellum, the dopamine, serotonin, and catabolite levels were not significantly different between the control rats and rats contaminated by U or {sup 137}Cs. These results are not in accordance with those previously described. (author)

  5. SEROTONIN METABOLISM FOLLOWING PLATINUM-BASED CHEMOTHERAPY COMBINED WITH THE SEROTONIN TYPE-3 ANTAGONIST TROPISETRON

    NARCIS (Netherlands)

    SCHRODER, CP; VANDERGRAAF, WTA; KEMA, IP; GROENEWEGEN, A; SLEIJFER, DT; DEVRIES, EGE

    1995-01-01

    The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3 antag

  6. ROLE OF SEROTONIN IN FISH REPRODUCTION

    Directory of Open Access Journals (Sweden)

    Parvathy ePrasad

    2015-06-01

    Full Text Available The neuroendocrine mechanism regulates reproduction through the hypothalamo-pituitary-gonadal (HPG axis which is evolutionarily conserved in vertebrates. The HPG axis is regulated by a variety of internal as well as external factors. Serotonin, a monoamine neurotransmitter, is involved in a wide range of reproductive functions. In mammals, serotonin regulates sexual behaviours, gonadotropin release and gonadotropin-release hormone (GnRH secretion. However, the serotonin system in teleost may play unique role in the control of reproduction as the mechanism of reproductive control in teleosts is not always the same as in the mammalian models. In fish, the serotonin system is also regulated by natural environmental factors as well as chemical substances. In particular, selective serotonin reuptake inhibitors (SSRIs are commonly detected as pharmaceutical contaminants in the natural environment. Those factors may influence fish reproductive functions via the serotonin system. This review summarizes the functional significance of serotonin in the teleosts reproduction.

  7. Serotonin interferes with Ca2+ and PKC signaling to reduce gonadotropin-releasing hormone-stimulated GH secretion in goldfish pituitary cells.

    Science.gov (United States)

    Yu, Yi; Wong, Anderson O L; Chang, John P

    2008-10-01

    In goldfish, two endogenous gonadotropin-releasing hormones (GnRH), salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), are thought to stimulate growth hormone (GH) release via protein kinase C (PKC) and subsequent increases in intracellular Ca(2+) levels ([Ca(2+)](i)). In contrast, the signaling mechanism for serotonin (5-HT) inhibition of GH secretion is still unknown. In this study, whether 5-HT inhibits GH release by actions at sites along the PKC and Ca(2+) signal transduction pathways leading to hormone release were examined in primary cultures of goldfish pituitary cells. Under static incubation and column perifusion conditions, 5-HT reduced basal, as well as sGnRH- and cGnRH-II-stimulated, GH secretion. 5-HT also suppressed GH responses to two PKC activators but had no effect on the GH-releasing action of the Ca(2+) ionophore ionomycin. Ca(2+)-imaging studies with identified somatotropes revealed that 5-HT did not alter basal [Ca(2+)](i) but attenuated the magnitude of the [Ca(2+)](i) responses to the two GnRHs. Prior treatment with 5-HT and cGnRH-II reduced the magnitude of the [Ca(2+)](i) responses induced by depolarizing levels of K(+). Similar inhibition, however, was not observed with prior treatment of 5-HT and sGnRH. These results suggest that 5-HT, by direct actions at the somatotrope level, interferes with PKC and Ca(2+) signaling pathways to reduce the GH-releasing effect of GnRH. 5-HT action may occur at the level of PKC activation or its downstream signaling events prior to the subsequent rise in [Ca(2+)](i.). The differential Ca(2+) responses by depolarizing doses of K(+) is consistent with our previous findings that sGnRH and cGnRH-II are coupled to overlapping and yet distinct Ca(2+)-dependent mechanisms. PMID:18723020

  8. Radioautographic identification of central monoaminergic neurons after local micro-instillation of tritiated serotonin and norepinephrine in the cat

    International Nuclear Information System (INIS)

    Monoaminergic neurons in nuclei raphe dorsalis and locus coeruleus of the cat may be visualized by radioautography after local micro-instillation of tritiated serotonin and noradrenaline. The concomitant administration of the appropriate tracer with the other biogenic amine in non radioactive form permits a specific identification of serotoninergic and catecholaminergic nerve cell bodies. A small contingent of presumptive serotoninergic neurons is thus demonstrated in the region of the locus coeruleus

  9. Importance of the Extracellular Loop 4 in the Human Serotonin Transporter for Inhibitor Binding and Substrate Translocation

    DEFF Research Database (Denmark)

    Rannversson, Hafsteinn; Wilson, Pamela; Kristensen, Kristina Birch;

    2015-01-01

    The serotonin transporter (SERT) terminates serotonergic neurotransmission by performing reuptake of released serotonin, and SERT is the primary target for antidepressants. SERT mediates the reuptake of serotonin through an alternating access mechanism, implying that a central substrate site......) in the extracellular loop 4 (EL4) of human SERT, which induced a remarkable gain-of-potency (up to >40-fold) for a range of SERT inhibitors. The effects were highly specific for L406E relative to six other mutations in the same position, including the closely related L406D mutation, showing that the effects induced...

  10. Visualisation of serotonin-1A (5-HT{sub 1A}) receptors in the central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Passchier, J.; Waarde, A. van [PET Center, University Hospital Groningen (Netherlands)

    2001-01-01

    The 5-HT{sub 1A} subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain and is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT{sub 1A} receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic behaviour, motion sickness and eating disorders, they are an important target for drug therapy. Here, we review the radioligands which are available for visualisation and quantification of this important neuroreceptor in the human brain, using positron emission tomography (PET) or single-photon emission tomography (SPET). More than 20 compounds have been labelled with carbon-11 (half-life 20 min), fluorine-18 (half-life 109.8 min) or iodine-123 (half-life 13.2 h): structural analogues of the agonist, 8-OH-DPAT, structural analogues of the antagonist, WAY 100635, and apomorphines. The most successful radioligands thus far are [carbonyl-{sup 11}C] WAY-100635 (WAY), [carbonyl-{sup 11}C]desmethyl-WAY-100635 (DWAY), p-[{sup 18}F]MPPF and [{sup 11}C]robalzotan (NAD-299). The high-affinity ligands WAY and DWAY produce excellent images of 5-HT{sub 1A} receptor distribution in the brain (even the raphe nuclei are visualised), but they cannot be distributed to remote facilities and they probably cannot be used to measure changes in endogenous serotonin. Binding of the moderate-affinity ligands MPPF and NAD-299 may be more sensitive to serotonin competition and MPPF can be distributed to PET centres within a flying distance of a few hours. Future research should be directed towards: (a) improvement of the metabolic stability in primates; (b) development of a fluorinated radioligand which can be produced in large quantities and (c) production of a radioiodinated or technetium-labelled ligand for SPET. (orig.)

  11. An integrated serotonin and octopamine neuronal circuit directs the release of an endocrine signal to control C. elegans body fat.

    Science.gov (United States)

    Noble, Tallie; Stieglitz, Jonathan; Srinivasan, Supriya

    2013-11-01

    Serotonin (5-hydroxytryptamine, 5-HT) is an ancient and conserved neuromodulator of energy balance. Despite its importance, the neural circuits and molecular mechanisms underlying 5-HT-mediated control of body fat remain poorly understood. Here, we decipher the serotonergic neural circuit for body fat loss in C. elegans and show that the effects of 5-HT require signaling from octopamine, the invertebrate analog of adrenaline, to sustain body fat loss. Our results provide a potential molecular explanation for the long-observed potent effects of combined serotonergic and adrenergic weight loss drugs. In metabolic tissues, we find that the conserved regulatory adipocyte triglyceride lipase ATGL-1 drives serotonergic fat loss. We show that the serotonergic chloride channel MOD-1 relays a long-range endocrine signal from C. elegans body cavity neurons to control distal ATGL-1 function, via the nuclear receptor NHR-76. Our findings establish a conserved neuroendocrine axis operated by neural serotonergic and adrenergic-like signaling to regulate body fat.

  12. An Integrated Serotonin and Octopamine Neuronal Circuit Directs The Release of An Endocrine Signal to Control C. elegans Body Fat

    Science.gov (United States)

    Noble, Tallie; Stieglitz, Jonathan; Srinivasan, Supriya

    2013-01-01

    SUMMARY Serotonin (5-hydroxytryptamine, 5-HT) is an ancient and conserved neuromodulator of energy balance. Despite its importance, the neural circuits and molecular mechanisms underlying 5-HT-mediated control of body fat remain poorly understood. Here we decipher the serotonergic neural circuit for body fat loss in C. elegans and show that the effects of 5-HT require signaling from octopamine, the invertebrate analog of adrenaline, to sustain body fat loss. Our results provide a potential molecular explanation for the long-observed potent effects of combined serotonergic and adrenergic weight loss drugs. In metabolic tissues we find that the conserved regulatory adipocyte triglyceride lipase ATGL-1 drives serotonergic fat loss. We show that the serotonergic chloride channel MOD-1 relays a long-range endocrine signal via C. elegans body cavity neurons to control distal ATGL-1 function, via the nuclear receptor NHR-76. Our findings establish a conserved neuroendocrine axis operated by neural serotonergic and adrenergic-like signaling, to regulate body fat. PMID:24120942

  13. Serotonin receptor B may lock the gate of PTTH release/synthesis in the Chinese silk moth, Antheraea pernyi; a diapause initiation/maintenance mechanism?

    Directory of Open Access Journals (Sweden)

    Qiushi Wang

    Full Text Available The release of prothoracicotropic hormone, PTTH, or its blockade is the major endocrine switch regulating the developmental channel either to metamorphosis or to pupal diapause in the Chinese silk moth, Antheraea pernyi. We have cloned cDNAs encoding two types of serotonin receptors (5HTRA and B. 5HTRA-, and 5HTRB-like immunohistochemical reactivities (-ir were colocalized with PTTH-ir in two pairs of neurosecretory cells at the dorsolateral region of the protocerebrum (DL. Therefore, the causal involvement of these receptors was suspected in PTTH release/synthesis. The level of mRNA(5HTRB responded to 10 cycles of long-day activation, falling to 40% of the original level before activation, while that of 5HTRA was not affected by long-day activation. Under LD 16:8 and 12:12, the injection of dsRNA(5HTRB resulted in early diapause termination, whereas that of dsRNA(5HTRA did not affect the rate of diapause termination. The injection of dsRNA(5HTRB induced PTTH accumulation, indicating that 5HTRB binding suppresses PTTH synthesis also. This conclusion was supported pharmacologically; the injection of luzindole, a melatonin receptor antagonist, plus 5th inhibited photoperiodic activation under LD 16:8, while that of 5,7-DHT, induced emergence in a dose dependent fashion under LD 12:12. The results suggest that 5HTRB may lock the PTTH release/synthesis, maintaining diapause. This could also work as diapause induction mechanism.

  14. Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome

    Directory of Open Access Journals (Sweden)

    Bianca eDe Filippis

    2015-04-01

    Full Text Available Rett syndrome (RTT is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2 cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that specific behavioral and brain molecular alterations can be rescued in MeCP2-308 male mice, a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R. This member of the serotonin receptor family – crucially involved in the regulation of brain structural plasticity and cognitive processes – can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective 5-HT7R agonist. The present study extends previous findings by demonstrating that the LP-211 treatment (0.25 mg/kg, once per day for 7 days rescues RTT-related phenotypic alterations, motor coordination (Dowel test, spatial reference memory (Barnes maze test and synaptic plasticity (hippocampal long-term-potentiation in MeCP2-308 heterozygous female mice, the genetic and hormonal milieu that resembles that of RTT patients. LP-211 also restores the activation of the ribosomal protein S6, the downstream target of mTOR and S6 kinase, in the hippocampus of RTT female mice. Notably, the beneficial effects on neurobehavioral and molecular parameters of a seven-day long treatment with LP-211 were evident up to two months after the last injection, thus suggesting long-lasting effects on RTT-related impairments. Taken together with our previous study, these results provide compelling preclinical evidence of the potential therapeutic value for RTT of a pharmacological approach targeting the brain 5-HT7R.

  15. Long-lasting beneficial effects of central serotonin receptor 7 stimulation in female mice modeling Rett syndrome.

    Science.gov (United States)

    De Filippis, Bianca; Chiodi, Valentina; Adriani, Walter; Lacivita, Enza; Mallozzi, Cinzia; Leopoldo, Marcello; Domenici, Maria Rosaria; Fuso, Andrea; Laviola, Giovanni

    2015-01-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that specific behavioral and brain molecular alterations can be rescued in MeCP2-308 male mice, a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family-crucially involved in the regulation of brain structural plasticity and cognitive processes-can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective 5-HT7R agonist. The present study extends previous findings by demonstrating that the LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues RTT-related phenotypic alterations, motor coordination (Dowel test), spatial reference memory (Barnes maze test) and synaptic plasticity (hippocampal long-term-potentiation) in MeCP2-308 heterozygous female mice, the genetic and hormonal milieu that resembles that of RTT patients. LP-211 also restores the activation of the ribosomal protein (rp) S6, the downstream target of mTOR and S6 kinase, in the hippocampus of RTT female mice. Notably, the beneficial effects on neurobehavioral and molecular parameters of a seven-day long treatment with LP-211 were evident up to 2 months after the last injection, thus suggesting long-lasting effects on RTT-related impairments. Taken together with our previous study, these results provide compelling preclinical evidence of the potential therapeutic value for RTT of a pharmacological approach targeting the brain 5-HT7R.

  16. Unbiased simulations reveal the inward-facing conformation of the human serotonin transporter and Na+ ion release

    DEFF Research Database (Denmark)

    Koldsø, Heidi; Noer, Pernille Rimmer; Grouleff, Julie;

    2011-01-01

    Monoamine transporters are responsible for termination of synaptic signaling and are involved in depression, control of appetite, and anxiety amongst other neurological processes. Despite extensive efforts, the structures of the monoamine transporters and the transport mechanism of ions and subst......Monoamine transporters are responsible for termination of synaptic signaling and are involved in depression, control of appetite, and anxiety amongst other neurological processes. Despite extensive efforts, the structures of the monoamine transporters and the transport mechanism of ions....... The simulations reveal a transition of hSERT from an outward-facing occluded conformation to an inward-facing conformation in a one-substrate-bound state. Simulations with a second substrate in the proposed symport effector site did not lead to conformational changes associated with translocation. The central...

  17. Herbicide Hardwood Crop Trees Release in Central West Virginia

    OpenAIRE

    Kochenderfer, Jeffrey Davis

    1999-01-01

    Repeated partial cutting in the Appalachian hardwood region has often favored the development of tolerant species like American beech (Fagus grandifolia Ehrh.) and stands with a high proportion of cull trees. Crop tree release is a widely recommended practice to improve species composition and growth rates in these unevenaged structured stands. Chemical control offers some distinct advantages from the standpoint of safety and residual stand damage, over mechani...

  18. The effects of serotonin, dopamine, gonadotropin-releasing hormones, and corazonin, on the androgenic gland of the giant freshwater prawn, Macrobrachium rosenbergii.

    Science.gov (United States)

    Siangcham, Tanapan; Tinikul, Yotsawan; Poljaroen, Jaruwan; Sroyraya, Morakot; Changklungmoa, Narin; Phoungpetchara, Ittipon; Kankuan, Wilairat; Sumpownon, Chanudporn; Wanichanon, Chaitip; Hanna, Peter J; Sobhon, Prasert

    2013-11-01

    Neurotransmitters and neurohormones are agents that control gonad maturation in decapod crustaceans. Of these, serotonin (5-HT) and dopamine (DA) are neurotransmitters with known antagonist roles in female reproduction, whilst gonadotropin-releasing hormones (GnRHs) and corazonin (Crz) are neurohormones that exercise both positive and negative controls in some invertebrates. However, the effects of these agents on the androgenic gland (AG), which controls testicular maturation and male sex development in decapods, via insulin-like androgenic gland hormone (IAG), are unknown. Therefore, we set out to assay the effects of 5-HT, DA, l-GnRH-III, oct-GnRH and Crz, on the AG of small male Macrobrachium rosenbergii (Mr), using histological studies, a BrdU proliferative cell assay, immunofluorescence of Mr-IAG, and ELISA of Mr-IAG. The results showed stimulatory effects by 5-HT and l-GnRH-III through significant increases in AG size, proliferation of AG cells, and Mr-IAG production (P<0.05). In contrast, DA and Crz caused inhibitory effects on the AG through significant decreases in AG size, proliferation of AG cells, and Mr-IAG production (P<0.05). Moreover, the prawns treated with Crz died before day 16 of the experimental period. We propose that 5-HT and certain GnRHs can be now used to stimulate reproduction in male M. rosenbergii, as they induce increases in AG and testicular size, IAG production, and spermatogenesis. The mechanisms by which these occur are part of our on-going research.

  19. Effects of acute treadmill running at different intensities on activities of serotonin and corticotropin-releasing factor neurons, and anxiety- and depressive-like behaviors in rats.

    Science.gov (United States)

    Otsuka, Tomomi; Nishii, Ayu; Amemiya, Seiichiro; Kubota, Natsuko; Nishijima, Takeshi; Kita, Ichiro

    2016-02-01

    Accumulating evidence suggests that physical exercise can reduce and prevent the incidence of stress-related psychiatric disorders, including depression and anxiety. Activation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is implicated in antidepressant/anxiolytic properties. In addition, the incidence and symptoms of these disorders may involve dysregulation of the hypothalamic-pituitary-adrenal axis that is initiated by corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN). Thus, it is possible that physical exercise produces its antidepressant/anxiolytic effects by affecting these neuronal activities. However, the effects of acute physical exercise at different intensities on these neuronal activation and behavioral changes are still unclear. Here, we examined the activities of 5-HT neurons in the DRN and CRF neurons in the PVN during 30 min of treadmill running at different speeds (high speed, 25 m/min; low speed, 15m/min; control, only sitting on the treadmill) in male Wistar rats, using c-Fos/5-HT or CRF immunohistochemistry. We also performed the elevated plus maze test and the forced swim test to assess anxiety- and depressive-like behaviors, respectively. Acute treadmill running at low speed, but not high speed, significantly increased c-Fos expression in 5-HT neurons in the DRN compared to the control, whereas high-speed running significantly enhanced c-Fos expression in CRF neurons in the PVN compared with the control and low-speed running. Furthermore, low-speed running resulted in decreased anxiety- and depressive-like behaviors compared with high-speed running. These results suggest that acute physical exercise with mild and low stress can efficiently induce optimal neuronal activation that is involved in the antidepressant/anxiolytic effects. PMID:26542811

  20. Ethanol and corticotropin releasing factor receptor modulation of central amygdala neurocircuitry: An update and future directions.

    Science.gov (United States)

    Silberman, Yuval; Winder, Danny G

    2015-05-01

    The central amygdala is a critical brain region for many aspects of alcohol dependence. Much of the work examining the mechanisms by which the central amygdala mediates the development of alcohol dependence has focused on the interaction of acute and chronic ethanol with central amygdala corticotropin releasing factor signaling. This work has led to a great deal of success in furthering the general understanding of central amygdala neurocircuitry and its role in alcohol dependence. Much of this work has primarily focused on the hypothesis that ethanol utilizes endogenous corticotropin releasing factor signaling to upregulate inhibitory GABAergic transmission in the central amygdala. Work that is more recent suggests that corticotropin releasing factor also plays an important role in mediating anxiety-like behaviors via the enhancement of central amygdala glutamatergic transmission, implying that ethanol/corticotropin releasing factor interactions may modulate excitatory neurotransmission in this brain region. In addition, a number of studies utilizing optogenetic strategies or transgenic mouse lines have begun to examine specific central amygdala neurocircuit dynamics and neuronal subpopulations to better understand overall central amygdala neurocircuitry and the role of neuronal subtypes in mediating anxiety-like behaviors. This review will provide a brief update on this literature and describe some potential future directions that may be important for the development of better treatments for alcohol addiction.

  1. Omega-3 fatty acid deficiency does not alter the effects of chronic fluoxetine treatment on central serotonin turnover or behavior in the forced swim test in female rats.

    Science.gov (United States)

    McNamara, Robert K; Able, Jessica A; Liu, Yanhong; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Lipton, Jack W

    2013-12-01

    While translational evidence suggests that long-chain omega-3 fatty acid status is positively associated with the efficacy of selective serotonin reuptake inhibitor drugs, the neurochemical mechanisms mediating this interaction are not known. Here, we investigated the effects of dietary omega-3 (n-3) fatty acid insufficiency on the neurochemical and behavioral effects of chronic fluoxetine (FLX) treatment. Female rats were fed diets with (CON, n=56) or without (DEF, n=40) the n-3 fatty acids during peri-adolescent development (P21-P90), and one half of each group was administered FLX (10mg/kg/day) for 30days (P60-P90) prior to testing. In adulthood (P90), regional brain serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) concentrations, presynaptic markers of 5-HT neurotransmission, behavioral responses in the forced swim test (FST), and plasma FLX and norfluoxetine (NFLX) concentrations were investigated. Peri-adolescent n-3 insufficiency led to significant reductions in cortical docosahexaenoic acid (DHA, 22:6n-3) composition in DEF (-25%, p≤0.0001) and DEF+FLX (-28%, p≤0.0001) rats. Untreated DEF rats exhibited significantly lower regional 5-HIAA/5-HT ratios compared with untreated CON rats, but exhibited similar behavioral responses in the FST. In both CON and DEF rats, chronic FLX treatment similarly and significantly decreased 5-HIAA concentrations and the 5-HIAA/5-HT ratio in the hypothalamus, hippocampus, and nucleus accumbens, brainstem tryptophan hydroxylase-2 mRNA expression, and immobility in the FST. While the FLX-induced reduction in 5-HIAA concentrations in the prefrontal cortex was significantly blunted in DEF rats, the reduction in the 5-HIAA/5-HT ratio was similar to CON rats. Although plasma FLX and NFLX levels were not significantly different in DEF and CON rats, the NFLX/FLX ratio was significantly lower in DEF+FLX rats. These preclinical data demonstrate that n-3 fatty acid deficiency does not significantly reduce the effects of chronic

  2. Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [{sup 11}C] DASB positron emission tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Hesse, Swen; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); Rullmann, Michael [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Leipzig (Germany); Luthardt, Julia; Becker, Georg-Alexander; Bresch, Anke; Patt, Marianne; Meyer, Philipp M. [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Winter, Karsten [University of Leipzig, Centre for Translational Regenerative Medicine, Leipzig (Germany); University of Leipzig, Institute for Medical Informatics, Statistics, and Epidemiology, Leipzig (Germany); Hankir, Mohammed K.; Zientek, Franziska; Reissig, Georg; Drabe, Mandy [Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); Regenthal, Ralf [University of Leipzig, Division of Clinical Pharmacology, Rudolf Boehm Institute of Pharmacology and Toxicology, Leipzig (Germany); Schinke, Christian [University of Leipzig, Department of Neurology, Leipzig (Germany); Arelin, Katrin [Max Planck Institute for Human Cognitive and Brain Sciences Leipzig, Leipzig (Germany); University of Leipzig, Day Clinic for Cognitive Neurology, Leipzig (Germany); Lobsien, Donald [University of Leipzig, Department of Neuroradiology, Leipzig (Germany); Fasshauer, Mathias; Fenske, Wiebke K.; Stumvoll, Michael [Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig (Germany); University of Leipzig, Medical Department III, Leipzig (Germany); Blueher, Matthias [University of Leipzig, Medical Department III, Leipzig (Germany); University of Leipzig, Collaborative Research Centre 1052 Obesity Mechanisms, Leipzig (Germany)

    2016-06-15

    The role of the central serotonin (5-hydroxytryptamine, 5-HT) system in feeding has been extensively studied in animals with the 5-HT family of transporters (5-HTT) being identified as key molecules in the regulation of satiety and body weight. Aberrant 5-HT transmission has been implicated in the pathogenesis of human obesity by in vivo positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging techniques. However, results obtained thus far from studies of central 5-HTT availability have been inconsistent, which is thought to be brought about mainly by the low number of individuals with a high body mass index (BMI) previously used. The aim of this study was therefore to assess 5-HTT availability in the brains of highly obese otherwise healthy individuals compared with non-obese healthy controls. We performed PET using the 5-HTT selective radiotracer [{sup 11}C] DASB on 30 highly obese (BMI range between 35 and 55 kg/m{sup 2}) and 15 age- and sex-matched non-obese volunteers (BMI range between 19 and 27 kg/m{sup 2}) in a cross-sectional study design. The 5-HTT binding potential (BP{sub ND}) was used as the outcome parameter. On a group level, there was no significant difference in 5-HTT BP{sub ND} in various cortical and subcortical regions in individuals with the highest BMI compared with non-obese controls, while statistical models showed minor effects of age, sex, and the degree of depression on 5-HTT BP{sub ND}. The overall finding of a lack of significantly altered 5-HTT availability together with its high variance in obese individuals justifies the investigation of individual behavioral responses to external and internal cues which may further define distinct phenotypes and subgroups in human obesity. (orig.)

  3. Central serotonin transporter availability in highly obese individuals compared with non-obese controls: A [11C] DASB positron emission tomography study

    International Nuclear Information System (INIS)

    The role of the central serotonin (5-hydroxytryptamine, 5-HT) system in feeding has been extensively studied in animals with the 5-HT family of transporters (5-HTT) being identified as key molecules in the regulation of satiety and body weight. Aberrant 5-HT transmission has been implicated in the pathogenesis of human obesity by in vivo positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging techniques. However, results obtained thus far from studies of central 5-HTT availability have been inconsistent, which is thought to be brought about mainly by the low number of individuals with a high body mass index (BMI) previously used. The aim of this study was therefore to assess 5-HTT availability in the brains of highly obese otherwise healthy individuals compared with non-obese healthy controls. We performed PET using the 5-HTT selective radiotracer [11C] DASB on 30 highly obese (BMI range between 35 and 55 kg/m2) and 15 age- and sex-matched non-obese volunteers (BMI range between 19 and 27 kg/m2) in a cross-sectional study design. The 5-HTT binding potential (BPND) was used as the outcome parameter. On a group level, there was no significant difference in 5-HTT BPND in various cortical and subcortical regions in individuals with the highest BMI compared with non-obese controls, while statistical models showed minor effects of age, sex, and the degree of depression on 5-HTT BPND. The overall finding of a lack of significantly altered 5-HTT availability together with its high variance in obese individuals justifies the investigation of individual behavioral responses to external and internal cues which may further define distinct phenotypes and subgroups in human obesity. (orig.)

  4. Serotonin 2c receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

    Science.gov (United States)

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor a...

  5. Distribution of serotonin and FMRF-amide in the brain of Lymnaea stagnalis with respect to the visual system

    Institute of Scientific and Technical Information of China (English)

    Oksana P.TUCHINA; Valery V.ZHUKOV; Victor B.MEYER-ROCHOW

    2012-01-01

    Despite serotonin's and FMRF-amide's wide distribution in the nervous system of invertebrates and their importance as neurotransmitters,the exact roles they play in neuronal networks leaves many questions.We mapped the presence of serotonin and FMRF-amide-immunoreactivity in the central nervous system and eyes of the pond snail Lymnaea stagnalis and interpreted the results in connection with our earlier findings on the central projections of different peripheral nerves.Since the chemical nature of the intercellular connections in the retina of L.stagnalis is still largely unknown,we paid special attention to clarifying the role of serotonin and FMRF-amide in the visual system of this snail and compared our findings with those reported from other species.At least one serotonin- and one FMRF-amidergic fibre were labeled in each optic nerve,and since no cell bodies in the eye showed immunoreactivity to these neurotransmitters,we believe that efferent fibres with somata located in the central ganglia branch at the base of the eye and probably release 5HT and FMRF-amide as neuro-hormones.Double labelling revealed retrograde transport of neurobiotin through the optic nerve,allowing us to conclude that the central pathways and serotonin- and FMRF-amide-immunoreactive cells and fibres have different locations in the CNS in L.stagnalis.The chemical nature of the fibres,which connect the two eyes in L.stagnalis,is neither serotoninergic nor FMRF-amidergic.

  6. In vivo imaging of cerebral serotonin transporter and serotonin(2A) receptor binding in 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and hallucinogen users

    DEFF Research Database (Denmark)

    Erritzoe, David; Frøkjær, Vibe; Holst, Klaus K;

    2011-01-01

    Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.......Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin....

  7. Central Serotonin-2A (5-HT2A Receptor Dysfunction in Depression and Epilepsy: The Missing Link?

    Directory of Open Access Journals (Sweden)

    Bruno Pierre Guiard

    2015-03-01

    Full Text Available 5-Hydroxytryptamine 2A receptors (5-HT2A-Rs are G-protein coupled receptors. In agreement with their location in the brain, they have been implicated not only in various central physiological functions including memory, sleep, nociception, eating and reward behaviors, but also in many neuropsychiatric disorders. Interestingly, a bidirectional link between depression and epilepsy is suspected since patients with depression and especially suicide attempters have an increased seizure risk, while a significant percentage of epileptic patients suffer from depression. Such epidemiological data led us to hypothesize that both pathologies may share common anatomical and neurobiological alteration of the 5-HT2A signaling. After a brief presentation of the pharmacological properties of the 5-HT2A-Rs, this review illustrates how these receptors may directly or indirectly control neuronal excitability in most networks involved in depression and epilepsy through interactions with the monoaminergic, GABAergic and glutamatergic neurotransmissions. It also synthetizes the preclinical and clinical evidence demonstrating the role of these receptors in antidepressant and antiepileptic responses.

  8. Research on sports teaching in the brain of 5-serotonin and exercise-induced central fatigue%体育教学中脑内5-羟色胺与运动性中枢疲劳的研究

    Institute of Scientific and Technical Information of China (English)

    沈一岚

    2013-01-01

      脑内5-羟色胺是中枢疲劳产生的重要介质,本文结合体育教学的有关内容,对其进行细致分析,提出就脑内5-羟色胺的代谢及生理功能、5-羟色胺浓度升高与中枢疲劳产生的潜在机制、运动对脑内5-羟色胺及代谢物的影响,营养干预对改变5-羟色胺和中枢疲劳的作用等等,以期延缓中枢性疲劳的发生,为我们的教学工作提供相应的指导,帮助学生们训练更为强健的体魄,为今后人们对运动性中枢疲劳的研究提供点滴参考。%Brain 5 - serotonin is central fatigue generated significant media, this article on brain 5- serotonin metabolism and physiological function of 5-HT concentration and central fatigue potential mechanisms of exercise on brain 5 - HT and metabolites the impact of nutrition intervention on changes by 5- serotonin and other aspects of the role of central fatigue were reviewed in order to delay the occurrence of central fatigue for the future people of central fatigue during exercise to provide drip reference.

  9. Linoleic acid derivative DCP-LA ameliorates stress-induced depression-related behavior by promoting cell surface 5-HT1A receptor translocation, stimulating serotonin release, and inactivating GSK-3β.

    Science.gov (United States)

    Kanno, Takeshi; Tanaka, Akito; Nishizaki, Tomoyuki

    2015-04-01

    Impairment of serotonergic neurotransmission is the major factor responsible for depression and glycogen synthase kinase 3β (GSK-3β) participates in serotonergic transmission-mediated signaling networks relevant to mental illnesses. In the forced-swim test to assess depression-like behavior, the immobility time for mice with restraint stress was significantly longer than that for nonstressed control mice. Postsynaptic cell surface localization of 5-HT1A receptor, but not 5-HT2A receptor, in the hypothalamus for mice with restraint stress was significantly reduced as compared with that for control mice, which highly correlated to prolonged immobility time, i.e., depression-like behavior. The linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) restored restraint stress-induced reduction of cell surface 5-HT1A receptor and improved depression-like behavior in mice with restraint stress. Moreover, DCP-LA stimulated serotonin release from hypothalamic slices and cancelled restraint stress-induced reduction of GSK-3β phosphorylation at Ser9. Taken together, the results of the present study indicate that DCP-LA could ameliorate depression-like behavior by promoting translocation of 5-HT1A receptor to the plasma membrane on postsynaptic cells, stimulating serotonin release, and inactivating GSK-3β. PMID:24788685

  10. Linoleic acid derivative DCP-LA ameliorates stress-induced depression-related behavior by promoting cell surface 5-HT1A receptor translocation, stimulating serotonin release, and inactivating GSK-3β.

    Science.gov (United States)

    Kanno, Takeshi; Tanaka, Akito; Nishizaki, Tomoyuki

    2015-04-01

    Impairment of serotonergic neurotransmission is the major factor responsible for depression and glycogen synthase kinase 3β (GSK-3β) participates in serotonergic transmission-mediated signaling networks relevant to mental illnesses. In the forced-swim test to assess depression-like behavior, the immobility time for mice with restraint stress was significantly longer than that for nonstressed control mice. Postsynaptic cell surface localization of 5-HT1A receptor, but not 5-HT2A receptor, in the hypothalamus for mice with restraint stress was significantly reduced as compared with that for control mice, which highly correlated to prolonged immobility time, i.e., depression-like behavior. The linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) restored restraint stress-induced reduction of cell surface 5-HT1A receptor and improved depression-like behavior in mice with restraint stress. Moreover, DCP-LA stimulated serotonin release from hypothalamic slices and cancelled restraint stress-induced reduction of GSK-3β phosphorylation at Ser9. Taken together, the results of the present study indicate that DCP-LA could ameliorate depression-like behavior by promoting translocation of 5-HT1A receptor to the plasma membrane on postsynaptic cells, stimulating serotonin release, and inactivating GSK-3β.

  11. Electrochemical measurements of serotonin (5-HT) release from the guinea pig mucosa using continuous amperometry with a boron-doped diamond microelectrode

    OpenAIRE

    Zhao, Hong; Bian, Xiaochun; Galligan, James J.; Swain, Greg M.

    2010-01-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder characterized by chronic abdominal discomfort, including pain, bloating and changes in bowel habits. The exact cause of IBS is not entirely understood. Recent studies have shown that IBS may be associated with altered serotonin (5-hydroxytryptamine, 5-HT) levels within the GI tract. About 90% of 5-HT in the human body is produced and stored in enterochromaffin (EC) cells that reside in the mucosal layer of the intestine...

  12. Neuromolecular Imaging Shows Temporal Synchrony Patterns between Serotonin and Movement within Neuronal Motor Circuits in the Brain

    Directory of Open Access Journals (Sweden)

    Patricia A. Broderick

    2013-06-01

    Full Text Available The present discourse links the electrical and chemical properties of the brain with neurotransmitters and movement behaviors to further elucidate strategies to diagnose and treat brain disease. Neuromolecular imaging (NMI, based on electrochemical principles, is used to detect serotonin in nerve terminals (dorsal and ventral striata and somatodendrites (ventral tegmentum of reward/motor mesocorticolimbic and nigrostriatal brain circuits. Neuronal release of serotonin is detected at the same time and in the same animal, freely moving and unrestrained, while open-field behaviors are monitored via infrared photobeams. The purpose is to emphasize the unique ability of NMI and the BRODERICK PROBE® biosensors to empirically image a pattern of temporal synchrony, previously reported, for example, in Aplysia using central pattern generators (CPGs, serotonin and cerebral peptide-2. Temporal synchrony is reviewed within the context of the literature on central pattern generators, neurotransmitters and movement disorders. Specifically, temporal synchrony data are derived from studies on psychostimulant behavior with and without cocaine while at the same time and continuously, serotonin release in motor neurons within basal ganglia, is detected. The results show that temporal synchrony between the neurotransmitter, serotonin and natural movement occurs when the brain is NOT injured via, e.g., trauma, addictive drugs or psychiatric illness. In striking contrast, in the case of serotonin and cocaine-induced psychostimulant behavior, a different form of synchrony and also asynchrony can occur. Thus, the known dysfunctional movement behavior produced by cocaine may well be related to the loss of temporal synchrony, the loss of the ability to match serotonin in brain with motor activity. The empirical study of temporal synchrony patterns in humans and animals may be more relevant to the dynamics of motor circuits and movement behaviors than are studies of

  13. Complement selectively elicits glutamate release from nerve endings in different regions of mammal central nervous system.

    Science.gov (United States)

    Merega, Elisa; Di Prisco, Silvia; Lanfranco, Massimiliano; Severi, Paolo; Pittaluga, Anna

    2014-05-01

    Our study was aimed at investigating whether complement, a complex of soluble and membrane-associated serum proteins, could, in addition to its well-documented post-synaptic activity, also pre-synaptically affect the release of classic neurotransmitters in central nervous system (CNS). Complement (dilution 1 : 10 to 1 : 10000) elicited the release of preloaded [(3) H]-d-aspartate ([(3) H]d-ASP) and endogenous glutamate from mouse cortical synaptosomes in a dilution-dependent manner. It also evoked [(3) H]d-ASP release from mouse hippocampal, cerebellar, and spinal cord synaptosomes, as well as from rat and human cortical nerve endings, but left unaltered the release of GABA, [(3) H]noradrenaline or [(3) H]acetylcholine. Lowering external Na(+) (from 140 to 40 mM) or Ca(2+) (from 1.2 to 0.1 mM) ions prevented the 1 : 300 complement-evoked [(3) H]d-ASP release from mouse cortical synaptosomes. Complement-induced releasing effect was unaltered in synaptosomes entrapped with the Ca(2+) ions chelator 1,2-bis-(2-aminophenoxy) ethane-N,N,N',N', tetra-acetic acid or with pertussis toxin. Nifedipine,/ω-conotoxin GVIA/ω-conotoxin MVIIC mixture as well as the vesicular ATPase blocker bafilomycin A1 were also inefficacious. The excitatory amino acid transporter blocker DL-threo-ß-benzyloxyaspartic acid, on the contrary, reduced the complement-evoked releasing effect in a concentration-dependent manner. We concluded that complement-induced releasing activity is restricted to glutamatergic nerve endings, where it was accounted for by carrier-mediated release. Our observations afford new insights into the molecular events accounting for immune and CNS crosstalk. We investigated whether complement, a complex of soluble and membrane-associated serum proteins, could pre-synaptically affect the release of classic neurotransmitters in the central nervous system (CNS). Our data provide evidence that complement-induced releasing activity is restricted to glutamatergic nerve endings

  14. Central release of nitric oxide mediates antinociception induced by aerobic exercise.

    Science.gov (United States)

    Galdino, G S; Duarte, I D; Perez, A C

    2015-09-01

    Nitric oxide (NO) is a soluble gas that participates in important functions of the central nervous system, such as cognitive function, maintenance of synaptic plasticity for the control of sleep, appetite, body temperature, neurosecretion, and antinociception. Furthermore, during exercise large amounts of NO are released that contribute to maintaining body homeostasis. Besides NO production, physical exercise has been shown to induce antinociception. Thus, the present study aimed to investigate the central involvement of NO in exercise-induced antinociception. In both mechanical and thermal nociceptive tests, central [intrathecal (it) and intracerebroventricular (icv)] pretreatment with inhibitors of the NO/cGMP/KATP pathway (L-NOArg, ODQ, and glybenclamide) prevented the antinociceptive effect induced by aerobic exercise (AE). Furthermore, pretreatment (it, icv) with specific NO synthase inhibitors (L-NIO, aminoguanidine, and L-NPA) also prevented this effect. Supporting the hypothesis of the central involvement of NO in exercise-induced antinociception, nitrite levels in the cerebrospinal fluid increased immediately after AE. Therefore, the present study suggests that, during exercise, the NO released centrally induced antinociception. PMID:25517916

  15. Central release of nitric oxide mediates antinociception induced by aerobic exercise

    Directory of Open Access Journals (Sweden)

    G.S. Galdino

    2014-01-01

    Full Text Available Nitric oxide (NO is a soluble gas that participates in important functions of the central nervous system, such as cognitive function, maintenance of synaptic plasticity for the control of sleep, appetite, body temperature, neurosecretion, and antinociception. Furthermore, during exercise large amounts of NO are released that contribute to maintaining body homeostasis. Besides NO production, physical exercise has been shown to induce antinociception. Thus, the present study aimed to investigate the central involvement of NO in exercise-induced antinociception. In both mechanical and thermal nociceptive tests, central [intrathecal (it and intracerebroventricular (icv] pretreatment with inhibitors of the NO/cGMP/KATP pathway (L-NOArg, ODQ, and glybenclamide prevented the antinociceptive effect induced by aerobic exercise (AE. Furthermore, pretreatment (it, icv with specific NO synthase inhibitors (L-NIO, aminoguanidine, and L-NPA also prevented this effect. Supporting the hypothesis of the central involvement of NO in exercise-induced antinociception, nitrite levels in the cerebrospinal fluid increased immediately after AE. Therefore, the present study suggests that, during exercise, the NO released centrally induced antinociception.

  16. Central release of nitric oxide mediates antinociception induced by aerobic exercise

    OpenAIRE

    Galdino, G.S.; Duarte, I D; Perez, A C

    2014-01-01

    Nitric oxide (NO) is a soluble gas that participates in important functions of the central nervous system, such as cognitive function, maintenance of synaptic plasticity for the control of sleep, appetite, body temperature, neurosecretion, and antinociception. Furthermore, during exercise large amounts of NO are released that contribute to maintaining body homeostasis. Besides NO production, physical exercise has been shown to induce antinociception. Thus, the present study aimed to investiga...

  17. Serotonin and the regulation of mammalian energy balance.

    OpenAIRE

    MichaelHDonovan

    2013-01-01

    Maintenance of energy balance requires regulation of the amount and timing of food intake. Decades of experiments utilizing pharmacological and later genetic manipulations have demonstrated the importance of serotonin signaling in this regulation. Much progress has been made in recent years in understanding how central nervous system serotonin systems acting through a diverse array of serotonin receptors impact feeding behavior and metabolism. Particular attention has been paid to mechanisms ...

  18. Serotonin and the regulation of mammalian energy balance

    OpenAIRE

    Donovan, Michael H.; Tecott, Laurence H.

    2013-01-01

    Maintenance of energy balance requires regulation of the amount and timing of food intake. Decades of experiments utilizing pharmacological and later genetic manipulations have demonstrated the importance of serotonin signaling in this regulation. Much progress has been made in recent years in understanding how central nervous system (CNS) serotonin systems acting through a diverse array of serotonin receptors impact feeding behavior and metabolism. Particular attention has been paid to mecha...

  19. Centrally injected histamine increases posterior hypothalamic acetylcholine release in hemorrhage-hypotensive rats.

    Science.gov (United States)

    Altinbas, Burcin; Yilmaz, Mustafa S; Savci, Vahide; Jochem, Jerzy; Yalcin, Murat

    2015-01-01

    Histamine, acting centrally as a neurotransmitter, evokes a reversal of hemorrhagic hypotension in rats due to the activation of the sympathetic and the renin-angiotensin systems as well as the release of arginine vasopressin and proopiomelanocortin-derived peptides. We demonstrated previously that central nicotinic cholinergic receptors are involved in the pressor effect of histamine. The aim of the present study was to examine influences of centrally administrated histamine on acetylcholine (ACh) release at the posterior hypothalamus-a region characterized by location of histaminergic and cholinergic neurons involved in the regulation of the sympathetic activity in the cardiovascular system-in hemorrhage-hypotensive anesthetized rats. Hemodynamic and microdialysis studies were carried out in Sprague-Dawley rats. Hemorrhagic hypotension was induced by withdrawal of a volume of 1.5 ml blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP), heart rate (HR), and an increase in extracellular posterior hypothalamic ACh and choline (Ch) levels by 56% and 59%, respectively. Intracerebroventricularly (i.c.v.) administered histamine (50, 100, and 200 nmol) dose- and time-dependently increased MAP and HR and caused an additional rise in extracellular posterior hypothalamic ACh and Ch levels at the most by 102%, as compared to the control saline-treated group. Histamine H1 receptor antagonist chlorpheniramine (50 nmol; i.c.v.) completely blocked histamine-evoked hemodynamic and extracellular posterior hypothalamic ACh and Ch changes, whereas H2 and H3/H4 receptor blockers ranitidine (50 nmol; i.c.v.) and thioperamide (50 nmol; i.c.v.) had no effect. In conclusion, centrally administered histamine, acting via H1 receptors, increases ACh release at the posterior hypothalamus and causes a pressor and tachycardic response in hemorrhage-hypotensive anesthetized rats.

  20. Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Yinxia Li

    Full Text Available Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

  1. Corticotropin releasing factor and catecholamines enhance glutamatergic neurotransmission in the lateral subdivision of the central amygdala.

    Science.gov (United States)

    Silberman, Yuval; Winder, Danny G

    2013-07-01

    Glutamatergic neurotransmission in the central nucleus of the amygdala (CeA) plays an important role in many behaviors including anxiety, memory consolidation and cardiovascular responses. While these behaviors can be modulated by corticotropin releasing factor (CRF) and catecholamine signaling, the mechanism(s) by which these signals modify CeA glutamatergic neurotransmission remains unclear. Utilizing whole-cell patch-clamp electrophysiology recordings from neurons in the lateral subdivision of the CeA (CeAL), we show that CRF, dopamine (DA) and the β-adrenergic receptor agonist isoproterenol (ISO) all enhance the frequency of spontaneous excitatory postsynaptic currents (sEPSC) without altering sEPSC kinetics, suggesting they increase presynaptic glutamate release. The effect of CRF on sEPSCs was mediated by a combination of CRFR1 and CRFR2 receptors. While previous work from our lab suggests that CRFRs mediate the effect of catecholamines on excitatory transmission in other subregions of the extended amygdala, blockade of CRFRs in the CeAL failed to significantly alter effects of DA and ISO on glutamatergic transmission. These findings suggest that catecholamine and CRF enhancement of glutamatergic transmission onto CeAL neurons occurs via distinct mechanisms. While CRF increased spontaneous glutamate release in the CeAL, CRF caused no significant changes to optogenetically evoked glutamate release in this region. The dissociable effects of CRF on different types of glutamatergic neurotransmission suggest that CRF may specifically regulate spontaneous excitatory transmission.

  2. Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology

    OpenAIRE

    Ciranna, L

    2006-01-01

    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...

  3. Presynaptic Release-Regulating mGlu1 Receptors in Central Nervous System.

    Science.gov (United States)

    Pittaluga, Anna

    2016-01-01

    Group I metabotropic glutamate (mGlu) receptors consists of mGlu1 and mGlu5 receptor subtypes. These receptors are widely distributed in the central nervous system (CNS), where they preferentially mediate facilitatory signaling in neurones and glial cells, mainly by favoring phospholipase (PLC) translocation. Based on the literature so far available, group I Metabotropic glutamate receptors (mGluRs) are preferentially expressed at the postsynaptic side of chemical synapsis, where they participate in the progression of the chemical stimulus. Studies, however, have shown the presence of these receptors also at the presynaptic level, where they exert several functions, including the modulation of transmitter exocytosis. Presynaptic Group I mGluRs can be both autoreceptors regulating release of glutamate and heteroreceptors regulating the release of various transmitters, including GABA, dopamine, noradrenaline, and acetylcholine. While the existence of presynaptic release-regulating mGlu5 receptors is largely recognized, the possibility that mGlu1 receptors also are present at this level has been a matter of discussion for a long time. A large body of evidence published in the last decade, however, supports this notion. This review aims at revisiting the data from in vitro studies concerning the existence and the role of release-regulating mGlu1 receptors presynaptically located in nerve terminals isolated from selected regions of the CNS. The functional interaction linking mGlu5 and mGlu1 receptor subtypes at nerve terminals and their relative contributions as modulators of central transmission will also be discussed. We apologize in advance for omission in our coverage of the existing literature. PMID:27630571

  4. Gonadothropin-releasing hormone agonist as a treatment of choice for central precocious puberty

    Directory of Open Access Journals (Sweden)

    Jose R.L. Batubara

    2010-11-01

    Full Text Available Precocious puberty is defi ned as pubertal development which occurs too early. The age limit in this term is based on the onset of puberty in normal population. Some points have to be taken into account, such as ethnicity, gender, nutritional conditions, and secular trends. In girls, precocious puberty is defi ned by breast development occured before 8 years old. In boys, precocious puberty is defi ned as gonadarche or pubarche before 9 years of age. The clinical course of precocious puberty varies widely, ranging from alternating, slowly progressive, and rapidly progressive    form. The rapidly progressive forms of idiopathic central precocious puberty need to be treated because it may result in early epiphyseal closure and short fi nal height, and also pyschosocial problems in the affected children and the family. The aims of treatment are to arrest physical maturation, prevent early menarche, and also improve adult height combined with normal body proportions. Gonadotropin releasing hormone analogue is the treatment of choice for central precocious puberty. Gonadotropin releasing horomone analogue has suppressive effect on the pituitarygonadal axis, therefore it suppresses LH secretion. This leads to the return of estradiol and testosterone to prepubertal levels. Treatment using gonadotropin releasing horomone analogue is shown to reduce breast size, pubic hair, ovarian and uterine size in girls, and decrease testicular size in boys. Gonadotropin releasing hormone analogue is effective in halting progression of secondary sexual characteristics development, presenting menstrual cycle, slowing bone-age advancement, and also improving fi nal height. (Med J Indones 2010; 19:287-92Keywords: gonadache, GRH analogue, pubarche , precocious puberty

  5. Serotonin in human skin

    Institute of Scientific and Technical Information of China (English)

    Jianguo Huang; Qiying Gong; Guiming Li

    2005-01-01

    In this review the authors summarize data of a potential role for serotonin in human skin physiology and pathology. The uncovering of endogenous serotonin synthesis and its transformation to melatonin underlines a putative important role of this pathway in melanocyte physiology and pathology. Pathways of the biosynthesis and biodegradation of serotonin have been characterized in human beings and its major cellular populations. Moreover, receptors of serotonin are expressed on keratinocytes, melanocytes, and fibroblasts and these mediate phenotypic actions on cellular proliferation and differentiation. And the widespread expression of a cutaneous seorotoninergic system indicates considerable selectivity of action to facilitate intra-, auto-, or paracrine mechanisms that define and influence skin function in a highly compartmentalized manner. Melatonin, in turn, can also act as a hormone, neurotransmitter, cytokine, biological modifier and immunomodulator. Thus, Serotonin local synthesis and cellular localization could thus become of great importance in the diagnosis and management of cutaneous pathology.

  6. The serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine facilitates noradrenaline release from rat spinal cord slices and inhibits monoamine oxidase activity.

    Science.gov (United States)

    Reimann, W; Schneider, F

    1993-03-01

    1. The influences of the purported serotonergic agonist 5-methoxy-N,N-dimethyltryptamine (MeODMT) on noradrenaline release and metabolism were investigated in a rat spinal cord release model and a monoamine oxidase (MAO) assay. 2. MeODMT inhibited the basal outflow of tritium from rat spinal cord slices preincubated with [3H]noradrenaline and enhanced the electrically-evoked overflow. 3. Effects on basal outflow were not observed, when monoamine oxidase (MAO) was inhibited by pargyline. Effects on the evoked overflow were not observed in the presence of metitepine or phentolamine. 4. Preferential inhibition by MeODMT of MAO A-type enzyme activity was found in a direct assay. 5. The results provide evidence for two different effects by which MeODMT reinforces noradrenergic neurotransmission in the rat spinal cord: facilitation of stimulation-evoked noradrenaline release and inhibition of noradrenaline metabolism by MAO inhibition. PMID:8482527

  7. Serotonin and conditioning: focus on Pavlovian psychostimulant drug conditioning.

    Science.gov (United States)

    Carey, Robert J; Damianopoulos, Ernest N

    2015-04-01

    Serotonin containing neurons are located in nuclei deep in the brainstem and send axons throughout the central nervous system from the spinal cord to the cerebral cortex. The vast scope of these connections and interactions enable serotonin and serotonin analogs to have profound effects upon sensory/motor processes. In that conditioning represents a neuroplastic process that leads to new sensory/motor connections, it is apparent that the serotonin system has the potential for a critical role in conditioning. In this article we review the basics of conditioning as well as the serotonergic system and point up the number of non-associative ways in which manipulations of serotonin neurotransmission have an impact upon conditioning. We focus upon psychostimulant drug conditioning and review the contribution of drug stimuli in the use of serotonin drugs to investigate drug conditioning and the important impact drug stimuli can have on conditioning by introducing new sensory stimuli that can create or mask a CS. We also review the ways in which experimental manipulations of serotonin can disrupt conditioned behavioral effects but not the associative processes in conditioning. In addition, we propose the use of the recently developed memory re-consolidation model of conditioning as an approach to assess the possible role of serotonin in associative processes without the complexities of performance effects related to serotonin treatment induced alterations in sensory/motor systems.

  8. Mifepristone modulates serotonin transporter function

    Institute of Scientific and Technical Information of China (English)

    Chaokun Li; Linlin Shan; Xinjuan Li; Linyu Wei; Dongliang Li

    2014-01-01

    Regulating serotonin expression can be used to treat psychotic depression. Mifepristone, a glu-cocorticoid receptor antagonist, is an effective candidate for psychotic depression treatment. However, the underlying mechanism related to serotonin transporter expression is poorly un-derstood. In this study, we cloned the human brain serotonin transporter into Xenopus oocytes, to establish an in vitro expression system. Two-electrode voltage clamp recordings were used to detect serotonin transporter activity. Our results show that mifepristone attenuates serotonin transporter activity by directly inhibiting the serotonin transporter, and suggests that the se-rotonin transporter is a pharmacological target of mifepristone for the treatment of psychotic depression.

  9. Conductive polymers for controlled release and treatment of central nervous system injury

    Science.gov (United States)

    Saigal, Rajiv

    As one of the most devastating forms of neurotrauma, spinal cord injury remains a challenging clinical problem. The difficulties in treatment could potentially be resolved by better technologies for therapeutic delivery. In order to develop new approaches to treating central nervous system injury, this dissertation focused on using electrically-conductive polymers, controlled drug release, and stem cell transplantation. We first sought to enhance the therapeutic potential of neural stem cells by electrically increasing their production of neurotrophic factors (NTFs), important molecules for neuronal cell survival, differentiation, synaptic development, plasticity, and growth. We fabricated a new cell culture device for growing neural stem cells on a biocompatible, conductive polymer. Electrical stimulation via the polymer led to upregulation of NTF production by neural stem cells. This approach has the potential to enhance stem cell function while avoiding the pitfalls of genetic manipulation, possibly making stem cells more viable as a clinical therapy. Seeing the therapeutic potential of conductive polymers, we extended our studies to an in vivo model of spinal cord injury (SCI). Using a novel fabrication and extraction technique, a conductive polymer was fabricated to fit to the characteristic pathology that follows contusive SCI. Assessed via quantitative analysis of MR images, the conductive polymer significantly reduced compression of the injured spinal cord. Further characterizing astroglial and neuronal response of injured host tissue, we found significant neuronal sparing as a result of this treatment. The in vivo studies also demonstrated improved locomotor recovery mediated by a conductive polymer scaffold over a non-conductive control. We next sought to take advantage of conductive polymers for local, electronically-controlled release of drugs. Seeking to overcome reported limitations in drug delivery via polypyrrole, we first embedded drugs in poly

  10. Serotonin Receptors in Hippocampus

    Directory of Open Access Journals (Sweden)

    Laura Cristina Berumen

    2012-01-01

    Full Text Available 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.

  11. A voltammetric and mathematical analysis of histaminergic modulation of serotonin in the mouse hypothalamus.

    Science.gov (United States)

    Samaranayake, Srimal; Abdalla, Aya; Robke, Rhiannon; Nijhout, H Frederik; Reed, Michael C; Best, Janet; Hashemi, Parastoo

    2016-08-01

    Histamine and serotonin are neuromodulators which facilitate numerous, diverse neurological functions. Being co-localized in many brain regions, these two neurotransmitters are thought to modulate one another's chemistry and are often implicated in the etiology of disease. Thus, it is desirable to interpret the in vivo chemistry underlying neurotransmission of these two molecules to better define their roles in health and disease. In this work, we describe a voltammetric approach to monitoring serotonin and histamine simultaneously in real time. Via electrical stimulation of the axonal bundles in the medial forebrain bundle, histamine release was evoked in the mouse premammillary nucleus. We found that histamine release was accompanied by a rapid, potent inhibition of serotonin in a concentration-dependent manner. We developed mathematical models to capture the experimental time courses of histamine and serotonin, which necessitated incorporation of an inhibitory receptor on serotonin neurons. We employed pharmacological experiments to verify that this serotonin inhibition was mediated by H3 receptors. Our novel approach provides fundamental mechanistic insights that can be used to examine the full extent of interconnectivity between histamine and serotonin in the brain. Histamine and serotonin are co-implicated in many of the brain's functions. In this paper, we develop a novel voltammetric method for simultaneous real-time monitoring of histamine and serotonin in the mouse premammillary nucleus. Electrical stimulation of the medial forebrain bundle evokes histamine and inhibits serotonin release. We show voltammetrically, mathematically, and pharmacologically that this serotonin inhibition is H3 receptor mediated.

  12. Post-release survival and movements patterns of roosterfish (Nematistius pectoralis off the Central American coastline

    Directory of Open Access Journals (Sweden)

    Chugey A Sepulveda

    2015-03-01

    Full Text Available Acoustic telemetry was used to assess immediate post-release survival and track the short-term movement patterns of roosterfish Nematistius pectoralis between 2008 and 2010. Seven roosterfish (85 to 146 cm fork length, FL were continuously tracked along the Central American coastline for periods of up to 28 h following capture on recreational fishing tackle. All seven roosterfish were initially captured and spent the duration of the track period proximal to the coastline in waters <100 m of depth. From depth records and horizontal movements, it was determined that all seven roosterfish survived the acute effects of capture. The greatest depth achieved by any of the tracked individuals was 62 m and collectively roosterfish spent over 90% of the track records between the surface and 12 m. For all tracks, fish size showed no effect on maximum or average dive depth and the average day (7 ± 2 m and night (6 ± 2 m depths were similar among individuals. Mean water temperature for all tracks was 28 ± 1°C, with the lowest temperature experienced at depth being 23°C. Total horizontal movements from the roosterfish in this study ranged from 14.7 to 42.2 km and averaged 1.5 ± 0.4 km h-1. Data on movements in relation to bathymetry, prey presence and habitat structure are discussed. Collectively, these data provide insight into the immediate post-release disposition and short-term movements of this poorly studied species along the coast of Central America.

  13. ROLE OF THE SEROTONIN IN MEMORY PROCESSES IN THE RAT

    Directory of Open Access Journals (Sweden)

    Andreea Ioana Hefco

    2005-08-01

    Full Text Available Chronic 5, 7-dihydroxytryptamine (5, 7-DHT, 150 μg,i.c.v. disruption of the central serotonergic function, is able to interfere with learning and memory processes in the rat. Serotonin depletion significantly diminished spontaneous alternation % in Y-maze task, which suggest the impairment of short-term memory. Long-term memory does not undergo significant changes. Parachlorophenylalanine (200μg i.c.v. x 3 days a semichronic serotonin neurotoxin, do not impaired long-term memory. This effect of serotonin depletion was not produced at the level of organism motricity that, in turn, would allow an enhancing efficiency of another neurotransmitters contribution to memory processes, as number of arm entries was not affected by serotonin depletion. It is concluded that learning and memory processes is a multitransmitter system function, in which serotonin play an important role

  14. Multiple messengers in descending serotonin neurons: localization and functional implications.

    Science.gov (United States)

    Hökfelt, T; Arvidsson, U; Cullheim, S; Millhorn, D; Nicholas, A P; Pieribone, V; Seroogy, K; Ulfhake, B

    2000-02-01

    In the present review article we summarize mainly histochemical work dealing with descending bulbospinal serotonin neurons which also express a number of neuropeptides, in particular substance P and thyrotropin releasing hormone. Such neurons have been observed both in rat, cat and monkey, and may preferentially innervate the ventral horns of the spinal cord, whereas the serotonin projections to the dorsal horn seem to lack these coexisting peptides. More recent studies indicate that a small population of medullary raphe serotonin neurons, especially at rostral levels, also synthesize the inhibitory neurotransmitter gamma-amino butyric acid (GABA). Many serotonin neurons contain the glutamate synthesizing enzyme glutaminase and can be labelled with antibodies raised against glutamate, suggesting that one and the same neuron may release several signalling substances, causing a wide spectrum of post- (and pre-) synaptic actions. PMID:10708921

  15. Bromine release during Plinian eruptions along the Central American Volcanic Arc

    Science.gov (United States)

    Hansteen, T. H.; Kutterolf, S.; Appel, K.; Freundt, A.; Perez-Fernandez, W.; Wehrmann, H.

    2010-12-01

    Volcanoes of the Central American Volcanic Arc (CAVA) have produced at least 72 highly explosive eruptions within the last 200 ka. The eruption columns of all these “Plinian” eruptions reached well into the stratosphere such that their released volatiles may have influenced atmospheric chemistry and climate. While previous research has focussed on the sulfur and chlorine emissions during such large eruptions, we here present measurements of the heavy halogen bromine by means of synchrotron radiation induced micro-XRF microanalysis (SR-XRF) with typical detection limits at 0.3 ppm (in Fe rich standard basalt ML3B glass). Spot analyses of pre-eruptive glass inclusions trapped in minerals formed in magma reservoirs were compared with those in matrix glasses of the tephras, which represent the post-eruptive, degassed concentrations. The concentration difference between inclusions and matrix glasses, multiplied by erupted magma mass determined by extensive field mapping, yields estimates of the degassed mass of bromine. Br is probably hundreds of times more effective in destroying ozone than Cl, and can accumulate in the stratosphere over significant time scales. Melt inclusions representing deposits of 22 large eruptions along the CAVA have Br contents between 0.5 and 13 ppm. Br concentrations in matrix glasses are nearly constant at 0.4 to 1.5 ppm. However, Br concentrations and Cl/Br ratios vary along the CAVA. The highest values of Br contents (>8 ppm) and lowest Cl/Br ratios (170 to 600) in melt inclusions occur across central Nicaragua and southern El Salvador, and correlate with bulk-rock compositions of high Ba/La > 85 as well as low La/Yb discharged 700 kilotons of Br. On average, each of the remaining 21 CAVA eruptions studied have discharged c.100 kilotons of bromine. During the past 200 ka, CAVA volcanoes have emitted a cumulative mass of 3.2 Mt of Br through highly explosive eruptions. There are six periods in the past (c. 2ka, 6ka, 25ka, 40ka, 60ka, 75

  16. Cocaine serves as a peripheral interoceptive conditioned stimulus for central glutamate and dopamine release.

    Directory of Open Access Journals (Sweden)

    Roy A Wise

    Full Text Available Intravenous injections of cocaine HCl are habit-forming because, among their many actions, they elevate extracellular dopamine levels in the terminal fields of the mesocorticolimbic dopamine system. This action, thought to be very important for cocaine's strong addiction liability, is believed to have very short latency and is assumed to reflect rapid brain entry and pharmacokinetics of the drug. However, while intravenous cocaine HCl has almost immediate effects on behavior and extracellular dopamine levels, recent evidence suggests that its central pharmacological effects are not evident until 10 or more seconds after IV injection. Thus the immediate effects of a given intravenous cocaine injection on extracellular dopamine concentration and behavior appear to occur before there is sufficient time for cocaine to act centrally as a dopamine uptake inhibitor. To explore the contribution of peripheral effects of cocaine to the early activation of the dopamine system, we used brain microdialysis to measure the effects of cocaine methiodide (MI--a cocaine analogue that does not cross the blood brain barrier--on glutamate (excitatory input to the dopamine cells. IP injections of cocaine MI were ineffective in cocaine-naïve animals but stimulated ventral tegmental glutamate release in rats previously trained to lever-press for cocaine HCl. This peripherally triggered glutamate input was sufficient to reinstate cocaine-seeking in previously trained animals that had undergone extinction of the habit. These findings offer an explanation for short-latency behavioral responses and immediate dopamine elevations seen following cocaine injections in cocaine-experienced but not cocaine-naïve animals.

  17. Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation

    OpenAIRE

    Emin Ozbek; Alper Otunctemur; Abdulmuttalip Simsek; Emre Can Polat; Levent Ozcan; Osman Köse; Mustafa Cekmen

    2014-01-01

    OBJECTIVES: Serotonin plays a central role in ejaculation and selective serotonin reuptake inhibitors have been successfully used to treat premature ejaculation. Here, we evaluated the relationship between a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the response of patients with premature ejaculation to SSRI medication. METHODS: Sixty-nine premature ejaculation patients were treated with 20 mg/d paroxetine for three months. The Intravaginal Ejac...

  18. Prenatal serotonin reuptake inhibitor (SRI) antidepressant exposure and serotonin transporter promoter genotype (SLC6A4) influence executive functions at 6 years of age

    OpenAIRE

    Whitney eWeikum; Ursula eBrain; Cecil MY Chau; Ruth Eckstein Grunau; W Thomas Boyce; Adele eDiamond; Oberlander, Tim F.

    2013-01-01

    Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants and maternal depression may affect prefrontal cognitive skills (executive functions; EFs) including self-control, working memory and cognitive flexibility. We examined long-term effects of prenatal SRI exposure on EFs to determine whether effects are moderated by maternal mood and/or genetic variations in SLC6A4 (a gene that codes for the serotonin transporter [5-HTT] central to the regulation of synaptic serotonin levels...

  19. Corticotropin-Releasing Hormone Microinfusion in the Central Amygdala Enhances Active Behaviour Responses in the Conditioned Defensive Burying Paradigm

    NARCIS (Netherlands)

    Wiersma, A.; Bohus, B.; Koolhaas, J.M.

    1997-01-01

    The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine, and behavioural responses in stress situations. The CeA contains large numbers of corticotropin-releasing hormone (CRH) cell bodies, terminals and functional recognition sites. In the pr

  20. Expression of serotonin receptor genes in cranial ganglia.

    Science.gov (United States)

    Maeda, Naohiro; Ohmoto, Makoto; Yamamoto, Kurumi; Kurokawa, Azusa; Narukawa, Masataka; Ishimaru, Yoshiro; Misaka, Takumi; Matsumoto, Ichiro; Abe, Keiko

    2016-03-23

    Taste cells release neurotransmitters to gustatory neurons to transmit chemical information they received. Sweet, umami, and bitter taste cells use ATP as a neurotransmitter. However, ATP release from sour taste cells has not been observed so far. Instead, they release serotonin when they are activated by sour/acid stimuli. Thus it is still controversial whether sour taste cells use ATP, serotonin, or both. By reverse transcription-polymerase chain reaction and subsequent in situ hybridization (ISH) analyses, we revealed that of 14 serotonin receptor genes only 5-HT3A and 5-HT3B showed significant/clear signals in a subset of neurons of cranial sensory ganglia in which gustatory neurons reside. Double-fluorescent labeling analyses of ISH for serotonin receptor genes with wheat germ agglutinin (WGA) in cranial sensory ganglia of pkd1l3-WGA mice whose sour neural pathway is visualized by the distribution of WGA originating from sour taste cells in the posterior region of the tongue revealed that WGA-positive cranial sensory neurons rarely express either of serotonin receptor gene. These results suggest that serotonin receptors expressed in cranial sensory neurons do not play any role as neurotransmitter receptor from sour taste cells. PMID:26854841

  1. Rotavirus and Serotonin Cross-Talk in Diarrhoea.

    Directory of Open Access Journals (Sweden)

    Sonja Bialowas

    Full Text Available Rotavirus (RV has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNANSP4 significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV infected EC tumor cells compared to siRNAVP4, siRNAVP6 and siRNAVP7. Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10 infants, but no (0/8 adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM diarrhoea in infant mice (2.9 vs 4.5 days. Ondansetron-treated mice (n = 11 had significantly (p < 0.05 less diarrhoea, lower diarrhoea severity score and lower total diarrhoea output as compared to mock-treated mice (n = 9. Similarly, Ondansetron-treated mice had better weight gain than mock-treated animals (p < 0.05. A most surprising finding was that the serotonin receptor antagonist significantly (p < 0.05 also attenuated total viral shedding. In summary, we show that intracellularly expressed NSP4 stimulates release of serotonin from human EC tumor cells and that serotonin participates in RV diarrhoea, which can be attenuated by Ondansetron.

  2. Rotavirus and Serotonin Cross-Talk in Diarrhoea.

    Science.gov (United States)

    Bialowas, Sonja; Hagbom, Marie; Nordgren, Johan; Karlsson, Thommie; Sharma, Sumit; Magnusson, Karl-Eric; Svensson, Lennart

    2016-01-01

    Rotavirus (RV) has been shown to infect and stimulate secretion of serotonin from human enterochromaffin (EC) cells and to infect EC cells in the small intestine of mice. It remains to identify which intracellularly expressed viral protein(s) is responsible for this novel property and to further establish the clinical role of serotonin in RV infection. First, we found that siRNA specifically silencing NSP4 (siRNANSP4) significantly attenuated secretion of serotonin from Rhesus rotavirus (RRV) infected EC tumor cells compared to siRNAVP4, siRNAVP6 and siRNAVP7. Second, intracellular calcium mobilization and diarrhoeal capacity from virulent and avirulent porcine viruses correlated with the capacity to release serotonin from EC tumor cells. Third, following administration of serotonin, all (10/10) infants, but no (0/8) adult mice, responded with diarrhoea. Finally, blocking of serotonin receptors using Ondansetron significantly attenuated murine RV (strain EDIM) diarrhoea in infant mice (2.9 vs 4.5 days). Ondansetron-treated mice (n = 11) had significantly (p < 0.05) less diarrhoea, lower diarrhoea severity score and lower total diarrhoea output as compared to mock-treated mice (n = 9). Similarly, Ondansetron-treated mice had better weight gain than mock-treated animals (p < 0.05). A most surprising finding was that the serotonin receptor antagonist significantly (p < 0.05) also attenuated total viral shedding. In summary, we show that intracellularly expressed NSP4 stimulates release of serotonin from human EC tumor cells and that serotonin participates in RV diarrhoea, which can be attenuated by Ondansetron. PMID:27459372

  3. Platelet serotonin in systemic sclerosis.

    OpenAIRE

    Klimiuk, P S; Grennan, A; Weinkove, C.; Jayson, M I

    1989-01-01

    Platelet serotonin concentrations were measured in 43 patients with systemic sclerosis, in 11 patients with primary Raynaud's phenomenon, and in 38 normal controls. Patients with the CREST variant (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia) had significantly lower platelet serotonin concentrations than normal controls. Patients with diffuse systemic sclerosis had normal platelet serotonin concentrations. In patients with CREST treatment with keta...

  4. A current view of serotonin transporters.

    Science.gov (United States)

    De Felice, Louis J

    2016-01-01

    Serotonin transporters (SERTs) are largely recognized for one aspect of their function-to transport serotonin back into the presynaptic terminal after its release. Another aspect of their function, however, may be to generate currents large enough to have physiological consequences. The standard model for electrogenic transport is the alternating access model, in which serotonin is transported with a fixed ratio of co-transported ions resulting in net charge per cycle. The alternating access model, however, cannot account for all the observed currents through SERT or other monoamine transporters.  Furthermore, SERT agonists like ecstasy or antagonists like fluoxetine generate or suppress currents that the standard model cannot support.  Here we survey evidence for a channel mode of transport in which transmitters and ions move through a pore. Available structures for dopamine and serotonin transporters, however, provide no evidence for a pore conformation, raising questions of whether the proposed channel mode actually exists or whether the structural data are perhaps missing a transient open state. PMID:27540474

  5. Growth retardation and altered autonomic control in mice lacking brain serotonin

    OpenAIRE

    Alenina, Natalia; Kikic, Dana; Todiras, Mihail; Mosienko, Valentina; Qadri, Fatimunnisa; Plehm, Ralph; Boyé, Philipp; Vilianovitch, Larissa; Sohr, Reinhard; Tenner, Katja; Hörtnagl, Heide; Bader, Michael

    2009-01-01

    Serotonin synthesis in mammals is initiated by 2 distinct tryptophan hydroxylases (TPH), TPH1 and TPH2. By genetically ablating TPH2, we created mice (Tph2−/−) that lack serotonin in the central nervous system. Surprisingly, these mice can be born and survive until adulthood. However, depletion of serotonin signaling in the brain leads to growth retardation and 50% lethality in the first 4 weeks of postnatal life. Telemetric monitoring revealed more extended daytime sleep, suppressed respirat...

  6. [Effect of phenibut on the respiratory arrest caused by serotonin].

    Science.gov (United States)

    Tarakanov, I A; Tarasova, N N; Belova, E A; Safonov, V A

    2006-01-01

    The role of the GABAergic system in mechanisms of the respiratory arrest caused by serotonin administration was studied in anaesthetized rats. Under normal conditions, the systemic administration of serotonin (20-60 mg/kg, i.v.) resulted in drastic changes of the respiratory pattern, whereby the initial phase of increased respiratory rate was followed by the respiratory arrest. The preliminary injection of phenibut (400 mg/kg, i.p.) abolished or sharply reduced the duration of the respiratory arrest phase induced by serotonin. Bilateral vagotomy following the phenibut injection potentiated the anti-apnoesic effect of phenibut, which was evidence of the additive action of vagotomy and phenibut administration. The mechanism of apnea caused by serotonin administration is suggested to include a central GABAergic element, which is activated by phenibut so as to counteract the respiratory arrest. PMID:16579056

  7. Serotonin syndrome presenting as pulmonary edema

    Directory of Open Access Journals (Sweden)

    Nilima Deepak Shah

    2016-01-01

    Full Text Available Serotonin syndrome (SS is a potentially life-threatening condition resulting from excessive central and peripheral serotonergic activity. Clinically, it is a triad of mental-status changes, neuromuscular abnormalities, and autonomic disturbances. It can be caused by intentional self-poisoning, overdose, or inadvertent drug interactions. We report the case of a 58-year-old male with type 2 diabetes mellitus and obsessive compulsive disorder who developed pulmonary edema as a possible complication of SS. SS was caused by a combination of three specific serotonin re-uptake inhibitors (fluoxetine, fluvoxamine, and sertraline, linezolid, and fentanyl. The hospital course was further complicated by difficult weaning from the ventilator. SS was identified and successfully treated with cyproheptadine and lorazepam. The case highlights the importance of effective consultation-liaison and prompt recognition of SS as the presentation may be complex in the presence of co-morbid medical illness.

  8. The Serotonin-6 Receptor as a Novel Therapeutic Target

    OpenAIRE

    Yun, Hyung-Mun; Rhim, Hyewhon

    2011-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter that is found in both the central and peripheral nervous systems. 5-HT mediates its diverse physiological responses through 7 different 5-HT receptor families: 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors. Among them, the 5-HT6 receptor (5-HT6R) is the most recently cloned serotonin receptor and plays important roles in the central nervous system (CNS) and in the etiology of neurological diseases. Compared...

  9. A role for central nervous growth hormone-releasing hormone signaling in the consolidation of declarative memories.

    Directory of Open Access Journals (Sweden)

    Manfred Hallschmid

    Full Text Available Contributions of somatotropic hormonal activity to memory functions in humans, which are suggested by clinical observations, have not been systematically examined. With previous experiments precluding a direct effect of systemic growth hormone (GH on acute memory formation, we assessed the role of central nervous somatotropic signaling in declarative memory consolidation. We examined the effect of intranasally administered growth hormone releasing-hormone (GHRH; 600 µg that has direct access to the brain and suppresses endogenous GHRH via an ultra-short negative feedback loop. Twelve healthy young men learned word-pair associates at 2030 h and were administered GHRH and placebo, respectively, at 2100 h. Retrieval was tested after 11 hours of wakefulness. Compared to placebo, intranasal GHRH blunted GH release within 3 hours after substance administration and reduced the number of correctly recalled word-pairs by ∼12% (both P<0.05. The impairment of declarative memory consolidation was directly correlated to diminished GH concentrations (P<0.05. Procedural memory consolidation as examined by the parallel assessment of finger sequence tapping performance was not affected by GHRH administration. Our findings indicate that intranasal GHRH, by counteracting endogenous GHRH release, impairs hippocampal memory processing. They provide first evidence for a critical contribution of central nervous somatotropic activity to hippocampus-dependent memory consolidation.

  10. Final adult height of girls with central precocious puberty or early and fast puberty could be improved by treatment of gonadotropin-releasing hormone analogs

    Institute of Scientific and Technical Information of China (English)

    陈秋莉

    2013-01-01

    Objective To assess the efficacy and impact factors of treatment with Gonadotropin-releasing hormone analogs(GnRHa) in central precocious puberty(CPP)or early and fast puberty(EFP)girls in a retrospective unicenter study

  11. Dietary exposure to the PCB mixture aroclor 1254 may compromise osmoregulation by altering central vasopressin release

    Energy Technology Data Exchange (ETDEWEB)

    Coburn, C.G. [Environmental Toxicology, Univ. of California at Riverside, CA (United States); Gillard, E.; Curras-Collazo, M. [Cell Biology and Neuroscience, Univ. of California at Riverside, CA (United States)

    2004-09-15

    Despite the importance of systemic osmoregulation, the potential deleterious effects of persistent organochlorines, such as polychlorinated biphenyls (PCBs), on body fluid regulation has not been thoroughly investigated. In an effort to ameliorate this deficit, the current study explores the toxic effects of PCBs on osmoregulation, and in particular, on the activity of the magnocellular neuroendocrine cell (MNC) system of the hypothalamus. MNCs of the supraoptic nucleus (SON) release oxytocin (OXY) and vasopressin (VP) from terminals in the neurohypophysis in response to dehydration. The latter is released to effect water conservation in response to dehydration via its action upon the kidney and through extra-renal actions. MNCs also secrete VP from their cell bodies and dendrites locally i.e., into the extracellular space of the SON. Although it has been shown that both intranuclear and systemic release rise in response to dehydration the physiological significance of intranuclear release has not been fully elucidated. We chose to use voluntary ingestion as the route of PCB exposure since it is more reflective of natural exposure compared to ip injection. One unexpected observation that resulted from pilot studies using ip injection of PCBs was the deleterious effects of the vehicle (corn oil) resulting in pooling of lipid within the abdominal cavity, mottling of the liver, fatty liver and general discoloration of all abdominal viscera at time of sacrifice. Therefore, all work described in this series of experiments have employed voluntary ingestion of the toxin. Work described in this paper suggests that PCBs in concentrations reflecting realistic lifetime exposure levels may negatively impact homeostatic mechanisms responsible for body water balance by altering somatodendritic (intranuclear) VP secretion in response to dehydration in vivo. The downstream consequences of such influence is currently under investigation, and preliminary evidence suggests that the

  12. Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses.

    Science.gov (United States)

    Sylantyev, Sergiy; Jensen, Thomas P; Ross, Ruth A; Rusakov, Dmitri A

    2013-03-26

    G protein-coupled receptor (GPR) 55 is sensitive to certain cannabinoids, it is expressed in the brain and, in cell cultures, it triggers mobilization of intracellular Ca(2+). However, the adaptive neurobiological significance of GPR55 remains unknown. Here, we use acute hippocampal slices and combine two-photon excitation Ca(2+) imaging in presynaptic axonal boutons with optical quantal analysis in postsynaptic dendritic spines to find that GPR55 activation transiently increases release probability at individual CA3-CA1 synapses. The underlying mechanism involves Ca(2+) release from presynaptic Ca(2+) stores, whereas postsynaptic stores (activated by spot-uncaging of inositol 1,4,5-trisphosphate) remain unaffected by GPR55 agonists. These effects are abolished by genetic deletion of GPR55 or by the GPR55 antagonist cannabidiol, a constituent of Cannabis sativa. GPR55 shows colocalization with synaptic vesicle protein vesicular glutamate transporter 1 in stratum radiatum. Short-term potentiation of CA3-CA1 transmission after a short train of stimuli reveals a presynaptic, Ca(2+) store-dependent component sensitive to cannabidiol. The underlying cascade involves synthesis of phospholipids, likely in the presynaptic cell, but not the endocannabinoids 2-arachidonoylglycerol or anandamide. Our results thus unveil a signaling role for GPR55 in synaptic circuits of the brain.

  13. Vasopressin release induced by water deprivation - Effects of centrally administered saralasin

    Science.gov (United States)

    Keil, L. C.; Dundore, R. L.; Wurpel, J. N. D.; Severs, W. B.; Barbella, Y. R.

    1983-01-01

    Uncertainty exists as to whether endogenous angiotensin activates brain mechanisms controlling vasopressin (AVP) secretion during dehydration. Various doses of saralasin were injected into a lateral cgrebroventricle (IVT) of conscious, male rats deprived of water for 48 h. The rats were killed at different times. The concentration of AVP in the plasma p(AVP), measured by radioimmunoassay, was unaffected by saralasin. IVT pretreatment with 1-Sar-8-Ile-angiotensin II blocked maximal AVP release by IVT angiotensin, but this pretreatment did not reduce p(AVP) after 24, 48 or 72 hr water deprivation. A 3-hour continuous IVT infusion of CSF or saralasin (10 micrograms/hour) into 48-hour water-deprived rats revealed equivalent p(AVP) concentration and urine volumes. When the infusions were continued for 3 h more with water available, control and saralasin-treated rats: (1) drank at similar rates, (2) excreted similar amounts of urine, and (3) reduced their p(AVP) concentration levels to the same extent. IVT saralasin did not affect p(AVP) concentration of rats dehydrated with hypertonic NaCl. Combined IVT saralasin and atropine reduced p(AVP) concentration of 48-hour water deprived rats about 30 percent (p less than 0.05). It is concluded that redundancy exists for sensing, integrating and releasing vasopressin in dehydrated rats.

  14. Sex Differences in Serotonin 1 Receptor Binding in Rat Brain

    Science.gov (United States)

    Fischette, Christine T.; Biegon, Anat; McEwen, Bruce S.

    1983-10-01

    Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.

  15. Drought-induced sulphate release from a wetland in south-central Ontario.

    Science.gov (United States)

    Eimers, M Catherine; Watmough, Shaun A; Buttle, James M; Dillon, Peter J

    2007-04-01

    Increased sulphate (SO(4)) export from wetlands following summer droughts in central Ontario, Canada has been associated with the delayed chemical recovery of downstream surface waters following decreased sulphur (S) emissions. Prolonged summer droughts result in a decrease or cessation of stream flow, declines in wetland water table level and oxidation of reduced S compounds to SO(4), which is subsequently flushed into drainage streams when stream flow resumes. Sulphate input-output budget calculations (1983-1995 and 1999-2001) at a conifer Sphagnum swamp in the Plastic Lake catchment, indicate that SO(4) is retained in most years but is exported on a net basis following particularly severe summer droughts that result in the cessation of stream flow for more than 54 days (95% CI: 41-72 days). Hindcast calculations using long-term (1916-2000) stream discharge records from a nearby station indicate that while droughts occurred frequently in south-central Ontario over the past 85 years, sufficiently dry conditions to cause net SO(4) export occurred in only 18 of the past 85 years, and indicate a cumulative positive SO(4) balance for the swamp (i.e. net SO(4) retention). Furthermore, the S pool at the Plastic Lake swamp has been estimated to be approximately 1500 kg S/ha in the upper 40 cm peat layer, which is large compared to the amount of net SO(4) export that occurs even in years with particularly dry summers (e.g. -43 kg S/ha in 1987/88). Together, these data suggest that the wetland S pool at Plastic Lake has not been depleted by previous droughts and will continue to sustain episodic drought-related SO(4) export for the foreseeable future.

  16. Central administration of thyrotropin releasing hormone (TRH) and related peptides inhibits feeding behavior in the Siberian hamster.

    Science.gov (United States)

    Steward, Carolyn A; Horan, Tracey L; Schuhler, Sandrine; Bennett, Geoffrey W; Ebling, Francis J P

    2003-04-15

    Centrally acting thyrotropin releasing hormone (TRH), independent of endocrine action, has been shown to regulate several metabolic and behavioral parameters in rats, including food intake and locomotor activity. The present study investigated and compared the effects of central TRH on feeding behavior in Siberian hamsters exposed to long (LP) or short (SP) photoperiods, which induce natural physiological states of obesity and leanness respectively. The effects of two TRH analogues, RX77368 (a metabolically stable TRH analogue) and TRH-Gly (an endogenous precursor to TRH with putative preferential action at the central TRH receptor, TRH-R2), were also investigated. All peptides were infused via the third ventricle (i.c.v.). Food intake was measured, and the proportion of time spent interacting with food, active or resting was scored. TRH (5 microg) significantly reduced food intake without producing associated changes in activity in hamsters maintained in both LP (p hamsters exposed to SP, indicating that there may be an underlying difference in sensitivity to TRH depending on metabolic state. RX77368 (1 microg) produced substantial hypophagia (p < 0.001) and decreased the proportion of time spent interacting with food, but, unlike TRH, may produce this via an increase in locomotor activity. TRH-Gly (5 microg) produced a small decrease in food intake (p < 0.05), lasting for 6 h. We conclude that TRH and TRH analogues possess anorexigenic capacities in this species, with a likely site of action in the hypothalamus. Increased sensitivity to the hypophagic effects of central TRH may contribute to the long-term catabolic state induced by short photoperiods.

  17. Plasma Histamine And Serotonin Levels In Children With Nephrotic Syndrome And Acute Poststreptococcal Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Nagwa Mohamed and Talaat El sayed

    2005-12-01

    Full Text Available Plasma histamine and serotonin concentrations were measured using fluorimeteric assay in 40 children with renal diseases. Minimal change nephrotic syndrome (15 focal segmental glomerulosclerosis(10 and acute poststreptococcal glomerulonephritis(15 to determine the relation between plasma levels of histamine and serotonin and these various types of renal diseases in children. Plasma histamine level was significantly increased in group of children with acute poststreptococcal glomerulonephritis. Plasma serotonin levels were significantly increased in all 3 groups of patient, when compared with those of controls. Raised plasma histamine in acute poststreptococcal glomerulonephritis group may be evidence of the acute immunological inflammation and defective renal excretion due to mild renal impairment in these children. Raised plasma serotonin in all 3 groups of patients may be due to diminished uptake and release of serotonin from platelets in children with minimal change nephrotic syndrome and focal segmental glomerulosclerosis and due to defective renal execretion in children with acute poststreptococcal glomerulo-nephritis.

  18. Possible involvement of serotonin 5-HT2 receptor in the regulation of feeding behavior through the histaminergic system.

    Science.gov (United States)

    Murotani, Tomotaka; Ishizuka, Tomoko; Isogawa, Yuka; Karashima, Michitaka; Yamatodani, Atsushi

    2011-01-01

    The central histaminergic system has been proven to be involved in several physiological functions including feeding behavior. Some atypical antipsychotics like risperidone and aripiprazole are known to affect feeding behavior and to antagonize the serotonin (5-HT) receptor subtypes. To examine the possible neural relationship between the serotonergic and histaminergic systems in the anorectic effect of the antipsychotics, we studied the effect of a single administration of these drugs on food intake and hypothalamic histamine release in mice using in vivo microdialysis. Single injection of risperidone (0.5mg/kg, i.p.) or aripiprazole (1mg/kg, i.p.), which have binding affinities to 5-HT(1A, 2A, 2B) and (2C) receptors decreased food intake in C57BL/6N mice with concomitant increase of hypothalamic histamine release. However, a selective D(2)-antagonist, haloperidol (0.5mg/kg, i.p.), did not have effects on food intake or histamine release. Furthermore, in histamine H(1) receptor-deficient mice, there was no reduction of food intake induced by atypical antipsychotics, although histamine release was increased. Moreover, selective 5-HT(2A)-antagonists, volinanserin (0.5, 1mg/kg, i.p.) and ketanserin (5, 10mg/kg, i.p.), significantly increased histamine release and 5-HT(2B/2C) -antagonist, SB206553 (2.5, 5mg/kg, i.p.), slightly increased it. On the contrary, 5-HT(1A) -selective antagonist, WAY100635 (1, 2mg/kg), did not affect the histaminergic tone. These findings suggest that serotonin tonically inhibits histamine release via 5-HT(2) receptors and that antipsychotics enhance the release of hypothalamic histamine by blockade of 5-HT(2) receptors resulting in anorexia via the H(1) receptor.

  19. Seasonal methane accumulation and release from a gas emission site in the central North Sea

    Science.gov (United States)

    Mau, S.; Gentz, T.; Körber, J.-H.; Torres, M. E.; Römer, M.; Sahling, H.; Wintersteller, P.; Martinez, R.; Schlüter, M.; Helmke, E.

    2015-09-01

    We investigated dissolved methane distributions along a 6 km transect crossing active seep sites at 40 m water depth in the central North Sea. These investigations were done under conditions of thermal stratification in summer (July 2013) and homogenous water column in winter (January 2014). Dissolved methane accumulated below the seasonal thermocline in summer with a median concentration of 390 nM, whereas during winter, methane concentrations were typically much lower (median concentration of 22 nM). High-resolution methane analysis using an underwater mass-spectrometer confirmed our summer results and was used to document prevailing stratification over the tidal cycle. We contrast estimates of methane oxidation rates (from 0.1 to 4.0 nM day-1) using the traditional approach scaled to methane concentrations with microbial turnover time values and suggest that the scaling to concentration may obscure the ecosystem microbial activity when comparing systems with different methane concentrations. Our measured and averaged rate constants (k') were on the order of 0.01 day-1, equivalent to a turnover time of 100 days, even when summer stratification led to enhanced methane concentrations in the bottom water. Consistent with these observations, we could not detect known methanotrophs and pmoA genes in water samples collected during both seasons. Estimated methane fluxes indicate that horizontal transport is the dominant process dispersing the methane plume. During periods of high wind speed (winter), more methane is lost to the atmosphere than oxidized in the water. Microbial oxidation seems of minor importance throughout the year.

  20. Efficacy of Subcutaneous Administration of Gonadotropin-releasing Hormone Agonist on Idiopathic Central Precocious Puberty

    Institute of Scientific and Technical Information of China (English)

    LIANG Yan; WEI Hong; ZHANG Jianling; HOU Ling; LUO Xiaoping

    2006-01-01

    In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty (ICPP), 46 girls with ICPP were treated with GnRHa.Triptorelin (Decapeptyl, 3.75 mg) was administered subcutaneously (SC) at 6-weeks intervals or intramuscularly (IM) at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage,bone age, uterine volume and ovarian size, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2), were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics.Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment.The height velocity was decreased significantly from 6.3±1.4 cm/year to 5.8±1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBA/deltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively.The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in diameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients,which disappeared after 6- 12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was

  1. Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin.

    Science.gov (United States)

    Yosten, Gina L C; Samson, Willis K

    2014-05-15

    Nesfatin-1 is produced in the periphery and in the brain where it has been demonstrated to regulate appetite, stress hormone secretion, and cardiovascular function. The anorexigenic action of central nesfatin-1 requires recruitment of neurons producing the melanocortins and centrally projecting oxytocin (OT) and corticotropin-releasing hormone (CRH) neurons. We previously have shown that two components of this pathway, the central melanocortin and oxytocin systems, contribute to the hypertensive action of nesfatin-1 as well. We hypothesized that the cardiovascular effect of nesfatin-1 also was dependent on activation of neurons expressing CRH receptors, and that the order of activation of the melanocortin-CRH-oxytocin circuit was preserved for both the anorexigenic and hypertensive actions of the peptide. Pretreatment of male rats with the CRH-2 receptor antagonist astressin2B abrogated nesfatin-1-induced increases in mean arterial pressure (MAP). Furthermore, the hypertensive action of CRH was blocked by pretreatment with an oxytocin receptor antagonist ornithine vasotocin (OVT), indicating that the hypertensive effect of nesfatin-1 may require activation of oxytocinergic (OTergic) neurons in addition to recruitment of CRH neurons. Interestingly, we found that the hypertensive effect of α-melanocyte stimulating hormone (α-MSH) itself was not blocked by either astressin2B or OVT. These data suggest that while α-MSH-producing neurons are part of a core melanocortin-CRH-oxytocin circuit regulating food intake, and a subpopulation of melanocortin neurons activated by nesfatin-1 do mediate the hypertensive action of the peptide, α-MSH can signal independently from this circuit to increase MAP.

  2. Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Hans; Erritzoe, David; Andersen, Rune;

    2010-01-01

    , in vivo studies of serotonin(2A) binding report conflicting results, presumably because sample sizes have been small or because schizophrenic patients who were not antipsychotic-naive were included. Furthermore, the relationships between serotonin(2A) binding, psychopathology, and central neurocognitive...

  3. Studies on the development of 99mTc labelled serotonin receptor avid molecules

    International Nuclear Information System (INIS)

    Among the central nervous system (CNS) receptors, serotonin is reported to be very important with respect to the study of brain disorders. Hence this work focuses on serotonin. A summary of the studies that were carried out is given. These include: (a) standardization of the method of serotonin receptor preparation from rat brains and development of a radioreceptor assay using radio-iodinated serotonin, (b) standardization of the method of radio-iodination of serotonin using a tyrosylmethyl ester derivative of serotonin and the preparation of 14C labelled serotonin, (c) synthesis of the SNS tridentate ligand (following the procedure developed by the Democritos National Centre of Scientific Research (NCSR), Athens) and evaluation of a 99mTc complex formed with the tridentate SNS ligand and thiocresol for use as a CNS receptor imaging agent and (d) evaluation of the 99mTc complex formed with a SNS piperazine based tridentate ligand and a monodentate co-ligand (thiophenol obtained from NCSR). This limited study on brain uptake of the complex in rats showed that more structural modification of the ligand is required for preparation of a complex suitable for CNS receptor imaging. Also included is a design for synthesis of a novel complex based on the reported information on the 5-iodo-2-[(2-dimethyl)aminomethylphynoxy]benzyl alcohol compound, which is reported to have a binding affinity for serotonin re-uptake sites. (author)

  4. Endurance training in Wistar rats decreases receptor sensitivity to a serotonin agonist.

    Science.gov (United States)

    Dwyer, D; Browning, J

    2000-11-01

    There is mounting evidence that increased brain serotonin during exercise is associated with the onset of CNS-mediated fatigue. Serotonin receptor sensitivity is likely to be an important determinant of this fatigue. Alterations in brain serotonin receptor sensitivity were examined in Wistar rats throughout 6 weeks of endurance training, running on a treadmill four times a week with two exercise tests per week to exhaustion. Receptor sensitivity was determined indirectly as the reduction in exercise time in response to a dose of a serotonin (1A) agonist, m-chlorophenylpiperazine (m-CPP). The two groups of controls were used to examine (i) the effect of the injection per se on exercise performance and (ii) changes in serotonin receptor sensitivity associated with maturation. In the test group, undrugged exercise performance significantly improved by 47% after 6 weeks of training (4518 +/- 729 to 6640 +/- 903 s, P=0.01). Drugged exercise performance also increased significantly from week 1 to week 6 (306 +/- 69-712 +/- 192 s, P = 0.04). Control group results indicated that the dose of m-CPP alone caused fatigue during exercise tests and that maturation was not responsible for any decrease in receptor sensitivity. Improved resistance to the fatiguing effects of the serotonin agonist suggests desensitization of central serotonin receptors, probably the 5-HT1A receptors. Endurance training appears to stimulate an adaptive response to the fatiguing effects of increased brain serotonin, which may enhance endurance exercise performance. PMID:11167306

  5. In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin(2A) Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and Hallucinogen Users

    DEFF Research Database (Denmark)

    Erritzoe, David; Frokjaer, Vibe G.; Holst, Klaus K.;

    2011-01-01

    Context: Both hallucinogens and 3,4-methylenedioxy-methamphetamine( MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.......Objective: To assess the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin(2A) receptor binding.Design: A positron emission tomography study of 24 young adult drug users and 21 nonusing control participants performed with carbon 11 (C-11)-labeled 3-amino-4-[2-[(di......(methyl) amino) methyl] phenyl]sulfanylbenzonitrile (DASB) and fluorine 18 (F-18)-labeled altanserin, respectively. Scans were performed in the user group after a minimum drug abstinence period of 11 days, and the group was subdivided into hallucinogen-preferring users (n=10) and MDMA-preferring users (n=14...

  6. Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala.

    Science.gov (United States)

    Itoga, Christy A; Roltsch Hellard, Emily A; Whitaker, Annie M; Lu, Yi-Ling; Schreiber, Allyson L; Baynes, Brittni B; Baiamonte, Brandon A; Richardson, Heather N; Gilpin, Nicholas W

    2016-09-01

    Hyperalgesia is an exaggerated response to noxious stimuli produced by peripheral or central plasticity. Stress modifies nociception, and humans with post-traumatic stress disorder (PTSD) exhibit co-morbid chronic pain and amygdala dysregulation. Predator odor stress produces hyperalgesia in rodents. Systemic blockade of corticotropin-releasing factor (CRF) type 1 receptors (CRFR1s) reduces stress-induced thermal hyperalgesia. We hypothesized that CRF-CRFR1 signaling in central amygdala (CeA) mediates stress-induced hyperalgesia in rats with high stress reactivity. Adult male Wistar rats were exposed to predator odor stress in a conditioned place avoidance paradigm and indexed for high (Avoiders) and low (Non-Avoiders) avoidance of predator odor-paired context, or were unstressed Controls. Rats were tested for the latency to withdraw hindpaws from thermal stimuli (Hargreaves test). We used pharmacological, molecular, and immunohistochemical techniques to assess the role of CRF-CRFR1 signaling in CeA in stress-induced hyperalgesia. Avoiders exhibited higher CRF peptide levels in CeA that did not appear to be locally synthesized. Intra-CeA CRF infusion mimicked stress-induced hyperalgesia. Avoiders exhibited thermal hyperalgesia that was reversed by systemic or intra-CeA injection of a CRFR1 antagonist. Finally, intra-CeA infusion of tetrodotoxin produced thermal hyperalgesia in unstressed rats and blocked the anti-hyperalgesic effect of systemic CRFR1 antagonist in stressed rats. These data suggest that rats with high stress reactivity exhibit hyperalgesia that is mediated by CRF-CRFR1 signaling in CeA.

  7. Function of the Serotonin Transporter in Vasculature of the Female Rat: comparison with the male

    OpenAIRE

    Linder, A. Elizabeth; Davis, Robert Patrick; Burnett, Robert; Watts, Stephanie W.

    2011-01-01

    The serotonin transporter (SERT) handles serotonin (5-hydroxytryptamine, 5-HT) and is blocked by the antidepressant SERT inhibitors fluoxetine and fluvoxamine. While the importance of SERT in the central nervous system is clear, SERT also functions in the peripheral vasculature. We tested the hypothesis that vasculature from female rats has increased SERT function compared to male rats because females are more responsive to SERT inhibitors.In addition to in vitro experiments, we imposed the c...

  8. Therapeutic Application of Diacylglycerol Oil for Obesity: Serotonin Hypothesis

    Directory of Open Access Journals (Sweden)

    Yuji Hirowatari

    2012-01-01

    Full Text Available ABSTRACT: Characteristics for the serum lipid abnormalities in the obesity/metabolic syndrome are elevated fasting, postprandial triglyceride (TG, and decreased high-density lipoprotein-cholesterol (HDL-C. Diacylglycerol (DAG oil ingestion has been reported to ameliorate postprandial hyperlipidemia and prevent obesity by increasing energy expenditure, due to the intestinal physiochemical dynamics that differ from triacylglycerol (TAG. Our study demonstrated that DAG suppresses postprandial increase in TG-rich lipoprotein, very low-density lipoprotein (VLDL, and insulin, as compared with TAG in young, healthy individuals. Interestingly, our study also presented that DAG significantly increases plasma serotonin, which is mostly present in the intestine, and mediates thermogenesis, proposing a possible mechanism for a postprandial increase in energy expenditure by DAG. Our other study demonstrated that DAG suppresses postprandial increase in TG, VLDL-C, and remnant-like particle-cholesterol, in comparison with TAG in an apolipoprotein C-II deficient subject, suggesting that DAG suppresses postprandial TG-rich lipoprotein independently of lipoprotein lipase. Further, to understand the molecular mechanisms for DAG-mediated increase in serotonin and energy expenditure, we studied the effects of 1-monoacylglycerol and 2(1:1-10 2-monoacylglycerol, distinct digestive products of DAG and TAG, respectively, on serotonin release from the Caco-2 cells, the human intestinal cell line. We also studied effects of 1- and 2-monoacylglycerol, and serotonin on the expression of mRNA associated with â-oxidation, fatty acids metabolism, and thermogenesis, in the Caco-2 cells. 1-monoacylglycerol significantly increased serotonin release from the Caco-2 cells, compared with 2-monoacylglycerol by approximately 40%. The expression of mRNA of acyl-CoA oxidase (ACO, fatty acid translocase (FAT, and uncoupling protein-2 (UCP-2, was significantly higher in 1-MOG

  9. Serotonin in the solitary tract nucleus shortens the laryngeal chemoreflex in anaesthetized neonatal rats.

    Science.gov (United States)

    Donnelly, William T; Bartlett, Donald; Leiter, J C

    2016-07-01

    What is the central question of this study? Failure to terminate apnoea and arouse is likely to contribute to sudden infant death syndrome (SIDS). Serotonin is deficient in the brainstems of babies who died of SIDS. Therefore, we tested the hypothesis that serotonin in the nucleus of the solitary tract (NTS) would shorten reflex apnoea. What is the main finding and its importance? Serotonin microinjected into the NTS shortened the apnoea and respiratory inhibition associated with the laryngeal chemoreflex. Moreover, this effect was achieved through a 5-HT3 receptor. This is a new insight that is likely to be relevant to the pathogenesis of SIDS. The laryngeal chemoreflex (LCR), an airway-protective reflex that causes apnoea and bradycardia, has long been suspected as an initiating event in the sudden infant death syndrome. Serotonin (5-HT) and 5-HT receptors may be deficient in the brainstems of babies who die of sudden infant death syndrome, and 5-HT seems to be important in terminating apnoeas directly or in causing arousals or as part of the process of autoresuscitation. We hypothesized that 5-HT in the brainstem would limit the duration of the LCR. We studied anaesthetized rat pups between 7 and 21 days of age and made microinjections into the cisterna magna or into the nucleus of the solitary tract (NTS). Focal, bilateral microinjections of 5-HT into the caudal NTS significantly shortened the LCR. The 5-HT1a receptor antagonist, WAY 100635, did not affect the LCR consistently, nor did a 5-HT2 receptor antagonist, ketanserin, alter the duration of the LCR. The 5-HT3 specific agonist, 1-(3-chlorophenyl)-biguanide, microinjected bilaterally into the caudal NTS significantly shortened the LCR. Thus, endogenous 5-HT released within the NTS may curtail the respiratory depression that is part of the LCR, and serotonergic shortening of the LCR may be attributed to activation of 5-HT3 receptors within the NTS. 5-HT3 receptors are expressed presynaptically on C

  10. Serotonin in the solitary tract nucleus shortens the laryngeal chemoreflex in anaesthetized neonatal rats.

    Science.gov (United States)

    Donnelly, William T; Bartlett, Donald; Leiter, J C

    2016-07-01

    What is the central question of this study? Failure to terminate apnoea and arouse is likely to contribute to sudden infant death syndrome (SIDS). Serotonin is deficient in the brainstems of babies who died of SIDS. Therefore, we tested the hypothesis that serotonin in the nucleus of the solitary tract (NTS) would shorten reflex apnoea. What is the main finding and its importance? Serotonin microinjected into the NTS shortened the apnoea and respiratory inhibition associated with the laryngeal chemoreflex. Moreover, this effect was achieved through a 5-HT3 receptor. This is a new insight that is likely to be relevant to the pathogenesis of SIDS. The laryngeal chemoreflex (LCR), an airway-protective reflex that causes apnoea and bradycardia, has long been suspected as an initiating event in the sudden infant death syndrome. Serotonin (5-HT) and 5-HT receptors may be deficient in the brainstems of babies who die of sudden infant death syndrome, and 5-HT seems to be important in terminating apnoeas directly or in causing arousals or as part of the process of autoresuscitation. We hypothesized that 5-HT in the brainstem would limit the duration of the LCR. We studied anaesthetized rat pups between 7 and 21 days of age and made microinjections into the cisterna magna or into the nucleus of the solitary tract (NTS). Focal, bilateral microinjections of 5-HT into the caudal NTS significantly shortened the LCR. The 5-HT1a receptor antagonist, WAY 100635, did not affect the LCR consistently, nor did a 5-HT2 receptor antagonist, ketanserin, alter the duration of the LCR. The 5-HT3 specific agonist, 1-(3-chlorophenyl)-biguanide, microinjected bilaterally into the caudal NTS significantly shortened the LCR. Thus, endogenous 5-HT released within the NTS may curtail the respiratory depression that is part of the LCR, and serotonergic shortening of the LCR may be attributed to activation of 5-HT3 receptors within the NTS. 5-HT3 receptors are expressed presynaptically on C

  11. Serotonin receptors as cardiovascular targets

    NARCIS (Netherlands)

    C.M. Villalón (Carlos); P.A.M. de Vries (Peter); P.R. Saxena (Pramod Ranjan)

    1997-01-01

    textabstractSerotonin exerts complex effects in the cardiovascular system, including hypotension or hypertension, vasodilatation or vasoconstriction, and/or bradycardia or tachycardia; the eventual response depends primarily on the nature of the 5-HT receptors involved. In the light of current 5-HT

  12. The effects of glycogen synthase kinase-3beta in serotonin neurons.

    Directory of Open Access Journals (Sweden)

    Wenjun Zhou

    Full Text Available Glycogen synthase kinase-3 (GSK3 is a constitutively active protein kinase in brain. Increasing evidence has shown that GSK3 acts as a modulator in the serotonin neurotransmission system, including direct interaction with serotonin 1B (5-HT1B receptors in a highly selective manner and prominent modulating effect on 5-HT1B receptor activity. In this study, we utilized the serotonin neuron-selective GSK3β knockout (snGSK3β-KO mice to test if GSK3β in serotonin neurons selectively modulates 5-HT1B autoreceptor activity and function. The snGSK3β-KO mice were generated by crossbreeding GSK3β-floxed mice and ePet1-Cre mice. These mice had normal growth and physiological characteristics, similar numbers of tryptophan hydroxylase-2 (TpH2-expressing serotonin neurons, and the same brain serotonin content as in littermate wild type mice. However, the expression of GSK3β in snGSK3β-KO mice was diminished in TpH2-expressing serotonin neurons. Compared to littermate wild type mice, snGSK3β-KO mice had a reduced response to the 5-HT1B receptor agonist anpirtoline in the regulation of serotonergic neuron firing, cAMP production, and serotonin release, whereas these animals displayed a normal response to the 5-HT1A receptor agonist 8-OH-DPAT. The effect of anpirtoline on the horizontal, center, and vertical activities in the open field test was differentially affected by GSK3β depletion in serotonin neurons, wherein vertical activity, but not horizontal activity, was significantly altered in snGSK3β-KO mice. In addition, there was an enhanced anti-immobility response to anpirtoline in the tail suspension test in snGSK3β-KO mice. Therefore, results of this study demonstrated a serotonin neuron-targeting function of GSK3β by regulating 5-HT1B autoreceptors, which impacts serotonergic neuron firing, serotonin release, and serotonin-regulated behaviors.

  13. The postradiation efficacy of serotonin and its dependence on the stage of embryonal growith of mice

    International Nuclear Information System (INIS)

    In earlier experiments, the authors discovered that if serotonin was given to the mouse after its exposure to radiation on the 8th or 9th day of pregnancy, i.e., in the period of intensive neurogenesis, during which this particular biogenic amine was accumulated in the neural tube, the radiation damage was lessened and the growth of the fetus was normalized. These findings suggested involvement of exogenous serotonin in the elimination of radiation damage to the central nervous system of the germ. A question rises: Can serotonin lessen radiation damage to the embryo if it is exposed to ionizing radiation at later periods of gestation, during the period when the bones and the muscles are formed? This is the object of the present study. If mice were irradiated on the 11th day of gestation at a dose of 2.63 Gy, the number of female mice with viable fetuses decreased to 76.9% (compared with 100% of intact controls). The number of fetuses per female decreases to 3.2 (vs. 5.14); all developed fetuses had abnormalities, while there were no malformations in the fetuses of the intact (not irradiated) animals. Comparison results, showing the absence of the therapeutic effect of serotonin at the stage of skeleton formation, with results of previous studies, which demonstrated serotonin efficacy at the stage of formation of the central nervous system, suggests that the therapeutic effect of serotonin depends on the stage of embryo growth during which the mother is exposed to radiation

  14. Serotonin in fear conditioning processes.

    Science.gov (United States)

    Bauer, Elizabeth P

    2015-01-15

    This review describes the latest developments in our understanding of how the serotonergic system modulates Pavlovian fear conditioning, fear expression and fear extinction. These different phases of classical fear conditioning involve coordinated interactions between the extended amygdala, hippocampus and prefrontal cortices. Here, I first define the different stages of learning involved in cued and context fear conditioning and describe the neural circuits underlying these processes. The serotonergic system can be manipulated by administering serotonin receptor agonists and antagonists, as well as selective serotonin reuptake inhibitors (SSRIs), and these can have significant effects on emotional learning and memory. Moreover, variations in serotonergic genes can influence fear conditioning and extinction processes, and can underlie differential responses to pharmacological manipulations. This research has considerable translational significance as imbalances in the serotonergic system have been linked to anxiety and depression, while abnormalities in the mechanisms of conditioned fear contribute to anxiety disorders.

  15. Serotonin receptors as cardiovascular targets

    OpenAIRE

    Villalón, Carlos; De Vries, Peter; Saxena, Pramod Ranjan

    1997-01-01

    textabstractSerotonin exerts complex effects in the cardiovascular system, including hypotension or hypertension, vasodilatation or vasoconstriction, and/or bradycardia or tachycardia; the eventual response depends primarily on the nature of the 5-HT receptors involved. In the light of current 5-HT receptor classification, the authors reanalyse the cardiovascular responses mediated by 5-HT receptors and discuss the established and potential therapeutic applications of 5-HT ligands in the trea...

  16. Exercise, Stress Resistance, and Central Serotonergic Systems

    OpenAIRE

    Greenwood, Benjamin N.; Fleshner, Monika

    2011-01-01

    Voluntary exercise reduces the incidence of stress-related psychiatric disorders in humans and prevents serotonin-dependent behavioral consequences of stress in rodents. Evidence reviewed herein is consistent with the hypothesis that exercise increases stress resistance by producing neuroplasticity at multiple sites of the central serotonergic system, which all help to limit the behavioral impact of acute increases in serotonin during stressor exposure.

  17. The involvement of central corticotropin-releasing hormone and its receptors in sleep-wake regulation of mice

    OpenAIRE

    Romanowski, Christoph

    2010-01-01

    The corticotropin-releasing hormone (CRH) is widely recognised as the major activator of the hypothalamic-pituitary-adrenocortical (HPA) axis, thereby mediating neuroendocrine, autonomic, and behavioural responses to stress. Dysregulation of the release of stress hormones, caused by excessive CRH secretion from the hypothalamus, is frequently observed in patients with affective disorders such as depression. One of the cardinal symptoms of major depression is a severe impairment of sleep (e.g....

  18. Mutational Mapping and Modeling of the Binding Site for (S)-Citalopram in the Human Serotonin Transporter*

    OpenAIRE

    Andersen, Jacob; Olsen, Lars; Hansen, Kasper B.; Taboureau, Olivier; Jørgensen, Flemming S.; Jørgensen, Anne Marie; Bang-Andersen, Benny; Egebjerg, Jan; Strømgaard, Kristian; Kristensen, Anders S.

    2009-01-01

    The serotonin transporter (SERT) regulates extracellular levels of the neurotransmitter serotonin (5-hydroxytryptamine) in the brain by facilitating uptake of released 5-hydroxytryptamine into neuronal cells. SERT is the target for widely used antidepressant drugs, including imipramine, fluoxetine, and (S)-citalopram, which are competitive inhibitors of the transport function. Knowledge of the molecular details of the antidepressant binding sites in SERT has been limited due to lack of struct...

  19. The serotonin transporter knockout rat : A review

    NARCIS (Netherlands)

    Olivier, Jocelien; Cools, Alexander; Ellenbroek, Bart A.; Cuppen, E.; Homberg, Judith; Kalueff, Allan V.; LaPorte, Justin L.

    2010-01-01

    This chapter dicusses the most recent data on the serotonin transporter knock-out rat, a unique rat model that has been generated by target-selected N-ethyl-N-nitrosourea (ENU) driven mutagenesis. The knock-out rat is the result of a premature stopcodon in the serotonin transporter gene, and the abs

  20. Serotonin increases synaptic activity in olfactory bulb glomeruli.

    Science.gov (United States)

    Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

    2016-03-01

    Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range. PMID:26655822

  1. Pore opening dynamics in the exocytosis of serotonin

    Science.gov (United States)

    Ramirez-Santiago, Guillermo; Cercos, Montserrat G.; Martinez-Valencia, Alejandro; Salinas Hernandez, Israel; Rodríguez-Sosa, Leonardo; de-Miguel, Francisco F.

    2015-03-01

    The current view of the exocytosis of transmitter molecules is that it starts with the formation of a fusion pore that connects the intravesicular and the extracellular spaces, and is completed by the release of the rest of the transmitter contained in the vesicle upon the full fusion and collapse of the vesicle with the plasma membrane. However, under certain circumstances, a rapid closure of the pore before the full vesicle fusion produces only a partial release of the transmitter. Here we show that whole release of the transmitter occurs through fusion pores that remain opened for tens of milliseconds without vesicle collapse. This was demonstrated through amperometric measurements of serotonin release from electrodense vesicles in the axon of leech Retzius neurons and mathematical modelling. By modeling transmitter release with a diffusion equation subjected to boundary conditions that are defined by the experiment, we showed that those pores with a fast half rise time constant remained opened and allowed the full quantum release without vesicle collapse, whereas pores with a slow rise time constant closed rapidly, thus producing partial release. We conclude that a full transmitter release may occur through the fusion pore in the absence of vesicle collapse. This work was founded by a DGAPA-UNAM grants IN200914 and IN118410 CONACYT GRANT 130031, and CONACyT doctoral fellowships.

  2. Age of menarche and near adult height after long-term gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty

    OpenAIRE

    Baek, Joon-Woo; Nam, Hyo-Kyoung; Jin, Dahee; Oh, Yeon Joung; Rhie, Young-Jun; Lee, Kee-Hyoung

    2014-01-01

    Purpose Gonadotropin-releasing hormone agonist (GnRHa) is known for improving final adult height in patients with central precocious puberty (CPP). This study aimed to investigate the age of menarche and near adult height in girls with CPP who had been treated with GnRHa. Methods In this retrospective study, we reviewed the medical records of 71 Korean girls with CPP who had started menarche or reached over 13 years of bone age after long-term GnRHa treatment. We estimated near adult height u...

  3. Final height in central precocious puberty after long term treatment with a slow release GnRH agonist

    NARCIS (Netherlands)

    Oostdijk, W; Rikken, B; Schreuder, S; Otten, B; Odink, R; Rouwe, C; Jansen, M; Gerver, WJ; Waelkens, J; Drop, S

    1996-01-01

    Objective-To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. Patients-31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were trea

  4. Euglycemia restoration by central leptin in type 1 diabetes requires STAT3 signaling but not fast-acting neurotransmitter release

    Science.gov (United States)

    Central leptin action is sufficient to restore euglycemia in insulinopenic type 1 diabetes (T1D); however, the underlying mechanism remains poorly understood. To examine the role of intracellular signal transducer and activator of transcription 3 (STAT3) pathways, we used LepRs/s mice with disrupted...

  5. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior.

    Science.gov (United States)

    Patrick, Rhonda P; Ames, Bruce N

    2015-06-01

    Serotonin regulates a wide variety of brain functions and behaviors. Here, we synthesize previous findings that serotonin regulates executive function, sensory gating, and social behavior and that attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior all share in common defects in these functions. It has remained unclear why supplementation with omega-3 fatty acids and vitamin D improve cognitive function and behavior in these brain disorders. Here, we propose mechanisms by which serotonin synthesis, release, and function in the brain are modulated by vitamin D and the 2 marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Brain serotonin is synthesized from tryptophan by tryptophan hydroxylase 2, which is transcriptionally activated by vitamin D hormone. Inadequate levels of vitamin D (∼70% of the population) and omega-3 fatty acids are common, suggesting that brain serotonin synthesis is not optimal. We propose mechanisms by which EPA increases serotonin release from presynaptic neurons by reducing E2 series prostaglandins and DHA influences serotonin receptor action by increasing cell membrane fluidity in postsynaptic neurons. We propose a model whereby insufficient levels of vitamin D, EPA, or DHA, in combination with genetic factors and at key periods during development, would lead to dysfunctional serotonin activation and function and may be one underlying mechanism that contributes to neuropsychiatric disorders and depression. This model suggests that optimizing vitamin D and marine omega-3 fatty acid intake may help prevent and modulate the severity of brain dysfunction.

  6. The Role of Central Gastrin-Releasing Peptide and Neuromedin B Receptors in the Modulation of Scratching Behavior in Rats

    OpenAIRE

    Su, Pin-Yen; Ko, Mei-Chuan

    2011-01-01

    Bombesin is a pruritogenic agent that causes intense itch-scratching activity in rodents. Bombesin has high affinity for the gastrin-releasing peptide (GRP) receptor (GRPr) and the neuromedin B (NMB) receptor (NMBr). The aim of this study was to investigate pharmacologically the ability of GRPr and NMBr to elicit scratching behavior in rats. The intracerebroventricular route was selected for drug delivery because the study focused on supraspinal sites of action. The magnitude and duration of ...

  7. Serotonin signaling mediates protein valuation and aging.

    Science.gov (United States)

    Ro, Jennifer; Pak, Gloria; Malec, Paige A; Lyu, Yang; Allison, David B; Kennedy, Robert T; Pletcher, Scott D

    2016-01-01

    Research into how protein restriction improves organismal health and lengthens lifespan has largely focused on cell-autonomous processes. In certain instances, however, nutrient effects on lifespan are independent of consumption, leading us to test the hypothesis that central, cell non-autonomous processes are important protein restriction regulators. We characterized a transient feeding preference for dietary protein after modest starvation in the fruit fly, Drosophila melanogaster, and identified tryptophan hydroxylase (Trh), serotonin receptor 2a (5HT2a), and the solute carrier 7-family amino acid transporter, JhI-21, as required for this preference through their role in establishing protein value. Disruption of any one of these genes increased lifespan up to 90% independent of food intake suggesting the perceived value of dietary protein is a critical determinant of its effect on lifespan. Evolutionarily conserved neuromodulatory systems that define neural states of nutrient demand and reward are therefore sufficient to control aging and physiology independent of food consumption. PMID:27572262

  8. Mast cell expression of the serotonin1A receptor in guinea pig and human intestine

    OpenAIRE

    Wang, Guo-Du; Wang, Xi-Yu; Zou, Fei; Qu, Meihua; Liu, Sumei; Fei, Guijun; Xia, Yun; Needleman, Bradley J.; Mikami, Dean J.; Wood, Jackie D.

    2013-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells i...

  9. Genetic moderation of child maltreatment effects on depression and internalizing symptoms by serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter (NET), and corticotropin releasing hormone receptor 1 (CRHR1) genes in African American children.

    Science.gov (United States)

    Cicchetti, Dante; Rogosch, Fred A

    2014-11-01

    Genetic moderation of the effects of child maltreatment on depression and internalizing symptoms was investigated in a sample of low-income maltreated and nonmaltreated African American children (N = 1,096). Lifetime child maltreatment experiences were independently coded from Child Protective Services records and maternal report. Child depression and internalizing problems were assessed in the context of a summer research camp by self-report on the Children's Depression Inventory and adult counselor report on the Teacher Report Form. DNA was obtained from buccal cell or saliva samples and genotyped for polymorphisms of the following genes: serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter, and corticotropin releasing hormone receptor 1. Analyses of covariance with age and gender as covariates were conducted, with maltreatment status and respective polymorphism as main effects and their Gene × Environment (G × E) interactions. Maltreatment consistently was associated with higher Children's Depression Inventory and Teacher Report Form symptoms. The results for child self-report symptoms indicated a G × E interaction for BDNF and maltreatment. In addition, BDNF and triallelic 5-HTTLPR interacted with child maltreatment in a G × G × E interaction. Analyses for counselor report of child anxiety/depression symptoms on the Teacher Report Form indicated moderation of child maltreatment effects by triallelic 5-HTTLPR. These effects were elaborated based on variation in developmental timing of maltreatment experiences. Norepinephrine transporter was found to further moderate the G × E interaction of 5-HTTLPR and maltreatment status, revealing a G × G × E interaction. This G × G × E was extended by consideration of variation in maltreatment subtype experiences. Finally, G × G × E effects were observed for the co-action of BDNF and the corticotropin releasing hormone receptor 1

  10. Disruption of Transient Serotonin Accumulation by Non-Serotonin-Producing Neurons Impairs Cortical Map Development

    Directory of Open Access Journals (Sweden)

    Xiaoning Chen

    2015-01-01

    Full Text Available Polymorphisms that alter serotonin transporter SERT expression and functionality increase the risks for autism and psychiatric traits. Here, we investigate how SERT controls serotonin signaling in developing CNS in mice. SERT is transiently expressed in specific sets of glutamatergic neurons and uptakes extrasynaptic serotonin during perinatal CNS development. We show that SERT expression in glutamatergic thalamocortical axons (TCAs dictates sensory map architecture. Knockout of SERT in TCAs causes lasting alterations in TCA patterning, spatial organizations of cortical neurons, and dendritic arborization in sensory cortex. Pharmacological reduction of serotonin synthesis during the first postnatal week rescues sensory maps in SERTGluΔ mice. Furthermore, knockdown of SERT expression in serotonin-producing neurons does not impair barrel maps. We propose that spatiotemporal SERT expression in non-serotonin-producing neurons represents a determinant in early life genetic programming of cortical circuits. Perturbing this SERT function could be involved in the origin of sensory and cognitive deficits associated with neurodevelopmental disorders.

  11. Estimating Groundwater Concentrations from Mass Releases to the Aquifer at Integrated Disposal Facility and Tank Farm Locations Within the Central Plateau of the Hanford Site

    Energy Technology Data Exchange (ETDEWEB)

    Bergeron, Marcel P.; Freeman, Eugene J.

    2005-06-09

    This report summarizes groundwater-related numerical calculations that will support groundwater flow and transport analyses associated with the scheduled 2005 performance assessment of the Integrated Disposal Facility (IDF) at the Hanford Site. The report also provides potential supporting information to other ongoing Hanford Site risk analyses associated with the closure of single-shell tank farms and related actions. The IDF 2005 performance assessment analysis is using well intercept factors (WIFs), as outlined in the 2001 performance assessment of the IDF. The flow and transport analyses applied to these calculations use both a site-wide regional-scale model and a local-scale model of the area near the IDF. The regional-scale model is used to evaluate flow conditions, groundwater transport, and impacts from the IDF in the central part of the Hanford Site, at the core zone boundary around the 200 East and 200 West Areas, and along the Columbia River. The local-scale model is used to evaluate impacts from transport of contaminants to a hypothetical well 100 m downgradient from the IDF boundaries. Analyses similar to the regional-scale analysis of IDF releases are also provided at individual tank farm areas as additional information. To gain insight on how the WIF approach compares with other approaches for estimating groundwater concentrations from mass releases to the unconfined aquifer, groundwater concentrations were estimated with the WIF approach for two hypothetical release scenarios and compared with similar results using a calculational approach (the convolution approach). One release scenario evaluated with both approaches (WIF and convolution) involved a long-term source release from immobilized low-activity waste glass containing 25,550 Ci of technetium-99 near the IDF; another involved a hypothetical shorter-term release of {approx}0.7 Ci of technetium over 600 years from the S-SX tank farm area. In addition, direct simulation results for both release

  12. Fast methods for analysis of neurotransmitters from single cell and monitoring their releases in central nervous system by capillary electrophoresis, fluorescence microscopy and luminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ziqiang

    1999-12-10

    Fast methods for separation and detection of important neurotransmitters and the releases in central nervous system (CNS) were developed. Enzyme based immunoassay combined with capillary electrophoresis was used to analyze the contents of amino acid neurotransmitters from single neuron cells. The release of amino acid neurotransmitters from neuron cultures was monitored by laser induced fluorescence imaging method. The release and signal transduction of adenosine triphosphate (ATP) in CNS was studied with sensitive luminescence imaging method. A new dual-enzyme on-column reaction method combined with capillary electrophoresis has been developed for determining the glutamate content in single cells. Detection was based on monitoring the laser-induced fluorescence of the reaction product NADH, and the measured fluorescence intensity was related to the concentration of glutamate in each cell. The detection limit of glutamate is down to 10{sup {minus}8} M level, which is 1 order of magnitude lower than the previously reported detection limit based on similar detection methods. The mass detection limit of a few attomoles is far superior to that of any other reports. Selectivity for glutamate is excellent over most of amino acids. The glutamate content in single human erythrocyte and baby rat brain neurons were determined with this method and results agreed well with literature values.

  13. Autoradiographic localization of 3H-paroxetine-labeled serotonin uptake sites in rat brain

    International Nuclear Information System (INIS)

    Paroxetine is a potent and selective inhibitor of serotonin uptake into neurons. Serotonin uptake sites have been identified, localized, and quantified in rat brain by autoradiography with 3H-paroxetine; 3H-paroxetine binding in slide-mounted sections of rat forebrain was of high affinity (KD = 10 pM) and the inhibition affinity constant (Ki) values of various drugs in competing 3H-paroxetine binding significantly correlated with their reported potencies in inhibiting synaptosomal serotonin uptake. Serotonin uptake sites labeled by 3H-paroxetine were highly concentrated in the dorsal and median raphe nuclei, central gray, superficial layer of the superior colliculus, lateral septal nucleus, paraventricular nucleus of the thalamus, and the islands of Calleja. High concentrations of 3H-paroxetine binding sites were found in brainstem areas containing dopamine (substantia nigra and ventral tegmental area) and norepinephrine (locus coeruleus) cell bodies. Moderate concentrations of 3H-paroxetine binding sites were present in laminae I and IV of the frontal parietal cortex, primary olfactory cortex, olfactory tubercle, regions of the basal ganglia, septum, amygdala, thalamus, hypothalamus, hippocampus, and some brainstem areas including the interpeduncular, trigeminal, and parabrachial nuclei. Lower densities of 3H-paroxetine binding sites were found in other regions of the neocortex and very low to nonsignificant levels of binding were present in white matter tracts and in the cerebellum. Lesioning of serotonin neurons with 3,4-methylenedioxyamphetamine caused large decreases in 3H-paroxetine binding. The autoradiographic distribution of 3H-paroxetine binding sites in rat brain corresponds extremely well to the distribution of serotonin terminals and cell bodies as well as with the pharmacological sites of action of serotonin

  14. Autoradiographic localization of /sup 3/H-paroxetine-labeled serotonin uptake sites in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    De Souza, E.B.; Kuyatt, B.L.

    1987-01-01

    Paroxetine is a potent and selective inhibitor of serotonin uptake into neurons. Serotonin uptake sites have been identified, localized, and quantified in rat brain by autoradiography with 3H-paroxetine; 3H-paroxetine binding in slide-mounted sections of rat forebrain was of high affinity (KD = 10 pM) and the inhibition affinity constant (Ki) values of various drugs in competing 3H-paroxetine binding significantly correlated with their reported potencies in inhibiting synaptosomal serotonin uptake. Serotonin uptake sites labeled by 3H-paroxetine were highly concentrated in the dorsal and median raphe nuclei, central gray, superficial layer of the superior colliculus, lateral septal nucleus, paraventricular nucleus of the thalamus, and the islands of Calleja. High concentrations of 3H-paroxetine binding sites were found in brainstem areas containing dopamine (substantia nigra and ventral tegmental area) and norepinephrine (locus coeruleus) cell bodies. Moderate concentrations of 3H-paroxetine binding sites were present in laminae I and IV of the frontal parietal cortex, primary olfactory cortex, olfactory tubercle, regions of the basal ganglia, septum, amygdala, thalamus, hypothalamus, hippocampus, and some brainstem areas including the interpeduncular, trigeminal, and parabrachial nuclei. Lower densities of 3H-paroxetine binding sites were found in other regions of the neocortex and very low to nonsignificant levels of binding were present in white matter tracts and in the cerebellum. Lesioning of serotonin neurons with 3,4-methylenedioxyamphetamine caused large decreases in 3H-paroxetine binding. The autoradiographic distribution of 3H-paroxetine binding sites in rat brain corresponds extremely well to the distribution of serotonin terminals and cell bodies as well as with the pharmacological sites of action of serotonin.

  15. A gonadotropin-releasing hormone-like molecule modulates the activity of diverse central neurons in a gastropod mollusk, Aplysia californica

    Directory of Open Access Journals (Sweden)

    Biao eSun

    2011-09-01

    Full Text Available In vertebrates, gonadotropin-releasing hormone (GnRH is a crucial decapeptide that activates the hypothalamic-pituitary-gonadal (HPG axis to ensure successful reproduction. Recently, a GnRH-like molecule has been isolated from a gastropod mollusk, Aplysia californica. This GnRH (ap-GnRH is deduced to be an undecapeptide, and its function remains to be explored. Our previous study demonstrated that ap-GnRH did not stimulate a range of reproductive parameters. Instead, it affected acute behavioral and locomotive changes unrelated to reproduction. In this study, we used electrophysiology and retrograde tracing to further explore the central role of ap-GnRH. Sharp electrode intracellular recordings revealed that ap-GnRH had diverse effects on central neurons that ranged from excitatory, inhibitory, to the alteration of membrane potential. Unexpectedly, extracellular recordings revealed that ap-GnRH suppressed the onset of electrical afterdischarge (AD in bag cell neurons, suggesting an inhibitory effect on female reproduction. Lastly, using immunocytochemistry (ICC coupled with nickel-backfill, we demonstrated that some ap-GnRH neurons projected to efferent nerves known to innervate the foot and parapodia, suggesting ap-GnRH may directly modulate the motor output of these peripheral tissues. Overall, our results suggested that in A. californica, ap-GnRH more likely functioned as a central modulator of complex behavior and motor regulation rather than as a conventional reproductive stimulator.

  16. The influence of serotonin on fear learning.

    Directory of Open Access Journals (Sweden)

    Catherine Hindi Attar

    Full Text Available 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.

  17. Serotonin 5-HT2A Receptor Function as a Contributing Factor to Both Neuropsychiatric and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Charles D. Nichols

    2009-01-01

    Full Text Available There are high levels of comorbidity between neuropsychiatric and cardiovascular disorders. A key molecule central to both cognitive and cardiovascular function is the molecule serotonin. In the brain, serotonin modulates neuronal activity and is actively involved in mediating many cognitive functions and behaviors. In the periphery, serotonin is involved in vasoconstriction, inflammation, and cell growth, among other processes. It is hypothesized that one component of the serotonin system, the 5-HT2A receptor, is a common and contributing factor underlying aspects of the comorbidity between neuropsychiatric and cardiovascular disorders. Within the brain this receptor participates in processes such as cognition and working memory, been implicated in effective disorders such as schizophrenia, and mediate the primary effects of hallucinogenic drugs. In the periphery, 5-HT2A receptors have been linked to vasoconstriction and hypertension, and to inflammatory processes that can lead to atherosclerosis.

  18. Delayed pressure urticaria treated with the selective serotonin reuptake inhibitor escitalopram.

    Science.gov (United States)

    Eskeland, S; Tanum, L; Halvorsen, J A

    2016-07-01

    There is increasing evidence of platelet activation and systemic inflammation in chronic spontaneous urticaria and delayed pressure urticaria (DPU). Inflammation may be central to understanding the high comorbidity of depression and anxiety in patients with chronic urticaria (CU). We report a case of DPU and depression in a patient, which responded favourably to treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram. Sustained administration of SSRIs is associated with downregulation of serotonin transporters/receptors and depletion of platelet stored serotonin, which may reduce the ability of platelets to aggregate after thrombotic triggers. SSRIs are easier to manage and have significantly less disturbing adverse effects and cardiotoxicity than the tricyclic antidepressants (TCAs). SSRIs may represent an alternative to the traditional use of TCAs in treatment of CU. PMID:27037523

  19. Microwave-induced post-exposure hyperthermia: Involvement of endogenous opioids and serotonin

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Chou, C.K.; Guy, A.W.; Horita, A.

    1984-08-01

    Acute exposure to pulsed microwaves (2450 MHz, 1 mW/ cm/sup 2/, SAR 0.6 W/kg, 2-..mu..s pulses, 500 pulses/s) induces a transient post-exposure hyperthermia in the rat. The hyperthermia was attenuated by treatment with either the narcotic antagonist naltrexone or one of the serotonin antagonists cinanserin, cyproheptadine, or metergoline. It was not affected, however, by treatment with the peripheral serotonin antagonist xylamidine nor the dopamine antagonist haloperidol. It thus appears that both endogenous opioids and central serotonin are involved. It is proposed that pulsed microwaves activate endogenous opioid systems, and that they in turn activate a serotonergic mechanism that induces the rise in body temperature.

  20. Role of serotonin in pathogenesis of analgesic induced headache

    Energy Technology Data Exchange (ETDEWEB)

    Srikiatkhachorn, A.

    1999-12-16

    Analgesic abuse has recently been recognized as a cause of deterioration in primary headache patients. Although the pathogenesis of this headache transformation is still obscure, and alteration of central pain control system is one possible mechanism. A number of recent studies indicated that simple analgesics exert their effect by modulating the endogenous pain control system rather than the effect at the peripheral tissue, as previously suggested. Serotonin (5-hydroxytryptamine ; 5-HT) has long been known to play a pivotal role in the pain modulatory system in the brainstem. In the present study, we investigated the changes in 5-HT system in platelets and brain tissue. A significant decrease in platelet 5-HT concentration (221.8{+-}30.7, 445.3{+-}37.4 and 467.2{+-}38.5 ng/10{sup 9} platelets, for patients with analgesic-induced headache and migraine patients, respectively, p<0.02) were evident in patients with analgesic induced headache. Chronic paracetamol administration induced a decrease in 5-HT{sub 2} serotonin receptor in cortical and brain stem tissue in experimental animals (B{sub max}=0.93{+-}0.04 and 1.79{+-}0.61 pmol/mg protein for paracetamol treated rat and controls, respectively, p<0.05). Our preliminary results suggested that chronic administration of analgesics interferes with central and peripheral 5-HT system and therefore possibly alters the 5-HT dependent antinociceptive system. (author)

  1. Water Input and Water Release from the Subducting Nazca Plate along Southern Central Chile (33°S-46°S)

    Science.gov (United States)

    Voelker, D.; Stipp, M.

    2015-12-01

    The fixation of water in the oceanic crust and upper mantle, the flux of stored water into subduction zones and the partial liberation of those fluids underneath the forearc and arc are mechanisms that impact on almost every aspect of subduction zone processes, e.g. intensity and type of arc volcanism, deposition of ores and seismicity of the subduction fault, but also on global geochemical budgets by recycling material back into the continental crust. Much of that water fixation happens at the outer rise of subduction zones in particular by deep percolation of fluids to the upper mantle along bend faults. Offshore Chile, the age of the subducting Nazca Plate varies between 0 Ma at the Chile Triple Junction (46°S) and ~38 Ma at the latitude of Valparaíso (32°S). Age-related variations in the thermal state of the subducting Nazca Plate impact on the water influx to the subduction zone, as well as the volumes of water that are released under the continental forearc or, alternatively, carried into the deeper mantle. Southern Central Chile is an ideal setting to study this effect, because other factors important for the subduction zone water budget appear constant. We determine the water influx by calculating the crustal water uptake and by modeling the upper mantle serpentinization at the outer rise of the Chile Trench. The water release under forearc and arc is determined by coupling FEM thermal models of the subducting plate with stability fields of water-releasing mineral reactions for upper and lower crust and hydrated mantle. Results show that both the influx and the release of water vary drastically over a length of 1500 km. In particular, the oldest and coldest segments carry roughly twice as much water into the subduction zone as the youngest and hottest segments, but their release flux to the forearc is only about one fourth of the latter. This high variability over a subduction zone of ~1500 km length shows that it is insufficient to consider subduction

  2. Immunomodulatory effects mediated by serotonin.

    Science.gov (United States)

    Arreola, Rodrigo; Becerril-Villanueva, Enrique; Cruz-Fuentes, Carlos; Velasco-Velázquez, Marco Antonio; Garcés-Alvarez, María Eugenia; Hurtado-Alvarado, Gabriela; Quintero-Fabian, Saray; Pavón, Lenin

    2015-01-01

    Serotonin (5-HT) induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a) membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b) downstream signaling transduction proteins; and (c) enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines. This review covers the clinical and experimental mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell-specific and depend on the expression of serotonergic components in immune cells. Consequently, 5-HT can modulate several immunological events, such as chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis. The effects of 5-HT on immune cells may be relevant in the clinical outcome of pathologies with an inflammatory component. Major depression, fibromyalgia, Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated with changes in the serotonergic system associated with leukocytes. Thus, pharmacological regulation of the serotonergic system may modulate immune function and provide therapeutic alternatives for these diseases. PMID:25961058

  3. Immunomodulatory Effects Mediated by Serotonin

    Directory of Open Access Journals (Sweden)

    Rodrigo Arreola

    2015-01-01

    Full Text Available Serotonin (5-HT induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b downstream signaling transduction proteins; and (c enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines. This review covers the clinical and experimental mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell-specific and depend on the expression of serotonergic components in immune cells. Consequently, 5-HT can modulate several immunological events, such as chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis. The effects of 5-HT on immune cells may be relevant in the clinical outcome of pathologies with an inflammatory component. Major depression, fibromyalgia, Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated with changes in the serotonergic system associated with leukocytes. Thus, pharmacological regulation of the serotonergic system may modulate immune function and provide therapeutic alternatives for these diseases.

  4. Transient Serotonin Syndrome by Concurrent Use of Electroconvulsive Therapy and Selective Serotonin Reuptake Inhibitor: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Nagahisa Okamoto

    2012-01-01

    Full Text Available The serotonin syndrome, which is characterized by psychiatric, autonomic nervous and neurological symptoms, is considered to be caused by excessive stimulation of the 5-HT1A and 5-HT2 receptors in the gray matter and spinal cord of the central nervous system, after the start of dosing or increase of the dose of a serotoninergic drug. There have been hardly any reports of induction of serotonin syndrome by electroconvulsive therapy (ECT in combination with antidepressant. We present the case of a female patient with major depressive disorder (MDD who developed transient serotonin syndrome soon after the first session of ECT in combination with paroxetine. Paroxetine was discontinued, and her psychiatric, autonomic nervous and neurological symptoms were gradually relieved and disappeared within 2 days. We performed the second ECT session 5 days after the initial session and performed 12 sessions of ECT without any changes in the procedure of ECT and anesthesia, but no symptoms of SS were observed. Finally, her MDD remitted. ECT might cause transiently increased blood-brain barrier (BBB permeability and enhance the transmissivity of the antidepressant in BBB. Therefore, it is necessary to pay attention to rare side effect of serotonin syndrome by ECT in combination with antidepressant.

  5. Lifelong disturbance of serotonin transporter functioning results in fear learning deficits: Reversal by blockade of CRF1 receptors.

    Science.gov (United States)

    Bijlsma, Elisabeth Y; Hendriksen, Hendrikus; Baas, Johanna M P; Millan, Mark J; Groenink, Lucianne

    2015-10-01

    The inability to associate aversive events with relevant cues (i.e. fear learning) may lead to maladaptive anxiety. To further study the role of the serotonin transporter (SERT) in fear learning, classical fear conditioning was studied in SERT knockout rats (SERT(-/-)) using fear potentiation of the startle reflex. Next, fear acquisition and concomitant development of contextual conditioned fear were monitored during training. To differentiate between developmental and direct effects of reduced SERT functioning, effects of acute and chronic SSRI treatment were studied in adult rats. Considering the known interactions between serotonin and corticotropin-releasing factor (CRF), we studied the effect of the CRFR1 antagonist CP154,526 on behavioral changes observed and determined CRF1 receptor levels in SERT(-/-) rats. SERT(-/-) showed blunted fear potentiation and enhanced contextual fear, which resulted from a deficit in fear acquisition. Paroxetine treatment did not affect acquisition or expression of fear-potentiated startle, suggesting that disturbed fear learning in SERT(-/-) results from developmental changes and not from reduced SERT functioning. Although CRF1 receptor levels did not differ significantly between genotypes, CP154,526 treatment normalized both cue- and contextual fear in SERT(-/-) during acquisition, but not expression of fear-potentiated startle. The disrupted fear acquisition and concomitant increase in contextual conditioned fear-potentiated startle fear in SERT(-/-) resembles the associative learning deficit seen in patients with panic disorder and suggests that normal SERT functioning is crucial for the development of an adequate fear neuro-circuitry. Moreover, the normalization of fear acquisition by CP154,526 suggests a role for central CRF signaling in the generalization of fear.

  6. The serotonin transporter in rhesus monkey brain: comparison of DASB and citalopram binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Zhizhen [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States)]. E-mail: zhizhen_zeng@merck.com; Chen, T.-B. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Miller, Patricia J. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Dean, Dennis [Labeled Compound Synthesis Group, Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065-0900 (United States); Tang, Y.S. [Labeled Compound Synthesis Group, Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065-0900 (United States); Sur, Cyrille [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Williams, David L. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States)

    2006-05-15

    We have characterized the interaction of the serotonin transporter ligand [{sup 3}H]-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)-benzylamine (DASB) with rhesus monkey brain in vitro using tissue homogenate binding and autoradiographic mapping. [{sup 3}H]-DASB, a tritiated version of the widely used [{sup 11}C] positron emission tomography tracer, was found to selectively bind to a single population of sites with high affinity (K {sub d}=0.20{+-}0.04 nM). The serotonin transporter density (B {sub max}) obtained for rhesus frontal cortex was found to be 66{+-}8 fmol/mg protein using [{sup 3}H]-DASB, similar to the B {sub max} value obtained using the reference radioligand [{sup 3}H]-citalopram, a well-characterized and highly selective serotonin reuptake inhibitor (83{+-}22 fmol/mg protein). Specific binding sites of both [{sup 3}H]-DASB and [{sup 3}H]-citalopram were similarly and nonuniformly distributed throughout the rhesus central nervous system, in a pattern consistent with serotonin transporter localization reported for human brain. Regional serotonin transporter densities, estimated from optical densities of the autoradiographic images, were well correlated between the two radioligands. Finally, DASB and fluoxetine showed dose-dependent full inhibition of [{sup 3}H]-citalopram binding in a competition autoradiographic study, with K {sub i} values in close agreement with those obtained from rhesus brain homogenates. This side-by-side comparison of [{sup 3}H]-DASB and [{sup 3}H]-citalopram binding sites in rhesus tissue homogenates and in adjacent rhesus brain slices provides additional support for the use of [{sup 11}C]-DASB to assess the availability and distribution of serotonin transporters in nonhuman primates.

  7. Substrate and Inhibitor-Specific Conformational Changes in the Human Serotonin Transporter Revealed by Voltage-Clamp Fluorometry

    DEFF Research Database (Denmark)

    Söderhielm, Pella C; Andersen, Jacob; Munro, Lachlan;

    2015-01-01

    of TM6, Ala419 in the interface between TM8 and extracellular loop (EL) 4, and Leu481 in EL5. The reporter positions were used for time-resolved measurement of conformational changes during 5-HT transport and binding of cocaine and the selective serotonin reuptake inhibitors fluoxetine and escitalopram......The serotonin transporter (SERT) regulates neurotransmission by the biogenic monoamine neurotransmitter serotonin (5-HT, 5-hydroxytryptamine) in the central nervous system, and drugs inhibiting SERT are widely used for the treatment of a variety of central nervous system diseases....... The conformational dynamics of SERT transport function and inhibition is currently poorly understood. We used voltage-clamp fluorometry to study conformational changes in human SERT (hSERT) during 5-HT transport and inhibitor binding. Cys residues were introduced at 12 positions in hSERT to enable covalent...

  8. The serotonin transporter in psychiatric disorders

    DEFF Research Database (Denmark)

    Spies, Marie; Knudsen, Karen Birgitte Moos; Lanzenberger, Rupert;

    2015-01-01

    and might therefore be relevant for stratification of patients into clinical subsets. PET has enabled the elucidation of mechanisms of response to selective serotonin reuptake inhibitors (SSRIs) and hence provides a basis for rational pharmacological treatment of major depressive disorder. Such imaging......Over the past 20 years, psychotropics affecting the serotonergic system have been used extensively in the treatment of psychiatric disorders. Molecular imaging, in particular PET, has allowed for elucidation of the essential contribution of the serotonin transporter to the pathophysiology...... of various psychiatric disorders and their treatment. We review studies that use PET to measure cerebral serotonin transporter activity in psychiatric disorders, focusing on major depressive disorder and antidepressant treatment. We also discuss opportunities and limitations in the application...

  9. Serotonin Syndrome Induced by Fentanyl in a Child: Case Report.

    Science.gov (United States)

    Robles, Luis A

    2015-01-01

    Serotonin syndrome (SS) is a potentially fatal condition associated with increased serotonergic activity in the central nervous system that can be attributed to certain drugs or interactions between drugs. There are some published articles reporting this syndrome caused by the combination of fentanyl and selective serotonin reuptake inhibitors antidepressants in adult patients; however, there are no reports of SS associated to the use of fentanyl as a single causative agent. The author reports a case of a 7-year-old boy who was admitted to the emergency department with neurological deterioration secondary to an intracerebral hemorrhage. The patient was operated to remove the bleeding. Postoperatively, he experienced a diversity of progressive neurological signs (shivering, tremor, hypertonia, hyperreflexia, clonus, bilateral mydriasis, and intracranial hypertension), which were initially considered to be signs of neurological deterioration, but finally, it was proved that they were part of a SS caused by fentanyl.The absence of concomitant use of another medications known to induce SS and the dramatic improving observed after stopping fentanyl strongly indicates that fentanyl was the causative agent in this case of SS.Fentanyl is a medication used frequently, and therefore, clinicians should be aware of this potential adverse effect when this drug is administered.

  10. Serotonin depletion results in a decrease of the neuronal activation caused by rivastigmine in the rat hippocampus

    DEFF Research Database (Denmark)

    Kornum, Birgitte Rahbek; Weikop, Pia; Moller, Arne;

    2006-01-01

    Interactions between the serotonergic and cholinergic systems are known to occur and are believed to play a role in the mechanism underlying both major depression and Alzheimer's disease. On a molecular level, studies suggest that acetylcholine (ACh) increases serotonin (5-HT) release through nic...

  11. Effect of 5-HT1A receptor-mediated serotonin augmentation on Fos immunoreactivity in rat brain

    NARCIS (Netherlands)

    Jongsma, ME; Sebens, JB; Bosker, FJ; Korf, J

    2002-01-01

    The consequences of pharmacologically evoked augmented serotonin (5-hydroxytryptamine, 5-HT) release on neuronal activity in the brain, as reflected by the cellular expression of the immediate early gene c-fos, were studied. Wistar rats were treated with saline, the 5-HT reuptake inhibitor citalopra

  12. Serotonin Transporter Gene Polymorphism, Childhood Trauma, and Cognition in Patients With Psychotic Disorders

    OpenAIRE

    Aas, Monica; Djurovic, Srdjan; Athanasiu, Lavinia; Steen, Nils Eiel; Agartz, Ingrid; Lorentzen, Steinar; Sundet, Kjetil; Andreassen, Ole A; Melle, Ingrid

    2011-01-01

    Objective: The functional polymorphism in the promoter region of the SLC6A4/5-HTT serotonin transporter gene (5-HTTLPR) has been linked to altered stress response. Carriers of the short (s-) allele have increased negative psychological reactions and stress hormone release compared with carriers of the long (l-) allele, interacting with severe life events including childhood trauma. High stress levels are associated with cognitive impairments in a variety of clinical and experimental studies. ...

  13. Generation of a Tph2 Conditional Knockout Mouse Line for Time- and Tissue-Specific Depletion of Brain Serotonin.

    Directory of Open Access Journals (Sweden)

    Barbara Pelosi

    Full Text Available Serotonin has been gaining increasing attention during the last two decades due to the dual function of this monoamine as key regulator during critical developmental events and as neurotransmitter. Importantly, unbalanced serotonergic levels during critical temporal phases might contribute to the onset of neuropsychiatric disorders, such as schizophrenia and autism. Despite increasing evidences from both animal models and human genetic studies have underpinned the importance of serotonin homeostasis maintenance during central nervous system development and adulthood, the precise role of this molecule in time-specific activities is only beginning to be elucidated. Serotonin synthesis is a 2-step process, the first step of which is mediated by the rate-limiting activity of Tph enzymes, belonging to the family of aromatic amino acid hydroxylases and existing in two isoforms, Tph1 and Tph2, responsible for the production of peripheral and brain serotonin, respectively. In the present study, we generated and validated a conditional knockout mouse line, Tph2flox/flox, in which brain serotonin can be effectively ablated with time specificity. We demonstrated that the Cre-mediated excision of the third exon of Tph2 gene results in the production of a Tph2null allele in which we observed the near-complete loss of brain serotonin, as well as the growth defects and perinatal lethality observed in serotonin conventional knockouts. We also revealed that in mice harbouring the Tph2null allele, but not in wild-types, two distinct Tph2 mRNA isoforms are present, namely Tph2Δ3 and Tph2Δ3Δ4, with the latter showing an in-frame deletion of amino acids 84-178 and coding a protein that could potentially retain non-negligible enzymatic activity. As we could not detect Tph1 expression in the raphe, we made the hypothesis that the Tph2Δ3Δ4 isoform can be at the origin of the residual, sub-threshold amount of serotonin detected in the brain of Tph2null/null mice

  14. Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype

    International Nuclear Information System (INIS)

    Homozygote carriers of two long (L) alleles of the serotonin transporter (5-HTT) regulatory region displayed in vitro a twofold increase in 5-HTT expression compared with carriers of one or two short (S) alleles. However, in vivo imaging studies yielded contradictory results. Recently, an A > G exchange leading to differential transcriptional activation of 5-HTT mRNA in lymphobalstoid cell lines was discovered in the 5-HTT regulatory region. In vitro and in vivo evidence suggests that [11C]DASB, a new 5-HTT ligand offers some advantages over the ligands used in previous studies in measuring 5-HTT density independent of synaptic levels of serotonin. We assessed 5-HTT binding potential (BP 2) in the midbrain of 19 healthy subjects with positron emission tomography and [11C]DASB. Accounting for the hypothesized functional similarity of LG and S in driving 5-HTT transcription, we assessed whether LALA homozygotes display increased midbrain BP2 compared with carriers of at least one S allele. BP2 in the midbrain was significantly increased in LALA homozygotes compared with carriers of at least one S allele. Interestingly, the genotype effect on the midbrain was significantly different from that on the thalamus and the amygdala where no group differences were detected. This in vivo study provides further evidence that subjects homozygous for the LA allele display increased expression of 5-HTT in the midbrain, the origin of central serotonergic projections. (author)

  15. Intragastric injection of Lactobacillus casei strain Shirota suppressed spleen sympathetic activation by central corticotrophin-releasing factor or peripheral 2-deoxy-d-glucose in anesthetized rats.

    Science.gov (United States)

    Tanida, Mamoru; Takada, Mai; Kato-Kataoka, Akito; Kawai, Mitsuhisa; Miyazaki, Kouji; Shibamoto, Toshishige

    2016-04-21

    Intragastric (IG) administration of probiotic strain Lactobacillus casei Shirota (LcS) decreases the sympathetic nerve outflow of anesthetized rats in a tissue-specific manner. In the present study, we examined the effects of IG administration of LcS on sympathetic activation induced by an intracerebroventricular (ICV) injection of corticotrophin-releasing factor (CRF) and an intravenous (IV) injection of 2-deoxy-d-glucose (2DG) or interleukin (IL)-1β in urethane-anesthetized rats. The IG administration of LcS differently affected the stimulatory responses of sympathetic nerve outflow to CRF. LcS suppressed the increase in splenic sympathetic nerve activity (Spleen-SNA), induced by central CRF, in a dose-dependent manner; however, it did not alter adrenal sympathetic nervous activity (ASNA). In contrast, LcS did not affect spleen-SNA and ASNA following an IV injection of IL-1β. On the other hand, IG administration of LcS suppressed the activation of ASNA following an IV injection of 2DG. These findings suggest that the suppression of central CRF-induced sympathetic activation by LcS is tissue-specific. Moreover, it can suppress the 2DG-induced sympathetic activation. Furthermore, we found that stomach-specific vagotomy attenuates the suppressive effect of LcS on CRF-mediated spleen-SNA activation. Thus, the present study suggests that LcS administered to the stomach may act on the afferent vagal nerve and send afferent signals to the brain to regulate efferent SNA induced by sympathetic stimulators. PMID:26971699

  16. Effects on selective serotonin antagonism on central neurotransmission

    Science.gov (United States)

    Aggression and cannibalism in laying hens can differ in intensity and degree due to many factors, including genetics. Behavioral analysis of DeKalb XL (DXL) and high group productivity and survivability (HGPS) strains revealed high and low aggressiveness, respectively. However, the exact genetic me...

  17. A current view of serotonin transporters [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Louis J. De Felice

    2016-07-01

    Full Text Available Serotonin transporters (SERTs are largely recognized for one aspect of their function—to transport serotonin back into the presynaptic terminal after its release. Another aspect of their function, however, may be to generate currents large enough to have physiological consequences. The standard model for electrogenic transport is the alternating access model, in which serotonin is transported with a fixed ratio of co-transported ions resulting in net charge per cycle. The alternating access model, however, cannot account for all the observed currents through SERT or other monoamine transporters.  Furthermore, SERT agonists like ecstasy or antagonists like fluoxetine generate or suppress currents that the standard model cannot support.  Here we survey evidence for a channel mode of transport in which transmitters and ions move through a pore. Available structures for dopamine and serotonin transporters, however, provide no evidence for a pore conformation, raising questions of whether the proposed channel mode actually exists or whether the structural data are perhaps missing a transient open state.

  18. Plasma levels of beta-endorphin and serotonin in response to specific spinal based exercises

    Directory of Open Access Journals (Sweden)

    O. Sokunbi

    2008-02-01

    Full Text Available Exercises as the primary mode of treatment for low back disorders aim to achieve pain reduction, improvement in functional abilityand quality of life of for low back disorder sufferers. However the bio-chemical events associated with the use of these exercises in terms of theireffects on pain relieving neuropeptides have not been well established. Thisstudy was carried out to investigate the effects of spinal stabilisation, backextension and treadmill walking exercises on plasma levels of serotonin andbeta-endorphin.Twenty volunteers (10 males and 10 females without low back pain participated in the study. They were randomly allocated either to one of theexercise groups, where participants carried out one of the spinal stabilisation, back extension and treadmill walkingexercises or the control (no exercise group. The main outcome measures used in this study were plasma levels of serotonin and beta-endorphin measured with Enzyme linked immuno absorbent assay (ELISA technique.The results of this study showed that spinal stabilisation and treadmill walking exercises produced significantincrease in plasma serotonin levels (P < 0.05 however there were no significant changes in the plasma levels of beta-endorphin in all the exercise groups (P > 0.05.It could be that biochemical effects associated with stabilisation and treadmill walking exercises therefore mayinvolve production of serotonin and its release into the plasma.

  19. Serotonin dependent masking of hippocampal sharp wave ripples.

    Science.gov (United States)

    ul Haq, Rizwan; Anderson, Marlene L; Hollnagel, Jan-Oliver; Worschech, Franziska; Sherkheli, Muhammad Azahr; Behrens, Christoph J; Heinemann, Uwe

    2016-02-01

    Sharp wave ripples (SPW-Rs) are thought to play an important role in memory consolidation. By rapid replay of previously stored information during slow wave sleep and consummatory behavior, they result from the formation of neural ensembles during a learning period. Serotonin (5-HT), suggested to be able to modify SPW-Rs, can affect many neurons simultaneously by volume transmission and alter network functions in an orchestrated fashion. In acute slices from dorsal hippocampus, SPW-Rs can be induced by repeated high frequency stimulation that induces long-lasting LTP. We used this model to study SPW-R appearance and modulation by 5-HT. Although stimulation in presence of 5-HT permitted LTP induction, SPW-Rs were "masked"--but appeared after 5-HT wash-out. This SPW-R masking was dose dependent with 100 nM 5-HT being sufficient--if the 5-HT re-uptake inhibitor citalopram was present. Fenfluramine, a serotonin releaser, could also mask SPW-Rs. Masking was due to 5-HT1A and 5-HT2A/C receptor activation. Neither membrane potential nor membrane conductance changes in pyramidal cells caused SPW-R blockade since both remained unaffected by combining 5-HT and citalopram. Moreover, 10 and 30 μM 5-HT mediated SPW-R masking preceded neuronal hyperpolarization and involved reduced presynaptic transmitter release. 5-HT, as well as a 5-HT1A agonist, augmented paired pulse facilitation and affected the coefficient of variance. Spontaneous SPW-Rs in mice hippocampal slices were also masked by 5-HT and fenfluramine. While neuronal ensembles can acquire long lasting LTP during higher 5-HT levels, lower 5-HT levels enable neural ensembles to replay previously stored information and thereby permit memory consolidation memory. PMID:26409781

  20. Activation of corticotropin releasing factor-containing neurons in the rat central amygdala and bed nucleus of the stria terminalis following exposure to two different anxiogenic stressors.

    Science.gov (United States)

    Butler, Ryan K; Oliver, Elisabeth M; Sharko, Amanda C; Parilla-Carrero, Jeffrey; Kaigler, Kris F; Fadel, Jim R; Wilson, Marlene A

    2016-05-01

    Rats exposed to the odor of a predator or to the elevated plus maze (EPM) express unique unconditioned fear behaviors. The extended amygdala has previously been demonstrated to mediate the response to both predator odor and the EPM. We seek to determine if divergent amygdalar microcircuits are associated with the different behavioral responses. The current experiments compared activation of corticotropin-releasing factor (CRF)-containing neuronal populations in the central amygdala and bed nucleus of the stria terminalis (BNST) of rats exposed to either the EPM (5 min) versus home cage controls, or predator (ferret) odor versus butyric acid, or no odor (30 min). Sections of the brains were prepared for dual-labeled immunohistochemistry and counts of c-Fos co-localized with CRF were made in the centrolateral and centromedial amygdala (CLA and CMA) as well as the dorsolateral (dl), dorsomedial (dm), and ventral (v) BNST. Ferret odor-exposed rats displayed an increase in duration and a decrease in latency of defensive burying versus control rats. Exposure to both predator stress and EPM induced neuronal activation in the BNST, but not the central amygdala, and similar levels of neuronal activation were seen in both the high and low anxiety groups in the BNST after EPM exposure. Dual-labeled immunohistochemistry showed a significant increase in the percentage of CRF/c-Fos co-localization in the vBNST of ferret odor-exposed rats compared to control and butyric acid-exposed groups as well as EPM-exposed rats compared to home cage controls. In addition, an increase in the percentage of CRF-containing neurons co-localized with c-Fos was observed in the dmBNST after EPM exposure. No changes in co-localization of CRF with c-Fos was observed with these treatments in either the CLA or CMA. These results suggest that predator odor and EPM exposure activates CRF neurons in the BNST to a much greater extent than CRF neurons of the central amygdala, and indicates unconditioned

  1. Measuring the serotonin uptake site using [3H]paroxetine--a new serotonin uptake inhibitor

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-01-01

    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.

  3. Regional distribution of gonadotropin-releasing hormone-like, beta-endorphin-like, and methionine-enkephalin-like immunoreactivities in the central nervous system of the goat.

    Science.gov (United States)

    Karuri, A R; Ayres, S; Kumar, M S

    2000-01-01

    Regional distribution of gonadotropin-releasing hormone (GnRH)-like-, beta-endorphin (beta-end)-like-, and methionine-enkephalin (met-enk)-like-immunoreactivity was quantified across various regions of the central nervous system (CNS) of male and female goats by using highly specific radioimmunoassays. All the animals were sacrificed during the months of March through June (non-breeding season). Although the distribution of these three neuropeptides was similar to other mammalian species, species-specific gender differences in the levels of neuropeptides were noticed in the goat CNS. Highest levels of GnRH-like immunoreactivities were found in the hypothalamus. The hypothalamus of male goats exhibited significantly higher levels of GnRH-like immunoreactivities compared to female goats. Other regions exhibiting GnRH-like immunoreactivities included olfactory bulbs, preoptic and supraoptic regions, and mamillary bodies. Both beta-end- and met-enk immunoreactivities were detected in all selected regions of goat CNS, but highest levels of these opioid peptide-like immunoreactivities were limited to the forebrain regions of the goat. The supraoptic area of the female goats contained significantly higher levels of beta-end-like immunoreactivities than that of the male goats. Met-enk-peptide-like immunoreactivity also exhibited gender-specific differences in its content in some regions of the CNS. The male goats exhibited significantly higher levels of met-enk-like immunoreactivity in both the striatal and hypothalamic regions of the brain.

  4. Mutational Mapping and Modeling of the Binding Site for (S)-Citalopram in the Human Serotonin Transporter

    DEFF Research Database (Denmark)

    Andersen, Jacob; Olsen, Lars; Hansen, Kasper B.;

    2010-01-01

    The serotonin transporter (SERT) regulates extracellular levels of the neurotransmitter serotonin (5-hydroxytryptamine) in the brain by facilitating uptake of released 5-hydroxytryptamine into neuronal cells. SERT is the target for widely used antidepressant drugs, including imipramine, fluoxetine......, and (S)-citalopram, which are competitive inhibitors of the transport function. Knowledge of the molecular details of the antidepressant binding sites in SERT has been limited due to lack of structural data on SERT. Here, we present a characterization of the (S)-citalopram binding pocket in human SERT (h...

  5. Serotonin's role in piglet mortality and thriftiness.

    Science.gov (United States)

    Dennis, R L; McMunn, K A; Cheng, H W; Marchant-Forde, J N; Lay, D C

    2014-11-01

    Improving piglet survivability rates is of high priority for swine production as well as for piglet well-being. Dysfunction in the serotonin (5-HT) system has been associated with growth deficiencies, infant mortalities, or failure to thrive in human infants. The aim of this research was to determine if a relationship exists between infant mortality and failure to thrive (or unthriftiness), and umbilical 5-HT concentration in piglets. Umbilical blood was collected from a total of 60 piglets from 15 litters for analysis of 5-HT and tryptophan (Trp; the AA precursor to 5-HT) concentrations. Behavior was scan sampled for the first 2 days after birth. Brain samples were also taken at 8 h after birth from healthy and unthrifty piglets (n = 4/group). The raphe nucleus was dissected out and analyzed for 5-HT and dopamine concentrations as well as their major metabolites 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), respectively. Data were analyzed by ANOVA. Piglets that died within 48 h of birth (n = 14) had significantly lower umbilical blood 5-HT concentrations at the time of their birth compared to their healthy counterparts (n = 46, P = 0.003). However, no difference in Trp was detected (P 0.38). Time spent under the heat lamp and sleeping were positively correlated with umbilical 5-HT levels (P = 0.004 and P = 0.02, respectively), while inactivity had a negative correlation with 5-HT levels (P = 0.04). In the raphe nucleus, the center for brain 5-HT biosynthesis, unthrifty piglets had a greater concentration of 5-HIAA (P = 0.02) and a trend for higher concentrations of 5-HT (P = 0.07) compared with healthy piglets. Dopamine levels did not differ between thrifty and unthrifty piglets (P = 0.45); however, its metabolite HVA tended to be greater in unthrifty piglets (P = 0.05). Our results show evidence of serotonergic dysfunction, at both the central and peripheral levels, accompanying early piglet mortalities. These data suggest a possible route for

  6. Serotonin Syndrome after Clomipramine Overdose in a Child

    Science.gov (United States)

    Direk, Meltem Çobanoğulları; Yıldırım, Veli; Güneş, Serkan; Bozlu, Gülçin; Okuyaz, Çetin

    2016-01-01

    Serotonin syndrome (SS) is a potentially life-threatening condition associated with increased serotonergic activity in central nervous system and may occur during the use of serotonergic drugs. Although increasing frequency of serotonergic drug use in children, pediatricians, emergency medicine and pediatric intensive care specialists have not enough knowledge and experience about SS that is a potentially life-threatening condition. A 12-year-old girl patient was admitted to our emergency room with the history of involuntary contractions on her extremities and alteration of consciousness. Her physical examination showed agitation, hyperthermia, dilated pupils, tremor, increased deep tendon reflexes, positive spontaneous clonus, agitation, flushed skin and diaphoresis, excessive perspiration, and continuous horizontal ocular movements. The patient diagnosed as SS by clinical history, physical and laboratory findings. In this paper, we will discuss SS occurred in a 12-year-old girl after concurrent clomipramine and risperidone use. PMID:27776393

  7. An Unusual Case of Serotonin Syndrome with Oxycodone and Citalopram

    Directory of Open Access Journals (Sweden)

    Clare Walter

    2012-01-01

    Full Text Available A 77-year-old female with recurrent non-small-cell lung cancer presented to a hospital outpatient clinic with tremor, weakness, inability to coordinate motor movements, and confusion. It was suspected that the symptoms were due to possible central nervous system metastases; however, a CT scan of her head was unremarkable. The lung clinic liaison pharmacist took a medication history from the patient, complimented by extra information from the patient’s community pharmacy. The pharmacist suspected the rare side effect of serotonin syndrome was responsible for the patient’s presenting symptoms caused by the combination of oxycodone and citalopram. The patient’s symptoms resolved soon after oxycodone was changed to morphine.

  8. Regulation of systemic energy homeostasis by serotonin in adipose tissues.

    Science.gov (United States)

    Oh, Chang-Myung; Namkung, Jun; Go, Younghoon; Shong, Ko Eun; Kim, Kyuho; Kim, Hyeongseok; Park, Bo-Yoon; Lee, Ho Won; Jeon, Yong Hyun; Song, Junghan; Shong, Minho; Yadav, Vijay K; Karsenty, Gerard; Kajimura, Shingo; Lee, In-Kyu; Park, Sangkyu; Kim, Hail

    2015-04-13

    Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.

  9. Modulation of Olfactory Bulb Network Activity by Serotonin: Synchronous Inhibition of Mitral Cells Mediated by Spatially Localized GABAergic Microcircuits

    Science.gov (United States)

    Schmidt, Loren J.; Strowbridge, Ben W.

    2014-01-01

    Although inhibition has often been proposed as a central mechanism for coordinating activity in the olfactory system, relatively little is known about how activation of different inhibitory local circuit pathways can generate coincident inhibition of principal cells. We used serotonin (5-HT) as a pharmacological tool to induce spiking in ensembles…

  10. Enhanced responsiveness to selective serotonin reuptake inhibitors during lactation.

    Directory of Open Access Journals (Sweden)

    Nicholas J Jury

    Full Text Available The physiology of mood regulation in the postpartum is poorly understood despite the fact that postpartum depression (PPD is a common pathology. Serotonergic mechanisms and their dysfunction are widely presumed to be involved, which has led us to investigate whether lactation induces changes in central or peripheral serotonin (5-HT systems and related affective behaviors. Brain sections from lactating (day 10 postpartum and age-matched nulliparous (non-pregnant C57BL/6J mice were processed for 5-HT immunohistochemistry. The total number of 5-HT immunostained cells and optical density were measured. Lactating mice exhibited lower immunoreactive 5-HT and intensity in the dorsal raphe nucleus when compared with nulliparous controls. Serum 5-HT was quantified from lactating and nulliparous mice using radioimmunoassay. Serum 5-HT concentrations were higher in lactating mice than in nulliparous controls. Affective behavior was assessed in lactating and non-lactating females ten days postpartum, as well as in nulliparous controls using the forced swim test (FST and marble burying task (MBT. Animals were treated for the preceding five days with a selective serotonin reuptake inhibitor (SSRI, citalopram, 5mg/kg/day or vehicle. Lactating mice exhibited a lower baseline immobility time during the FST and buried fewer marbles during the MBT as compared to nulliparous controls. Citalopram treatment changed these behaviors in lactating mice with further reductions in immobility during the FST and decreased marble burying. In contrast, the same regimen of citalopram treatment had no effect on these behaviors in either non-lactating postpartum or nulliparous females. Our findings demonstrate changes in both central and peripheral 5-HT systems associated with lactation, independent of pregnancy. They also demonstrate a significant interaction of lactation and responsiveness to SSRI treatment, which has important implications in the treatment of PPD. Although

  11. Treatment of Parkinson's disease: nanostructured sol–gel silica–dopamine reservoirs for controlled drug release in the central nervous system

    Directory of Open Access Journals (Sweden)

    Tessy López

    2010-12-01

    -induced rotation behavior in hemiparkisonian rats.Results: The in vitro dopamine delivery profiles indicate two regimes of release, a fast and sustained dopamine delivery was observed up to 24 hours, and after this time the rate of delivery became constant. Histologic analysis of formalin-fixed brains performed 24–32 weeks after reservoir implantation revealed that silica–dopamine implants had a reddish-brown color, suggesting the presence of oxidized dopamine, likely caused by the fixation procedure, while implants without dopamine were always translucent.Conclusion: The major finding of the study was that intrastriatal silica–dopamine implants reversed the rotational asymmetry induced by apomorphine, a dopamine agonist, in hemiparkinsonian rats. No dyskinesias or other motor abnormalities were observed in animals implanted with silica or silica–dopamine.Keywords: Parkinson's disease, silica–dopamine, controlled drug release, central nervous system, reservoirs

  12. A dualistic conformational response to substrate binding in the human serotonin transporter reveals a high affinity state for serotonin

    DEFF Research Database (Denmark)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida;

    2015-01-01

    Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across...... that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation...

  13. High- and low-affinity binding of S-citalopram to the human serotonin transporter mutated at 20 putatively important amino acid positions

    DEFF Research Database (Denmark)

    Plenge, Per; Wiborg, Ove

    2005-01-01

    The serotonin transporter (SERT) is responsible for terminating or modulating the action of serotonin released from the presynaptic neuron and is the major target for most antidepressants including the tricyclic antidepressants and the selective serotonin uptake inhibitors. Two binding sites...... for uptake inhibitors and serotonin (5-HT) have been found on SERT. At one site, uptake inhibitors bind with high-affinity to SERT, thereby blocking the uptake of 5-HT. The other site is a low-affinity allosteric site, which influences the dissociation of uptake inhibitors, such as imipramine, paroxetine......, and citalopram from the first site, when occupied by 5-HT and a few uptake inhibitors like paroxetine and citalopram. In this study, the connection between the high-affinity binding site and the allosteric affinity-modulating site was investigated by introducing 20 single amino acid substitutions into positions...

  14. Role of serotonin in the discriminative stimulus properties of mescaline.

    Science.gov (United States)

    Browne, R G; Ho, B T

    1975-01-01

    Rats were trained to discriminate intraperitoneally administered mescaline from saline in a two-lever operant chamber for food reinforcement. Reward was contingent upon responses made greater than 15 sec apart (DRL-15) on the appropriate lever paired with either drug or saline administration. Following the establishment of discriminative response control by mescaline, the animals were tested for stimulus generalization produced by mescaline after: (a) blockade of periphreral and central serotonin (5-HT) receptors with cinanserin, methysergide, or cyproheptadine; (b) blockade of peripheral 5-HT receptors with xylamidine tosylate; and (c) depletion of brain 5-HT with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA). The results show that all three central 5-HT antagonists greatly reduced the discriminability of mescaline while the peripheral antagonist, xylamidine tosylate, was without effect. Furthermore, these agents at the doses employed did not effect the discriminability of saline. Depletion of 5-HT with PCPA potentiated the effects of a sub-threshold dose of mescaline and slightly reduced the discriminability of saline. The results indicate that mescaline produces its discriminative stimulus properties by directly stimulating central serotonergic receptors.

  15. L-Tryptophan, Melatonin, Serotonin Profiles in the Foods and their Effects on Health

    Directory of Open Access Journals (Sweden)

    Seda Kurtulmuş

    2015-11-01

    Full Text Available Nowadays, depending on the progress of science and technology, our eating habits have changed. The shape and quality of nutrition is important for human health. Especially, some food components have various effect on central nervous system such as depression, anxiety, sleep, appetite. Food constituents are transported into the central nervous system via the neutral amino acids such as phenylalanine, leucine, isoleucine, tyrosine and valine. Amino acids have an important role in human nutrition. It cannot be synthesized in the body and one of the essential amino acids that must be taken outside, trytophan, is indispensable in human nutrition because of it has the many functions. In recent years, scientific community concentrated on the various functions of L-Trytophan (L-Trp as pioneer in the secretion of the hormones serotonin and melatoninin in the human body. The hormones serotonin and melatonin is responsible for activities such as psychology, sleep, body temperature, blood pressure balance, antioxidant effect, cancer inhibitor, sexuality, autism and circadian rhythms in human body that they are available in various foods such as milk, kefir, yogurt, orange, strawberry, grape, olive oil, walnut, prune, nut, pomegranate, coffee, kiwi and banana. In this study, L-Trp, serotonin and melatonin biosynthesis and metabolism, food profiles and in terms of their physiological and biological effects on human health has been compiled.

  16. Genetic polymorphism in the serotonin transporter gene-linked polymorphic region and response to serotonin reuptake inhibitors in patients with premature ejaculation

    Directory of Open Access Journals (Sweden)

    Emin Ozbek

    2014-11-01

    Full Text Available OBJECTIVES: Serotonin plays a central role in ejaculation and selective serotonin reuptake inhibitors have been successfully used to treat premature ejaculation. Here, we evaluated the relationship between a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR and the response of patients with premature ejaculation to SSRI medication. METHODS: Sixty-nine premature ejaculation patients were treated with 20 mg/d paroxetine for three months. The Intravaginal Ejaculatory Latency Time and International Index of Erectile Function scores were compared with baseline values. The patients were scored as having responded to therapy when a 2-fold or greater increase was observed in Intravaginal Ejaculatory Latency Time compared with baseline values after three months. Three genotypes of 5-HTTLPR were studied: LL, LS and SS. The appropriateness of the allele frequencies in 5-HTTLPR were analyzed according to Hardy-Weinberg equilibrium using the χ2-test. RESULTS: The short (S allele of 5-HTTLPR was significantly more frequent in responders than in nonresponders (p<0.05. Out of the 69 total PE patients, 41 patients (59% responded to therapy. There was no significant difference in the International Index of Erectile Function score at the end of therapy between the responder and nonresponder groups. The frequencies of the L allele and S allele were 20% and 39%, respectively, in the responder group (p<0.05. CONCLUSION: We conclude that premature ejaculation patients with the SS genotype respond well to selective serotonin reuptake inhibitor therapy. Further studies with large patient groups are necessary to confirm this conclusion.

  17. The antimalarial drug quinine interferes with serotonin biosynthesis and action.

    Science.gov (United States)

    Islahudin, Farida; Tindall, Sarah M; Mellor, Ian R; Swift, Karen; Christensen, Hans E M; Fone, Kevin C F; Pleass, Richard J; Ting, Kang-Nee; Avery, Simon V

    2014-01-01

    The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmitter serotonin (5-HT), here we test the hypothesis that quinine disrupts serotonin function. Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells. One possible cause of this effect is through inhibition of 5-HT receptor activation by quinine, as we observed here. Furthermore, cells exhibited marked decreases in serotonin production during incubation with quinine. By assaying activity and kinetics of the rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase (TPH2), we showed that quinine competitively inhibits TPH2 in the presence of the substrate tryptophan. The study shows that quinine disrupts both serotonin biosynthesis and function, giving important new insight to the action of quinine on mammalian cells.

  18. Platelet Serotonin Transporter Function Predicts Default-Mode Network Activity

    OpenAIRE

    Christian Scharinger; Ulrich Rabl; Christian H. Kasess; Meyer, Bernhard M.; Tina Hofmaier; Kersten Diers; Lucie Bartova; Gerald Pail; Wolfgang Huf; Zeljko Uzelac; Beate Hartinger; Klaudius Kalcher; Thomas Perkmann; Helmuth Haslacher; Andreas Meyer-Lindenberg

    2014-01-01

    Background The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence. Methods A functional magnetic resonance study was performed in 48 healthy...

  19. The two faces of serotonin in bone biology

    OpenAIRE

    Ducy, Patricia; Karsenty, Gerard

    2010-01-01

    The serotonin molecule has some remarkable properties. It is synthesized by two different genes at two different sites, and, surprisingly, plays antagonistic functions on bone mass accrual at these two sites. When produced peripherally, serotonin acts as a hormone to inhibit bone formation. In contrast, when produced in the brain, serotonin acts as a neurotransmitter to exert a positive and dominant effect on bone mass accrual by enhancing bone formation and limiting bone resorption. The effe...

  20. Methylene Blue Causing Serotonin Syndrome Following Cystocele Repair.

    Science.gov (United States)

    Kapadia, Kailash; Cheung, Felix; Lee, Wai; Thalappillil, Richard; Florence, F Barry; Kim, Jason

    2016-11-01

    Methylene blue is an intravenously administered agent that may potentiate serotonin syndrome. The usage of methylene blue to evaluate ureters for injuries and patency during urological surgeries is recognized as common practice. However, there is no mention of serotonin syndrome caused by methylene blue in urological literature or for urological surgery. We report the first urological case in order to raise awareness of the risk for serotonin toxicity with utilizing methylene blue. PMID:27617215

  1. Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter

    OpenAIRE

    Davis, Bruce A.; Anu Nagarajan; Forrest, Lucy R.; Singh, Satinder K.

    2016-01-01

    The serotonin transporter (SERT) is an integral membrane protein that exploits preexisting sodium-, chloride-, and potassium ion gradients to catalyze the thermodynamically unfavorable movement of synaptic serotonin into the presynaptic neuron. SERT has garnered significant clinical attention partly because it is the target of multiple psychoactive agents, including the antidepressant paroxetine (Paxil), the most potent selective serotonin reuptake inhibitor known. However, the binding site a...

  2. Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking.

    Science.gov (United States)

    McClintick, Jeanette N; McBride, William J; Bell, Richard L; Ding, Zheng-Ming; Liu, Yunlong; Xuei, Xiaoling; Edenberg, Howard J

    2015-02-01

    Alcohol binge-drinking during adolescence is a serious public health concern with long-term consequences. We used RNA sequencing to assess the effects of excessive adolescent ethanol binge-drinking on gene expression in the dorsal raphe nucleus (DRN) of alcohol preferring (P) rats. Repeated binges across adolescence (three 1h sessions across the dark-cycle per day, 5 days per week for 3 weeks starting at 28 days of age; ethanol intakes of 2.5-3 g/kg/session) significantly altered the expression of approximately one-third of the detected genes. Multiple neurotransmitter systems were altered, with the largest changes in the serotonin system (21 of 23 serotonin-related genes showed decreased expression) and GABA-A receptors (8 decreased and 2 increased). Multiple neuropeptide systems were also altered, with changes in the neuropeptide Y and corticotropin-releasing hormone systems similar to those associated with increased drinking and decreased resistance to stress. There was increased expression of 21 of 32 genes for potassium channels. Expression of downstream targets of CREB signaling was increased. There were also changes in expression of genes involved in inflammatory processes, axonal guidance, growth factors, transcription factors, and several intracellular signaling pathways. These widespread changes indicate that excessive binge drinking during adolescence alters the functioning of the DRN and likely its modulation of many regions of the central nervous system, including the mesocorticolimbic system.

  3. Immunodetection of the serotonin transporter protein is a more valid marker for serotonergic fibers than serotonin

    DEFF Research Database (Denmark)

    Nielsen, Kirsten; Brask, Dorthe; Knudsen, Gitte M.;

    2006-01-01

    transporter (SERT) protein, on the other hand, is less liable to metabolism and for that reason we hypothetized that SERT immunostaining is a more stable marker of serotonergic fibers. Rats were pretreated with monoamine oxidase (MAO) inhibitor and compared with placebo treated rats. Brains were double...... was observed in the number of the SERT positive fibers. Colocalization between serotonin and SERT positive fibers was close to 100% in MAO inhibitor treated animals but only 30% in untreated rats. We conclude that the rapid metabolism of serotonin leads to an underestimation of immunodetected serotonergic...

  4. Infrared Thermography in Serotonin-Induced Itch Model in Rats

    DEFF Research Database (Denmark)

    Jasemian, Yousef; Gazerani, Parisa; Dagnæs-Hansen, Frederik

    2012-01-01

    The study validated the application of infrared thermography in a serotonin-induced itch model in rats since the only available method in animal models of itch is the count of scratching bouts. Twenty four adult Sprague-Dawley male rats were used in 3 experiments: 1) local vasomotor response...... with no scratching reflex was investigated. Serotonin elicited significant scratching and lowered the local temperature at the site of injection. A negative dose-temperature relationship of serotonin was found by thermography. Vasoregulation at the site of serotonin injection took place in the absence of scratching...

  5. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

    Science.gov (United States)

    Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

    2015-07-01

    Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

  6. Serotonin Improves High Fat Diet Induced Obesity in Mice.

    Directory of Open Access Journals (Sweden)

    Hitoshi Watanabe

    Full Text Available There are two independent serotonin (5-HT systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.

  7. Serotonin Improves High Fat Diet Induced Obesity in Mice.

    Science.gov (United States)

    Watanabe, Hitoshi; Nakano, Tatsuya; Saito, Ryo; Akasaka, Daisuke; Saito, Kazuki; Ogasawara, Hideki; Minashima, Takeshi; Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Inoue, Nao; Ikeda, Ikuo; Chen, Xiangning; Miyake, Masato; Kitazawa, Haruki; Shirakawa, Hitoshi; Sato, Kan; Tahara, Kohji; Nagasawa, Yuya; Rose, Michael T; Ohwada, Shyuichi; Watanabe, Kouichi; Aso, Hisashi

    2016-01-01

    There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle. PMID:26766570

  8. Brain serotonin and pituitary-adrenal functions

    Science.gov (United States)

    Vernikos-Danellis, J.; Berger, P.; Barchas, J. D.

    1973-01-01

    It had been concluded by Scapagnini et al. (1971) that brain serotonin (5-HT) was involved in the regulation of the diurnal rhythm of the pituitary-adrenal system but not in the stress response. A study was conducted to investigate these findings further by evaluating the effects of altering brain 5-HT levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. In a number of experiments brain 5-HT synthesis was inhibited with parachlorophenylalanine. In other tests it was tried to raise the level of brain 5-HT with precursors.

  9. Hippocampal serotonin responses in short and long attack latency mice

    NARCIS (Netherlands)

    van Riel, E; Meijer, OC; Veenema, AH; Joels, M

    2002-01-01

    Short and long attack latency mice, which are selected based on their offensive behaviour in a resident-intruder model, differ in their neuroendocrine regulation as well as in aspects of their brain serotonin system. Previous studies showed that the binding capacity and expression of serotonin-1A re

  10. Selective serotonin reuptake inhibitors for fibromyalgia syndrome

    Science.gov (United States)

    Walitt, Brian; Urrútia, Gerard; Nishishinya, María Betina; Cantrell, Sarah E; Häuser, Winfried

    2016-01-01

    Background Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms. Objectives The objective was to assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in the treatment of fibromyalgia. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5), MEDLINE (1966 to June 2014), EMBASE (1946 to June 2014), and the reference lists of reviewed articles. Selection criteria We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline. Data collection and analysis Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. Main results The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks) and 383 participants, who were pooled together. All studies had one or more sources of potential major bias. There was a small (10%) difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6%)) and placebo (39/171 (22.8%)) risk difference (RD) 0.10, 95% confidence interval (CI) 0.01 to 0.20; number needed to treat for an additional

  11. Depression, osteoporosis, serotonin and cell membrane viscosity between biology and philosophical anthropology

    Directory of Open Access Journals (Sweden)

    Gabrielli Fabio

    2011-03-01

    Full Text Available Abstract Due to the relationship between biology and culture, we believe that depression, understood as a cultural and existential phenomenon, has clear markers in molecular biology. We begin from an existential analysis of depression constituting the human condition and then shift to analysis of biological data confirming, according to our judgment, its original (ontological structure. In this way philosophy is involved at the anthropological level, in as much as it detects the underlying meanings of depression in the original biological-cultural horizon of human life. Considering the integration of knowledge it is the task of molecular biology to identify the aforementioned markers, to which the existential aspects of depression are linked to. In particular, recent works show the existence of a link between serotonin and osteoporosis as a result of a modified expression of the low-density lipoprotein receptor-related protein 5 gene. Moreover, it is believed that the hereditary or acquired involvement of tryptophan hydroxylase 2 (Tph2 or 5-hydroxytryptamine transporter (5-HTT is responsible for the reduced concentration of serotonin in the central nervous system, causing depression and affective disorders. This work studies the depression-osteoporosis relationship, with the aim of focusing on depressive disorders that concern the quantitative dynamic of platelet membrane viscosity and interactome cytoskeleton modifications (in particular Tubulin and Gsα protein as a possible condition of the involvement of the serotonin axis (gut, brain and platelet, not only in depression but also in connection with osteoporosis.

  12. Determinação simultânea de precursores de serotonina - triptofano e 5-hidroxitriptofano - em café Simultaneous determination of serotonin precursors - tryptophan and 5-hidroxytryptophan - in coffee

    OpenAIRE

    Ana Carolina C. L. Martins; Tarliane M. Silva; M. Beatriz A. Gloria

    2010-01-01

    Epidemiological studies attributed positive effects in the central nervous system (CNS) to coffee. Among possible active constituents, serotonin, a neurotransmitter in the CNS, is present; but dietary sources do not cross the blood-brain barrier. Tryptophan and 5-hidroxytryptophan (5-HTP) are serotonin precursors and can affect brain concentrations. An ion-pair-HPLC, post-column derivatization with o-phthalaldehyde and fluorimetric detection before and after hydrolysis with NaOH and extractio...

  13. Involvement of serotonergic pathways in mediating the neuronal activity and genetic transcription of neuroendocrine corticotropin-releasing factor in the brain of systemically endotoxin-challenged rats

    Energy Technology Data Exchange (ETDEWEB)

    Laflamme, N.; Feuvrier, E.; Richard, D.; Rivest, S. [Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, 2705 boul. Laurier, Ste-Foy Quebec (Canada)

    1999-01-01

    factor transcription and plasma corticosterone release. Indeed, lipopolysaccharide caused a selective expression of corticotropin-releasing factor primary transcript in the paraventricular nucleus of the hypothalamus and this effect was significantly reduced by treatment with the serotonin inhibitor. However, basal expression of corticotropin-releasing factor messenger RNA across the brain (bed nucleus of the stria terminalis, medial preoptic area, paraventricular nucleus of the hypothalamus, central nucleus of the amygdala, etc.) was not affected by the para-chlorophenylalanine treatment. These results suggest that the integrity of serotonin pathways plays a role in the neuronal activity triggered by the systemic endotoxin insult. The fact that serotonin depletion largely prevented activation of neurosecretory parvocellular neurons of the paraventricular nucleus of the hypothalamus and neuroendocrine corticotropin-releasing factor gene transcription in response to immunogenic challenge provides the evidence that serotonergic system is part of the brain circuitry involved in the corticotroph axis-immune interface. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  14. The serotonin-dopamine interaction measured with positron emission tomography (PET) and C-11 raclopride in normal human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Smith, G.S.; Dewey, S.L.; Logan, J. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1994-05-01

    Our previous studies have shown that the interaction between serotonin and dopamine can be measured with C-11 raclopride and PET in the baboon brain. A series of studies was undertaken to extend dim findings to the normal human brain. PET studies were conducted in male control subjects (n=8) using the CTI 931 tomograph. Two C-11 raclopride scans were performed, prior to and 180 minutes following administration of the selective serotonin releasing agent, fenfluramine (60mg/PO). The neuroendocrine response to fenfluramine challenge is commonly used in psychiatric research as an index of serotonin activity. The C-11 raclopride data were analyzed with the distribution volume method. For the group of subjects, an increase was observed in the striatum to cerebellum ratio (specific to non-specific binding ratio), in excess of the test-retest variability of the ligand. Variability in response was observed across subjects. These results are consistent with our previous findings in the baboon that citalopram administration increased C-11 raclopride binding, consistent with a decrease in endogenous dopamine. In vivo microdialysis studies in freely moving rats confirmed that citalopram produces a time-dependent decrease in extracellular dopamine levels, consistent with the PET results. In vivo PET studies of the serotonin-dopamine interaction are relevant to the evaluation of etiologic and therapeutic mechanisms in schizophrenia and affective disorder.

  15. Centrally Applied Somatostatin Inhibits the Estrogen-Induced Luteinizing Hormone Surge via Hypothalamic Gonadotropin-Releasing Hormone Cell Activation in Female Rats

    NARCIS (Netherlands)

    Vugt, van H.H.; Swarts, J.J.M.; Heijning, van de H.J.M.; Beek, van der E.M.

    2004-01-01

    Overexpression of growth hormone (GH) as well as GH-deficiency dramatically impairs reproductive function. Decreased reproductive function as a result of altered GH release is, at least partially, due to changes at the hypothalamic-pituitary level. We hypothesize that hypothalamic somatostatin (SOM)

  16. Serotonin regulates osteoblast proliferation and function in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Dai, S.Q.; Yu, L.P. [Department of Orthopedic Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); Shi, X. [Department of Obstetrics and Gynecology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China); Wu, H. [Emergency Department, The First Affiliated Hospital, Soochow University, Suzhou (China); Shao, P.; Yin, G.Y.; Wei, Y.Z. [Department of Orthopedic Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu (China)

    2014-08-01

    The monoamine serotonin (5-hydroxytryptamine, 5-HT), a well-known neurotransmitter, also has important functions outside the central nervous system. The objective of this study was to investigate the role of 5-HT in the proliferation, differentiation, and function of osteoblasts in vitro. We treated rat primary calvarial osteoblasts with various concentrations of 5-HT (1 nM to 10 µM) and assessed the rate of osteoblast proliferation, expression levels of osteoblast-specific proteins and genes, and the ability to form mineralized nodules. Next, we detected which 5-HT receptor subtypes were expressed in rat osteoblasts at different stages of osteoblast differentiation. We found that 5-HT could inhibit osteoblast proliferation, differentiation, and mineralization at low concentrations, but this inhibitory effect was mitigated at relatively high concentrations. Six of the 5-HT receptor subtypes (5-HT{sub 1A}, 5-HT{sub 1B}, 5-HT{sub 1D}, 5-HT{sub 2A}, 5-HT{sub 2B}, and 5-HT{sub 2C}) were found to exist in rat osteoblasts. Of these, 5-HT{sub 2A} and 5-HT{sub 1B} receptors had the highest expression levels, at both early and late stages of differentiation. Our results indicated that 5-HT can regulate osteoblast proliferation and function in vitro.

  17. Fractalkine/CX3CL1 enhances GABA synaptic activity at serotonin neurons in the rat dorsal raphe nucleus

    OpenAIRE

    Heinisch, Silke; Kirby, Lynn G.

    2009-01-01

    Serotonin (5-hydroxytryptamine; 5-HT) has an important role in mood regulation, and its dysfunction in the central nervous system (CNS) is associated with depression. Reports of mood and immune disorder co-morbidities indicate that immune-5-HT interactions may mediate depression present in immune compromised disease states including HIV/AIDS, multiple sclerosis, and Parkinson’s disease. Chemokines, immune proteins that induce chemotaxis and cellular adhesion, and their G-protein coupled recep...

  18. Serotonin and Early Cognitive Development: Variation in the Tryptophan Hydroxylase 2 Gene Is Associated with Visual Attention in 7-Month-Old Infants

    Science.gov (United States)

    Leppanen, Jukka M.; Peltola, Mikko J.; Puura, Kaija; Mantymaa, Mirjami; Mononen, Nina; Lehtimaki, Terho

    2011-01-01

    Background: Allelic variation in the promoter region of a gene that encodes tryptophan hydroxylase isoform 2 (TPH2), a rate-limiting enzyme of serotonin synthesis in the central nervous system, has been associated with variations in cognitive function and vulnerability to affective spectrum disorders. Little is known about the effects of this gene…

  19. Serotonin suppresses food anticipatory activity and synchronizes the food-entrainable oscillator during time-restricted feeding.

    Science.gov (United States)

    Rozenblit-Susan, Sigal; Chapnik, Nava; Genzer, Yoni; Froy, Oren

    2016-01-15

    The serotonergic and circadian systems are intertwined as serotonin modulates the response of the central brain suprachiasmatic nuclei (SCN) clock to light. Time-restricted feeding (RF) is characterized by increased food anticipatory activity (FAA) and controlled by the food-entrainable oscillator (FEO) rather than the SCN. Our objective was to test whether serotonin affects the FEO. Mice were treated with the selective serotonin reuptake inhibitor (SSRI) fluvoxamine (FLX) or the tryptophan hydroxylase inhibitor parachlorophenylalanine (PCPA) and locomotor activity under ad libitum feeding, RF and different lighting conditions was monitored. Under AL, FLX administration did not affect 24-h locomotor activity, while mice treated with PCPA exhibited increased activity. RF-FLX-treated mice showed less FAA 2h before food availability (ZT2-ZT4) compared to RF- or RF-PCPA-fed mice. Under DD, RF-PCPA-treated mice displayed increased activity, as was seen under LD conditions. Surprisingly, RF-PCPA-treated mice showed free running in the FAA component. These results emphasize the role of serotonin in SCN-mediated activity inhibition and FEO entrainment and activity. PMID:26467604

  20. Am5-HT7: molecular and pharmacological characterization of the first serotonin receptor of the honeybee (Apis mellifera).

    Science.gov (United States)

    Schlenstedt, Jana; Balfanz, Sabine; Baumann, Arnd; Blenau, Wolfgang

    2006-09-01

    The biogenic amine serotonin (5-HT) plays a key role in the regulation and modulation of many physiological and behavioural processes in both vertebrates and invertebrates. These functions are mediated through the binding of serotonin to its receptors, of which 13 subtypes have been characterized in vertebrates. We have isolated a cDNA from the honeybee Apis mellifera (Am5-ht7) sharing high similarity to members of the 5-HT(7) receptor family. Expression of the Am5-HT(7) receptor in HEK293 cells results in an increase in basal cAMP levels, suggesting that Am5-HT(7) is expressed as a constitutively active receptor. Serotonin application to Am5-ht7-transfected cells elevates cyclic adenosine 3',5'-monophosphate (cAMP) levels in a dose-dependent manner (EC(50) = 1.1-1.8 nm). The Am5-HT(7) receptor is also activated by 5-carboxamidotryptamine, whereas methiothepin acts as an inverse agonist. Receptor expression has been investigated by RT-PCR, in situ hybridization, and western blotting experiments. Receptor mRNA is expressed in the perikarya of various brain neuropils, including intrinsic mushroom body neurons, and in peripheral organs. This study marks the first comprehensive characterization of a serotonin receptor in the honeybee and should facilitate further analysis of the role(s) of the receptor in mediating the various central and peripheral effects of 5-HT. PMID:16945110

  1. Plasma and platelet serotonin levels in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To analyze the relationship between plasmaand platelet serotonin levels and the degree of liverinsufficiency.METHODS: The prospective study included 30 patients with liver cirrhosis and 30 healthy controls. The degree of liver failure was assessed according to the Child-Pugh classification. Platelet and platelet poor plasma serotonin levels were determined.RESULTS: The mean plasma serotonin level was higher in liver cirrhosis patients than in healthy subjects (215.0± 26.1 vs 63.1 ± 18.1 nmol/L; P < 0.0001). The mean platelet serotonin content was not significantly different in patients with liver cirrhosis compared with healthy individuals (4.8 ± 0.6; 4.2 ± 0.3 nmol/platelet; P > 0.05).Plasma serotonin levels were significantly higher in ChildPugh grade A/B than in grade C patients (246.8 ± 35.0vs132.3 ± 30.7 nmol/L; P < 0.05). However, platelet serotonin content was not significantly different between Child-Pugh grade C and grade A/B (4.6 ± 0.7 vs 5.2 ± 0.8nmol/platelet; P > 0.05).CONCLUSION: Plasma serotonin levels are significantly higher in patients with cirrhosis than in the controls and represent the degree of liver insufficiency. In addition,platelet poor plasma serotonin estimation is a better marker for liver insufficiency than platelet serotonin content.

  2. Cycling of dense core vesicles involved in somatic exocytosis of serotonin by leech neurons

    Directory of Open Access Journals (Sweden)

    Citlali eTrueta

    2012-06-01

    Full Text Available We studied the cycling of dense core vesicles producing somatic exocytosis of serotonin. Our experiments were made using electron microscopy and vesicle staining with fluorescent dye FM1-43 in Retzius neurons of the leech, which secrete serotonin from clusters of dense core vesicles in a frequency-dependent manner. Electron micrographs of neurons at rest or after 1 Hz stimulation showed two pools of dense core vesicles. A perinuclear pool near Golgi apparatuses, from which vesicles apparently form, and a peripheral pool with vesicle clusters at a distance from the plasma membrane. By contrast, after 20 Hz electrical stimulation 47% of the vesicle clusters were apposed to the plasma membrane, with some omega exocytosis structures. Dense core and small clear vesicles apparently originating from endocytosis were incorporated in multivesicular bodies. In another series of experiments, neurons were stimulated at 20 Hz while bathed in a solution containing peroxidase. Electron micrographs of these neurons contained gold particles coupled to anti-peroxidase antibodies in dense core vesicles and multivesicular bodies located near the plasma membrane. Cultured neurons depolarized with high potassium in the presence of FM1-43 displayed superficial fluorescent spots, each reflecting a vesicle cluster. A partial bleaching of the spots followed by another depolarization in the presence of FM1-43 produced restaining of some spots, other spots disappeared, some remained without restaining and new spots were formed. Several hours after electrical stimulation the FM1-43 spots accumulated at the center of the somata. This correlated with electron micrographs of multivesicular bodies releasing their contents near Golgi apparatuses. Our results suggest that dense core vesicle cycling related to somatic serotonin release involves two steps: the production of clear vesicles and multivesicular bodies after exocytosis, and the formation of new dense core vesicles in

  3. Prenatal serotonin reuptake inhibitor (SRI antidepressant exposure and serotonin transporter promoter genotype (SLC6A4 influence executive functions at 6 years of age

    Directory of Open Access Journals (Sweden)

    Whitney eWeikum

    2013-10-01

    Full Text Available Prenatal exposure to serotonin reuptake inhibitor (SRI antidepressants and maternal depression may affect prefrontal cognitive skills (executive functions; EFs including self-control, working memory and cognitive flexibility. We examined long-term effects of prenatal SRI exposure on EFs to determine whether effects are moderated by maternal mood and/or genetic variations in SLC6A4 (a gene that codes for the serotonin transporter [5-HTT] central to the regulation of synaptic serotonin levels and behavior. Children who were exposed to SRIs prenatally (SRI-exposed N=26 and non-exposed (N=38 were studied at age 6 years (M=6.3 SD=0.5 using the Hearts & Flowers task (H&F to assess EFs. Maternal mood was measured during pregnancy (3rd trimester and when the child was age 6 years (Hamilton Depression Scale. Parent reports of child behavior were also obtained (MacArthur Health & Behavior Questionnaire. Parents of prenatally SRI-exposed children reported fewer child externalizing and inattentive (ADHD behaviors. Generalized estimate equation modeling showed a significant 3-way interaction between prenatal SRI exposure, SLC6A4 variant, and maternal mood at the 6-year time-point on H&F accuracy. For prenatally SRI-exposed children, regardless of maternal mood, the H&F accuracy of children with reduced 5HTT expression (a short [S] allele remained stable. Even with increasing maternal depressive symptoms (though all below clinical threshold, EFs of children with at least one short allele were comparable to children with the same genotype whose mothers reported few if any depressive symptoms – in this sense they showed resilience. Children with two long (L alleles were more sensitive to context. When their mothers had few depressive symptoms, LL children showed extremely good EF performance – better than any other group. When their mothers reported more depressive symptoms, LL children’s EF performance was worse than that of any other group.

  4. Serotonin syndrome:case report and current concepts.

    LENUS (Irish Health Repository)

    Fennell, J

    2005-05-01

    Selective serotonin reuptake inhibitors (SSRI\\'s) are increasingly being used as the first line therapeutic agent for the depression. It is therefore not unusual to see a case of overdose with these agents. More commonly an adverse drug reaction may be seen among the older patients who are particularly vulnerable to the serotonin syndrome due to multiple co-morbidity and polypharmacy. The clinical picture of serotonin syndrome (SS) is non-specific and there is no confirmatory test. SS may go unrecognized because it is often mistaken for a viral illness, anxiety, neurological disorder or worsening psychiatric condition.

  5. 4-haloethenylphenyl tropane:serotonin transporter imaging agents

    Science.gov (United States)

    Goodman, Mark M.; Martarello, Laurent

    2005-01-18

    A series of compounds in the 4-fluoroalkyl-3-halophenyl nortropanes and 4-haloethenylphenyl tropane families are described as diagnostic and therapeutic agents for diseases associated with serotonin transporter dysfunction. These compounds bind to serotonin transporter protein with high affinity and selectivity. The invention provides methods of synthesis which incorporate radioisotopic halogens at a last step which permit high radiochemical yield and maximum usable product life. The radiolabeled compounds of the invention are useful as imaging agents for visualizing the location and density of serotonin transporter by PET and SPECT imaging.

  6. Possible involvement of serotonin in extinction.

    Science.gov (United States)

    Beninger, R J; Phillips, A G

    1979-01-01

    In Experiment 1, rats were trained to leverpress for continuous reinforcement with food; half were then intubated with the serotonin synthesis inhibitor parachlorophenylalanine (PCPA: 400 mg/kg) and half with water. In extinction the PCPA-treated rats responded at a higher rate. In Experiment 2, rats were trained on a random interval schedule and then assigned to two groups, treated as in Experiment 1, and tested in extinction. There was no significant difference in the resistance to extinction of the two groups. In Experiment 3, the responding of rats trained in a punished stepdown response paradigm and then given an intragastric injection of PCPA took longer to recover than the responding of water-injected controls. These observations suggest that serotonergic neurons might play a role in extinction processes. PMID:155820

  7. Central Interleukin-1β Suppresses the Nocturnal Secretion of Melatonin.

    Science.gov (United States)

    Herman, A P; Bochenek, J; Król, K; Krawczyńska, A; Antushevich, H; Pawlina, B; Herman, A; Romanowicz, K; Tomaszewska-Zaremba, D

    2016-01-01

    In vertebrates, numerous processes occur in a rhythmic manner. The hormonal signal reliably reflecting the environmental light conditions is melatonin. Nocturnal melatonin secretion patterns could be disturbed in pathophysiological states, including inflammation, Alzheimer's disease, and depression. All of these states share common elements in their aetiology, including the overexpression of interleukin- (IL-) 1β in the central nervous system. Therefore, the present study was designed to determine the effect of the central injection of exogenous IL-1β on melatonin release and on the expression of the enzymes of the melatonin biosynthetic pathway in the pineal gland of ewe. It was found that intracerebroventricular injections of IL-1β (50 µg/animal) suppressed (P < 0.05) nocturnal melatonin secretion in sheep regardless of the photoperiod. This may have resulted from decreased (P < 0.05) synthesis of the melatonin intermediate serotonin, which may have resulted, at least partially, from a reduced expression of tryptophan hydroxylase. IL-1β also inhibited (P < 0.05) the expression of the melatonin rhythm enzyme arylalkylamine-N-acetyltransferase and hydroxyindole-O-methyltransferase. However, the ability of IL-1β to affect the expression of these enzymes was dependent upon the photoperiod. Our study may shed new light on the role of central IL-1β in the aetiology of disruptions in melatonin secretion. PMID:27212805

  8. 星点设计-效应面法优化香青兰黄酮缓释片处方%Optimization of Dracocephalum moldevica flavones sustained-release tablets formulation by central composite design-response surface methodology

    Institute of Scientific and Technical Information of China (English)

    杨秀; 邢建国; 王新春; 李悦; 薛桂蓬; 马祖文; 任文东

    2011-01-01

    目的:通过星点设计-效应面法优化香青兰黄酮缓释片处方并探讨释药机制.方法:以HPMC的用量和乳糖/淀粉(1:1)的用量为考察因素,以2,6,12 h的累积释放度为考察指标,分别用线性和二项式模型描述因素与考察指标之间的数学关系,根据模型绘制等高线图,通过重叠等高线图确定优化处方并进行验证实验,探讨药物释放机制.结果:优化后的处方为HPMC 50 mg,乳糖68 mg,淀粉68 mg,主药150 mg,释放模型符合Higuchi方程.结论:星点设计-效应面法优化香青兰黄酮缓释片的处方具有良好的预测性.%OBJECTIVE To optimize the formulation of sustained-release preparation by the central composite design-response surface methodology. METHODS The amounts of HPMC and lactose:strarch (1:1) as independent variables were optimized with RSM plus CCD by selecting percentages of in vitro cumulative releases at 2,6 and 12 h as dependent variables. Multi-linear and quadratic models were used to estimate the relationship between the dependent and the independent variables, and to delineate RSM and overlay contour plots in order to select the optimal formulations with the application of hypothesized in vitro cumulative release(%) at 2,6 and 12 h. RESULTS Regression coefficients of second-order models were higher than first-order model. Optimized formulation was proposed to consist of HPMC 50 mg,lactose 68 mg,starch 68 mg,remedium car-dinale 150 mg. In vitro release indicated that there existed high approximation between the observed and estimated values. The release was conformed to Higuchi equation. CONCLUSION Central composite design-response surface methodology can be applied to optimize the coating formulation for Dracocephalum moldevica flavones sustained release tablets and the models are proved to be predictable.

  9. Syntaxin 1B, but not syntaxin 1A, is necessary for the regulation of synaptic vesicle exocytosis and of the readily releasable pool at central synapses.

    Directory of Open Access Journals (Sweden)

    Tatsuya Mishima

    Full Text Available Two syntaxin 1 (STX1 isoforms, HPC-1/STX1A and STX1B, are coexpressed in neurons and function as neuronal target membrane (t-SNAREs. However, little is known about their functional differences in synaptic transmission. STX1A null mutant mice develop normally and do not show abnormalities in fast synaptic transmission, but monoaminergic transmissions are impaired. In the present study, we found that STX1B null mutant mice died within 2 weeks of birth. To examine functional differences between STX1A and 1B, we analyzed the presynaptic properties of glutamatergic and GABAergic synapses in STX1B null mutant and STX1A/1B double null mutant mice. We found that the frequency of spontaneous quantal release was lower and the paired-pulse ratio of evoked postsynaptic currents was significantly greater in glutamatergic and GABAergic synapses of STX1B null neurons. Deletion of STX1B also accelerated synaptic vesicle turnover in glutamatergic synapses and decreased the size of the readily releasable pool in glutamatergic and GABAergic synapses. Moreover, STX1A/1B double null neurons showed reduced and asynchronous evoked synaptic vesicle release in glutamatergic and GABAergic synapses. Our results suggest that although STX1A and 1B share a basic function as neuronal t-SNAREs, STX1B but not STX1A is necessary for the regulation of spontaneous and evoked synaptic vesicle exocytosis in fast transmission.

  10. Agonist-directed signaling of serotonin 5-HT2C receptors: differences between serotonin and lysergic acid diethylamide (LSD).

    Science.gov (United States)

    Backstrom, J R; Chang, M S; Chu, H; Niswender, C M; Sanders-Bush, E

    1999-08-01

    For more than 40 years the hallucinogen lysergic acid diethylamide (LSD) has been known to modify serotonin neurotransmission. With the advent of molecular and cellular techniques, we are beginning to understand the complexity of LSD's actions at the serotonin 5-HT2 family of receptors. Here, we discuss evidence that signaling of LSD at 5-HT2C receptors differs from the endogenous agonist serotonin. In addition, RNA editing of the 5-HT2C receptor dramatically alters the ability of LSD to stimulate phosphatidylinositol signaling. These findings provide a unique opportunity to understand the mechanism(s) of partial agonism.

  11. Melatonin and N-acetyl-serotonin cross the red blood cell membrane and evoke calcium mobilization in malarial parasites

    Directory of Open Access Journals (Sweden)

    Hotta C.T.

    2003-01-01

    Full Text Available The duration of the intraerythrocytic cycle of Plasmodium is a key factor in the pathogenicity of this parasite. The simultaneous attack of the host red blood cells by the parasites depends on the synchronicity of their development. Unraveling the signals at the basis of this synchronicity represents a challenging biological question and may be very important to develop alternative strategies for therapeutic approaches. Recently, we reported that the synchrony of Plasmodium is modulated by melatonin, a host hormone that is synthesized only during the dark phases. Here we report that N-acetyl-serotonin, a melatonin precursor, also releases Ca2+ from isolated P. chabaudi parasites at micro- and nanomolar concentrations and that the release is blocked by 250 mM luzindole, an antagonist of melatonin receptors, and 20 mM U73122, a phospholipase C inhibitor. On the basis of confocal microscopy, we also report the ability of 0.1 µM melatonin and 0.1 µM N-acetyl-serotonin to cross the red blood cell membrane and to mobilize intracellular calcium in parasites previously loaded with the fluorescent calcium indicator Fluo-3 AM. The present data represent a step forward into the understanding of the signal transduction process in the host-parasite relationship by supporting the idea that the host hormone melatonin and N-acetyl-serotonin generate IP3 and therefore mobilize intracellular Ca2+ in Plasmodium inside red blood cells.

  12. [3]tetrahydrotrazodone binding. Association with serotonin binding sites

    International Nuclear Information System (INIS)

    High (17 nM) and low (603 nM) affinity binding sites for [3]tetrahydrotrazodone ([3] THT), a biologically active analogue of trazodone, have been identified in rat brain membranes. The substrate specificity, concentration, and subcellular and regional distributions of these sites suggest that they may represent a component of the serotonin transmitter system. Pharmacological analysis of [3]THT binding, coupled with brain lesion and drug treatment experiments, revealed that, unlike other antidepressants, [3] THT does not attach to either a biogenic amine transporter or serotonin binding sites. Rather, it would appear that [3]THT may be an antagonist ligand for the serotonin binding site. This probe may prove of value in defining the mechanism of action of trazodone and in further characterizing serotonin receptors

  13. Serotonin blockade delays learning performance in a cooperative fish.

    Science.gov (United States)

    Soares, Marta C; Paula, José R; Bshary, Redouan

    2016-09-01

    Animals use learning and memorizing to gather information that will help them to make ecologically relevant decisions. Neuro-modulatory adjustments enable them to make associations between stimuli and appropriate behavior. A key candidate for the modulation of cooperative behavior is serotonin. Previous research has shown that modulation of the serotonergic system spontaneously affects the behavior of the cleaner wrasse Labroides dimidiatus during interactions with so-called 'client' reef fish. Here, we asked whether shifts in serotonin function affect the cleaners' associative learning abilities when faced with the task to distinguish two artificial clients that differ in their value as a food source. We found that the administration of serotonin 1A receptor antagonist significantly slowed learning speed in comparison with saline treated fish. As reduced serotonergic signaling typically enhances fear, we discuss the possibility that serotonin may affect how cleaners appraise, acquire information and respond to client-derived stimuli via manipulation of the perception of danger. PMID:27107861

  14. Halogenated naphthyl methoxy piperidines for mapping serotonin transporter sites

    Science.gov (United States)

    Goodman, M.M.; Faraj, B.

    1999-07-06

    Halogenated naphthyl methoxy piperidines having a strong affinity for the serotonin transporter are disclosed. Those compounds can be labeled with positron-emitting and/or gamma emitting halogen isotopes by a late step synthesis that maximizes the useable lifeterm of the label. The labeled compounds are useful for localizing serotonin transporter sites by positron emission tomography and/or single photon emission computed tomography.

  15. Structure and Function of Serotonin G protein Coupled Receptors

    OpenAIRE

    McCorvy, John D.; Roth, Bryan L.

    2015-01-01

    Serotonin receptors are prevalent throughout the nervous system and the periphery, and remain one of the most lucrative and promising drug discovery targets for disorders ranging from migraine headaches to neuropsychiatric disorders such as schizophrenia and depression. There are 14 distinct serotonin receptors, of which 13 are G protein coupled receptors (GPCRs), which are targets for approximately 40% of the approved medicines. Recent crystallographic and biochemical evidence has provided a...

  16. X-ray structures and mechanism of the human serotonin transporter.

    Science.gov (United States)

    Coleman, Jonathan A; Green, Evan M; Gouaux, Eric

    2016-04-21

    The serotonin transporter (SERT) terminates serotonergic signalling through the sodium- and chloride-dependent reuptake of neurotransmitter into presynaptic neurons. SERT is a target for antidepressant and psychostimulant drugs, which block reuptake and prolong neurotransmitter signalling. Here we report X-ray crystallographic structures of human SERT at 3.15 Å resolution bound to the antidepressants (S)-citalopram or paroxetine. Antidepressants lock SERT in an outward-open conformation by lodging in the central binding site, located between transmembrane helices 1, 3, 6, 8 and 10, directly blocking serotonin binding. We further identify the location of an allosteric site in the complex as residing at the periphery of the extracellular vestibule, interposed between extracellular loops 4 and 6 and transmembrane helices 1, 6, 10 and 11. Occupancy of the allosteric site sterically hinders ligand unbinding from the central site, providing an explanation for the action of (S)-citalopram as an allosteric ligand. These structures define the mechanism of antidepressant action in SERT, and provide blueprints for future drug design. PMID:27049939

  17. Mutational scanning of the human serotonin transporter reveals fast translocating serotonin transporter mutants

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Larsen, Mads B; Johnsen, Laust B;

    2004-01-01

    The serotonin transporter (SERT) belongs to a family of sodium-chloride-dependent transporters responsible for uptake of amino acids and biogenic amines from the extracellular space. SERT represents a major pharmacological target in the treatment of several clinical conditions, including depression...... affinities, as well as ion dependencies, were drastic. Effects were synergistic compared to the corresponding single mutants. In conclusion, we suggest that mutating threonine-178 to an alanine and phenylalanine-263 to a cysteine mainly alter the overall uptake kinetics of SERT by affecting...

  18. Is domestication driven by reduced fear of humans? Boldness, metabolism and serotonin levels in divergently selected red junglefowl (Gallus gallus).

    Science.gov (United States)

    Agnvall, Beatrix; Katajamaa, Rebecca; Altimiras, Jordi; Jensen, Per

    2015-09-01

    Domesticated animals tend to develop a coherent set of phenotypic traits. Tameness could be a central underlying factor driving this, and we therefore selected red junglefowl, ancestors of all domestic chickens, for high or low fear of humans during six generations. We measured basal metabolic rate (BMR), feed efficiency, boldness in a novel object (NO) test, corticosterone reactivity and basal serotonin levels (related to fearfulness) in birds from the fifth and sixth generation of the high- and low-fear lines, respectively (44-48 individuals). Corticosterone response to physical restraint did not differ between selection lines. However, BMR was higher in low-fear birds, as was feed efficiency. Low-fear males had higher plasma levels of serotonin and both low-fear males and females were bolder in an NO test. The results show that many aspects of the domesticated phenotype may have developed as correlated responses to reduced fear of humans, an essential trait for successful domestication.

  19. Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain

    DEFF Research Database (Denmark)

    Borg, J; Cervenka, S; Kuja-Halkola, R;

    2016-01-01

    The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about...... and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain. Eleven monozygotic and 10 dizygotic healthy male twin pairs were examined with PET and [(11)C]raclopride binding to the D2- and D3-dopamine receptor and [(11)C]WAY100635 binding to the serotonin 5-HT1A...... receptor. Heritability, shared environmental effects and individual-specific non-shared effects were estimated for regional D2/3 and 5-HT1A receptor availability in projection areas. We found a major contribution of genetic factors (0.67) on individual variability in striatal D2/3 receptor binding...

  20. Premenstrual dysphoria and the serotonin system: pathophysiology and treatment.

    Science.gov (United States)

    Steiner, M; Pearlstein, T

    2000-01-01

    The inclusion of research diagnostic criteria for premenstrual dysphoric disorder (PMDD) in the DSM-IV recognizes the fact that some women have extremely distressing emotional and behavioral symptoms premenstrually. PMDD can be differentiated from premenstrual syndrome (PMS), which presents with milder physical symptoms, headache, and more minor mood changes. In addition, PMDD can be differentiated from premenstrual magnification of physical and/or psychological symptoms of a concurrent psychiatric and/or medical disorder. As many as 75% of women with regular menstrual cycles experience some symptoms of PMS, according to epidemiologic surveys. PMDD is much less common; it affects only 3% to 8% of women in this group. The etiology of PMDD is largely unknown, but the current consensus is that normal ovarian function (rather than hormone imbalance) is the cyclical trigger for PMDD-related biochemical events within the central nervous system and other target organs. The serotonergic system is in close reciprocal relationship with the gonadal hormones and has been identified as the most plausible target for interventions. Thus, beyond the conservative treatment options such as lifestyle and stress management, other nonantidepressant treatments, or the more extreme interventions that eliminate ovulation altogether, the serotonin reuptake inhibitors (SRIs) are emerging as the most effective treatment option for this population. Results from several randomized, placebo-controlled trials in women with PMDD have clearly demonstrated that the SRIs have excellent efficacy and minimal side effects. More recently, several preliminary studies indicate that intermittent (premenstrual only) treatment with selective SRIs is equally effective in these women and, thus, may offer an attractive treatment option for a disorder that is itself intermittent.

  1. Altered serotonin transporter availability in patients with multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Hesse, Swen; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig (Germany); Moeller, Franziska; Thomae, Eva; Then Bergh, Florian [University of Leipzig, Department of Neurology, Leipzig (Germany); Petroff, David [University of Leipzig, Coordinating Centre for Clinical Studies, Leipzig (Germany); Lobsien, Donald [University of Leipzig, Department of Neuroradiology, Leipzig (Germany); Luthardt, Julia; Becker, Georg-Alexander; Patt, Marianne; Seese, Anita; Meyer, Philipp M. [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Regenthal, Ralf [University of Leipzig, Clinical Pharmacology, Rudolf-Boehm-Institute of Pharmacology and Toxicology, Leipzig (Germany)

    2014-05-15

    Modulation of the immune system by the CNS may involve serotonergic regulation via the brain serotonin transporters (SERT). This regulation may be disturbed in patients with CNS disorders including multiple sclerosis (MS). Central serotonergic mechanisms have not been investigated in MS by in vivo imaging. The objective of the study was to assess the availability of SERT in antidepressant-naive patients with MS by means of PET. Included in this study were 23 patients with MS and 22 matched healthy volunteers who were investigated with PET and the SERT-selective marker [{sup 11}C]DASB, and distribution volume ratios were determined. Clinical assessment of the patients included the expanded disability status scale, the MS fatigue scale Wuerzburger Erschoepfungsinventar bei MS (WEIMuS) and the Beck Depression Inventory (BDI). The PET data were analysed with both volume-of-interest and voxel-based analyses to determine regional SERT availability. Patients had lower SERT availability in the cingulate cortex, the thalamus and the insula, and increased availability in the orbitofrontal cortex. Patients with relapsing/remitting MS tended to have lower SERT in the hippocampus, whereas patients with primary progressive disease showed increased SERT availability in prefrontal regions. There was a positive correlation between SERT availability in the insula and both depression and fatigue scores (r = 0.56 vs. BDI, p = 0.02; r = 0.49 vs. WEIMuS, p = 0.05). Serotonergic neurotransmission in MS patients is altered in limbic and paralimbic regions as well as in the frontal cortex that this appears to contribute to psychiatric symptoms of MS. (orig.)

  2. Thermostabilization of the Human Serotonin Transporter in an Antidepressant-Bound Conformation.

    Directory of Open Access Journals (Sweden)

    Evan M Green

    Full Text Available Serotonin is a ubiquitous chemical transmitter with particularly important roles in the gastrointestinal, cardiovascular and central nervous systems. Modulation of serotonergic signaling occurs, in part, by uptake of the transmitter by the serotonin transporter (SERT. In the brain, SERT is the target for numerous antidepressants including tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs. Despite the importance of SERT in human physiology, biochemical, biophysical and high-resolution structural studies have been hampered due to the instability of SERT in detergent micelles. To identify a human SERT (hSERT construct suitable for detailed biochemical and structural studies, we developed an efficient thermostability screening protocol and rapidly screened 219 mutations for thermostabilization of hSERT in complex with the SSRI paroxetine. We discovered three mutations-Y110A, I291A and T439S -that, when combined into a single construct, deemed TS3, yielded a hSERT variant with an apparent melting temperature (Tm 19°C greater than that of the wild-type transporter, albeit with a loss of transport activity. Further investigation yielded a double mutant-I291A and T439S-defined as TS2, with a 12°C increase in Tm and retention of robust transport activity. Both TS2 and TS3 were more stable in short-chain detergents in comparison to the wild-type transporter. This thermostability screening protocol, as well as the specific hSERT variants, will prove useful in studies of other integral membrane receptors and transporters and in the investigation of structure and function relationships in hSERT.

  3. Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain.

    Science.gov (United States)

    Sagheddu, Claudia; Aroni, Sonia; De Felice, Marta; Lecca, Salvatore; Luchicchi, Antonio; Melis, Miriam; Muntoni, Anna Lisa; Romano, Rosaria; Palazzo, Enza; Guida, Francesca; Maione, Sabatino; Pistis, Marco

    2015-10-01

    In humans, affective consequences of neuropathic pain, ranging from depression to anxiety and anhedonia, severely impair quality of life and are a major disease burden, often requiring specific medications. Depressive- and anxiety-like behaviors have also been observed in animal models of peripheral nerve injury. Dysfunctions in central nervous system monoamine transmission have been hypothesized to underlie depressive and anxiety disorders in neuropathic pain. To assess whether these neurons display early changes in their activity that in the long-term might lead to chronicization, maladaptive plasticity and affective consequences, we carried out in vivo extracellular single unit recordings from serotonin neurons in the dorsal raphe nucleus (DRN) and from dopamine neurons in ventral tegmental area (VTA) in the spared nerve injury (SNI) model of neuropathic pain in rats. Extracellular dopamine levels and the expression of dopamine D1, D2 receptors and tyrosine hydroxylase (TH) were measured in the nucleus accumbens. We report that, two weeks following peripheral nerve injury, discharge rate of serotonin DRN neurons and burst firing of VTA dopamine cells are enhanced, when compared with sham-operated animals. We also observed higher extracellular dopamine levels and reduced expression of D2, but not D1, receptors and TH in the nucleus accumbens. Our study confirms that peripheral neuropathy induces changes in the serotonin and dopamine systems that might be the early result of chronic maladaptation to persistent pain. The allostatic activation of these neural systems, which mirrors that already described as a consequence of stress, might lead to depression and anxiety previously observed in neuropathic animals but also an attempt to cope positively with the negative experience. PMID:26113399

  4. Association between a genetic variant in the serotonin transporter gene (SLC6A4) and suicidal behavior in patients with schizophrenia

    DEFF Research Database (Denmark)

    Lindholm Carlstrom, Eva; Saetre, Peter; Rosengren, Anders;

    2012-01-01

    ABSTRACT: BACKGROUND: The serotonin (5-hydroxytryptamin; 5-HT) system has a central role in the circuitry of cognition and emotions. Multiple lines of evidence suggest that genetic variation in the serotonin transporter gene (SLC6A4; 5-HTT) is associated with schizophrenia and suicidal behavior. ...... SLC6A4 appears to be involved in suicidal ideation among patients with schizophrenia. Independent replication is needed before more firm conclusions can be drawn.......ABSTRACT: BACKGROUND: The serotonin (5-hydroxytryptamin; 5-HT) system has a central role in the circuitry of cognition and emotions. Multiple lines of evidence suggest that genetic variation in the serotonin transporter gene (SLC6A4; 5-HTT) is associated with schizophrenia and suicidal behavior....... In this study, we wanted to elucidate whether SLC6A4 variations is involved in attempted suicide among patients with schizophrenia in a Scandinavian case-control sample. METHODS: Patients diagnosed with schizophrenia from three Scandinavian samples were assessed for presence or absence of suicide attempts...

  5. Synergism between insecticides permethrin and propoxur occurs through activation of presynaptic muscarinic negative feedback of acetylcholine release in the insect central nervous system.

    Science.gov (United States)

    Corbel, Vincent; Stankiewicz, Maria; Bonnet, Julien; Grolleau, Françoise; Hougard, Jean Marc; Lapied, Bruno

    2006-07-01

    Although synergism between pesticides has been widely documented, the physiological mechanisms by which an insecticide synergizes another remains unclear. Toxicological and electrophysiological studies were carried out on two susceptible pest species (the mosquito Culex quinquefasciatus and the cockroach Periplaneta americana) to understand better the physiological process involved in pyrethroid and carbamate interactions. Larval bioassays were conducted with the susceptible reference strain SLAB of C. quinquefasciatus to assess the implication of multi-function oxidases and non-specific esterases in insecticide detoxification and synergism. Results showed that the general theory of synergism (competition between pesticides for a common detoxification enzyme) was unlikely to occur in the SLAB strain since the level of synergy recorded between permethrin and propoxur was unchanged in the presence of piperonyl butoxide and tribufos, two inhibitors of oxidases and esterases, respectively (synergism ratios were similar with and without synergists). We also showed that addition of a sub-lethal concentration of nicotine significantly increased the toxicity of permethrin and propoxur at the lower range of the dose-mortality regression lines, suggesting the manifestation of important physiological disruptions at synaptic level. The effects of both permethrin and propoxur were studied on the cercal-afferent giant-interneuron synapses in the terminal abdominal ganglion of the cockroach P. americana using the single-fibre oil-gap method. We demonstrated that permethrin and propoxur increased drastically the ACh concentration within the synaptic cleft, which thereby stimulated a negative feedback of ACh release. Atropine, a muscarinic receptor antagonist, reversed the effect of permethrin and propoxur mixtures. This demonstrates the implication of the presynaptic muscarinic receptors in the negative feedback regulation process and in synergism. Based on these findings, we

  6. Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: reduction by a selective serotonin reuptake inhibitor.

    Science.gov (United States)

    Esler, Murray; Lambert, Elisabeth; Alvarenga, Marlies; Socratous, Florentia; Richards, Jeff; Barton, David; Pier, Ciaran; Brenchley, Celia; Dawood, Tye; Hastings, Jacqueline; Guo, Ling; Haikerwal, Deepak; Kaye, David; Jennings, Garry; Kalff, Victor; Kelly, Michael; Wiesner, Glen; Lambert, Gavin

    2007-08-01

    Since the brain neurotransmitter changes characterising panic disorder remain uncertain, we quantified brain noradrenaline and serotonin turnover in patients with panic disorder, in the absence of a panic attack. Thirty-four untreated patients with panic disorder and 24 matched healthy volunteers were studied. A novel method utilising internal jugular venous sampling, with thermodilution measurement of jugular blood flow, was used to directly quantify brain monoamine turnover, by measuring the overflow of noradrenaline and serotonin metabolites from the brain. Radiographic depiction of brain venous sinuses allowed differential venous sampling from cortical and subcortical regions. The relation of brain serotonin turnover to serotonin transporter genotype and panic disorder severity were evaluated, and the influence of an SSRI drug, citalopram, on serotonin turnover investigated. Brain noradrenaline turnover in panic disorder patients was similar to that in healthy subjects. In contrast, brain serotonin turnover, estimated from jugular venous overflow of the metabolite, 5-hydroxyindole acetic acid, was increased approximately 4-fold in subcortical brain regions and in the cerebral cortex (P < 0.01). Serotonin turnover was highest in patients with the most severe disease, was unrelated to serotonin transporter genotype, and was reduced by citalopram (P < 0.01). Normal brain noradrenaline turnover in panic disorder patients argues against primary importance of the locus coeruleus in this condition. The marked increase in serotonin turnover, in the absence of a panic attack, possibly represents an important underlying neurotransmitter substrate for the disorder, although this point remains uncertain. Support for this interpretation comes from the direct relationship which existed between serotonin turnover and illness severity, and the finding that SSRI administration reduced serotonin turnover. Serotonin transporter genotyping suggested that increased whole brain

  7. Genetic linkage study of bipolar disorder and the serotonin transporter

    Energy Technology Data Exchange (ETDEWEB)

    Kelsoe, J.R.; Morison, M.; Mroczkowski-Parker, Z.; Bergesch, P.; Rapaport, M.H.; Mirow, A.L. [Univ. of California, San Diego, CA (United States)] [and others

    1996-04-09

    The serotonin transporter (HTT) is an important candidate gene for the genetic transmission of bipolar disorder. It is the site of action of many antidepressants, and plays a key role in the regulation of serotonin neurotransmission. Many studies of affectively ill patients have found abnormalities in serotonin metabolism, and dysregulation of the transporter itself. The human serotonin transporter has been recently cloned and mapped to chromosome 17. We have identified a PstI RFLP at the HTT locus, and here report our examination of this polymorphism for possible linkage to bipolar disorder. Eighteen families were examined from three populations: the Old Order Amish, Iceland, and the general North American population. In addition to HTT, three other microsatellite markers were examined, which span an interval known to contain HTT. Linkage analyses were conducted under both dominant and recessive models, as well as both narrow (bipolar only) and broad (bipolar + recurrent unipolar) diagnostic models. Linkage could be excluded to HTT under all models examined. Linkage to the interval spanned by the microsatellites was similarly excluded under the dominant models. In two individual families, maximum lod scores of 1.02 and 0.84 were obtained at D17S798 and HTT, respectively. However, these data overall do not support the presence of a susceptibility locus for bipolar disorder near the serotonin transporter. 20 refs., 2 tabs.

  8. Aggravation of viral hepatitis by platelet-derived serotonin.

    Science.gov (United States)

    Lang, Philipp A; Contaldo, Claudio; Georgiev, Panco; El-Badry, Ashraf Mohammad; Recher, Mike; Kurrer, Michael; Cervantes-Barragan, Luisa; Ludewig, Burkhard; Calzascia, Thomas; Bolinger, Beatrice; Merkler, Doron; Odermatt, Bernhard; Bader, Michael; Graf, Rolf; Clavien, Pierre-Alain; Hegazy, Ahmed N; Löhning, Max; Harris, Nicola L; Ohashi, Pamela S; Hengartner, Hans; Zinkernagel, Rolf M; Lang, Karl S

    2008-07-01

    More than 500 million people worldwide are persistently infected with hepatitis B virus or hepatitis C virus. Although both viruses are poorly cytopathic, persistence of either virus carries a risk of chronic liver inflammation, potentially resulting in liver steatosis, liver cirrhosis, end-stage liver failure or hepatocellular carcinoma. Virus-specific T cells are a major determinant of the outcome of hepatitis, as they contribute to the early control of chronic hepatitis viruses, but they also mediate immunopathology during persistent virus infection. We have analyzed the role of platelet-derived vasoactive serotonin during virus-induced CD8(+) T cell-dependent immunopathological hepatitis in mice infected with the noncytopathic lymphocytic choriomeningitis virus. After virus infection, platelets were recruited to the liver, and their activation correlated with severely reduced sinusoidal microcirculation, delayed virus elimination and increased immunopathological liver cell damage. Lack of platelet-derived serotonin in serotonin-deficient mice normalized hepatic microcirculatory dysfunction, accelerated virus clearance in the liver and reduced CD8(+) T cell-dependent liver cell damage. In keeping with these observations, serotonin treatment of infected mice delayed entry of activated CD8(+) T cells into the liver, delayed virus control and aggravated immunopathological hepatitis. Thus, vasoactive serotonin supports virus persistence in the liver and aggravates virus-induced immunopathology.

  9. [Case of prolonged recovery from serotonin syndrome caused by paroxetine].

    Science.gov (United States)

    Ochiai, Yusuke; Katsu, Hisatoshi; Okino, Shinji; Wakutsu, Noriyuki; Nakayama, Kazuhiko

    2003-01-01

    We report a case of serotonin syndrome in a patient being treated with paroxetine for depression. Despite prompt discontinuation of medication, his serotonin syndrome continued for 10 days before full consciousness was restored. The patient was a 48-year-old male with chief complaints of hypobulia and suicidal thoughts. He consulted as a psychiatric outpatient, and oral paroxetine 20 mg/day, etizolam 1.0 mg/day, and brotizolam 0.25 mg/day were immediately started. Upsurge of feeling and disinhibition state were noted the following day, then on treatment day 6 his condition deteriorated to substupor state and he was admitted for further treatment. On admission, change of mental condition (consciousness disturbance), perspiration, hyperreflexia, myoclonus and tremor were seen, and serotonin syndrome caused by paroxetine was suspected. Paroxetine was thus discontinued, and under intravenous drip his condition gradually improved. However, it was not until the 10th hospital day that he became fully alert. In examinations, no infectious, metabolic or organic diseases were detected. The patient's condition often improves with in 24 hours of discontinuation of the causative medication in serotonin syndrome. Symptoms continued for 10 days in this patient, however, perhaps because paroxetine was administered for 6 days before discontinuation. In addition, interaction with other medications may have occurred. Therefore, when serotonin syndrome is suspected, prompt discontinuation of the suspected causative medication, followed by close monitoring of the pharmacokinetics is warranted. PMID:15027311

  10. Serotonin deficiency exacerbates acetaminophen-induced liver toxicity in mice.

    Science.gov (United States)

    Zhang, Jingyao; Song, Sidong; Pang, Qing; Zhang, Ruiyao; Zhou, Lei; Liu, Sushun; Meng, Fandi; Wu, Qifei; Liu, Chang

    2015-01-29

    Acetaminophen (APAP) overdose is a major cause of acute liver failure. Peripheral 5-hydroxytryptamine (serotonin, 5-HT) is a cytoprotective neurotransmitter which is also involved in the hepatic physiological and pathological process. This study seeks to investigate the mechanisms involved in APAP-induced hepatotoxicity, as well as the role of 5-HT in the liver's response to APAP toxicity. We induced APAP hepatotoxicity in mice either sufficient of serotonin (wild-type mice and TPH1-/- plus 5- Hydroxytryptophan (5-HTP)) or lacking peripheral serotonin (Tph1-/- and wild-type mice plus p-chlorophenylalanine (PCPA)). Mice with sufficient 5-HT exposed to acetaminophen have a significantly lower mortality rate and a better outcome compared with mice deficient of 5-HT. This difference is at least partially attributable to a decreased level of inflammation, oxidative stress and endoplasmic reticulum (ER) stress, Glutathione (GSH) depletion, peroxynitrite formation, hepatocyte apoptosis, elevated hepatocyte proliferation, activation of 5-HT2B receptor, less activated c-Jun NH₂-terminal kinase (JNK) and hypoxia-inducible factor (HIF)-1α in the mice sufficient of 5-HT versus mice deficient of 5-HT. We thus propose a physiological function of serotonin that serotonin could ameliorate APAP-induced liver injury mainly through inhibiting hepatocyte apoptosis ER stress and promoting liver regeneration.

  11. Interactions of melatonin and serotonin with lactoperoxidase enzyme.

    Science.gov (United States)

    Şişecioğlu, Melda; Çankaya, Murat; Gülçin, İlhami; Özdemir, Hasan

    2010-12-01

    Melatonin is the chief secretory product of the pineal gland and is synthesized enzymatically from serotonin. These indoleamine derivatives play an important role in the prevention of oxidative damage. Lactoperoxidase (LPO; EC 1.11.1.7) was purified from bovine milk with three purification steps: Amberlite CG-50 resin, CM-Sephadex C-50 ion-exchange, and Sephadex G-100 gel filtration chromatography, respectively. LPO was purified with a yield of 21.6%, a specific activity of 34.0 EU/mg protein, and 14.7-fold purification. To determine the enzyme purity, SDS-PAGE was performed and a single band was observed. The R(z) (A(412)/A(280)) value for LPO was 0.9. The effect of melatonin and serotonin on lactoperoxidase was determined using ABTS as chromogenic substrate. The half-maximal inhibitory concentration (IC(50)) values for melatonin and serotonin were found to be 1.46 and 1.29 μM, respectively. Also, the inhibition constants (K(i)) for melatonin and serotonin were 0.82 ± 0.28 and 0.26 ± 0.04 μM, respectively. Both melatonin and serotonin were found to be competitive inhibitors.

  12. Suppressions of serotonin-induced increased vascular permeability and leukocyte infiltration by Bixa orellana leaf extract.

    Science.gov (United States)

    Yong, Yoke Keong; Sulaiman, NurShahira; Hakim, Muhammad Nazrul; Lian, Gwendoline Ee Cheng; Zakaria, Zainul Amirudin; Othman, Fauziah; Ahmad, Zuraini

    2013-01-01

    The aim of the present study was to evaluate the anti-inflammatory activities of aqueous extract of Bixa orellana (AEBO) leaves and its possible mechanisms in animal models. The anti-inflammatory activity of the extract was evaluated using serotonin-induced rat paw edema, increased peritoneal vascular permeability, and leukocyte infiltrations in an air-pouch model. Nitric oxide (NO), indicated by the sum of nitrites and nitrates, and vascular growth endothelial growth factor (VEGF) were measured in paw tissues of rats to determine their involvement in the regulation of increased permeability. Pretreatments with AEBO (50 and 150 mg kg⁻¹) prior to serotonin inductions resulted in maximum inhibitions of 56.2% of paw volume, 45.7% of Evans blue dye leakage in the peritoneal vascular permeability model, and 83.9% of leukocyte infiltration in the air-pouch model. 57.2% maximum inhibition of NO and 27% of VEGF formations in rats' paws were observed with AEBO at the dose of 150 mg kg⁻¹. Pharmacological screening of the extract showed significant (P < 0.05) anti-inflammatory activity, indicated by the suppressions of increased vascular permeability and leukocyte infiltration. The inhibitions of these inflammatory events are probably mediated via inhibition of NO and VEGF formation and release. PMID:24224164

  13. Suppressions of Serotonin-Induced Increased Vascular Permeability and Leukocyte Infiltration by Bixa orellana Leaf Extract

    Directory of Open Access Journals (Sweden)

    Yoke Keong Yong

    2013-01-01

    Full Text Available The aim of the present study was to evaluate the anti-inflammatory activities of aqueous extract of Bixa orellana (AEBO leaves and its possible mechanisms in animal models. The anti-inflammatory activity of the extract was evaluated using serotonin-induced rat paw edema, increased peritoneal vascular permeability, and leukocyte infiltrations in an air-pouch model. Nitric oxide (NO, indicated by the sum of nitrites and nitrates, and vascular growth endothelial growth factor (VEGF were measured in paw tissues of rats to determine their involvement in the regulation of increased permeability. Pretreatments with AEBO (50 and 150 mg kg−1 prior to serotonin inductions resulted in maximum inhibitions of 56.2% of paw volume, 45.7% of Evans blue dye leakage in the peritoneal vascular permeability model, and 83.9% of leukocyte infiltration in the air-pouch model. 57.2% maximum inhibition of NO and 27% of VEGF formations in rats’ paws were observed with AEBO at the dose of 150 mg kg−1. Pharmacological screening of the extract showed significant (P<0.05 anti-inflammatory activity, indicated by the suppressions of increased vascular permeability and leukocyte infiltration. The inhibitions of these inflammatory events are probably mediated via inhibition of NO and VEGF formation and release.

  14. Serotonin mediates a learned increase in attraction to high concentrations of benzaldehyde in aged C. elegans.

    Science.gov (United States)

    Tsui, David; van der Kooy, Derek

    2008-11-01

    We utilized olfactory-mediated chemotaxis in Caenorhabditis elegans to examine the effect of aging on information processing and animal behavior. Wild-type (N2) young adults (day 4) initially approach and eventually avoid a point source of benzaldehyde. Aged adult animals (day 7) showed a stronger initial approach and a delayed avoidance to benzaldehyde compared with young adults. This delayed avoidance is due to an increased attraction rather than a decreased avoidance to benzaldehyde because (1) aged odr-3 mutants that are defective in odor attraction showed no delayed benzaldehyde avoidance, and (2) the delay in avoidance was also observed with another attractant diacetyl, but not the repellent octanol. Interestingly, the stronger expression of attractive behavior was only observed at benzaldehyde concentrations of 1% or higher. When worms were grown on nonbacterial growth media instead of Escherichia coli, thus removing the contingency between odors released from the food and the food itself, the increase in attraction to benzaldehyde disappeared. The increased attraction recovered after reinitiating the odor-food contingency by returning animals to E. coli food or supplementing axenic media with benzaldehyde. Moreover, serotonin-deficient mutants showed a deficit in the age-enhanced attraction. These results suggest that the increased attraction to benzaldehyde in aged worms is (1) serotonin mediated, (2) specific to high concentration of odorants, and (3) dependent on a learned association of odor metabolites with the presence of food. We propose that associative learning may selectively modify pathways at or downstream from a low-affinity olfactory receptor.

  15. Involvement of Central Endothelin ETA and Cannabinoid CB1 Receptors and Arginine Vasopressin Release in Sepsis Induced by Cecal Ligation and Puncture in Rats.

    Science.gov (United States)

    Leite-Avalca, Mariane C G; Lomba, Luis A; Bastos-Pereira, Amanda L; Brito, Haissa O; Fraga, Daniel; Zampronio, Aleksander R

    2016-09-01

    We previously reported that endothelin-1 (ET-1) reduced the frequency of spontaneous excitatory currents in vasopressinergic magnocellular cells through the activation of endothelin ETA receptors in rat brain slices. This effect was abolished by a cannabinoid CB1 receptor antagonist, suggesting the involvement of endocannabinoids. The present study investigated whether the blockade of ETA or CB1 receptors during the phase of increased levels of ET-1 after severe sepsis increases the survival rate of animals concomitantly with an increase in plasma arginine vasopressin (AVP) levels. Sepsis was induced in male Wistar rats by cecal ligation and puncture (CLP). Treatment with the CB1 receptor antagonist rimonabant (Rim; 10 and 20 mg/kg, orally) 4 h after CLP (three punctures) significantly increased the survival rate compared with the CLP per vehicle group. Intracerebroventricular treatment with the ETA receptor antagonist BQ123 (100 pmol) or with Rim (2 μg) 4 and 8 h after CLP but not the ETB receptor antagonist BQ788 (100 pmol), also significantly improved the survival rate. Sham-operated and CLP animals that were treated with Rim had significantly lower core temperature than CLP animals. However, oral treatment with Rim did not change bacterial count in the peritoneal exudate, neutrophil migration to the peritoneal cavity, leucopenia or increased plasma interleukin-6 levels induced by CLP. Both Rim and BQ123 also increased AVP levels 12 h after CLP. The blockade of central CB1 and ETA receptors in the late phase of sepsis increased the survival rate, reduced body temperature and increased the circulating AVP levels. PMID:26925810

  16. Ex vivo evaluation of the serotonin 1A receptor partial agonist [³H]CUMI-101 in awake rats

    DEFF Research Database (Denmark)

    Palner, Mikael; Underwood, Mark D; Kumar, Dileep J S;

    2011-01-01

    -DL-phenylalanine, a serotonin synthesis inhibitor, did not show any effect on the standardized uptake values (SUVs) in any region. Citalopram did alter SBR, but this was due to changes in cerebellar SUVs. Our results indicate that [³H]CUMI-101 is a good radioligand for imaging 5-HT(1A) high-density regions in rats; however...... different challenge paradigms. [³H]CUMI-101 shows good uptake and good specific binding ratio (SBR) in frontal cortex 5.18 and in hippocampus 3.18. Binding was inhibited in a one-binding-site fashion by WAY100635 and unlabeled CUMI-101. The ex vivo B(max) of [³H]CUMI-101 in frontal cortex (98.7 fmol....../mg) and hippocampus (131 fmol/kg) agree with the ex vivo B(max) of [³H]MPPF in frontal cortex (147.1 fmol/mg) and hippocampus (72.1 fmol/mg) and with in vitro values reported with 8-OH-DPAT. Challenges with citalopram, a selective serotonin reuptake inhibitor, fenfluramine, a serotonin releaser, and 4-chloro...

  17. Organization of Monosynaptic Inputs to the Serotonin and Dopamine Neuromodulatory Systems

    Directory of Open Access Journals (Sweden)

    Sachie K. Ogawa

    2014-08-01

    Full Text Available Serotonin and dopamine are major neuromodulators. Here, we used a modified rabies virus to identify monosynaptic inputs to serotonin neurons in the dorsal and median raphe (DR and MR. We found that inputs to DR and MR serotonin neurons are spatially shifted in the forebrain, and MR serotonin neurons receive inputs from more medial structures. Then, we compared these data with inputs to dopamine neurons in the ventral tegmental area (VTA and substantia nigra pars compacta (SNc. We found that DR serotonin neurons receive inputs from a remarkably similar set of areas as VTA dopamine neurons apart from the striatum, which preferentially targets dopamine neurons. Our results suggest three major input streams: a medial stream regulates MR serotonin neurons, an intermediate stream regulates DR serotonin and VTA dopamine neurons, and a lateral stream regulates SNc dopamine neurons. These results provide fundamental organizational principles of afferent control for serotonin and dopamine.

  18. Spontaneous release of epiretinal membrane in a young weight-lifting athlete by presumed central rupture and centrifugal pull

    Directory of Open Access Journals (Sweden)

    Mansour AM

    2014-11-01

    edges of the ERM and gradual separation from the edges towards the center (remodeling common in youngsters; and 3 acute tearing of ERM at its weakest central point and retraction of part of the membrane towards the epicenter (current case report. Keywords: valsalva maneuver, posterior vitreous detachment

  19. Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter.

    Science.gov (United States)

    Davis, Bruce A; Nagarajan, Anu; Forrest, Lucy R; Singh, Satinder K

    2016-01-01

    The serotonin transporter (SERT) is an integral membrane protein that exploits preexisting sodium-, chloride-, and potassium ion gradients to catalyze the thermodynamically unfavorable movement of synaptic serotonin into the presynaptic neuron. SERT has garnered significant clinical attention partly because it is the target of multiple psychoactive agents, including the antidepressant paroxetine (Paxil), the most potent selective serotonin reuptake inhibitor known. However, the binding site and orientation of paroxetine in SERT remain controversial. To provide molecular insight, we constructed SERT homology models based on the Drosophila melanogaster dopamine transporter and docked paroxetine to these models. We tested the predicted binding configurations with a combination of radioligand binding and flux assays on wild-type and mutant SERTs. Our data suggest that the orientation of paroxetine, specifically its fluorophenyl ring, in SERT's substrate binding site directly depends on this pocket's charge distribution, and thereby provide an avenue toward understanding and enhancing high-affinity antidepressant activity. PMID:27032980

  20. The 5-HT2A serotonin receptor in executive function: Implications for neuropsychiatric and neurodegenerative diseases.

    Science.gov (United States)

    Aznar, Susana; Hervig, Mona El-Sayed

    2016-05-01

    Executive function entails the interplay of a group of cognitive processes enabling the individual to anticipate consequences, attain self-control, and undertake appropriate goal-directed behaviour. Serotonin signalling at serotonin 2A receptors (5-HT2AR) has important effects on these behavioural and cognitive pathways, with the prefrontal cortex (PFC) as the central actor. Indeed, the 5-HT2ARs are highly expressed in PFC, where they modulate cortical activity and local network oscillations (brain waves). Numerous psychiatric and neurodegenerative diseases result in disrupted executive function. Animal and human studies have linked these disorders with alterations in the 5-HT2AR system, making this an important pharmacological target for the treatment of disorders with impaired cognitive function. This review aims to describe the current state of knowledge on the role of 5-HT2AR signalling in components of executive function, and how 5-HT2AR systems may relate to executive dysfunctions occurring in psychiatric and neurodegenerative diseases. We hope thereby to provide insight into how pharmacotherapy targeting the 5-HT2AR may ameliorate (or exacerbate) aspects of these disorders. PMID:26891819

  1. Age-related effect of serotonin transporter genotype on amygdala and prefrontal cortex function in adolescence

    OpenAIRE

    Wiggins, Jillian Lee; Bedoyan, Jirair K.; Carrasco, Melisa; Swartz, Johnna R.; Martin, Donna M.; Monk, Christopher S.

    2012-01-01

    The S and LG alleles of the serotonin transporter-linked polymorphic region (5-HTTLPR) lower serotonin transporter expression. These low expressing alleles are linked to increased risk for depression and brain activation patterns found in depression (increased amygdala activation and decreased amygdala-prefrontal cortex connectivity). Paradoxically, serotonin transporter blockade relieves depression symptoms. Rodent models suggest that decreased serotonin transporter in early life produces de...

  2. Brain serotonin 4 receptor binding is associated with the cortisol awakening response

    DEFF Research Database (Denmark)

    Jakobsen, Gustav R; Fisher, Patrick M; Dyssegaard, Agnete;

    2016-01-01

    Serotonin signalling is considered critical for an appropriate and dynamic adaptation to stress. Previously, we have shown that prefrontal serotonin transporter (SERT) binding is positively associated with the cortisol awakening response (CAR) (Frokjaer et al., 2013), which is an index of hypotha......Serotonin signalling is considered critical for an appropriate and dynamic adaptation to stress. Previously, we have shown that prefrontal serotonin transporter (SERT) binding is positively associated with the cortisol awakening response (CAR) (Frokjaer et al., 2013), which is an index...

  3. Coaction of Stress and Serotonin Transporter Genotype in Predicting Aggression at the Transition to Adulthood

    Science.gov (United States)

    Conway, Christopher C.; Keenan-Miller, Danielle; Hammen, Constance; Lind, Penelope A.; Najman, Jake M.; Brennan, Patricia A.

    2012-01-01

    Despite consistent evidence that serotonin functioning affects stress reactivity and vulnerability to aggression, research on serotonin gene-stress interactions (G x E) in the development of aggression remains limited. The present study investigated variation in the promoter region of the serotonin transporter gene (5-HTTLPR) as a moderator of the…

  4. 21 CFR 862.1390 - 5-Hydroxyindole acetic acid/serotonin test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false 5-Hydroxyindole acetic acid/serotonin test system... Test Systems § 862.1390 5-Hydroxyindole acetic acid/serotonin test system. (a) Identification. A 5-hydroxyindole acetic acid/serotonin test system is a device intended to measure 5-hydroxyindole acetic...

  5. How the cerebral serotonin homeostasis predicts environmental changes

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Kalbitzer, Urs; Knudsen, Gitte Moos;

    2013-01-01

    Molecular imaging studies with positron emission tomography have revealed that the availability of serotonin transporter (5-HTT) in the human brain fluctuates over the course of the year. This effect is most pronounced in carriers of the short allele of the 5-HTT promoter region (5-HTTLPR), which...... of cerebral serotonin transmission to seasonal and other forms of environmental change imparts greater behavioral flexibility, at the expense of increased vulnerability to stress. This model may explain the somewhat higher prevalence of the s-allele in some human populations dwelling at geographic latitudes...

  6. Endocannabinoids blunt the augmentation of synaptic transmission by serotonin 2A receptors in the nucleus tractus solitarii (nTS)

    OpenAIRE

    Austgen, James R.; Kline, David D.

    2013-01-01

    Serotonin (5-Hydroxytryptamine, 5-HT) and the 5-HT2 receptor modulate cardiovascular and autonomic function in part through actions in the nTS, the primary termination and integration point for cardiorespiratory afferents in the brainstem. In other brain regions, 5-HT2 receptors (5-HT2R) modify synaptic transmission directly, as well as through 5-HT2AR-induced endocannabinoid release. This study examined the role of 5-HT2AR as well as their interaction with endocannabinoids on neurotransmissi...

  7. Effects of cyclooxygenase and lipoxygenase inhibition on basal- and serotonin-induced ion transport in rat colon

    DEFF Research Database (Denmark)

    Engelmann, Bodil Elisabeth; Bindslev, Niels; Poulsen, Steen Seier;

    2002-01-01

    The purpose of this study was to determine the effect of a selective cyclooxygenase (COX)-2 inhibitor as compared to non-selective COX and lipoxygenase (LOX) inhibitors in rat colon. Basal- and serotonin (5-hydroxytryptamine, 5-HT)-induced electrogenic ion transport (short circuit current, SCC......), prostaglandin E2 (PGE2) release and histological characteristics were measured. Muscle-stripped mucosal sheets of the proximal and distal segment of rat colon were investigated by employing the Ussing chamber technique, radioimmunoassays for PGE2 and light microscopy examinations for control of tissue integrity...... reduced both basal- and 5-HT-induced SCC in both segments. Nordihydroguaiaretic acid reduced the 5-HT-induced increase in SCC, but did not change basal SCC. 5-HT-induced a concentration-dependent release of PGE2. Only high concentrations of piroxicam and indomethacin reduced basal PGE2 release and 5-HT...

  8. Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation

    DEFF Research Database (Denmark)

    Frokjaer, Vibe Gedsoe; Pinborg, Anja; Holst, Klaus Kähler;

    2015-01-01

    BACKGROUND: An adverse response to acute and pronounced changes in sex-hormone levels during, for example, the perimenopausal or postpartum period appears to heighten risk for major depression in women. The underlying risk mechanisms remain elusive but may include transiently compromised serotone...... provoke depressive symptoms and thus provide a rationale for future preventive strategies in high-risk groups.......BACKGROUND: An adverse response to acute and pronounced changes in sex-hormone levels during, for example, the perimenopausal or postpartum period appears to heighten risk for major depression in women. The underlying risk mechanisms remain elusive but may include transiently compromised...... serotonergic brain signaling. Here, we modeled a biphasic ovarian sex hormone fluctuation using a gonadotropin-releasing hormone agonist (GnRHa) and evaluated if emergence of depressive symptoms was associated with change in cerebral serotonin transporter (SERT) binding following intervention. METHODS...

  9. Effects of serotonin-2A receptor binding and gender on personality traits and suicidal behavior in borderline personality disorder.

    Science.gov (United States)

    Soloff, Paul H; Chiappetta, Laurel; Mason, Neale Scott; Becker, Carl; Price, Julie C

    2014-06-30

    Impulsivity and aggressiveness are personality traits associated with a vulnerability to suicidal behavior. Behavioral expression of these traits differs by gender and has been related to central serotonergic function. We assessed the relationships between serotonin-2A receptor function, gender, and personality traits in borderline personality disorder (BPD), a disorder characterized by impulsive-aggression and recurrent suicidal behavior. Participants, who included 33 BPD patients and 27 healthy controls (HC), were assessed for Axis I and II disorders with the Structured Clinical Interview for DSM-IV and the International Personality Disorders Examination, and with the Diagnostic Interview for Borderline Patients-Revised for BPD. Depressed mood, impulsivity, aggression, and temperament were assessed with standardized measures. Positron emission tomography with [(18)F]altanserin as ligand and arterial blood sampling was used to determine the binding potentials (BPND) of serotonin-2A receptors in 11 regions of interest. Data were analyzed using Logan graphical analysis, controlling for age and non-specific binding. Among BPD subjects, aggression, Cluster B co-morbidity, antisocial PD, and childhood abuse were each related to altanserin binding. BPND values predicted impulsivity and aggression in BPD females (but not BPD males), and in HC males (but not HC females.) Altanserin binding was greater in BPD females than males in every contrast, but it did not discriminate suicide attempters from non-attempters. Region-specific differences in serotonin-2A receptor binding related to diagnosis and gender predicted clinical expression of aggression and impulsivity. Vulnerability to suicidal behavior in BPD may be related to serotonin-2A binding through expression of personality risk factors.

  10. Serotonin increases ERK1/2 phosphorylation in astrocytes by stimulation of 5-HT2B and 5-HT2C receptors.

    Science.gov (United States)

    Li, Baoman; Zhang, Shiquen; Li, Min; Hertz, Leif; Peng, Liang

    2010-11-01

    We have previously shown that fluoxetine causes ERK(1/2) phosphorylation in cultured mouse astrocytes mediated exclusively by stimulation of 5-HT(2B) receptors (Li et al., 2008b). This raises the question whether this is also the case for serotonin (5-HT) itself. In the present study serotonin was found to induce ERK(1/2) phosphorylation by stimulation of 5-HT(2B) receptors with high affinity (EC(50): 20-30 pM), and by stimulation of 5-HT(2C) receptor with low affinity (EC(50): 1 microM or higher). ERK(1/2) phosphorylation induced by stimulation of either 5-HT(2B) or 5-HT(2C) receptors was mediated by epidermal growth factor (EGF) receptor transactivation (Peng et al., this issue), shown by the inhibitory effect of AG1478, an inhibitor of the EGF receptor tyrosine kinase, and GM6001, an inhibitor of Zn-dependent metalloproteinases, and thus of 5-HT(2B) receptor-mediated EGF receptor agonist release. It is discussed that the high potency of the 5-HT(2B)-mediated effect is consistent with literature data for binding affinity of serotonin to cloned human 5-HT(2B) receptors and with observations of low extracellular concentrations of serotonin in brain, which would allow a demonstrated moderate and modality-dependent increase in specific brain areas to activate 5-HT(2B) receptors. In contrast the relevance of the observed 5-HT(2C) receptors on astrocytes is questioned.

  11. 星点设计-效应面法优化盐酸二甲双胍缓释片处方%Optimization of metformin hydrochloride sustained-release tablets by central composite design/response surface methodology

    Institute of Scientific and Technical Information of China (English)

    谈颖; 林巧平; 刘春晖; 狄留庆

    2011-01-01

    目的 应用星点设计-效应面法优化盐酸二甲双胍缓释片的处方.方法 以HPMC K100M的用量和Carbopol 71GNF的用量为考察因素,以1,3,6和10 h的累积释放度为考察指标,采用多元线性回归和多元非线性回归拟合选择合适的模型,根据最佳模型绘制效应面图和等高线图,选择最佳处方并进行验证.采用相似因子对自研片和国外进口片在不同介质中的累积释放度进行比较研究.结果 优化处方中HPMC K100M和Carbopol 71GNF的用量分别为片重的8%~15%和10%~13%.最佳处方在各时间点的累积释放度的实测值与预测值的偏差均在6%以内.自研片和国外进口片在pH=4.5、pH=6.8和水中的累积释放度相似性因子f 2分别为:76.60、75.58和72.38.结论 通过星点设计-效应面法建立的模型可以用于盐酸二甲双胍缓释片处方的优化.%Aim To optimize the formulation of metformin hydrochloride sustained-release tablets by central composite design/response surface methodology( CCD ). Methods The independent variables were the amount of HPMC KIOOM and Carbopol 71GNF, and the dependent variables were the dissolution of metformin hydrochloride at 1 ,3 ,6 ,10 h. Linear or nonlinear mathematic models were used to estimate the relationship between the independent and the dependent variables. Response surface and 2D-contour map were delineated according to the hest-fit mathematic models to select the optimized formulation and assess the observed and predicted values. The release rate of the sustained-release tablets and imported tablets were studied by similarity factor. Results Optimized forruulation of metformin hydrochloride sustained-release tablets were proposed to consist of 8% - 15% HPMC K1OOM and 10%~ 13% Carbopol 7IGNF. Bias hetween the observed and predicted values was within 6% . The f2 for the sustained-release tablets and imported tablets in different dissolution mediums( pH =4. 5 ,pH =6. 8 and water )were 76

  12. Regional serotonin transporter availability and depression are correlated in Wilson's disease.

    Science.gov (United States)

    Hesse, S; Barthel, H; Hermann, W; Murai, T; Kluge, R; Wagner, A; Sabri, O; Eggers, B

    2003-08-01

    In patients with Wilson's disease (WD), depression is a frequent psychiatric symptom. In vivo neuroimaging studies suggest that depression and other neuropsychiatric disorders are associated with central serotonergic deficits. However, in vivo measurements of serotonergic neurotransmission have not until now been performed in patients with this copper deposition disorder. The present prospective study revealed that depressive symptomatology is related to an alteration of presynaptic serotonin transporters (SERT) availability as measured by [123I]-2beta-carbomethoxy-3beta-(iodophenyl)tropane ([123I]beta-CIT) and high-resolution single-photon emission computed tomography (SPECT). SERT imaging with [123I]beta-CIT-SPECT could therefore become a useful tool for diagnosis and therapy monitoring in depressed WD patients. PMID:12898347

  13. The reciprocal interaction between serotonin and social behaviour.

    NARCIS (Netherlands)

    Kiser, D.; Steemers, B.; Branchi, I.; Homberg, J.R.

    2012-01-01

    Serotonin (5-HT) is an ancient molecule directing behavioural responses to environmental stimuli. The social environment is the most powerful environmental factor. It is well recognized that 5-HT plays a key role in shaping social responses, and that the serotonergic system itself is highly responsi

  14. The serotonin transporter gene and startle response during nicotine deprivation.

    Science.gov (United States)

    Minnix, Jennifer A; Robinson, Jason D; Lam, Cho Y; Carter, Brian L; Foreman, Jennifer E; Vandenbergh, David J; Tomlinson, Gail E; Wetter, David W; Cinciripini, Paul M

    2011-01-01

    Affective startle probe methodology was used to examine the effects of nicotine administration and deprivation on emotional processes among individuals carrying at least one s allele versus those with the l/l genotype of the 5-Hydroxytryptamine (Serotonin) Transporter Linked Polymorphic Region, 5-HTTLPR in the promoter region of the serotonin transporter gene [solute ligand carrier family 6 member A4 (SLC6A4) or SERT]. Smokers (n=84) completed four laboratory sessions crossing deprivation (12-h deprived vs. non-deprived) with nicotine spray (nicotine vs. placebo). Participants viewed affective pictures (positive, negative, neutral) while acoustic startle probes were administered. We found that smokers with the l/l genotype showed significantly greater suppression of the startle response when provided with nicotine vs. placebo than those with the s/s or s/l genotypes. The results suggest that l/l smokers, who may have higher levels of the serotonin transporter and more rapid synaptic serotonin clearance, experience substantial reduction in activation of the defensive system when exposed to nicotine.

  15. Serotonin transporter genotype x construction stress interaction in rats

    NARCIS (Netherlands)

    Schipper, P.; Nonkes, L.J.P.; Karel, P.G.A.; Kiliaan, A.J.; Homberg, J.R.

    2011-01-01

    A well-known example for gene x environment interactions in psychiatry is the one involving the low activity (s) allelic variant of the serotonin transporter (5-HTT) promoter polymorphism (5-HTTLPR) that in the context of stress increases risk for depression. In analogy, 5-HTT knockout rodents are h

  16. Mood state moderates the role of serotonin in cognitive biases

    NARCIS (Netherlands)

    Robinson, O.; Cools, R.; Crockett, M.; Sahakian, B.

    2010-01-01

    Reduction of the monoamine serotonin (5-HT) via the dietary manipulation of tryptophan (acute tryptophan depletion; ATD) has been shown to induce negative cognitive biases similar to those found in depression in healthy individuals. However, evidence also indicates that there can be positive effects

  17. Mood state moderates the role of serotonin in cognitive biases.

    NARCIS (Netherlands)

    Robinson, O.J.; Cools, R.; Crockett, M.J.; Sahakian, B.J.

    2010-01-01

    Reduction of the monoamine serotonin (5-HT) via the dietary manipulation of tryptophan (acute tryptophan depletion; ATD) has been shown to induce negative cognitive biases similar to those found in depression in healthy individuals. However, evidence also indicates that there can be positive effects

  18. Selective serotonin reuptake inhibitors as a novel class of immunosuppressants

    NARCIS (Netherlands)

    Gobin, Veerle; Van Steendam, Katleen; Denys, D.; Deforce, Dieter

    2014-01-01

    In the past decades, selective serotonin reuptake inhibitors (SSRIs) have been shown to exert several immunological effects, such as reduced lymphocyte proliferation, alteration of cytokine secretion and induction of apoptosis. Based on these effects, SSRIs were proposed as drugs for the treatment o

  19. Binding-Induced Fluorescence of Serotonin Transporter Ligands

    DEFF Research Database (Denmark)

    Wilson, James; Ladefoged, Lucy Kate; Babinchak, Michael;

    2014-01-01

    The binding-induced fluorescence of 4-(4-(dimethylamino)-phenyl)-1-methylpyridinium (APP(+)) and two new serotonin transporter (SERT)-binding fluorescent analogues, 1-butyl-4-[4-(1-dimethylamino)phenyl]-pyridinium bromide (BPP(+)) and 1-methyl-4-[4-(1-piperidinyl)phenyl]-pyridinium (PPP(+)), has ...

  20. Síndrome serotoninérgica associada ao uso de paroxetina: relato de caso Serotonin syndrome associated to the use of paroxetine: case report

    OpenAIRE

    LUÍS OTÁVIO CAVALLAZZI; ANDERSON K. GREZESIUK

    1999-01-01

    Relatamos um caso de síndrome serotoninérgica pelo uso de inibidor da recaptação da serotonina, a paroxetina. Tal síndrome por esta droga, sem combinações, ainda não tinha sido descrita na literatura.We report on a case of serotonin syndrome associated to the use of the paroxetine, a serotonin reuptake inhibitor drug. Serotonin syndrome related to this drug not combined with other drugs had not yet been described in literature.

  1. Serotonin and calcium homeostasis during the transition period.

    Science.gov (United States)

    Weaver, S R; Laporta, J; Moore, S A E; Hernandez, L L

    2016-07-01

    The transition from pregnancy to lactation puts significant, sudden demands on maternal energy and calcium reserves. Although most mammals are able to effectively manage these metabolic adaptations, the lactating dairy cow is acutely susceptible to transition-related disorders because of the high amounts of milk being produced. Hypocalcemia is a common metabolic disorder that occurs at the onset of lactation. Hypocalcemia is also known to result in poor animal welfare conditions. In addition, cows that develop hypocalcemia are more susceptible to a host of other negative health outcomes. Different feeding tactics, including manipulating the dietary cation-anion difference and administering low-calcium diets, are commonly used preventative strategies. Despite these interventions, the incidence of hypocalcemia in the subclinical form is still as high as 25% to 30% in the United States dairy cow population, with a 5% to 10% incidence of clinical hypocalcemia. In addition, although there are various effective treatments in place, they are administered only after the cow has become noticeably ill, at which point there is already significant metabolic damage. This emphasizes the need for developing alternative prevention strategies, with the monoamine serotonin implicated as a potential therapeutic target. Our research in rodents has shown that serotonin is critical for the induction of mammary parathyroid hormone-related protein, which is necessary for the mobilization of bone tissue and subsequent restoration of maternal calcium stores during lactation. We have shown that circulating serotonin concentrations are positively correlated with serum total calcium on the first day of lactation in dairy cattle. Administration of serotonin's immediate precursor through feeding, injection, or infusion to various mammalian species has been shown to increase circulating serotonin concentrations, with positive effects on other components of maternal metabolism. Most recently

  2. Selective serotonin reuptake inhibitor (SSRI antidepressants, prolactin and breast cancer

    Directory of Open Access Journals (Sweden)

    Janet eAshbury

    2012-12-01

    Full Text Available Selective serotonin reuptake inhibitors (SSRIs are a widely prescribed class of anti-depressants. Laboratory and epidemiologic evidence suggests that a prolactin-mediated mechanism secondary to increased serotonin levels at neuronal synapses could lead to a potentially carcinogenic effect of SSRIs. In this population-based case-control study, we evaluated the association between SSRI use and breast cancer risk as a function of their relative degree of inhibition of serotonin reuptake as a proxy for their impact on prolactin levels. Cases were 2,129 women with primary invasive breast cancer diagnosed from 2003-2007, and controls were 21,297 women randomly selected from the population registry. Detailed information for each SSRI prescription dispensed was compiled using the Saskatchewan prescription database. Logistic regression was used to evaluate the impact of use of high and lower inhibitors of serotonin reuptake and duration of use, as well as to assess the effect of individual high inhibitors on the risk of breast cancer. Exclusive users of high or lower inhibitors of serotonin reuptake were not at increased risk for breast cancer compared with nonusers of SSRIs (OR = 1.01, CI = 0.88-1.17 and OR = 0.91, CI = 0.67-1.25 respectively, regardless of their duration of use or menopausal status. While we cannot rule out the possibility of a clinically important risk increase (OR = 1.83, CI = 0.99-3.40 for long-term users of sertraline (≥24 prescriptions, given the small number of exposed cases (n=12, the borderline statistical significance and the wide confidence interval, these results need to be interpreted cautiously. In this large population-based case-control study, we found no conclusive evidence of breast cancer risk associated with the use of SSRIs even after assessing the degree of serotonin reuptake inhibition and duration of use. Our results do not support the serotonin-mediated pathway for the prolactin-breast cancer hypothesis.

  3. Antidepressants are selective serotonin neuronal reuptake inhibitors: 40-year history

    Directory of Open Access Journals (Sweden)

    D. S. Danilov

    2015-01-01

    Full Text Available The paper presents historical prerequisites for designing antidepressants from a group of selective serotonin neuronal reuptake inhibitors (SSRIs: to determine a lower serotonin concentration in the different tissues of depressed patients; to establish a higher serotonin concentration in the treatment of depressed patients with tricyclic antidepressants, and to formulate the serotonergic theory of depression. It also provides a consecutive account of the history of clinical introduction of individual SSRI representatives, such as fluoxetine, zimelidine, fluvoxamine, indalpine, citalopram, sertraline, paroxetine, and escitalopram. There are data from the history of studying the mechanism of SSRI action: from the theory of the importance of an increase in the concentration of serotonin in the synaptic cleft to the current understanding of complex successive intracellular rearrangements at the level of the postsynaptic neuron. The history of studying the efficacy of SSRIs in treating depression is considered in detail. Emphasis is laid on the reasons for a paradoxical difference in the evaluations of the efficiency of therapy with SSRIs versus other groups of antidepressants at different developmental stages of psychopharmacology. The role of marketing technologies in disseminating the data on the efficacy of this or that group of antidepressants is described. The practical significance of differences in individual SSRI representatives (the potency of serotonin uptake inhibition; the degree of selectivity and activity against the serotonergic system; the likelihood of an unfavorable pharmacokinetic interaction with other drugs; the half-life of elimination; the quickness of achieving a therapeutic dose is analyzed. Whether it is possible and reasonable to differentially choose different SSRI representatives in the treatment of depressions at the present stage is discussed. The authors state their belief that researches should be continued to

  4. Association between serotonin transporter gene polymorphism and recurrent aphthous stomatitis

    Science.gov (United States)

    Manchanda, Aastha; Iyengar, Asha R.; Patil, Seema

    2016-01-01

    Background: Anxiety-related traits have been attributed to sequence variability in the genes coding for serotonin transmission in  the brain. Two alleles, termed long (L) and short (S) differing by 44 base pairs, are found in a polymorphism identified in the promoter region of serotonin transporter gene. The presence of the short allele  and SS and LS genotypes is found to be associated with the reduced expression of this gene decreasing the uptake of serotonin in the brain leading to various anxiety-related traits. Recurrent aphthous stomatitis (RAS) is an oral mucosal disease with varied etiology including the presence of stress, anxiety, and genetic influences. The present study aimed to determine this serotonin transporter gene polymorphism in patients with RAS and compare it with normal individuals. Materials and Methods: This study included 20 subjects with various forms of RAS and 20 normal healthy age- and gender-matched individuals. Desquamated oral mucosal cells were collected for DNA extraction and subjected to polymerase chain reaction for studying insertion/deletion in the 5-HTT gene-linked polymorphic region. Cross tabulations followed by Chi-square tests were performed to compare the significance of findings, P < 0.05 was considered statistically significant. Results: The LS genotype was the most common genotype found in the subjects with aphthous stomatitis (60%) and controls (40%). The total percentage of LS and SS genotypes and the frequency of S allele were found to be higher in the subjects with aphthous stomatitis as compared to the control group although a statistically significant correlation could not be established, P = 0.144 and 0.371, respectively. Conclusion: Within the limitations of this study, occurrence of RAS was not found to be associated with polymorphic promoter region in serotonin transporter gene. PMID:27274339

  5. A Dialogue between the Sirène Pathway in Synergids and the Fertilization Independent Seed Pathway in the Central Cell Controls Male Gamete Release during Double Fertilization in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Nicolas Rotman; Mathieu Gourgues; Anne-Elisabeth Guitton; Jean-Emmanuel Faure; Frédéric Berger

    2008-01-01

    Angiosperms sexual reproduction involves interactions between the two female gametes in the embryo sac and the two male gametes released by the pollen tube.The two synergids of the embryo sac express the FERONIA/SIRENE receptor-like kinase,which controls the discharge of the two sperm cells from the pollen tube.FER/SRN may respond to a ligand from the pollen tube.Alternatively,the interaction between FER/SRN and a ligand from the embryo sac may lead to a state of competence of the synergids allowing pollen tube discharge.Here,we report the new mutant scylla(syl)impaired in the controI of pollen tube discharge.This mutant also produces autonomous endosperm development in absence of tertilization-a trait associated with the FERTILIZATION INDEPENDENT SEED (FIS) mutant class.This led us to identify autonomous endosperm in srn mutants and to demonstrate synergistic interactions between srn and the fis mutants.In addition,the fis mutants display defects in pollen tube discharge as in srn and syl mutants,confirming the interaction between the two pathways.Our findings suggest that pollen tube discharge is controlled by an interaction between the synergids expressing SRN/FER and the central cell expressing FIS genes.

  6. Mapping of the serotonin 5-HT{sub 1D{beta}} autoreceptor gene on chromosome 6 and direct analysis for sequence variants

    Energy Technology Data Exchange (ETDEWEB)

    Lappalainen, J.; Dean, M.; Virkkunen, M. [National Cancer Institute, Fredrick, MD (United States)] [and others

    1995-04-24

    Abnormal brain serotonin function may be characteristic of several neuropsychiatric disorders. Thus, it is important to identify polymorphic genes and screen for functional variants at loci coding for genes that control normal serotonin functions. 5-HT{sub 1D{beta}} is a terminal serotonin autoreceptor which may play a role in regulating serotonin synthesis and release. Using an SSCP technique we screened for 5-HT{sub 1D{beta}} coding sequence variants in psychiatrically interviewed populations, which included controls, alcoholics, and alcoholic arsonists and alcoholic violent offenders with low CSF concentrations of the main serotonin metabolite 5-HIAA. A common polymorphism was identified in the 5-HT{sub 1D{beta}} gene with allele frequencies of 0.72 and 0.28. The SSCP variant was caused by a silent G to C substitution at nucleotide 861 of the coding region. This polymorphism could also be detected as a HincII RFLP of amplified DNA. DNAs from informative CEPH families were typed for the HincII RFLP and analyzed with respect to 20 linked markers on chromosome 6. Multipoint analysis placed the 5-HT{sub 1D{beta}} receptor gene between markers D6S286 and D6S275. A maximum two-point lod score of 10.90 was obtained to D6S26, which had been previously localized on 6q14-15. Chromosomal aberrations involving this region have been previously shown to cause retinal anomalies, developmental delay, and abnormal brain development. This region also contains the gene for North Carolina-type macular dystrophy. 34 refs., 3 figs., 1 tab.

  7. L-arginine abolishes the hypothalamic serotonergic activation induced by central interleukin-1β administration to normal rats

    OpenAIRE

    Iuras, Anderson; Telles, Mônica M; Andrade, Iracema S; Santos, Gianni MS; Lila M. Oyama; Nascimento, Cláudia MO; Silveira, Vera LF; Ribeiro, Eliane B

    2013-01-01

    IL-1β-induced anorexia may depend on interactions of the cytokine with neuropeptides and neurotransmitters of the central nervous system control of energy balance and serotonin is likely to be one catabolic mediator targeted by IL-1β. In the complex interplay involved in feeding modulation, nitric oxide has been ascribed a stimulatory action, which could be of significance in counteracting IL-1β effects. The present study aims to explore the participation of the nitric oxide and the serotonin...

  8. Intrahippocampal Infusions of Anisomycin Produce Amnesia: Contribution of Increased Release of Norepinephrine, Dopamine, and Acetylcholine

    Science.gov (United States)

    Qi, Zhenghan; Gold, Paul E.

    2009-01-01

    Intra-amygdala injections of anisomycin produce large increases in the release of norepinephrine (NE), dopamine (DA), and serotonin in the amygdala. Pretreatment with intra-amygdala injections of the beta-adrenergic receptor antagonist propranolol attenuates anisomycin-induced amnesia without reversing the inhibition of protein synthesis, and…

  9. Local renal ischemia during burn shock in rat effected by thromboxane A2 and serotonin.

    Science.gov (United States)

    Haugan, A; Kirkebø, A

    1986-01-01

    Intermittent patchy ischemia in the renal cortex during traumatic shock has previously been observed in dogs and rats. In recent experiments on rats a high rate of abrupt changes in local blood flow was observed after scalding. To try to reveal endogenous factors causing such ischemic episodes, we scalded six series of anesthetized rats (50% of body surface for 30 s in 80 degrees C water) and measured arterial pressure (AP), hematocrit (Hct), and local renal cortical blood flow (RCF). RCF was recorded by the local H2 washout technique. After scalding, RCF decreased markedly in all series whereas AP was relatively well preserved. In accordance with previous experiments, 11% of the washout curves recorded 0-75 min after scalding showed abrupt changes in local blood flow, rising to 27% during the next 60 min in drug-untreated rats. In contrast, blocking of serotonin S2 receptors with Ketanserin abolished the phenomenon. However, in rats treated with the prostaglandin synthesis blockers, indomethacin (general) or 3-ethyl pyridin (thromboxane A2 blocker), the phenomenon was observed in only 2-3% of the washout curves. Furthermore, after blocking the AngII receptors by saralasin or alpha receptors by phentolamine in separate series, the frequency of abrupt flow shifts was reduced in comparison to the frequency in untreated rats. The results indicate that intermittent, patchy vasoconstriction is mediated by serotonin and thromboxane A2 (TxA2), probably released from platelets. The occurrence of ischemic episodes also depends on the local AngII and alpha-adrenergic tonus present after scalding. PMID:3021355

  10. Role of glycogenolysis in memory and learning: regulation by noradrenaline, serotonin and ATP

    Directory of Open Access Journals (Sweden)

    Marie Elizabeth Gibbs

    2016-01-01

    Full Text Available This paper reviews the role played by glycogen breakdown (glycogenolysis and glycogen re-synthesis in memory processing in two different chick brain regions, (1 the hippocampus and (2 the avian equivalent of the mammalian cortex, the intermediate medial mesopallium (IMM. Memory processing is regulated by the neuromodulators noradrenaline and serotonin soon after training and glycogen breakdown and re-synthesis are involved. In day-old domestic chicks, memory formation is dependent on the breakdown of glycogen (glycogenolysis at three specific times during the first 60 min after learning (around 2.5, 30 and 55 min. The chicks learn to discriminate in a single trial between beads of two colours and tastes. Inhibition of glycogen breakdown by the inhibitor of glycogen phosphorylase 1,4-dideoxy-1,4-imino-D-arabinitol (DAB given at specific times prior to the formation of long-term memory prevents memory forming. Noradrenergic stimulation of cultured chicken astrocytes by a selective β2-adrenergic (AR agonist reduces glycogen levels and we believe that in vivo this triggers memory consolidation at the second stage of glycogenolysis. Serotonin acting at 5-HT2B receptors acts on the first stage, but not on the second. We have shown that noradrenaline, acting via post-synaptic α2-ARs, is also responsible for the synthesis of glycogen and our experiments suggest that there is a readily accessible labile pool of glycogen in astrocytes which is depleted within 10 min if glycogen synthesis is inhibited. Endogenous ATP promotion of memory consolidation at 2.5 and 30 min is also dependent on glycogen breakdown. ATP acts at P2Y1 receptors and the action of thrombin suggests that it causes the release of internal calcium ([Ca2+]i] in astrocytes. Glutamate and GABA, the primary neurotransmitters in the brain, cannot be synthesized in neurons de novo. Neurons rely on astrocytic glutamate synthesis, requiring glycogenolysis.

  11. Kinetics and autoradiography of high affinity uptake of serotonin by primary astrocyte cultures

    International Nuclear Information System (INIS)

    Primary astrocyte cultures prepared from the cerebral cortices of neonatal rats showed significant accumulation of serotonin (5-hydroxytryptamine; [3H]-5-HT). At concentrations in the range of 0.01 to 0.7 microM [3H]-5-HT, this uptake was 50 to 85% Na+ dependent and gave a Km of 0.40 +/- 0.11 microM [3H]-5-HT and a Vmax of 6.42 +/- 0.85 (+/- SEM) pmol of [3H]-5-HT/mg of protein/4 min for the Na+-dependent component. In the absence of Na+ the uptake was nonsaturable. Omission of the monoamine oxidase inhibitor pargyline markedly reduced the Na+-dependent component of [3H]-5-HT uptake but had a negligible effect on the Na+-independent component. This suggest significant oxidative deamination of serotonin after it has been taken up by the high affinity system, followed by release of its metabolite. The authors estimated that this system enabled the cells to concentrate [3H]-5-HT up to 44-fold at an external [3H]-5-HT concentration of 10(-7) M. Inhibition of [3H]-5-HT uptake by a number of clinically effective antidepressants was also consistent with a specific high affinity uptake mechanism for 5-HT, the order of effectiveness of inhibition being chlorimipramine greater than fluoxetine greater than imipramine = amitriptyline greater than desmethylimipramine greater than iprindole greater than mianserin. Uptake of [3H]-5-HT was dependent on the presence of Cl- as well as Na+ in the medium, and the effect of omission of both ions was nonadditive. Varying the concentration of K+ in the media from 1 to 50 mM had a limited effect on [3H]-5-HT uptake

  12. Selective serotonin-norepinephrine reuptake inhibitors-induced Takotsubo cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Rahul Vasudev

    2016-01-01

    Full Text Available Context: Takotsubo translates to "octopus pot" in Japanese. Takotsubo cardiomyopathy (TTC is characterized by a transient regional systolic dysfunction of the left ventricle. Catecholamine excess is the one most studied and favored theories explaining the pathophysiology of TTC. Case Report: We present the case of a 52-year-old Hispanic female admitted for venlafaxine-induced TTC with a review literature on all the cases of Serotonin-norepinephrine reuptake inhibitors (SNRI-associated TTC published so far. Conclusion: SNRI inhibit the reuptake of catecholamines into the presynaptic neuron, resulting in a net gain in the concentration of epinephrine and serotonin in the neuronal synapses and causing iatrogenic catecholamine excess, ultimately leading to TTC.

  13. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J;

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT......-existing Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of psychiatric and somatic disorders were included in the matched high- and low-HA groups. The main outcome measure was regional 5-HTT binding potential (BPND) in high- and low-HA groups estimated with PET and [11C]N,N-dimethyl-2......-(2-amino-4-methylphenylthio)benzylamine ([11C]MADAM). In secondary analyses, 5-HTT BPND was correlated with other TCI dimensions....

  14. Hippocampal volume and serotonin transporter polymorphism in major depressive disorder

    DEFF Research Database (Denmark)

    Ahdidan, Jamila; Foldager, Leslie; Rosenberg, Raben;

    2013-01-01

    Objective: The main aim of the present study was to replicate a previous finding in major depressive disorder (MDD) of association between reduced hippocampal volume and the long variant of the di- and triallelic serotonin transporter polymorphism in SLC6A4 on chromosome 17q11.2. Secondarily, we...... volume and tensor-based morphometry was used to elucidate structural brain differences. A triallelic genetic marker resulting from two SLC6A4 promoter region polymorphisms, 5-HTTLPR and rs25531, was analysed for association with MDD and quantitative traits. Results: Healthy controls had a smaller...... that we aimed to replicate, and no significant associations with the serotonin transporter polymorphism were found. Conclusions: The present quantitative and morphometric MRI study was not able to replicate the previous finding of association between reduced hippocampal volume in depressed patients...

  15. Expression analysis for inverted effects of serotonin transporter inactivation

    International Nuclear Information System (INIS)

    Inactivation of serotonin transporter (HTT) by pharmacologically in the neonate or genetically increases risk for depression in adulthood, whereas pharmacological inhibition of HTT ameliorates symptoms in depressed patients. The differing role of HTT function during early development and in adult brain plasticity in causing or reversing depression remains an unexplained paradox. To address this we profiled the gene expression of adult Htt knockout (Htt KO) mice and HTT inhibitor-treated mice. Inverted profile changes between the two experimental conditions were seen in 30 genes. Consistent results of the upstream regulatory element search and the co-localization search of these genes indicated that the regulation may be executed by Pax5, Pax7 and Gata3, known to be involved in the survival, proliferation, and migration of serotonergic neurons in the developing brain, and these factors are supposed to keep functioning to regulate downstream genes related to serotonin system in the adult brain

  16. [Pulmonary arterial hypertension, bone marrow, endothelial cell precursors and serotonin].

    Science.gov (United States)

    Ayme-Dietrich, Estelle; Banas, Sophie M; Monassier, Laurent; Maroteaux, Luc

    2016-01-01

    Serotonin and bone-marrow-derived stem cells participate together in triggering pulmonary hypertension. Our work has shown that the absence of 5-HT2B receptors generates permanent changes in the composition of the blood and bone-marrow in the myeloid lineages, particularly in endothelial cell progenitors. The initial functions of 5-HT2B receptors in pulmonary arterial hypertension (PAH) are restricted to bone-marrow cells. They contribute to the differentiation/proliferation/mobilization of endothelial progenitor cells from the bone-marrow. Those bone-marrow-derived cells have a critical role in the development of pulmonary hypertension and pulmonary vascular remodeling. These data indicate that bone-marrow derived endothelial progenitors play a key role in the pathogenesis of PAH and suggest that interactions involving serotonin and bone morphogenic protein type 2 receptor (BMPR2) could take place at the level of the bone-marrow. PMID:27687599

  17. Serotonin competence of mouse beta cells during pregnancy.

    Science.gov (United States)

    Goyvaerts, Lotte; Schraenen, Anica; Schuit, Frans

    2016-07-01

    Pregnancy is a key mammalian reproductive event in which growth and differentiation of the fetus imposes extra metabolic and hormonal demands on the mother. Its successful outcome depends on major changes in maternal blood circulation, metabolism and endocrine function. One example is the endocrine pancreas, where beta cells undergo a number of changes in pregnancy that result in enhanced functional beta cell mass in order to compensate for the rising metabolic needs for maternal insulin. During the last 5 years, a series of studies have increased our understanding of the molecular events involved in this functional adaptation. In the mouse, a prominent functional change during pregnancy is the capacity of some beta cells to produce serotonin. In this review we will discuss the mechanism and potential effects of pregnancy-related serotonin production in beta cells, considering functional consequences at the local intra-islet and systemic level. PMID:27056372

  18. Rationality and emotionality: serotonin transporter genotype influences reasoning bias.

    Science.gov (United States)

    Stollstorff, Melanie; Bean, Stephanie E; Anderson, Lindsay M; Devaney, Joseph M; Vaidya, Chandan J

    2013-04-01

    Reasoning often occurs under emotionally charged, opinion-laden circumstances. The belief-bias effect indexes the extent to which reasoning is based upon beliefs rather than logical structure. We examined whether emotional content increases this effect, particularly for adults genetically predisposed to be more emotionally reactive. SS/SL(G) carriers of the serotonin transporter genotype (5-HTTLPR) were less accurate selectively for evaluating emotional relational reasoning problems with belief-logic conflict relative to L(A)L(A) carriers. Trait anxiety was positively associated with emotional belief-bias, and the 5-HTTLPR genotype significantly accounted for the variance in this association. Thus, deductive reasoning, a higher cognitive ability, is sensitive to differences in emotionality rooted in serotonin neurotransmitter function.

  19. A novel serotonin transporter ligand: (5-Iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, Z.-P.; Choi, S.-R.; Hou, Catherine; Mu Mu; Kung, M.-P. E-mail: kunghf@sunmac.spect.upenn.edu; Acton, Paul D.; Kung, Hank F

    2000-02-01

    The serotonin transporters (SERT) are the primary binding sites for selective serotonin reuptake inhibitors, commonly used antidepressants such as fluoxetine, sertraline, and paroxetine. Imaging of SERT with positron emission tomography and single photon emission computed tomography in humans would provide a useful tool for understanding how alterations of this system are related to depressive illnesses and other psychiatric disorders. In this article the synthesis and characterization of [{sup 125}I]ODAM [(5-iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol, 9)] as an imaging agent in the evaluation of central nervous system SERT are reported. A new reaction scheme was developed for the preparation of compound 9, ODAM, and the corresponding tri-n-butyltin derivative 10. Upon reacting 10 with hydrogen peroxide and sodium[{sup 125}I]iodide, the radiolabeled [{sup 125}I]9 was obtained in good yield (94% yield, radiochemical purity >95%). In an initial binding study using cortical membrane homogenates of rat brain, ODAM displayed a good binding affinity with a value of K{sub i}=2.8{+-}0.88 nM. Using LLC-PK{sub 1} cells specifically expressing the individual transporter (i.e. dopamine [DAT], norepinephrine [NET], and SERT, respectively), ODAM showed a strong inhibition on SERT (K{sub i}=0.12{+-}0.02 nM). Inhibition constants for the other two transporters were lower (K{sub i}=3.9{+-}0.7 {mu}M and 20.0 {+-} 1.9 nM for DAT and NET, respectively). Initial biodistribution study in rats after an intravenous (IV) injection of [{sup 125}I]ODAM showed a rapid brain uptake and washout (2.03, 1.49, 0.79, 0.27, and 0.07% dose/organ at 2, 30, 60, 120, and 240 min, respectively). The hypothalamus region where the serotonin neurons are located exhibited a high specific uptake. Ratios of hypothalamus-cerebellum/cerebellum based on percent dose per gram of these two regions showed values of 0.35, 0.86, 0.86, 0.63, and 0.34 at 2, 30, 60, 120, and 240 min, post-IV injection

  20. Molecular cloning, expression and characterization of a bovine serotonin transporter

    DEFF Research Database (Denmark)

    Mortensen, O V; Kristensen, A S; Rudnick, G;

    1999-01-01

    The serotonin transporter (SERT) is a member of a highly homologous family of sodium/chloride dependent neurotransmitter transporters responsible for reuptake of biogenic amines from the extracellular fluid. SERT constitutes the pharmacological target of several clinically important antidepressan......-methylenedioxymethamphetamine (MDMA) was mainly unchanged. RT-PCR amplification of RNA from different tissues demonstrated expression of SERT in placenta, brain stem, bone marrow, kidney, lung, heart, adrenal gland, liver, parathyroid gland, thyroid gland, small intestine and pancreas....

  1. Selective Serotonin Reuptake Inhibitors and Violent Crime: A Cohort Study

    OpenAIRE

    Yasmina Molero; Paul Lichtenstein; Johan Zetterqvist; Clara Hellner Gumpert; Seena Fazel

    2015-01-01

    Editors' Summary Background Antidepressants—drugs that treat depression (unbearable feelings of sadness and despair caused by changes in brain chemistry)—are widely prescribed in many countries. In the US, for example, about one in ten people over 12 years old take antidepressants. The first antidepressants—monoamine oxidase inhibitors and tricyclic antidepressants—were developed in the 1950s. Experts think that both these classes of drugs treat depression by increasing serotonin levels in th...

  2. In vivo Monitoring of Serotonin by Nanomaterial Functionalized Acupuncture Needle

    OpenAIRE

    Yu-Tao Li; Li-Na Tang; Yong Ning; Qing Shu; Feng-Xia Liang; Hua Wang; Guo-Jun Zhang

    2016-01-01

    Acupuncture treatment is amazing but controversial. Up to now, the mechanism of treating diseases by acupuncture and moxibustion is still unclear, especially the occurrence of the molecular events in local acupoints. Herein, we report an extremely stable microsensor by modifying carbon nanotube (CNT) to the tip surface of acupuncture needle and applying this CNT-modified acupuncture needle for real time monitoring of serotonin (5-HT) in vivo. To stabilize CNT modification on the needle tip su...

  3. Rationality and emotionality: serotonin transporter genotype influences reasoning bias

    OpenAIRE

    Stollstorff, Melanie; Bean, Stephanie E.; Anderson, Lindsay M.; Devaney, Joseph M.; Vaidya, Chandan J.

    2012-01-01

    Reasoning often occurs under emotionally charged, opinion-laden circumstances. The belief-bias effect indexes the extent to which reasoning is based upon beliefs rather than logical structure. We examined whether emotional content increases this effect, particularly for adults genetically predisposed to be more emotionally reactive. SS/SLG carriers of the serotonin transporter genotype (5-HTTLPR) were less accurate selectively for evaluating emotional relational reasoning problems with belief...

  4. APRESS: apical regulatory super system, serotonin, and dopamine interaction

    OpenAIRE

    Hinz M; Stein A; Uncini T

    2011-01-01

    Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics, Inc, Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3DBS Labs, Duluth, MN, USABackground: The monoamines serotonin and dopamine are known to exist in two separate states: the endogenous state and the competitive inhibition state. The presence of the competitive inhibition state has been known to science for many years, but from a functional standpoint it has been noted in the literatur...

  5. APRESS: apical regulatory super system, serotonin, and dopamine interaction

    Directory of Open Access Journals (Sweden)

    Hinz M

    2011-08-01

    Full Text Available Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics, Inc, Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3DBS Labs, Duluth, MN, USABackground: The monoamines serotonin and dopamine are known to exist in two separate states: the endogenous state and the competitive inhibition state. The presence of the competitive inhibition state has been known to science for many years, but from a functional standpoint it has been noted in the literature as being "meaningless."Methods: A large database of monoamine transporter response to amino acid precursor administration variations with clinical outcomes was accumulated. In the process, a new organic cation transporter (OCT model has been published, and OCT functional status determination along with amino acid precursor manipulation methods have been invented and refined.Results: Methodology was developed whereby manipulation of the OCT, in the competitive inhibition state, is carried out in a predictable manner. This, in turn, has disproved the long-held assertion that the monoamine competitive inhibition state is functionally meaningless.Conclusion: The most significant aspect of this paper is the documentation of newly recognized relationships between serotonin and dopamine. When transport of serotonin and dopamine are both in the competitive inhibition state, manipulation of the concentrations of one will lead to predictable changes in concentrations of the other. From a functional standpoint, processes regulated and controlled by changes to only serotonin can now be controlled by changes to dopamine, and vice versa, in a predictable manner.Keywords: catecholamine, monoamine, competitive inhibition state

  6. An interesting case of serotonin syndrome precipitated by escitalopram

    Directory of Open Access Journals (Sweden)

    Sanyal Debasish

    2010-01-01

    Full Text Available Serotonin syndrome is a known entity, which occurs with multiple drugs acting on serotonergic receptors. A 73-year-old lady presented with a history of agitation, altered sensorium, and autonomic hyperactivity after starting escitalopram on therapeutic dosage for her depressive syndrome who was on selegiline for her parkinsonism. This syndrome with therapeutic dose escitalopram warrants the careful and judicious use of the drug especially with other serotonergic drugs, so that this serious medical complication can be avoided.

  7. Selective serotonin reuptake inhibitors as a novel class of immunosuppressants

    OpenAIRE

    Gobin, Veerle; Van Steendam, Katleen; DENYS, D; Deforce, Dieter

    2014-01-01

    In the past decades, selective serotonin reuptake inhibitors (SSRIs) have been shown to exert several immunological effects, such as reduced lymphocyte proliferation, alteration of cytokine secretion and induction of apoptosis. Based on these effects, SSRIs were proposed as drugs for the treatment of autoimmune pathologies and graft-versus-host disease. This review summarizes preclinical and clinical evidence supporting a role for SSRIs in autoimmune diseases and graft-versus-host disease, an...

  8. Revisiting the Serotonin Hypothesis: Implications for Major Depressive Disorders.

    Science.gov (United States)

    Fakhoury, Marc

    2016-07-01

    Major depressive disorder (MDD) is a heritable neuropsychiatric disease associated with severe changes at cellular and molecular levels. Its diagnosis mainly relies on the characterization of a wide range of symptoms including changes in mood and behavior. Despite the availability of antidepressant drugs, 10 to 30 % of patients fail to respond after a single or multiple treatments, and the recurrence of depression among responsive patients is very high. Evidence from the past decades suggests that the brain neurotransmitter serotonin (5-HT) is incriminated in MDD, and that a dysfunction of 5-HT receptors may play a role in the genesis of this disease. The 5-HT membrane transporter protein (SERT), which helps regulate the serotonergic transmission, is also implicated in MDD and is one of the main targets of antidepressant therapy. Although a number of behavioral tests and animal models have been developed to study depression, little is known about the neurobiological bases of MDD. Understanding the role of the serotonergic pathway will significantly help improve our knowledge of the pathophysiology of depression and may open up avenues for the development of new antidepressant drugs. The overarching goal of this review is to present recent findings from studies examining the serotonergic pathway in MDD, with a focus on SERT and the serotonin 1A (5-HT1A), serotonin 1B (5-HT1B), and serotonin 2A (5-HT2A) receptors. This paper also describes some of the main molecules involved in the internalization of 5-HT receptors and illustrates the changes in 5-HT neurotransmission in knockout mice and animal model of depression. PMID:25823514

  9. Early fluorescence signals detect transitions at mammalian serotonin transporters.

    OpenAIRE

    Li, Ming; Lester, Henry A.

    2002-01-01

    The mammalian serotonin transporters rSERT or hSERT were expressed in oocytes and labeled with sulforhodamine-MTS. The endogenous Cys-109 residue contributes most of the signal, and the labeled transporter shows normal function. The SERT fluorescence decreases in the presence of 5-HT and also depends on the inorganic substrates of SERT. The fluorescence also increases with membrane depolarization. During voltage-jump experiments, fluorescence relaxations show little inactivation or history de...

  10. Structural Basis for Molecular Recognition at Serotonin Receptors

    OpenAIRE

    Wang, Chong; Jiang, Yi; Ma, Jinming; Wu, Huixian; Wacker, Daniel; Katritch, Vsevolod; Han, Gye Won; Liu, Wei; Huang, Xi-Ping; Vardy, Eyal; McCorvy, John D.; Gao, Xiang; Zhou, Edward X.; Melcher, Karsten; Zhang, Chenghai

    2013-01-01

    Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist anti-migraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserv...

  11. [A case of serotonin syndrome following minimum doses of sertraline].

    Science.gov (United States)

    Kan, Rumiko; Endou, Masatoshi; Unno, Yukihiro

    2009-01-01

    We report a 75-year-old woman developing serotonin syndrome following minimum doses of sertraline. She showed a depressed mood, insomnia, and general fatigue and was taking sulpiride at 300 mg/day, alprazolam at 1.2 mg/day, zopiclone at 7.5 mg/day, and etizolam at 1 mg/day. As she remained symptomatic, sertraline at 25 mg/day was added. Within 14 hours of starting sertraline, the patient began to experience delirium, impaired coordination, diaphoresis, tremulousness of the upper limbs bilaterally, and agitation. Sertraline was thus discontinued, and all of the above-mentioned symptoms disappeared rapidly. Serotonin syndrome is rarely reported in patients taking sertraline in Japan. To our knowledge, ours is the second case of serotonin syndrome associated with sertraline in Japan. According to Drug in Japan, sertraline must be started at the lowest efficacious dose with slow titration and is contraindicated for patients who are taking pimozide or monoamine oxidase inhibitors (MAOIs). Also, the coadministration of sertraline with other agents such as lithium, tricyclic antidepressants, and triptans necessitates the close observation of symptoms and signs. However, our case didn't take any of these combinations, and she was administered 25 mg/day, the lowest efficacious dose. This report emphasizes that caution is needed when prescribing sertraline to elderly patients and on its coadministration. PMID:19999561

  12. Ventilatory adaptation to hypoxia occurs in serotonin-depleted rats.

    Science.gov (United States)

    Olson, E B

    1987-08-01

    To test the hypothesis that serotonin mediated respiratory activity is involved in ventilatory adaptation to hypoxia, rats were treated with parachlorophenylalanine (PCPA), a potent, long-acting inhibitor of tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin. In normoxia, a single, intraperitoneal injection of 300 mg PCPA/kg body weight decreased the Paco2 from a control level at 39.1 +/- 0.6 Torr (mean +/- 95% confidence limits) to 34.0 +/- 0.6 Torr measured during a period from 1 to 48 h following PCPA treatment. This PCPA-produced hyperventilation corresponds to an increase of 3.7 +/- 0.5 in the VA (BTPS)/Vco2 (STPD) ratio. Hyperventilation during ventilatory adaptation to hypoxia (PIO2 approximately equal to 90 Torr) was superimposed in an additive fashion on the underlying hyperventilation due to PCPA pretreatment. Specifically, PCPA pretreatment caused an average 3.5 +/- 1.2 increase in the VA/VCO2 ratio determined in acute (1 h) hypoxia, chronic (24 h) hypoxia and acute return to normoxia following chronic hypoxia. Since ventilatory adaptation to hypoxia occurred in rats treated with PCPA, the prolonged, serotonin mediated respiratory activity described by Millhorn et al. (1980b) is probably not important in ventilatory acclimatization to - or deacclimatization from - hypoxia. PMID:2957766

  13. Regional distribution of serotonin transporter protein in postmortem human brain

    Energy Technology Data Exchange (ETDEWEB)

    Kish, Stephen J. [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)]. E-mail: Stephen_Kish@CAMH.net; Furukawa, Yoshiaki [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Chang Lijan [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Tong Junchao [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Ginovart, Nathalie [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Wilson, Alan [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Meyer, Jeffrey H. [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

    2005-02-01

    Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met.

  14. Platelet serotonin transporter function predicts default-mode network activity.

    Directory of Open Access Journals (Sweden)

    Christian Scharinger

    Full Text Available The serotonin transporter (5-HTT is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence.A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD activity and platelet Vmax.The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity.This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation.

  15. Regional distribution of serotonin transporter protein in postmortem human brain

    International Nuclear Information System (INIS)

    Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met

  16. Role of serotonin in patients with acute respiratory failure.

    Science.gov (United States)

    Huval, W V; Lelcuk, S; Shepro, D; Hechtman, H B

    1984-08-01

    An early event in the evolution of acute respiratory failure (ARF) is thought to be the activation of platelets, their pulmonary entrapment and subsequent release of the smooth muscle constrictor serotonin (5HT). This study tests the thesis that inhibition of 5HT will improve lung function. The etiology of ARF in the 18 study patients was sepsis (N = 10), aspiration (N = 3), pancreatitis (N = 1), embolism (N = 2), and abdominal aortic aneurysm surgery (N = 2). Patients were divided into two groups determined by whether their period of endotracheal intubation was less than or equal to 4 days (early ARF, N = 12) or greater than 4 days (late ARF, N = 6). Transpulmonary platelet counts in the early group showed entrapment of 26,300 +/- 5900 platelets/mm3 in contrast to the late group where there was no entrapment (p less than 0.05). The platelet 5HT levels in the early group were 55 +/- 5 ng/10(9) platelets, values lower than 95 +/- 15 ng/10(9) platelets in the late ARF group (p less than 0.05), and 290 +/- 70 ng/10(9) platelets in normals. The selective 5HT receptor antagonist, ketanserin was given as an intravenous bolus over 3 minutes in a dose of 0.1 mg/kg, followed by a 30-minute infusion of 0.08 mg/kg. During this period mean arterial pressure (MAP) fell from 87 +/- 5 to 74 +/- 6 mmHg (mean +/- SEM) (p less than 0.05). One and one-half hours following the start of therapy, MAP returned to baseline. At this time, patients with early ARF showed decreases in: physiologic shunt (Qs/QT) from 26 +/- 3 to 19 +/- 3 (p less than 0.05); peak inspiratory pressure from 35 +/- 2 to 32 +/- 2 cmH2O (p less than 0.05) and in mean pulmonary arterial pressure from 32 +/- 2 to 29 +/- 1 mmHg (p less than 0.05). At 4 hours all changes returned to baseline levels. In early ARF ketanserin did not alter pretreatment values of: pulmonary arterial wedge pressure, 17 +/- 3 mmHg; cardiac index, 2.8 +/- 0.3 L/min X m2; platelet count, 219,000 +/- 45,000/mm3; platelet 5HT, 55 +/- 5 ng/10

  17. The role of mechanical forces and adenosine in the regulation of intestinal enterochromaffin cell serotonin secretion.

    Science.gov (United States)

    Chin, A; Svejda, B; Gustafsson, B I; Granlund, A B; Sandvik, A K; Timberlake, A; Sumpio, B; Pfragner, R; Modlin, I M; Kidd, M

    2012-02-01

    Enterochromaffin (EC) cells of the diffuse neuroendocrine cell system secrete serotonin (5-HT) with activation of gut motility, secretion, and pain. These cells express adenosine (ADORA) receptors and are considered to function as mechanosensors. Physiological pathways mediating mechanosensitivity and adenosine responsiveness remain to be fully elucidated, as do their roles in inflammatory bowel disease (IBD) and neoplasia. Pure (98-99%) FACS-sorted normal and IBD human EC cells and neoplastic EC cells (KRJ-I) were studied. IBD-EC cells and KRJ-I overexpressed ADORA2B. NECA, a general ADORA receptor agonist, stimulated, whereas the A2B receptor antagonist MRS1754 inhibited, 5-HT release (EC50 = 1.8 × 10-6 M; IC50 = 3.7 × 10-8 M), which was associated with corresponding alterations in intracellular cAMP levels and pCREB (Ser133). Mechanical stimulation using a rhythmic flex model induced transcription and activation of Tph1 (tryptophan hydroxylase) and VMAT₁ (vesicular monoamine transporter 1) and the release of 5-HT, which could be inhibited by MRS1754 and amplified by NECA. Secretion was also inhibited by H-89 (PKA inhibitor) while Tph1 and VMAT₁ transcription was regulated by PKA/MAPK and PI₃K-mediated signaling. Normal and IBD-EC cells also responded to NECA and mechanical stimulation with PKA activation, cAMP production, and 5-HT release, effects reversible by MRS1754. EC cells express stimulatory ADORA2B, and rhythmic stretch induces A2B activation, PKA/MAPK/IP3-dependent transcription, and PKA-dependent secretion of 5-HT synthesis and secretion. Receptor expression is amplified in IBD and neoplasia, and 5-HT release is increased. Determination of factors that regulate EC cell function are necessary for understanding its role as a mechanosensory cell and to facilitate the development of agents that can selectively target cell function in EC cell-associated disease. PMID:22038827

  18. Autocrine and paracrine roles for ATP and serotonin in mouse taste buds.

    Science.gov (United States)

    Huang, Yijen A; Dando, Robin; Roper, Stephen D

    2009-11-01

    Receptor (type II) taste bud cells secrete ATP during taste stimulation. In turn, ATP activates adjacent presynaptic (type III) cells to release serotonin (5-hydroxytryptamine, or 5-HT) and norepinephrine (NE). The roles of these neurotransmitters in taste buds have not been fully elucidated. Here we tested whether ATP or 5-HT exert feedback onto receptor (type II) cells during taste stimulation. Our previous studies showed NE does not appear to act on adjacent taste bud cells, or at least on receptor cells. Our data show that 5-HT released from presynaptic (type III) cells provides negative paracrine feedback onto receptor cells by activating 5-HT(1A) receptors, inhibiting taste-evoked Ca(2+) mobilization in receptor cells, and reducing ATP secretion. The findings also demonstrate that ATP exerts positive autocrine feedback onto receptor (type II) cells by activating P2Y1 receptors and enhancing ATP secretion. These results begin to sort out how purinergic and aminergic transmitters function within the taste bud to modulate gustatory signaling in these peripheral sensory organs.

  19. 5-HT2A : a serotonin receptor with a possible role in joint diseases

    OpenAIRE

    Kling, Anders

    2013-01-01

    Background Serotonin (5-HT), an amino acid derivative and neurotransmitter, has for long been studied in relation to inflammation. It is an endogenous ligand for several different types of serotonin receptors. The serotonin receptor 5-HT2A has been reported to have a role in the pathophysiology of arthritis in animal experiment models. However, no studies into this subject have been reported in man. Objective The objectives of this project were firstly, to examine possible associations for th...

  20. Serotonin transporter gene polymorphism and psychiatric disorders: Is there a link?

    OpenAIRE

    Margoob, Mushtaq A.; Mushtaq, Dhuha

    2011-01-01

    Though still in infancy, the field of psychiatric genetics holds great potential to contribute to the development of new diagnostic and therapeutic options to treat these disorders. Among a large number of existing neurotransmitter systems, the serotonin system dysfunction has been implicated in many psychiatric disorders and therapeutic efficacy of many drugs is also thought to be based on modulation of serotonin. Serotonin transporter gene polymorphism is one of the most extensively studied...

  1. Molekulare und pharmakologische Charakterisierung von Serotonin-Rezeptoren der Honigbiene Apis mellifera

    OpenAIRE

    Schlenstedt, Jana

    2006-01-01

    Die Honigbiene Apis mellifera gilt seit langem als Modell-Organismus zur Untersuchung von Lern- und Gedächtnisvorgängen sowie zum Studium des Sozialverhaltens und der Arbeitsteilung. Bei der Steuerung und Regulation dieser Verhaltensweisen spielt das Indolalkylamin Serotonin eine wesentliche Rolle. Serotonin entfaltet seine Wirkung durch die Bindung an G-Protein-gekoppelte Rezeptoren (GPCRs). In der vorliegenden Arbeit wird der erste Serotonin-Rezeptor aus der Honigbiene molekular charakteris...

  2. The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

    OpenAIRE

    Sanchez, CL; Biskup, CS; Herpertz, S.; Gaber, TJ; Kuhn, CM; Hood, SH; Zepf, FD

    2015-01-01

    The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals wit...

  3. Chronic Citalopram Administration Causes a Sustained Suppression of Serotonin Synthesis in the Mouse Forebrain

    OpenAIRE

    Gerard Honig; Jongsma, Minke E.; Marieke C G van der Hart; Tecott, Laurence H.

    2009-01-01

    BACKGROUND: Serotonin (5-HT) is a neurotransmitter with important roles in the regulation of neurobehavioral processes, particularly those regulating affect in humans. Drugs that potentiate serotonergic neurotransmission by selectively inhibiting the reuptake of serotonin (SSRIs) are widely used for the treatment of psychiatric disorders. Although the regulation of serotonin synthesis may be an factor in SSRI efficacy, the effect of chronic SSRI administration on 5-HT synthesis is not well un...

  4. Serotonin and Histamine Therapy Increases Tetanic Forces of Myoblasts, Reduces Muscle Injury, and Improves Grip Strength Performance of Dmdmdx Mice

    Directory of Open Access Journals (Sweden)

    Volkan Gurel

    2015-11-01

    Full Text Available Duchenne muscular dystrophy (DMD is a recessive X-linked fatal disorder caused by a mutation in the dystrophin gene. Although several therapeutic approaches have been studied, none has led to substantial long-term effects in patients. The aim of this study was to test a serotonin and histamine (S&H combination on human skeletal myoblasts and Dmdmdx mice for its effects on muscle strength and injury. Normal human bioartificial muscles (BAMs were treated, and muscle tetanic forces and muscle injury tests were performed using the MyoForce Analysis System. Dmdmdx mice, the murine model of DMD, were administered serotonin, histamine, or S&H combination twice daily for 6 weeks, and functional performance tests were conducted once a week. The S&H combination treatment caused significant increases in tetanic forces at all time points and concentrations tested as compared to the saline controls. Dose response of the BAMs to the treatment demonstrated a significant increase in force generation at all concentrations compared to the controls after 3 to 4 days of drug treatment. The highest 3 concentrations had a significant effect on lowering contractile-induced injury as measured by a reduction in the release of adenylate kinase. Histamine-only and S&H treatments improved grip strength of Dmdmdx mice, whereas serotonin-only treatment resulted in no significant improvement in muscle strength. The results of this study indicate that S&H therapy might be a promising new strategy for muscular dystrophies and that the mechanism should be further investigated.

  5. Early Life Stress and Macaque Amygdala Hypertrophy: Preliminary Evidence for a Role for the Serotonin Transporter Gene.

    Directory of Open Access Journals (Sweden)

    Jeremy D Coplan

    2014-10-01

    Full Text Available Background: Children exposed to early life stress (ELS exhibit enlarged amygdala volume in comparison to controls. The primary goal of this study was to examine amygdala volumes in bonnet macaques subjected to maternal variable foraging demand (VFD rearing, a well-established model of ELS. Preliminary analyses examined the interaction of ELS and the serotonin transporter gene on amygdala volume. Secondary analyses were conducted to examine the association between amygdala volume and other stress-related variables previously found to distinguish VFD and non-VFD reared animals. Methods: Twelve VFD-reared and nine normally reared monkeys completed MRI scans on a 3T system (mean age=5.2 years. Results: Left amygdala volume was larger in VFD versus control macaques. Larger amygdala volume was associated with: high cerebrospinal fluid concentrations of corticotropin releasing-factor (CRF determined when the animals were in adolescence (mean age=2.7 years; reduced fractional anisotropy of the anterior limb of the internal capsule during young adulthood (mean age=5.2 years and timid anxiety-like responses to an intruder during full adulthood (mean age=8.4 years. Right amygdala volume varied inversely with left hippocampal neurogenesis assessed in late adulthood (mean age=8.7 years. Exploratory analyses also showed a gene-by-environment effect, with VFD-reared macaques with a single short allele of the serotonin transporter gene exhibiting larger amygdala volume compared to VFD-reared subjects with only the long allele and normally reared controls. Conclusion: These data suggest that the left amygdala exhibits hypertrophy after ELS, particularly in association with the serotonin transporter gene, and that amygdala volume variation occurs in concert with other key stress-related behavioral and neurobiological parameters observed across the lifecycle. Future research is required to understand the mechanisms underlying these diverse and persistent changes a

  6. Depressing Antidepressant: Fluoxetine Affects Serotonin Neurons Causing Adverse Reproductive Responses in Daphnia magna.

    Science.gov (United States)

    Campos, Bruno; Rivetti, Claudia; Kress, Timm; Barata, Carlos; Dircksen, Heinrich

    2016-06-01

    Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants. As endocrine disruptive contaminants in the environment, SSRIs affect reproduction in aquatic organisms. In the water flea Daphnia magna, SSRIs increase offspring production in a food ration-dependent manner. At limiting food conditions, females exposed to SSRIs produce more but smaller offspring, which is a maladaptive life-history strategy. We asked whether increased serotonin levels in newly identified serotonin-neurons in the Daphnia brain mediate these effects. We provide strong evidence that exogenous SSRI fluoxetine selectively increases serotonin-immunoreactivity in identified brain neurons under limiting food conditions thereby leading to maladaptive offspring production. Fluoxetine increases serotonin-immunoreactivity at low food conditions to similar maximal levels as observed under high food conditions and concomitantly enhances offspring production. Sublethal amounts of the neurotoxin 5,7-dihydroxytryptamine known to specifically ablate serotonin-neurons markedly decrease serotonin-immunoreactivity and offspring production, strongly supporting the effect to be serotonin-specific by reversing the reproductive phenotype attained under fluoxetine. Thus, SSRIs impair serotonin-regulation of reproductive investment in a planktonic key organism causing inappropriately increased reproduction with potentially severe ecological impact. PMID:27128505

  7. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action.

    Science.gov (United States)

    Vollenweider, F X; Vollenweider-Scherpenhuyzen, M F; Bäbler, A; Vogel, H; Hell, D

    1998-12-01

    Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone, but were increased by the dopamine antagonist and typical antipsychotic haloperidol. These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation, independently of dopamine stimulation. Thus, serotonin-2A overactivity may be involved in the pathophysiology of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics.

  8. Fetal serotonin signaling: setting pathways for early childhood development and behavior.

    Science.gov (United States)

    Oberlander, Tim F

    2012-08-01

    Finely tuning levels of the key neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) during early life is essential for brain development and setting pathways for health and disorder across the early life span. Given the central role of 5-HT in brain development, regulation of mood, stress reactivity, and risk for psychiatric disorders, alterations in 5-HT signaling early in life have critical implications for behavior and mental health in childhood and adolescence. This article reviews the developmental consequences of two key influences that alter fetal 5-HT signaling: (1) in utero exposure to 5-HT reuptake inhibitor antidepressants, and (2) genetic variations in the 5-HT transporter gene (SLC6A4). The consequences of altered prenatal 5-HT signaling vary greatly, and developmental outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations), experiential (prenatal drug or maternal mood exposure), and contextual (postnatal social environment) variables. Emerging evidence suggests both exposure to 5-HT reuptake inhibitors and genetic variations that affect 5-HT signaling may increase sensitivity to negative social contexts for some individuals, whereas for others, they may confer sensitivity to positive life circumstances. In this sense, factors that change central 5-HT levels may function less like influences that predict "vulnerability," but rather act like "plasticity factors." Understanding the impact of early changes in serotonergic programming offers critical insights that might explain patterns of individual differences in developmental risk and resilience. PMID:22794534

  9. Interference of paracetamol (acetaminophen) with a commercially available high-performance liquid chromatography analysis of serotonin leading to falsely low serotonin levels.

    Science.gov (United States)

    Pfäfflin, Albrecht; Müssig, Karsten; Schleicher, Erwin

    2009-03-01

    Serotonin is frequently analysed by high-performance liquid chromatography (HPLC) with electrochemical detection. However, the accuracy of these methods may be affected by the presence of certain drugs. We describe for the first time the interference of paracetamol in therapeutic dosages in a routine HPLC method for serotonin determination in vivo and in vitro. The retention time coincides with N-methylserotonin used as an internal standard in this method. Erroneous increases of the internal standard will lead, if not recognized and corrected, to falsely low serotonin determinations.

  10. Multiple receptor subtypes mediate the effects of serotonin on rat subfornical organ neurons

    Science.gov (United States)

    Scrogin, K. E.; Johnson, A. K.; Schmid, H. A.

    1998-01-01

    The subfornical organ (SFO) receives significant serotonergic innervation. However, few reports have examined the functional effects of serotonin on SFO neurons. This study characterized the effects of serotonin on spontaneously firing SFO neurons in the rat brain slice. Of 31 neurons tested, 80% responded to serotonin (1-100 microM) with either an increase (n = 15) or decrease (n = 10) in spontaneous activity. Responses to serotonin were dose dependent and persisted after synaptic blockade. Excitatory responses could also be mimicked by the 5-hydroxytryptamine (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI; 1-10 microM) and could be blocked by the 5-HT2A/2C-receptor antagonist LY-53,857 (10 microM). LY-53,857 unmasked inhibitory responses to serotonin in 56% of serotonin-excited cells tested. Serotonin-inhibited cells were also inhibited by the 5-HT1A-receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT; 1-10 microM; n = 7). The data indicate that SFO neurons are responsive to serotonin via postsynaptic activation of multiple receptor subtypes. The results suggest that excitatory responses to serotonin are mediated by 5-HT2A or 5-HT2C receptors and that inhibitory responses may be mediated by 5-HT1A receptors. In addition, similar percentages of serotonin-excited and -inhibited cells were also sensitive to ANG II. As such the functional relationship between serotonin and ANG II in the SFO remains unclear.

  11. Serotonergic systems in the balance: CRHR1 and CRHR2 differentially control stress-induced serotonin synthesis.

    Science.gov (United States)

    Donner, Nina C; Siebler, Philip H; Johnson, Danté T; Villarreal, Marcos D; Mani, Sofia; Matti, Allison J; Lowry, Christopher A

    2016-01-01

    Anxiety and affective disorders are often associated with hypercortisolism and dysfunctional serotonergic systems, including increased expression of TPH2, the gene encoding the rate-limiting enzyme of neuronal serotonin synthesis. We previously reported that chronic glucocorticoid exposure is anxiogenic and increases rat Tph2 mRNA expression, but it was still unclear if this also translates to increased TPH2 protein levels and in vivo activity of the enzyme. Here, we found that adult male rats treated with corticosterone (CORT, 100 μg/ml) via the drinking water for 21 days indeed show increased TPH2 protein expression in the dorsal and ventral part of the dorsal raphe nucleus (DRD, DRV) during the light phase, abolishing the enzyme's diurnal rhythm. In a second study, we systemically blocked the conversion of 5-hydroxytryptophan (5-HTP) to serotonin immediately before rats treated with CORT or vehicle were either exposed to 30 min acoustic startle stress or home cage control conditions. This allowed us to measure 5-HTP accumulation as a direct readout of basal versus stress-induced in vivo TPH2 activity. As expected, basal TPH2 activity was elevated in the DRD, DRV and MnR of CORT-treated rats. In response to stress, a multitude of serotonergic systems reacted with increased TPH2 activity, but the stress-, anxiety-, and learned helplessness-related dorsal and caudal DR (DRD/DRC) displayed stress-induced increases in TPH2 activity only after chronic CORT-treatment. To address the mechanisms underlying this region-specific CORT-dependent sensitization, we stereotaxically implanted CORT-treated rats with cannulae targeting the DR, and pharmacologically blocked either corticotropin-releasing hormone receptor type 1 (CRHR1) or type 2 (CRHR2) 10 min prior to acoustic startle stress. CRHR2 blockade prevented stress-induced increases of TPH2 activity within the DRD/DRC, while blockade of CRHR1 potentiated stress-induced TPH2 activity in the entire DR. Stress-induced TPH2

  12. Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats.

    NARCIS (Netherlands)

    Homberg, J.R.; Boer, SF De; Raaso, H.S.; Olivier, J.D.A.; Verheul, M.; Ronken, E.; Cools, A.R.; Ellenbroek, B.A.; Schoffelmeer, A.N.; Schuren, L.J. van der; Vries, TJ De; Cuppen, E.

    2008-01-01

    RATIONALE: While individual differences in vulnerability to psychostimulants have been largely attributed to dopaminergic neurotransmission, the role of serotonin is not fully understood. OBJECTIVES: To study the rewarding and motivational properties of cocaine in the serotonin transporter knockout

  13. Adaptations in pre- and postsynaptic 5-HT(1A) receptor function and cocaine supersensitivity in serotonin transporter knockout rats

    NARCIS (Netherlands)

    Homberg, Judith R; De Boer, Sietse F; Raasø, Halfdan S; Olivier, Jocelien D A; Verheul, Mark; Ronken, Eric; Cools, Alexander R; Ellenbroek, Bart A; Schoffelmeer, Anton N M; Vanderschuren, Louk J M J; De Vries, Taco J; Cuppen, Edwin

    2008-01-01

    RATIONALE: While individual differences in vulnerability to psychostimulants have been largely attributed to dopaminergic neurotransmission, the role of serotonin is not fully understood. OBJECTIVES: To study the rewarding and motivational properties of cocaine in the serotonin transporter knockout

  14. On the roles of serotonin and dopamine in the settlement of the cyprids of the barnacle Balanus amphitrite (= Amphibalanus amphitrite

    Directory of Open Access Journals (Sweden)

    L. Gallus

    2011-01-01

    Full Text Available In the cyprid of Balanus amphitrite (=Amphibalanus amphitrite was investigated by settlement tests the role of serotonin, related substances and dopamine. The results indicate an activity of serotonin in B. amphitrite cyprid as settlement inhibitors.

  15. Induction of depersonalization by the serotonin agonist meta-chlorophenylpiperazine.

    Science.gov (United States)

    Simeon, D; Hollander, E; Stein, D J; DeCaria, C; Cohen, L J; Saoud, J B; Islam, N; Hwang, M

    1995-09-29

    Sixty-seven subjects, including normal volunteers and patients with obsessive-compulsive disorder, social phobia, and borderline personality disorder, received ratings of depersonalization after double-blind, placebo-controlled challenges with the partial serotonin agonist meta-chlorophenylpiperazine (m-CPP). Challenge with m-CPP induced depersonalization significantly more than did placebo. Subjects who became depersonalized did not differ in age, sex, or diagnosis from those who did not experience depersonalization. There was a significant correlation between the induction of depersonalization and increase in panic, but not nervousness, anxiety, sadness, depression, or drowsiness. This report suggests that serotonergic dysregulation may in part underlie depersonalization.

  16. Serotonin transporter evolution and impact of polymorphic transcriptional regulation

    DEFF Research Database (Denmark)

    Søeby, Karen; Larsen, Svend Ask; Olsen, Line;

    2005-01-01

    extensively across the great apes and monkeys as well as in rodents while it is absent in non-mammals. As in humans, the VNTR sequence may be polymorphic within species and thus it may underlie both inter- and intraspecies differences. Also, we find new putative binding sites for several transcription factors...... in the VNTRs of all mammalian SERT genes. The number of these putative binding sites varies proportionally to the length of the VNTR. We propose that the intronic VNTR have been selectively targeted through mammalian evolution to finetune transcriptional regulation of the serotonin expression....

  17. Identification of genes associated with reproduction in the Mud Crab (Scylla olivacea and their differential expression following serotonin stimulation.

    Directory of Open Access Journals (Sweden)

    Napamanee Kornthong

    Full Text Available The central nervous system (CNS is often intimately involved in reproduction control and is therefore a target organ for transcriptomic investigations to identify reproduction-associated genes. In this study, 454 transcriptome sequencing was performed on pooled brain and ventral nerve cord of the female mud crab (Scylla olivacea following serotonin injection (5 µg/g BW. A total of 197,468 sequence reads was obtained with an average length of 828 bp. Approximately 38.7% of 2,183 isotigs matched with significant similarity (E value < 1e-4 to sequences within the Genbank non-redundant (nr database, with most significant matches being to crustacean and insect sequences. Approximately 32 putative neuropeptide genes were identified from nonmatching blast sequences. In addition, we identified full-length transcripts for crustacean reproductive-related genes, namely farnesoic acid o-methyltransferase (FAMeT, estrogen sulfotransferase (ESULT and prostaglandin F synthase (PGFS. Following serotonin injection, which would normally initiate reproductive processes, we found up-regulation of FAMeT, ESULT and PGFS expression in the female CNS and ovary. Our data here provides an invaluable new resource for understanding the molecular role of the CNS on reproduction in S. olivacea.

  18. Cognitive function is related to fronto-striatal serotonin transporter levels--a brain PET study in young healthy subjects

    DEFF Research Database (Denmark)

    Madsen, Karine; Erritzøe, David Frederik; Mortensen, Erik Lykke;

    2011-01-01

    Pharmacological manipulation of serotonergic neurotransmission in healthy volunteers impacts on cognitive test performance. Specifically, markers of serotonin function are associated with attention and executive functioning, long-term memory, and general cognitive ability. The serotonin transporter...... (SERT) protein is a key regulator in the serotonin system. We hypothesized that higher performance on tests sensitive to serotonin would be associated with higher SERT levels in specific fronto-striatal brain regions....

  19. Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations.

    Science.gov (United States)

    Koldsø, Heidi; Autzen, Henriette Elisabeth; Grouleff, Julie; Schiøtt, Birgit

    2013-01-01

    The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design. PMID:23776432

  20. Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Heidi Koldsø

    Full Text Available The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design.

  1. Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder

    Science.gov (United States)

    Marler, Sarah; Ferguson, Bradley J.; Lee, Evon Batey; Peters, Brittany; Williams, Kent C.; McDonnell, Erin; Macklin, Eric A.; Levitt, Pat; Gillespie, Catherine Hagan; Anderson, George M.; Margolis, Kara Gross; Beversdorf, David Q.; Veenstra-VanderWeele, Jeremy

    2016-01-01

    Elevated whole blood serotonin levels are observed in more than 25% of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD,…

  2. Inhibition of serotonin transport by (+)McN5652 is noncompetitive

    Energy Technology Data Exchange (ETDEWEB)

    Hummerich, Rene [Biochemical Laboratory, Central Institute of Mental Health, 68159 Mannheim (Germany); Schulze, Oliver [Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany); Raedler, Thomas [Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany); Mikecz, Pal [Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany); Reimold, Matthias [Department of Nuclear Medicine, University Hospital Tuebingen, D-72076 Tuebingen (Germany); Brenner, Winfried [Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany); Clausen, Malte [Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany); Schloss, Patrick [Biochemical Laboratory, Central Institute of Mental Health, 68159 Mannheim (Germany); Buchert, Ralph [Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg (Germany)]. E-mail: buchert@uke.uni-hamburg.de

    2006-04-15

    Introduction: Imaging of the serotonergic innervation of the brain using positron emission tomography (PET) with the serotonin transporter (SERT) ligand [{sup 11C}] (+)McN5652 might be affected by serotonin in the synaptic cleft if there is relevant interaction between [{sup 11}C] (+)McN5652 and serotonin at the SERT. The aim of the present study therefore was to pharmacologically characterize the interaction of [{sup 11}C] (+)McN5652 and serotonin at the SERT. Methods: In vitro saturation analyses of [{sup 3}H]serotonin uptake into HEK293 cells stably expressing the human SERT were performed in the absence and presence of unlabelled (+)McN5652. Data were evaluated assuming Michaelis-Menten kinetics. Results: Unlabelled (+)McN5652 significantly reduced the maximal rate of serotonin transport V {sub max} of SERT without affecting the Michaelis-Menten constant K {sub M}. Conclusions: This finding indicates that (+)McN5652 inhibits serotonin transport through the SERT in a noncompetitive manner. This might suggest that [{sup 11}C] (+)McN5652 PET is not significantly affected by endogenous serotonin.

  3. Asthma Medication and the Role of Serotonin in the Development of Cognitive and Psychological Difficulties

    Science.gov (United States)

    Pretorius, E.

    2005-01-01

    This literature review will focus on the discussion of asthma and how it affects the sufferer. The role of serotonin and its physiological working at a neural level will follow, as well as the effects of corticosteroids on the brain and how low serotonin levels are linked to depression and corticosteroid use.

  4. Inhibition of serotonin transport by (+)McN5652 is noncompetitive

    International Nuclear Information System (INIS)

    Introduction: Imaging of the serotonergic innervation of the brain using positron emission tomography (PET) with the serotonin transporter (SERT) ligand [11C] (+)McN5652 might be affected by serotonin in the synaptic cleft if there is relevant interaction between [11C] (+)McN5652 and serotonin at the SERT. The aim of the present study therefore was to pharmacologically characterize the interaction of [11C] (+)McN5652 and serotonin at the SERT. Methods: In vitro saturation analyses of [3H]serotonin uptake into HEK293 cells stably expressing the human SERT were performed in the absence and presence of unlabelled (+)McN5652. Data were evaluated assuming Michaelis-Menten kinetics. Results: Unlabelled (+)McN5652 significantly reduced the maximal rate of serotonin transport V max of SERT without affecting the Michaelis-Menten constant K M. Conclusions: This finding indicates that (+)McN5652 inhibits serotonin transport through the SERT in a noncompetitive manner. This might suggest that [11C] (+)McN5652 PET is not significantly affected by endogenous serotonin

  5. Characterisation of the zebrafish serotonin transporter functionally links TM10 to the ligand binding site

    DEFF Research Database (Denmark)

    Severinsen, Kasper; Müller, Heidi Kaastrup; Wiborg, Ove;

    2008-01-01

    and inhibitors. To identify domains and individual amino acids important for ligand binding, we cloned the serotonin transporter from zebrafish, Danio rerio, (drSERT) and compared its pharmacological profile to that of the human serotonin transporter (hSERT) with respect to inhibition of [(3)H]5-HT uptake...

  6. Prenatal exposure to selective serotonin reuptake inhibitors and childhood overweight at 7 years of age

    DEFF Research Database (Denmark)

    Grzeskowiak, Luke E; Gilbert, Andrew L; Sørensen, Thorkild;

    2013-01-01

    To investigate a possible association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and childhood overweight at 7 years of age.......To investigate a possible association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and childhood overweight at 7 years of age....

  7. Augmentation of SSRI effects on serotonin by 5-HT2C antagonists : Mechanistic studies

    NARCIS (Netherlands)

    Cremers, Thomas I. F. H.; Rea, Kieran; Bosker, Fokko J.; Wikstrom, Hakan V.; Hogg, Sandra; Mork, Arne; Westerink, Ben H. C.

    2007-01-01

    The treatment of depression may be improved by using an augmentation approach involving selective serotonin reuptake inhibitors (SSRIs) in combination with compounds that focus on antagonism of inhibitory serotonin receptors. Using microdialysis coupled to HPLC, it has recently been shown that the s

  8. Similar serotonin-2A receptor binding in rats with different coping styles or levels of aggression

    DEFF Research Database (Denmark)

    Visser, Anniek Kd; Ettrup, Anders; Klein, Anders Bue;

    2015-01-01

    Individual differences in coping style emerge as a function of underlying variability in the activation of a mesocorticolimbic brain circuitry. Particularly serotonin seems to play an important role. For this reason, we assessed serotonin-2A receptor (5-HT2A R) binding in the brain of rats with d...

  9. Synthesis of a selective serotonin uptake inhibitor: ( sup 11 C)citalopram

    Energy Technology Data Exchange (ETDEWEB)

    Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Wagner, H.N. Jr. (Johns Hopkins Medical Institutions, Baltimore, MD (USA))

    1990-01-01

    Citalopram, a selective serotonin uptake inhibitor, was labeled with {sup 11}C for non-invasive in vivo studies of serotonin uptake sites in the human brain using positron emission tomography. The synthesis was completed in approximately 17 min using ({sup 11}C)methyl iodide as the precursor. The synthesis, purification, characterization, and determination of specific activity are described. (author).

  10. Activation of serotonin receptors promotes microglial injury-induced motility but attenuates phagocytic activity

    NARCIS (Netherlands)

    Krabbe, Grietje; Matyash, Vitali; Pannasch, Ulrike; Mamer, Lauren; Boddeke, Hendrikus W. G. M.; Kettenmann, Helmut

    2012-01-01

    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 disea

  11. Serotonin 2B receptor: upregulated with age and hearing loss in mouse auditory system.

    Science.gov (United States)

    Tadros, Sherif F; D'Souza, Mary; Zettel, Martha L; Zhu, XiaoXia; Lynch-Erhardt, Martha; Frisina, Robert D

    2007-07-01

    Serotonin (5-HT) is a monoamine neurotransmitter. Serotonin may modulate afferent fiber discharges in the cochlea, inferior colliculus (IC) and auditory cortex. Specific functions of serotonin are exerted upon its interaction with specific receptors; one of those receptors is the serotonin 2B receptor. The aim of this study was to investigate the differences in gene expression of serotonin 2B receptors with age in cochlea and IC, and the possible correlation between gene expression and functional hearing measurements in CBA/CaJ mice. Immunohistochemical examinations of protein expression of IC in mice of different age groups were also performed. Gene expression results showed that serotonin 2B receptor gene was upregulated with age in both cochlea and IC. A significant correlation between gene expression and functional hearing results was established. Immunohistochemical protein expression studies of IC showed more serotonin 2B receptor cells in old mice relative to young adult mice, particularly in the external nucleus. We conclude that serotonin 2B receptors may play a role in the pathogenesis of age-related hearing loss.

  12. Reduced availability of serotonin transporters in obsessive-compulsive disorder correlates with symptom severity - a [11C]DASB PET study

    International Nuclear Information System (INIS)

    Reduced availability of brainstem serotonin transporters (5-HTT) has been observed in vivo in obsessive-compulsive disorder (OCD). However, results vary and may be influenced by competition with endogenous serotonin. Using positron emission tomography (PET) and [11C]DASB, a specific 5-HTT ligand that showed no competition with serotonin for 5-HTT binding in vitro, we tested the hypothesis that 5-HTT availability is reduced in OCD patients and correlated with OCD severity. 5-HTT availability in the thalamus and the midbrain was measured in nine drug-free OCD patients and compared with 19 healthy controls, matched for the individual combination of 5-HTT genotype, gender and smoking status. OCD severity was assessed with the Yale-Brown obsessive compulsive scale (Y-BOCS). 5-HTT availability was significantly reduced in the thalamus and midbrain of OCD patients. Age and 5-HTT in the thalamus explained 83 % of OCD severity in patients that were drug-free for at least 1 year. This PET study confirms a central role of the serotonergic system, particularly the thalamus in the pathogenesis of obsessive compulsive disorder. (author)

  13. [Serotonin and treatment of mental disorders. Present status and future perspectives].

    Science.gov (United States)

    Sevcík, J; Masek, K

    1997-07-14

    Serotoninergic system is involved in the regulation of diverse biological and psychological functions and a variety of serotonin receptor subtypes represent a possible target for a new generation of medications. 5-HT receptors play an important role in both schizophrenia and depression. Modern strategies for treating schizophrenia profit from the existence of interaction between serotonin and dopamine systems. New drugs called serotonin-dopamine antagonists (SDAs) offer wider spectra of activity and lower extrapyramidal side effects liability. The principle of the SDAs is that the drug should be a potent serotonin 5-HT 2A antagonist, with slightly less potent dopamine D2 receptor-blocking properties. New pharmacological agents with great therapeutic potential and fewer side effects were recently developed also for the treatment of depression. Among these new antidepressives the serotonin selective reuptake inhibitors (SSRIs) currently play the most important role. PMID:9340186

  14. Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder

    Science.gov (United States)

    Marler, Sarah; Ferguson, Bradley J.; Lee, Evon Batey; Peters, Brittany; Williams, Kent C.; McDonnell, Erin; Macklin, Eric A.; Levitt, Pat; Gillespie, Catherine Hagan; Anderson, George M.; Margolis, Kara Gross; Beversdorf, David Q.; Veenstra-VanderWeele, Jeremy

    2016-01-01

    Elevated whole blood serotonin levels are observed in more than 25 % of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen between functional constipation diagnosis and serotonin levels in the hyperserotonemia range, suggesting that this correlation is not driven by a single subgroup. More specific assessment of gut function, including the microbiome, will be necessary to evaluate the contribution of gut physiology to serotonin levels in ASD. PMID:26527110

  15. Intact coding region of the serotonin transporter gene in obsessive-compulsive disorder

    Energy Technology Data Exchange (ETDEWEB)

    Altemus, M.; Murphy, D.L.; Greenberg, B. [NIMH, NIH, Bethesda, MD (United States); Lesch, K.P. [Univ. of Wuerzburg (Germany)

    1996-07-26

    Epidemiologic studies indicate that obsessive-compulsive disorder is genetically transmitted in some families, although no genetic abnormalities have been identified in individuals with this disorder. The selective response of obsessive-compulsive disorder to treatment with agents which block serotonin reuptake suggests the gene coding for the serotonin transporter as a candidate gene. The primary structure of the serotonin-transporter coding region was sequenced in 22 patients with obsessive-compulsive disorder, using direct PCR sequencing of cDNA synthesized from platelet serotonin-transporter mRNA. No variations in amino acid sequence were found among the obsessive-compulsive disorder patients or healthy controls. These results do not support a role for alteration in the primary structure of the coding region of the serotonin-transporter gene in the pathogenesis of obsessive-compulsive disorder. 27 refs.

  16. Serotonin Promotes Development and Regeneration of Spinal Motor Neurons in Zebrafish.

    Science.gov (United States)

    Barreiro-Iglesias, Antón; Mysiak, Karolina S; Scott, Angela L; Reimer, Michell M; Yang, Yujie; Becker, Catherina G; Becker, Thomas

    2015-11-01

    In contrast to mammals, zebrafish regenerate spinal motor neurons. During regeneration, developmental signals are re-deployed. Here, we show that, during development, diffuse serotonin promotes spinal motor neuron generation from pMN progenitor cells, leaving interneuron numbers unchanged. Pharmacological manipulations and receptor knockdown indicate that serotonin acts at least in part via 5-HT1A receptors. In adults, serotonin is supplied to the spinal cord mainly (90%) by descending axons from the brain. After a spinal lesion, serotonergic axons degenerate caudal to the lesion but sprout rostral to it. Toxin-mediated ablation of serotonergic axons also rostral to the lesion impaired regeneration of motor neurons only there. Conversely, intraperitoneal serotonin injections doubled numbers of new motor neurons and proliferating pMN-like progenitors caudal to the lesion. Regeneration of spinal-intrinsic serotonergic interneurons was unaltered by these manipulations. Hence, serotonin selectively promotes the development and adult regeneration of motor neurons in zebrafish.

  17. Serotonin transporter is not required for the development of severe pulmonary hypertension in the Sugen hypoxia rat model

    NARCIS (Netherlands)

    de Raaf, Michiel Alexander; Kroeze, Yvet; Middelman, Anthonieke; de Man, Frances S.; de Jong, Helma; Vonk-Noordegraaf, Anton; de Korte, Chris; Voelkel, Norbert F.; Homberg, Judith; Bogaard, Harm Jan

    2015-01-01

    Increased serotonin serum levels have been proposed to play a key role in pulmonary arterial hypertension (PAH) by regulating vessel tone and vascular smooth muscle cell proliferation. An intact serotonin system, which critically depends on a normal function of the serotonin transporter (SERT), is r

  18. Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms

    NARCIS (Netherlands)

    F.C.W. van Nieuwerburgh; D.A.J.P. Denys; H.G.M. Westenberg; D.L.D. Deforce

    2009-01-01

    The cornerstone of pharmacotherapy for OCD is serotonin reuptake inhibition, either with clomipramine or with selective serotonin reuptake inhibitors (SSRIs). In spite of the success of serotonin reuptake inhibiting drugs, nearly half of OCD patients do not respond to treatment. Treatment response m

  19. Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells

    Science.gov (United States)

    Hasni Ebou, Moina; Singh-Estivalet, Amrit; Launay, Jean-Marie; Callebert, Jacques; Tronche, François; Ferré, Pascal; Gautier, Jean-François; Guillemain, Ghislaine; Bréant, Bernadette

    2016-01-01

    Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1) and 2 (Tph2), leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells. PMID:26901633

  20. Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells.

    Directory of Open Access Journals (Sweden)

    Moina Hasni Ebou

    Full Text Available Diabetes is a major complication of chronic Glucocorticoids (GCs treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1 and 2 (Tph2, leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells.

  1. Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder.

    Science.gov (United States)

    Mc Mahon, Brenda; Andersen, Sofie B; Madsen, Martin K; Hjordt, Liv V; Hageman, Ida; Dam, Henrik; Svarer, Claus; da Cunha-Bang, Sofi; Baaré, William; Madsen, Jacob; Hasholt, Lis; Holst, Klaus; Frokjaer, Vibe G; Knudsen, Gitte M

    2016-05-01

    Cross-sectional neuroimaging studies in non-depressed individuals have demonstrated an inverse relationship between daylight minutes and cerebral serotonin transporter; this relationship is modified by serotonin-transporter-linked polymorphic region short allele carrier status. We here present data from the first longitudinal investigation of seasonal serotonin transporter fluctuations in both patients with seasonal affective disorder and in healthy individuals. Eighty (11)C-DASB positron emission tomography scans were conducted to quantify cerebral serotonin transporter binding; 23 healthy controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding in the summer but in their symptomatic phase during winter, patients with seasonal affective disorder had higher serotonin transporter than the healthy control subjects (P = 0.01). Compared to the healthy controls, patients with seasonal affective disorder changed their serotonin transporter significantly less between summer and winter (P sex- (P = 0.02) and genotype- (P = 0.04) dependent. In the patients with seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom severity, as indexed by Hamilton Rating Scale for Depression - Seasonal Affective Disorder version scores (P = 0.01). Our findings suggest that the development of depressive symptoms in winter is associated with a failure to downregulate serotonin transporter levels appropriately during exposure to the environmental stress of winter, especially in individuals with high predisposition to affective disorders.media-1vid110.1093/brain/aww043_video_abstractaww043_video_abstract. PMID:26994750

  2. Methane release

    International Nuclear Information System (INIS)

    The Swiss Gas Industry has carried out a systematic, technical estimate of methane release from the complete supply chain from production to consumption for the years 1992/1993. The result of this survey provided a conservative value, amounting to 0.9% of the Swiss domestic output. A continuation of the study taking into account new findings with regard to emission factors and the effect of the climate is now available, which provides a value of 0.8% for the target year of 1996. These results show that the renovation of the network has brought about lower losses in the local gas supplies, particularly for the grey cast iron pipelines. (author)

  3. Functional characterization of serotonin receptor subtypes in human duodenal secretion

    DEFF Research Database (Denmark)

    Engelmann, Bodil Elisabeth; Bindslev, Niels; Poulsen, Steen Seier;

    2006-01-01

    Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum of dyspep......Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum...... of dyspeptic patients with or without Helicobacter pylori infection, and to determine the 5-HT receptor subtypes functionally involved. Biopsies from the second part of duodenum were obtained from 43 dyspeptic patients during routine endoscopy. Biopsies were mounted in modified Ussing chambers with air suction...... for measurements of short-circuit current by a previously validated technique. Short-circuit current was measured before and after application of graded cumulative doses of 5-HT and a single dose of bumetanide (an inhibitor of chloride/bicarbonate transport), or one of the selective 5-HT receptor antagonists...

  4. Selective serotonin reuptake inhibitor associated suicidal ideation: a case report

    Directory of Open Access Journals (Sweden)

    Shatavisa Mukherjee

    2014-08-01

    Full Text Available This report describes a patient suffering from somatoform disorder that developed suicidal ideation specifically due to the treatment with sertraline. After 6-7 months on the regimen, she presented slight suicidal ideations. However, with gradual progress of time and continuation of the therapy, the ideation became intense. She complained of intense restlessness and anxiety. She presented with fresh cuts and bruises on her left arm and neck. On reporting the problem, the drug was withdrawn. Patient experienced gradual improvement in her state. The case report underlines the importance of onset of suicide risk in panic disorders due to specific antidepressants, selective serotonin reuptake inhibitors (SSRIs. The exact neurobiological basis of depression though being uncertain, the role of serotonin has been mostly implicated. Hypothetically, biological alterations in the serotonergic system might have contributed to the suicidal ideation/attempt in the presence of an SSRI. The present case attempts to highlight an incidence of development of suicidal ideation in a patient who is on chronic SSRI therapy. [Int J Basic Clin Pharmacol 2014; 3(4.000: 738-740

  5. Levomilnacipran (Fetzima): A New Serotonin-Norepinephrine Reuptake Inhibitor for the Treatment of Major Depressive Disorder.

    Science.gov (United States)

    Saraceni, Megan M; Venci, Jineane V; Gandhi, Mona A

    2014-08-01

    In July 2013, the US Food and Drug Administration approved levomilnacipran extended release (ER; Fetzima), a serotonin-norepinephrine reuptake inhibitor, for the treatment of adults with major depressive disorder. Levomilnacipran is an active enantiomer of the racemic drug milnacipran that is currently approved in the United States for the treatment of fibromyalgia. This article provides an overview of the mechanism of action, pharmacokinetic properties, clinical efficacy, safety, and tolerability of levomilnacipran ER. Relevant information was identified through a search of databases using the key word levomilnacipran. Additional information was obtained from fda.gov, by a review of the reference lists of identified articles, and from posters and abstracts from scientific meetings. Levomilnacipran ER, dosed once daily, is generally well tolerated and has demonstrated favorable effects compared to placebo in clinical trials of patients with major depressive disorder. The increased potency for norepinephrine reuptake inhibition is a characteristic that may represent a novel contribution for levomilnacipran. Additional studies comparing levomilnacipran ER to other commonly prescribed antidepressants are needed to further evaluate its place in therapy. PMID:24381243

  6. Serotonin 5-HT2 receptor interactions with dopamine function: implications for therapeutics in cocaine use disorder.

    Science.gov (United States)

    Howell, Leonard L; Cunningham, Kathryn A

    2015-01-01

    Cocaine exhibits prominent abuse liability, and chronic abuse can result in cocaine use disorder with significant morbidity. Major advances have been made in delineating neurobiological mechanisms of cocaine abuse; however, effective medications to treat cocaine use disorder remain to be discovered. The present review will focus on the role of serotonin (5-HT; 5-hydroxytryptamine) neurotransmission in the neuropharmacology of cocaine and related abused stimulants. Extensive research suggests that the primary contribution of 5-HT to cocaine addiction is a consequence of interactions with dopamine (DA) neurotransmission. The literature on the neurobiological and behavioral effects of cocaine is well developed, so the focus of the review will be on cocaine with inferences made about other monoamine uptake inhibitors and releasers based on mechanistic considerations. 5-HT receptors are widely expressed throughout the brain, and several different 5-HT receptor subtypes have been implicated in mediating the effects of endogenous 5-HT on DA. However, the 5-HT2A and 5-HT2C receptors in particular have been implicated as likely candidates for mediating the influence of 5-HT in cocaine abuse as well as to traits (e.g., impulsivity) that contribute to the development of cocaine use disorder and relapse in humans. Lastly, new approaches are proposed to guide targeted development of serotonergic ligands for the treatment of cocaine use disorder. PMID:25505168

  7. ATMOSPHERIC RELEASES OF HEXAVALENT CHROMIUM FROM HARD CHROMIUM PLATING OPERATIONS

    Science.gov (United States)

    The University of Central Florida Department of Civil and Environmental Engineering is investigating methods for improved estimation of chemical releases which require reporting under provisions of SARA Title III (Toxic Release Inventory, Form R). This paper describes results fr...

  8. Serotonin 2a Receptor and serotonin 1a receptor interact within the medial prefrontal cortex during recognition memory in mice

    Directory of Open Access Journals (Sweden)

    Juan Facundo Morici

    2015-12-01

    Full Text Available Episodic memory, can be defined as the memory for unique events. The serotonergic system one of the main neuromodulatory systems in the brain appears to play a role in it. The serotonin 2a receptor (5-HT2aR one of the principal post-synaptic receptors for 5-HT in the brain, is involved in neuropsychiatric and neurological disorders associated with memory deficits. Recognition memory can be defined as the ability to recognize if a particular event or item was previously encountered and is thus considered, under certain conditions, a form of episodic memory. As human data suggest that a constitutively decrease of 5-HT2A signaling might affect episodic memory performance we decided to compare the performance of mice with disrupted 5-HT2aR signaling (htr2a -/- with wild type (htr2a+/+ littermates in different recognition memory and working memory tasks that differed in the level of proactive interference. We found that ablation of 5-HT2aR signaling throughout development produces a deficit in tasks that cannot be solved by single item strategy suggesting that 5-HT2aR signaling is involved in interference resolution. We also found that in the absence of 5-HT2aR signaling serotonin has a deleterious effect on recognition memory retrieval through the activation of 5-HT1aR in the medial prefrontal cortex.

  9. Impact of elevated plasma serotonin on global gene expression of murine megakaryocytes.

    Directory of Open Access Journals (Sweden)

    Charles P Mercado

    Full Text Available BACKGROUND: Serotonin (5-HT is a biogenic amine that also acts as a mitogen and a developmental signal early in rodent embryogenesis. Genetic and pharmacological disruption of 5-HT signaling causes various diseases and disorders via mediating central nervous system, cardiovascular system, and serious abnormalities on a growing embryo. Today, neither the effective modulators on 5-HT signaling pathways nor the genes affected by 5-HT signal are well known yet. METHODOLOGY/PRINCIPAL FINDINGS: In an attempt to identify the genes altered by 5-HT signaling pathways, we analyzed the global gene expression via the Illumina array platform using the mouse WG-6 v2.0 Expression BeadChip containing 45,281 probe sets representing 30,854 genes in megakaryocytes isolated from mice infused with 5-HT or saline. We identified 723 differentially expressed genes of which 706 were induced and 17 were repressed by elevated plasma 5-HT. CONCLUSIONS/SIGNIFICANCE: Hierarchical gene clustering analysis was utilized to represent relations between groups and clusters. Using gene ontology mining tools and canonical pathway analyses, we identified multiple biological pathways that are regulated by 5-HT: (i cytoskeletal remodeling, (ii G-protein signaling, (iii vesicular transport, and (iv apoptosis and survival. Our data encompass the first extensive genome-wide based profiling in the progenitors of platelets in response to 5-HT elevation in vivo.

  10. Analysis of serotonin in brain microdialysates using capillary electrophoresis and native laser-induced fluorescence detection.

    Science.gov (United States)

    Benturquia, Nadia; Couderc, François; Sauvinet, Valérie; Orset, Cyrille; Parrot, Sandrine; Bayle, Christophe; Renaud, Bernard; Denoroy, Luc

    2005-03-01

    Serotonin or 5-hydroxytryptamine (5-HT) is a major neurotransmitter in the central nervous system. In this work, a method for analyzing 5-HT in brain microdialysis samples using a commercially available capillary electrophoresis (CE) system has been developed. A pH-mediated in-capillary preconcentration of samples was performed, and after separation by capillary zone electrophoresis, native fluorescence of 5-HT was detected by a 266 nm solid-state laser. The separation conditions for the analysis of 5-HT in standard solutions and microdialysates have been optimized, and this method has been validated on both pharmacological and analytical bases. Separation of 5-HT was performed using a 80 mmol/L citrate buffer, pH 2.5, containing 20 mmol/L hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and +30 kV voltage. The detection limit was 2.5 x 10(-10) mol/L. This method allows the in vivo brain monitoring of 5-HT using a simple, accurate CE measurement in underivatized microdialysis samples.

  11. Statistical distribution of blood serotonin as a predictor of early autistic brain abnormalities

    Directory of Open Access Journals (Sweden)

    Janušonis Skirmantas

    2005-07-01

    Full Text Available Abstract Background A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin in blood platelets (platelet hyperserotonemia. The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor. Results The identity of this factor was studied by using a novel, quantitative approach that was applied to published distributions of the platelet 5-HT levels in normal and autistic groups. It was shown that the published data are consistent with the hypothesis that a factor that interferes with brain development in autism may also regulate the release of 5-HT from gut enterochromaffin cells. Numerical analysis revealed that this factor may be non-functional in autistic individuals. Conclusion At least some biological factors, the abnormal function of which leads to the development of the autistic brain, may regulate the release of 5-HT from the gut years after birth. If the present model is correct, it will allow future efforts to be focused on a limited number of gene candidates, some of which have not been suspected to be involved in autism (such as the 5-HT4 receptor gene based on currently available clinical and

  12. EFFECTS OF 5, 7-DIHYDROXYTRYPTAMINE-INDUCED DEPLETION OF BRAIN SEROTONIN ON RADIAL ARM-MAZE TASK IN RATS

    Directory of Open Access Journals (Sweden)

    Vasile Hefco

    2005-08-01

    Full Text Available Adult rats pretreated with desipramine (25 mg/kg i.p.30 min before anesthesia in order to protect noradrenergic system, were subjected to intracerebroventriculare injection of 5, 7 –dihydroxytryptamine (5, 7-DHT, 150 μg, 4.5 μl/ventricle, a chronic neurotoxin of the central serotonergic function. After 1.5 months later, we assessed the working memory and reference memory in radial 8 arm-mazes. Serotonergic depletion impaired more significantly shortterm memory tested by means of the average working memory errors, entries to repeat and average time taken to consume all five baits during 12 days training. Long-term memory, explored by means of reference memory errors, was less impaired. It is concluded that serotonin, among other neurotransmitters, play one important role in cognitive functions, including learning and memory.

  13. Early life stress and serotonin transporter gene variation interact to affect the transcription of the glucocorticoid and mineralocorticoid receptors, and the co-chaperone FKBP5, in the adult rat brain

    OpenAIRE

    van der Doelen, Rick H. A.; Calabrese, Francesca; Guidotti, Gianluigi; Geenen, Bram; Riva, Marco A.; Kozicz, Tamás; Homberg, Judith R.

    2014-01-01

    The short allelic variant of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) has been associated with the etiology of major depression by interaction with early life stress (ELS). A frequently observed endophenotype in depression is the abnormal regulation of levels of stress hormones such as glucocorticoids. It is hypothesized that altered central glucocorticoid influence on stress-related behavior and memory processes could underlie the depressogenic interact...

  14. The role of phosphatidylinositol signaling pathway in regulating serotonin-induced oocyte maturation in Mercenaria mercenaria

    Institute of Scientific and Technical Information of China (English)

    WANG Qing; ZHANG Tao

    2011-01-01

    Serotonin (5-HT) has been found to stimulate meiotic maturation of oocytes in many molluscs. During maturation, several signaling pathways are involved, especially the phosphatidylinositol and cAMP pathways. In order to examine the possible role of the phosphatidylinositol signaling pathway in regulating oocyte maturation in Mercenaria mercenaria, the effects of the activator/inhibitor of phospholipase (PLC) and protein kinase C (PKC) on serotonin-induced maturation were studied. Results show that high-concentrations of neomycin (inhibitor of PLC) blocked oocyte maturation, while 9, 10-dimethyl- 1, 2-benzanthracene (DMBA, activator of PLC) promoted oocyte maturation in the presence of serotonin. It was also found that in the presence of serotonin, phorbol 12-myristate 13-acetate (PMA,activator of PKC) inhibited oocyte maturation, while sphingosine (inhibitor of PKC) stimulated oocyte maturation. These results indicate that serotonin-induced oocyte maturation requires the activation of the phosphatidylinositol pathway. Decrease of PLC inhibited serotonin-induced oocyte maturation, whereas a decrease of PKC stimulated the maturation. Thus, our study indicates that serotonin promotes maturation of M. mercenaria oocytes through PLC stimulated increase in calcium ion concentration via inositol-1,4, 5-trisphosphate (IP3) but not PKC.

  15. Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory.

    Science.gov (United States)

    Hartley, Catherine A; McKenna, Morgan C; Salman, Rabia; Holmes, Andrew; Casey, B J; Phelps, Elizabeth A; Glatt, Charles E

    2012-04-01

    Growing evidence suggests serotonin's role in anxiety and depression is mediated by its effects on learned fear associations. Pharmacological and genetic manipulations of serotonin signaling in mice alter the retention of fear extinction learning, which is inversely associated with anxious temperament in mice and humans. Here, we test whether genetic variation in serotonin signaling in the form of a common human serotonin transporter polyadenylation polymorphism (STPP/rs3813034) is associated with spontaneous fear recovery after extinction. We show that the risk allele of this polymorphism is associated with impaired retention of fear extinction memory and heightened anxiety and depressive symptoms. These STPP associations in humans mirror the phenotypic effects of serotonin transporter knockout in mice, highlighting the STPP as a potential genetic locus underlying interindividual differences in serotonin transporter function in humans. Furthermore, we show that the serotonin transporter polyadenylation profile associated with the STPP risk allele is altered through the chronic administration of fluoxetine, a treatment that also facilitates retention of extinction learning. The propensity to form persistent fear associations due to poor extinction recall may be an intermediate phenotype mediating the effects of genetic variation in serotonergic function on anxiety and depression. The consistency and specificity of these data across species provide robust support for this hypothesis and suggest that the little-studied STPP may be an important risk factor for mood and anxiety disorders in humans.

  16. Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants.

    Directory of Open Access Journals (Sweden)

    Katerina V Savelieva

    Full Text Available The neurotransmitter serotonin (5-HT plays an important role in both the peripheral and central nervous systems. The biosynthesis of serotonin is regulated by two rate-limiting enzymes, tryptophan hydroxylase-1 and -2 (TPH1 and TPH2. We used a gene-targeting approach to generate mice with selective and complete elimination of the two known TPH isoforms. This resulted in dramatically reduced central 5-HT levels in Tph2 knockout (TPH2KO and Tph1/Tph2 double knockout (DKO mice; and substantially reduced peripheral 5-HT levels in DKO, but not TPH2KO mice. Therefore, differential expression of the two isoforms of TPH was reflected in corresponding depletion of 5-HT content in the brain and periphery. Surprisingly, despite the prominent and evolutionarily ancient role that 5-HT plays in both vertebrate and invertebrate physiology, none of these mutations resulted in an overt phenotype. TPH2KO and DKO mice were viable and normal in appearance. Behavioral alterations in assays with predictive validity for antidepressants were among the very few phenotypes uncovered. These behavioral changes were subtle in the TPH2KO mice; they were enhanced in the DKO mice. Herein, we confirm findings from prior descriptions of TPH1 knockout mice and present the first reported phenotypic evaluations of Tph2 and Tph1/Tph2 knockout mice. The behavioral effects observed in the TPH2 KO and DKO mice strongly confirm the role of 5-HT and its synthetic enzymes in the etiology and treatment of affective disorders.

  17. Relations between peripheral and brain serotonin measures and behavioural responses in a novelty test in pigs.

    Science.gov (United States)

    Ursinus, Winanda W; Bolhuis, J Elizabeth; Zonderland, Johan J; Rodenburg, T Bas; de Souza, Adriana S; Koopmanschap, Rudie E; Kemp, Bas; Korte-Bouws, Gerdien A H; Korte, S Mechiel; van Reenen, Cornelis G

    2013-06-13

    Pigs differ in their behavioural responses towards environmental challenges. Individual variation in maladaptive responses such as tail biting, may partly originate from underlying biological characteristics related to (emotional) reactivity to challenges and serotonergic system functioning. Assessing relations between behavioural responses and brain and blood serotonin parameters may help in understanding susceptibility to the development of maladaptive responses. The objective of the current study was, therefore, to assess the relationship between the pigs' serotonergic parameters measured in both blood and brain, and the behaviour of pigs during a novelty test. Pigs (n=31) were subjected to a novelty test at 11weeks of age, consisting of 5-min novel environment exposure after which a novel object (a bucket) was introduced for 5min. Whole blood serotonin, platelet serotonin level, and platelet serotonin uptake were determined at 13weeks of age. Levels of serotonin, its metabolite and serotonin turnover were determined at 19weeks of age in the frontal cortex, hypothalamus and hippocampus. The behaviour of the pigs was different during exposure to a novel object compared to the novel environment only, with more fear-related behaviours exhibited during novel object exposure. Platelet serotonin level and brain serotonergic parameters in the hippocampus were interrelated. Notably, the time spent exploring the test arena was significantly correlated with both platelet serotonin level and right hippocampal serotonin activity (turnover and concentration). In conclusion, the existence of an underlying biological trait - possibly fearfulness - may be involved in the pig's behavioural responses toward environmental challenges, and this is also reflected in serotonergic parameters. PMID:23685231

  18. Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice.

    Directory of Open Access Journals (Sweden)

    Jimena Laporta

    Full Text Available Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood into the ductal lumen (milk. Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1, which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2 and basolateral (CaSR, ORAI-1 membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2. Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2 are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation.

  19. Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse

    Directory of Open Access Journals (Sweden)

    Koepsell Hermann

    2006-04-01

    Full Text Available Abstract Background It has been proposed that serotonin (5-HT-mediated constriction of the murine trachea is largely dependent on acetylcholine (ACh released from the epithelium. We recently demonstrated that ACh can be released from non-neuronal cells by corticosteroid-sensitive polyspecific organic cation transporters (OCTs, which are also expressed by airway epithelial cells. Hence, the hypothesis emerged that 5-HT evokes bronchoconstriction by inducing release of ACh from epithelial cells via OCTs. Methods We tested this hypothesis by analysing bronchoconstriction in precision-cut murine lung slices using OCT and muscarinic ACh receptor knockout mouse strains. Epithelial ACh content was measured by HPLC, and the tissue distribution of OCT isoforms was determined by immunohistochemistry. Results Epithelial ACh content was significantly higher in OCT1/2 double-knockout mice (42 ± 10 % of the content of the epithelium-denuded trachea, n = 9 than in wild-type mice (16.8 ± 3.6 %, n = 11. In wild-type mice, 5-HT (1 μM caused a bronchoconstriction that slightly exceeded that evoked by muscarine (1 μM in intact bronchi but amounted to only 66% of the response to muscarine after epithelium removal. 5-HT-induced bronchoconstriction was undiminished in M2/M3 muscarinic ACh receptor double-knockout mice which were entirely unresponsive to muscarine. Corticosterone (1 μM significantly reduced 5-HT-induced bronchoconstriction in wild-type and OCT1/2 double-knockout mice, but not in OCT3 knockout mice. This effect persisted after removal of the bronchial epithelium. Immunohistochemistry localized OCT3 to the bronchial smooth muscle. Conclusion The doubling of airway epithelial ACh content in OCT1/2-/- mice is consistent with the concept that OCT1 and/or 2 mediate ACh release from the respiratory epithelium. This effect, however, does not contribute to 5-HT-induced constriction of murine intrapulmonary bronchi. Instead, this activity involves 1 a non

  20. Serotonin transporter and dopamine transporter imaging in the canine brain

    Energy Technology Data Exchange (ETDEWEB)

    Peremans, Kathelijne [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Goethals, Ingeborg [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium); De Vos, Filip [Laboratory of Radiopharmacy, Pharmaceutical Sciences, Ghent University, B-9000 Ghent (Belgium); Dobbeleir, A. [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Ham, Hamphrey [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium); Van Bree, Henri [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Heeringen, Cees van [Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, B-9000, Ghent (Belgium); Audenaert, Kurt [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium) and Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, B-9000, Ghent (Belgium)]. E-mail: kurt.audenaert@ugent.be

    2006-10-15

    The serotonergic and dopaminergic systems are involved in a wide range of emotional and behavioral aspects of animals and humans and are involved in many neuropsychiatric disorders. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are designed to block the 5-HT transporter (SERT), thereby increasing the available 5-HT in the brain. Functional imaging with specific SERT and dopamine transporter (DAT) ligands contributes to the study of the SSRI-transporter interaction. First, we evaluated the feasibility of a canine model in the study of the SERT and DAT with the radioligands [{sup 123}I]-{beta}-CIT and [{sup 123}I]-FP-CIT as well as single-photon emission computed tomography imaging. Second, we studied the effect of SSRIs (sertraline, citalopram and escitalopram) on the SERT and DAT in two dogs. The position of the canine model in the study of the SERT and DAT is discussed and compared with other animal models.

  1. Prenatal exposure to serotonin reuptake inhibitors: a case report

    Directory of Open Access Journals (Sweden)

    Solinas Agostina

    2010-03-01

    Full Text Available Abstract Two premature twins (33 weeks gestation were born to a woman who had used paroxetine during pregnancy for an anxiety-depression disorder. They were admitted to the NICU, where they showed prolonged RDS, cardiovascular malformations, and facial dysmorphisms. Soon after birth, they also presented abnormal neurobehavioral and motor signs, which partially disappeared during the following weeks, although alterations of tone persisted even at discharge. Selective serotonin reuptake inhibitor (SSRI antidepressants are considered the primary treatments for depression and anxiety in pregnancy. Since intrauterine exposure to these drugs has been associated with poor neonatal adaptation, low birth weight, RDS, neurobehavioural symptoms, and potential teratogenic effects, further studies are needed to assess risks and mechanism of action of SSRIs. Meanwhile, it is advisable to evaluate for each patient the real risk/benefit ratio of continuing or suspending treatment during pregnancy.

  2. Use of selective serotonin reuptake inhibitors reduces fertility in men.

    Science.gov (United States)

    Nørr, L; Bennedsen, B; Fedder, J; Larsen, E R

    2016-05-01

    Clinical review of the present data on the effects of selective serotonin reuptake inhibitors (SSRIs) on male fertility was the objective of the study. PubMed and Scopus were searched for publications in English or Danish and reviewed. Human trials, animal studies and in vitro studies were included. Use of SSRIs negatively affects semen parameters in most studies. In some studies, SSRIs are also shown to reduce DNA integrity. SSRIs can also delay ejaculation. Depression and anxiety can cause reduced libido, erectile dysfunction and delayed ejaculation as well. The use of SSRIs seems to reduce male fertility by affecting semen parameters, although most studies have a degree of confounding by indication caused by the underlying depression. PMID:27019308

  3. Structural basis for molecular recognition at serotonin receptors.

    Science.gov (United States)

    Wang, Chong; Jiang, Yi; Ma, Jinming; Wu, Huixian; Wacker, Daniel; Katritch, Vsevolod; Han, Gye Won; Liu, Wei; Huang, Xi-Ping; Vardy, Eyal; McCorvy, John D; Gao, Xiang; Zhou, X Edward; Melcher, Karsten; Zhang, Chenghai; Bai, Fang; Yang, Huaiyu; Yang, Linlin; Jiang, Hualiang; Roth, Bryan L; Cherezov, Vadim; Stevens, Raymond C; Xu, H Eric

    2013-05-01

    Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs. PMID:23519210

  4. Measuring Central Bank Communication:

    OpenAIRE

    David Lucca; Francesco Trebbi

    2008-01-01

    We present a new automated, objective and intuitive scoring method to measure the content of central bank communication about future policy rate moves. We apply the methodology to statements released by the Federal Open Market Commitee (FOMC) after monetary policy meetings. Using high-frequency financial data, we find that yields on short-term risk-free nominal rates respond both to changes in policy rates and the content of the statements, whereas, medium and long-term rates only respond to ...

  5. Patterns of circulating serotonin and related metabolites in multiparous dairy cows in the peripartum period.

    Science.gov (United States)

    Moore, S A E; Laporta, J; Crenshaw, T D; Hernandez, L L

    2015-06-01

    Dairy cows are challenged to maintain Ca and glucose homeostasis during the transition period. Serotonin (5-HT) is a monoamine that modulates Ca and glucose homeostasis in rodents. Serotonin is positively correlated with Ca and glucose status in dairy cows on d 1 of lactation. However, the pattern of circulating concentrations of 5-HT over the course of a 305-d lactation is unknown. In this observational, longitudinal study, we examined the metabolite patterns of 5-HT, Ca, glucose, parathyroid hormone-related protein, and β-hydroxybutyrate on 2 commercial dairy farms in south-central Wisconsin. Cows sampled on farm 1 were multiparous Jersey cows (n=30) that calved within a 23-d period; cows on farm 2 were multiparous Holstein cows (n=35) that calved within a 20-d period. Blood samples were collected daily between d -5 and d 10 relative to parturition and on d 30, 60, 90, 150, and 300 of lactation. Farms 1 and 2 were analyzed individually because of the presence of a farm effect in the initial analysis; a time effect was present on both farms. Concentrations of 5-HT decreased near parturition compared with prepartum by 57.9 and 29.5% on farm 1 and 2, respectively. Transition period 5-HT nadirs were observed on d 1 on farm 1, and on d 1 and 9 on farm 2. Serotonin recovered to prepartum concentrations by d 5 on farm 1. On farm 2, 5-HT recovered to prepartum concentrations by d 4, with a subsequent decrease of 34.6% on d 9 to a level similar to that observed on d 1. Furthermore, 5-HT increased markedly in cows on both farms near peak lactation (d 60, 90, and 150) and decreased on d 300. Compared with prepartum concentrations, Ca decreased by 34.2 and 11.2% on farms 1 and 2, respectively. Circulating total Ca nadir was observed on d 1 on both farms. Circulating 5-HT and circulating Ca were positively correlated during the early lactation period (d 1 to 5 and d 6 to 10) on farm 1 (r=0.31 and r=0.22, respectively) and d 6 to 10 on farm 2 (r=0.16). Circulating 5-HT and

  6. Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

    Energy Technology Data Exchange (ETDEWEB)

    Tiradentes, R.V. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Pires, J.G.P. [Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Escola de Medicina da Empresa Brasileira de Ensino, Vitória, ES (Brazil); Silva, N.F. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Ramage, A.G. [Department of Neuroscience, Physiology and Pharmacology, University College London, London (United Kingdom); Santuzzi, C.H. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Futuro, H.A. Neto [Escola de Medicina da Empresa Brasileira de Ensino, Vitória, ES (Brazil); Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Escola Superior de Ciências da Saúde, Santa Casa de Misericórdia de Vitória, Vitória, ES (Brazil)

    2014-05-30

    Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

  7. Sunshine and specific binding of serotonin transporters in Finnish man

    International Nuclear Information System (INIS)

    Aim: Visible light (400-700 nm) exposure decreases melatonin, norepinephrine, and acetylcholine whereas cortisol, serotonin, CABA, and dopamine levels increase. Light could be of particular relevance in the pathophysiology of neuropsychiatric disorders such as winter type affective disorder. The aim of the present study was to measure seasonal variation of specific binding of serotonin transporters (SERT) in man. Material and Methods: Thirty six white Caucasian males were studied. Their mean age was 38 years (range: 19-64 years). All subjects were medically health. A dose of 185 MBq of [123I]nor-b-CIT (supplied by MAP Medical Technologies Oy, Tikkakoski, Finland) was intravenously injected. SPECT scans were performed on a triple-head Siemens Multi SPECT 3 gamma camera equipped with fan-beam collimators. Regions of interest were drawn onto the midbrain (free + non-specific + specific binding) and onto the cerebellum (free + non-specific binding). The specific binding of the midbrain was calculated as (midbrain-cerebellum)/cerebellum. The findings of the study subjects were grouped onto the 6 sub-groups (six subjects per sub-group: January, March, May, July, September and November). In addition, blood platelets content was followed up for 12 months in 18 healthy males. The maximal binding potential (Bmax: fmol/mg protein) of platelets was determined. Results: Dependence of the specific binding of SERT in the midbrain and Bmax of human blood platelets on daily sunshine is presented. The data suggest lower specific binding of SERT in summer than in winter although this difference did not reach a statistical significance due to a small number of study subjects. Conclusion: Visible light exposure can alter specific binding of SERT in Finnish healthy males. The findings of in vivo molecular imaging support seasonal variation of human blood platelets content

  8. Selective serotonin reuptake inhibitors and the risk of bleeding

    Directory of Open Access Journals (Sweden)

    Padma L

    2013-06-01

    Full Text Available Background: Selective serotonin reuptake inhibitors (SSRIs are commonly prescribed agents for various conditions in general psychiatry. There is a strong consensus that blockade of serotonin reuptake affects primary hemostasis, namely platelet activity, thus resulting in a bleeding tendency. Considering that SSRIs are commonly prescribed, this study was conducted to assess if they were associated with an increased risk of bleeding. Methods: This was a prospective, open-label study of 30 patients attending the Psychiatry out-patient department, Dr. B. R. Ambedkar Medical College, Bangalore who satisfied DSM-IV criteria for a primary diagnosis of depression, treated with SSRIs. Bleeding time, clotting time, prothrombin time, partial thromboplastin time and platelet count were assessed at baseline and at the end of 6 weeks of treatment or occurrence of bleeding symptom. Results: The patients aged between 18-55 years of whom 21 were females, were treated with an SSRI (fluoxetine 12, escitalopram 12 and sertraline 6 patients. Six patients had overt symptoms of bleeding (upper gastrointestinal bleeding (hematemesis 4; epistaxis 2 and petechiae 2 of whom one patient gave a history of both hematemesis and petechiae and another of hematemesis and epistaxis. The average day after treatment beginning, on which patients reported with bleeding was 30.33 (26-40 days. There was a significant increase in the bleeding time (p=0.028 and clotting time (p=0.042, implying derangement in platelet aggregation. There was no significant change in the other parameters. Conclusion: Treatment with SSRIs increases the risk of bleeding. However, large, randomized controlled trials are required to re-affirm these findings. [Int J Basic Clin Pharmacol 2013; 2(3.000: 272-274

  9. Impulsivity, gender, and the platelet serotonin transporter in healthy subjects

    Directory of Open Access Journals (Sweden)

    Donatella Marazziti

    2009-12-01

    Full Text Available Donatella Marazziti, Stefano Baroni, Irene Masala, Francesca Golia, Giorgio Consoli, Gabriele Massimetti, Michela Picchetti, Mario Catena Dell’Osso, Gino Giannaccini, Laura Betti, Antonio Lucacchini, Antonio CiapparelliDipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, ItalyAbstract: The present study explored the possible relationships between impulsivity, gender, and a peripheral serotonergic marker, the platelet serotonin (5-HT transporter (SERT, in a group of 32 healthy subjects. The impulsivity was measured by means of the Barratt Impulsivity Scale, version 11 (BIS-11, a widely used self-report questionnaire, and the platelet SERT was evaluated by means of the specific binding of 3H-paroxetine (3H-Par to platelet membranes, according to standardized protocols. The results showed that women had a higher BIS-11 total score than men, and also higher scores of two factors of the same scale: the motor impulsivity and the cognitive complexity. The analysis of the correlations revealed that the density of the SERT proteins, as measured by the maximum binding capacity (Bmax of 3H-Par, was significantly and positively related to the cognitive complexity factor, but only in men. Men showed also a significant and negative correlation with the dissociation constant, Kd, of (3H-Par binding, and the motor impulsivity factor. These findings suggest that women are generally more impulsive than men, but that the 5-HT system is more involved in the impulsivity of men than in that of women.Keywords: impulsivity, gender, serotonin transporter, Barratt Impulsivity Scale, platelets, 3H-paroxetine

  10. Optimization (Central Composite Design and Validation of HPLC Method for Investigation of Emtricitabine Loaded Poly(lactic-co-glycolic acid Nanoparticles: In Vitro Drug Release and In Vivo Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    Gurinder Singh

    2014-01-01

    Full Text Available The objective of the current study is to develop nanoparticles (NPs drug delivery system of emtricitabine solely using poly(lactic-co-glycolic acid (PLGA and evaluate its in vitro and in vivo release performance by systematically optimized HPLC method using Formulation by Design (FbD. NPs were evaluated for in vitro release and in vivo absorption study. The desired chromatographic separation was achieved on a Phenomenex C18 (250 mm × 4.6 mm I.D., 5 μm column, under isocratic conditions using UV detection at 280 nm. The optimized mobile phase consisted of a mixture of 40 mM phosphate dihydrogen phosphate buffer (pH 6.8, methanol, and 2% acetonitrile in a ratio of (83 : 15 : 2, v/v/v at a flow rate of 1 mL/min. The linear regression analysis for the calibration curves showed a good linear correlation over the concentration range 0.040–2.0 μg/mL, with retention time of 4.39 min. An average encapsulation efficiency of 74.34% was obtained for NPs. In vitro studies showed zero-order release and about 95% drug being released within 15 days in PBS (pH 7.4. In conclusion, the proposed optimized method was successfully applied for the determination of in vitro and in vivo release studies of emtricitabine NPs.

  11. Selective serotonin reuptake inhibitors potentiate the rapid antidepressant-like effects of serotonin4 receptor agonists in the rat.

    Directory of Open Access Journals (Sweden)

    Guillaume Lucas

    Full Text Available BACKGROUND: We have recently reported that serotonin(4 (5-HT(4 receptor agonists have a promising potential as fast-acting antidepressants. Here, we assess the extent to which this property may be optimized by the concomitant use of conventional antidepressants. METHODOLOGY/PRINCIPAL FINDINGS: We found that, in acute conditions, the 5-HT(4 agonist prucalopride was able to counteract the inhibitory effect of the selective serotonin reuptake inhibitors (SSRI fluvoxamine and citalopram on 5-HT neuron impulse flow, in Dorsal Raphé Nucleus (DRN cells selected for their high (>1.8 Hz basal discharge. The co-administration of both prucalopride and RS 67333 with citalopram for 3 days elicited an enhancement of DRN 5-HT neuron average firing rate, very similar to what was observed with either 5-HT(4 agonist alone. At the postsynaptic level, this translated into the manifestation of a tonus on hippocampal postsynaptic 5-HT(1A receptors, that was two to three times stronger when the 5-HT(4 agonist was combined with citalopram. Similarly, co-administration of citalopram synergistically potentiated the enhancing effect of RS 67333 on CREB protein phosphorylation within the hippocampus. Finally, in the Forced Swimming Test, the combination of RS 67333 with various SSRIs (fluvoxamine, citalopram and fluoxetine was more effective to reduce time of immobility than the separate administration of each compound. CONCLUSIONS/SIGNIFICANCE: These findings strongly suggest that the adjunction of an SSRI to a 5-HT(4 agonist may help to optimize the fast-acting antidepressant efficacy of the latter.

  12. Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate

    DEFF Research Database (Denmark)

    Hertel, Niels; Stoltenberg, Meredin; Juul, A;

    1993-01-01

    Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s...

  13. Validation of infrared thermography in serotonin-induced itch model in rats

    DEFF Research Database (Denmark)

    Dagnæs-Hansen, Frederik; Jasemian, Yousef; Gazerani, Parisa

    The number of scratching bouts is generally used as a standard method in animal models of itch. The aim of the present study was to validate the application of infrared thermography (IR-Th) in a serotonin-induced itch model in rats. Adult Sprague-Dawley male rats (n = 24) were used in 3 consecutive...... experiments. The first experiment evaluated vasomotor response (IR-Th) and scratching behavior (number of bouts) induced by intradermal serotonin (10 μl, 2%). Isotonic saline (control: 10 μl, 0.9%) and Methysergide (antagonist: 10 μl, 0.047 mg/ml) were used. The second experiment evaluated the dose......-response effect of intradermal serotonin (1%, 2% and 4%) on local temperature. The third experiment evaluated the anesthetized rats to test the local vasomotor responses in absent of scratching. Serotonin elicited significant scratching and lowered the local temperature at the site of injection. A dose...

  14. In utero exposure to selective serotonin reuptake inhibitors and risk for autism spectrum disorder

    DEFF Research Database (Denmark)

    Gidaya, Nicole B; Lee, Brian K; Burstyn, Igor;

    2014-01-01

    We investigated whether there is an association between increased risk for autism spectrum disorders (ASD) and selective serotonin reuptake inhibitors (SSRIs) used during pregnancy. This study used Denmark's health and population registers to obtain information regarding prescription drugs, ASD d...

  15. Genetic polymorphism of serotonin transporter 5-HTTLPR: involvement in smoking behaviour

    Indian Academy of Sciences (India)

    Maria Angelica Ehara Watanabe; Sandra Odebrechet Vargas Nunes; Marla Karine Amarante; Roberta Losi Guembarovski; Julie Massayo Maeda Oda; Kalil William Alves De Lima; Maria Helena Pelegrinelli Fungaro

    2011-04-01

    Data suggest that the serotonin (5-hydroxytryptamine, 5-HT) system is implicated in the pathogenesis of multiple neuropsychiatric disorders and may also be involved in smoking behaviour since nicotine increases brain serotonin secretion. It is known that smoking behaviour is influenced by both genetic and environmental factors. The present review examines the role of the serotonin transporter gene (5-HTT) in smoking behaviour and investigating studies that showed association of 5-HTT gene with smoking. This study discusses a polymorphism which has been investigated by many researchers, as the bi-allelic insertion/deletion polymorphism in the 5′-flanking promoter region (5-HTTLPR). This gene has received considerable attention in attempts to understand the molecular determinants of smoking. Therefore, in the present study, the relationship between genetic polymorphism of serotonin transporter in smoking behaviour is reviewed considering the interactive effect of genetic factors.

  16. Tryptophan-free diet: a new means for rapidly decreasing brain tryptophan content and serotonin synthesis.

    Science.gov (United States)

    Gessa, G L; Biggio, G; Fadda, F; Corsini, G U; Tagliamonte, A

    1975-01-01

    Changes in the synthesis rate of brain serotonin are positively correlated with changes in the concentration of brain tryptophan, indicating that the concentration of tryptophan in the whole brain reflects that at sites of serotonin synthesis. In turn, the concentration of brain tryptophan is positively correlated with that of free serum tryptophan (tryptophan is the only amino acid bound to serum proteins) and negatively to that of other amino acids competing with tryptophan for the same transport from blood to brain. Consistently, experiments in rats have shown that treatments which increase free tryptophan in serum (in respect to competing amino acids) also increase brain tryptophan and serotonin turnover. Conversely, the ingestion of diets containing all amino acids except tryptophan cause a dramatic fall in free serum tryptophan and a parallel decline in brain tryptophan and serotonin synthesis. In man the administration of an amino acid mixture lacking trytophan produces a marked depletion in serum tryptophan concentration.

  17. Selective Serotonin Reuptake Inhibitors Affect Neurobehavioral Development in the Human Fetus

    NARCIS (Netherlands)

    Mulder, Eduard J. H.; Ververs, Frederique F. T.; de Heus, Roel; Visser, Gerard H. A.

    2011-01-01

    The aim of this prospective study was to investigate whether selective serotonin reuptake inhibitors (SSRIs) utilized by pregnant women influence fetal neurobehavioral development. In this observational study we investigated developmental milestones of fetal behavior during the pregnancy of women wi

  18. Improved cognitive flexibility in serotonin transporter knockout rats is unchanged following chronic cocaine self-administration

    NARCIS (Netherlands)

    Nonkes, L.J.; Maes, J.H.R.; Homberg, J.R.

    2013-01-01

    Cocaine dependence is associated with orbitofrontal cortex (OFC)-dependent cognitive inflexibility in both humans and laboratory animals. A critical question is whether cocaine self-administration affects pre-existing individual differences in cognitive flexibility. Serotonin transporter knockout (5

  19. The role of mesenchymal stem cells and serotonin in the development of experimental pancreatitis.

    Science.gov (United States)

    Lazebnic, L B; Lychkova, A E; Knyazev, O V

    2013-08-01

    Pancreatitis was modeled before and after preliminary transplantation of stem cells and serotonin. It was demonstrated that transplantation of mesenchymal stem cells and activation of serotoninergic system prevent the development of pancreatitis. PMID:24143388

  20. From the selective serotonin transporter inhibitor citalopram to the selective norepinephrine transporter inhibitor talopram

    DEFF Research Database (Denmark)

    Eildal, Jonas Nii Nortey; Andersen, Jacob; Kristensen, Anders Skov;

    2008-01-01

    Citalopram and talopram are structurally closely related, but they have very distinct pharmacological profiles as selective inhibitors of the serotonin and norepinephrine transporters, respectively. A systematic structure-activity relationship study was performed, in which each of the four...

  1. Rare Variants of the Serotonin Transporter Are Associated With Psychiatric Comorbidity in Irritable Bowel Syndrome.

    Science.gov (United States)

    Kohen, Ruth; Tracy, Julia H; Haugen, Eric; Cain, Kevin C; Jarrett, Monica E; Heitkemper, Margaret M

    2016-07-01

    Alterations in serotonin signaling are suspected in the pathophysiology of irritable bowel syndrome (IBS). By modulating the extracellular reuptake of serotonin, the serotonin transporter (SERT) acts as a key regulator of the bioavailability of serotonin. This study is the first to investigate the impact of rare SERT variants (i.e., those with a minor allele frequency of gastrointestinal (GI) symptom level, response to cognitive-behavioral treatment, and psychiatric comorbidity. We sequenced a 0.19 megabase chromosomal stretch containing the SERT gene and surrounding regions in a community sample of 304 IBS patients and 83 controls. We found no significant associations between rare variants in and around the SERT gene and IBS risk, GI symptom profile, or response to treatment. We found preliminary evidence, however, that IBS subjects with a history of either depression or anxiety were significantly more likely to carry multiple rare likely functional variant alleles than IBS patients without psychiatric comorbidity. PMID:26912503

  2. Experiment and Demonstration of Application Effects of Slow -release Fertilizer on Summer Corn in Central Region of Shandong%高效缓释肥在鲁中夏玉米上的应用效果试验示范

    Institute of Scientific and Technical Information of China (English)

    郭跃升; 马荣辉; 高瑞杰; 邢晓飞; 王健; 严芳; 王桂香; 马文丽

    2015-01-01

    The effects of slow -release fertilizer on the agronomic characters,yield and nitrogen utiliza-tion under synchronized seeding and fertilization were studied by the field experiment.The results showed that the corn agronomic characteristics were effectively improved by application of slow -release fertilizer,single basal application could solve the problem of fertilizer shortage at the late growth stage of corn.The summer corn yields under the slow -release fertilizer treatment and 90% slow -release fertilizer treatment had no sig-nificant difference,but both were significantly higher than the yield under conventional fertilizer treatment. The yield under 90% slow -release fertilizer treatment was the highest,that of two experiment sites reached 688.3 kg and 711.0 kg per 666.7m2 .The nitrogen utilization of slow -release fertilizer treatment was signifi-cantly higher than the formula fertilizer and conventional fertilization.The nitrogen utilization under 90% slow-release fertilizer was the highest,which was higher than conventional fertilization by 11.25,15.68 percent point and 14.42,21.01 percent point respectively.The results indicated that the treatment of 90% slow -re-lease fertilizer had significant effect on decreasing cost and increasing benefit.%通过大田试验示范研究了缓释肥在玉米种肥同播条件下对玉米农艺性状、产量及氮肥利用率的影响。结果表明:施用缓释肥能有效改善玉米各农艺性状,一次性施用不会造成玉米生长后期脱肥;对比各处理玉米产量,全量缓控释肥和90%缓释肥两处理差异不显著,极显著高于习惯施肥处理,90%缓释肥处理玉米产量最高,两处试验点666.7m2产量分别为688.3 kg 和711.0 kg;全量缓释肥处理的氮肥利用率明显高于普通配方肥和习惯施肥,其中,以90%缓释肥处理氮肥利用率最高,比普通配方肥提高11.25个和15.68个百分点,分别比习惯施肥提高14.42

  3. Efficacy of serotonin in lessening radiation damage to mouse embryo depending on time of its administration following radiation exposure

    International Nuclear Information System (INIS)

    Our earlier studies demonstrated that serotonin lessons radiation damage to an 8-day mouse embryo. Moreover, this biogenic amine was equally effective when administered before and after intrauterine exposure of the embryo to ionizing radiation. The radiotherapeutic effect of serotonin was manifested by disorders in the embryo growth of various intensity, within the range of the studied radiation doses (1.31, 1.74, and 2.18 Gy). The therapeutic effect of serotonin in the embryos exposed to various doses of radiation depended on the amount of serotonin administered. The effective doses of this substance were determined by the severity of the damage inflicted. In this series of experiments, serotonin was administered immediately after exposure to ionizing radiation. The object of the present study was to determine whether or not the radiotherapeutic effect of serotonin depends on the time that elapses between the end of radiation exposure and the administration of serotonin to pregnant mice. It was established that serotonin produces a radiotherapeutic effect during 24 h following the intrauterine exposure of the fetus to ionizing radiation on the 8th day of gestation. The best therapeutic effect is attained with the administration of serotonin immediately after radiation exposure. The effect is slightly lower is serotonin is administered within 5 or 24 h following radiation exposure

  4. Highly sensitive isotope-dilution liquid-chromatography-electrospray ionization-tandem-mass spectrometry approach to study the drug-mediated modulation of dopamine and serotonin levels in Caenorhabditis elegans.

    Science.gov (United States)

    Schumacher, Fabian; Chakraborty, Sudipta; Kleuser, Burkhard; Gulbins, Erich; Schwerdtle, Tanja; Aschner, Michael; Bornhorst, Julia

    2015-11-01

    Dopamine (DA) and serotonin (SRT) are monoamine neurotransmitters that play a key role in regulating the central and peripheral nervous system. Their impaired metabolism has been implicated in several neurological disorders, such as Parkinson's disease and depression. Consequently, it is imperative to monitor changes in levels of these low-abundant neurotransmitters and their role in mediating disease. For the first time, a rapid, specific and sensitive isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of DA and SRT in the nematode Caenorhabditis elegans (C. elegans). This model organism offers a unique approach for studying the effect of various drugs and environmental conditions on neurotransmitter levels, given by the conserved DA and SRT biology, including synaptic release, trafficking and formation. We introduce a novel sample preparation protocol incorporating the usage of sodium thiosulfate in perchloric acid as extraction medium that assures high recovery of the relatively unstable neurotransmitters monitored. Moreover, the use of both deuterated internal standards and the multiple reaction monitoring (MRM) technique allows for unequivocal quantification. Thereby, to the best of our knowledge, we achieve a detection sensitivity that clearly exceeds those of published DA and SRT quantification methods in various matrices. We are the first to show that exposure of C. elegans to the monoamine oxidase B (MAO-B) inhibitor selegiline or the catechol-O-methyltransferase (COMT) inhibitor tolcapone, in order to block DA and SRT degradation, resulted in accumulation of the respective neurotransmitter. Assessment of a behavioral output of the dopaminergic system (basal slowing response) corroborated the analytical LC-MS/MS data. Thus, utilization of the C. elegans model system in conjunction with our analytical method is well-suited to investigate drug-mediated modulation of the DA and

  5. Prediction of Long-Term Treatment Response to Selective Serotonin Reuptake Inhibitors (SSRIs Using Scalp and Source Loudness Dependence of Auditory Evoked Potentials (LDAEP Analysis in Patients with Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Bun-Hee Lee

    2015-03-01

    Full Text Available Background: Animal and clinical studies have demonstrated that the loudness dependence of auditory evoked potentials (LDAEP is inversely related to central serotonergic activity, with a high LDAEP reflecting weak serotonergic neurotransmission and vice versa, though the findings in humans have been less consistent. In addition, a high pretreatment LDAEP appears to predict a favorable response to antidepressant treatments that augment the actions of serotonin. The aim of this study was to test whether the baseline LDAEP is correlated with response to long-term maintenance treatment in patients with major depressive disorder (MDD. Methods: Scalp N1, P2 and N1/P2 LDAEP and standardized low resolution brain electromagnetic tomography-localized N1, P2, and N1/P2 LDAEP were evaluated in 41 MDD patients before and after they received antidepressant treatment (escitalopram (n = 32, 10.0 ± 4.0 mg/day, sertraline (n = 7, 78.6 ± 26.7 mg/day, and paroxetine controlled-release formulation (n = 2, 18.8 ± 8.8 mg/day for more than 12 weeks. A treatment response was defined as a reduction in the Beck Depression Inventory (BDI score of >50% between baseline and follow-up. Results: The responders had higher baseline scalp P2 and N1/P2 LDAEP than nonresponders (p = 0.017; p = 0.036. In addition, changes in total BDI score between baseline and follow-up were larger in subjects with a high baseline N1/P2 LDAEP than those with a low baseline N1/P2 LDAEP (p = 0.009. There were significantly more responders in the high-LDAEP group than in the low-LDAEP group (p = 0.041. Conclusions: The findings of this study reveal that a high baseline LDAEP is associated with a clinical response to long-term antidepressant treatment.

  6. Elevated Serotonin 1A Binding in Remitted Major Depressive Disorder: Evidence for a Trait Biological Abnormality

    OpenAIRE

    Miller, Jeffrey M.; Brennan, Kathleen G.; R. Todd Ogden; Oquendo, Maria A.; Sullivan, Gregory M.; John Mann, J; Parsey, Ramin V.

    2009-01-01

    Background Several biological abnormalities in major depressive disorder (MDD) persist during episode remission, including altered serotonin neurotransmission, and may reflect underlying pathophysiology. We previously described elevated brain serotonin 1A (5-HT1A) receptor binding in antidepressant-naïve subjects with MDD within a major depressive episode (MDE) compared to healthy controls using positron emission tomography (PET). In the current study, we measured 5-HT1A receptor binding in u...

  7. Reduced Forebrain Serotonin Transmission is Causally Involved in the Development of Compulsive Cocaine Seeking in Rats

    OpenAIRE

    Pelloux, Yann; Dilleen, Ruth; Economidou, Daina; Theobald, David; Everitt, Barry J.

    2012-01-01

    Whereas the majority of cocaine users quit as they experience the negative consequences of drug use, some lose control over their drug taking and compulsively seek drugs. We report that 20% of rats compulsively seek cocaine despite intermittent negative outcomes after escalating their cocaine self-administration. This compulsive subgroup showed marked reductions in forebrain serotonin utilization; increasing serotonin transmission reduced their compulsive cocaine seeking. Depleting forebrain ...

  8. Serotonin promotes acinar dedifferentiation following pancreatitis-induced regeneration in the adult pancreas.

    Science.gov (United States)

    Saponara, Enrica; Grabliauskaite, Kamile; Bombardo, Marta; Buzzi, Raphael; Silva, Alberto B; Malagola, Ermanno; Tian, Yinghua; Hehl, Adrian B; Schraner, Elisabeth M; Seleznik, Gitta M; Zabel, Anja; Reding, Theresia; Sonda, Sabrina; Graf, Rolf

    2015-12-01

    The exocrine pancreas exhibits a distinctive capacity for tissue regeneration and renewal following injury. This regenerative ability has important implications for a variety of disorders, including pancreatitis and pancreatic cancer, diseases associated with high morbidity and mortality. Thus, understanding its underlying mechanisms may help in developing therapeutic interventions. Serotonin has been recognized as a potent mitogen for a variety of cells and tissues. Here we investigated whether serotonin exerts a mitogenic effect in pancreatic acinar cells in three regenerative models, inflammatory tissue injury following pancreatitis, tissue loss following partial pancreatectomy, and thyroid hormone-stimulated acinar proliferation. Genetic and pharmacological techniques were used to modulate serotonin levels in vivo. Acinar dedifferentiation and cell cycle progression during the regenerative phase were investigated over the course of 2 weeks. By comparing acinar proliferation in the different murine models of regeneration, we found that serotonin did not affect the clonal regeneration of mature acinar cells. Serotonin was, however, required for acinar dedifferentiation following inflammation-mediated tissue injury. Specifically, lack of serotonin resulted in delayed up-regulation of progenitor genes and delayed the formation of acinar-to-ductal metaplasia and defective acinar cell proliferation. We identified serotonin-dependent acinar secretion as a key step in progenitor-based regeneration, as it promoted acinar cell dedifferentiation and the recruitment of type 2 macrophages. Finally, we identified a regulatory Hes1-Ptfa axis in the uninjured adult pancreas, activated by zymogen secretion. Our findings indicated that serotonin plays a critical role in the regeneration of the adult pancreas following pancreatitis by promoting the dedifferentiation of acinar cells.

  9. Effects of fentanyl on serotonin syndrome-like behaviors in rats.

    Science.gov (United States)

    Kitamura, Sonoe; Kawano, Takashi; Kaminaga, Satomi; Yamanaka, Daiki; Tateiwa, Hiroki; Locatelli, Fabricio M; Yokoyama, Masataka

    2016-02-01

    Emerging evidence from case reports suggests that fentanyl may precipitate potentially life-threatening serotonin syndrome in patients taking serotonergic drugs. However, the underlying mechanism of the association between serotonin syndrome and fentanyl remains under investigation. We therefore investigated the pharmacological effects of an analgesic dose of fentanyl (0.2 mg/kg) injected subcutaneously (s.c.) on serotonergic toxicity-like responses in rats. Rats were s.c. injected with 0.75 mg/kg 8-OH-DPAT, a full 5-HT1A agonist, as an animal model of serotonin syndrome. The 8-OH-DPAT-treated rats showed well-characterized serotonin syndrome-like behaviors (low body posture, forepaw treading), hyperlocomotion, and decreased body temperature. Rats injected s.c. with fentanyl alone showed no significant changes in any of the parameters measured, while concomitant administration of fentanyl + 8-OH-DPAT resulted in exaggerated 8-OH-DPAT-induced serototoxic responses. A separate dose-response experiment showed that the serototoxic effect of fentanyl was dose-dependent. Pretreatment with naloxone [2.0 mg/kg, intraperitoneal (i.p.) injection], an opioid receptor antagonist, failed to antagonize the fentanyl-induced exaggerated serotonin syndrome-like behaviors. In contrast, pretreatment with WAY-100653, a serotonin 5-HT1A receptor antagonist (0.5 mg/kg, i.p. injection) completely inhibited all responses. Our findings provide preclinical proof-of-concept that an analgesic dose of fentanyl enhances serotonin toxicity, likely via its serotonin-reuptake inhibitory activity, independently of interaction with the opioid receptors.

  10. Mice Genetically Depleted of Brain Serotonin do not Display a Depression-like Behavioral Phenotype

    OpenAIRE

    Angoa-Pérez, Mariana; Kane, Michael J.; Briggs, Denise I.; Herrera-Mundo, Nieves; Sykes, Catherine E.; Francescutti, Dina M.; Kuhn, Donald M

    2014-01-01

    Reductions in function within the serotonin (5HT) neuronal system have long been proposed as etiological factors in depression. Serotonin selective reuptake inhibitors (SSRIs) are the most common treatment for depression and their therapeutic effect is generally attributed to their ability to increase the synaptic levels of 5HT. Tryptophan hydroxylase 2 (TPH2) is the initial and rate-limiting enzyme in the biosynthetic pathway of 5HT in the CNS and losses in its catalytic activity lead to red...

  11. Dramatically decreased cocaine self-administration in dopamine but not serotonin transporter knockout mice

    OpenAIRE

    Thomsen, Morgane; Hall, F. Scott; Uhl, George R.; Caine, S. Barak

    2009-01-01

    There has been much interest in the relative importance of dopamine and serotonin transporters in the abuse-related-effects of cocaine. We tested the hypotheses that mice lacking the dopamine transporter (DAT−/−), the serotonin transporter (SERT−/−), or both (DAT−/−SERT−/−) exhibit decreased reinforcing effects of cocaine. We also assessed whether observed effects on self-administration are specific to cocaine or if operant behavior maintained by food or a direct dopamine agonist are similarl...

  12. Revisiting the serotonin-aggression relation in humans: a meta-analysis.

    Science.gov (United States)

    Duke, Aaron A; Bègue, Laurent; Bell, Rob; Eisenlohr-Moul, Tory

    2013-09-01

    The inverse relation between serotonin and human aggression is often portrayed as "reliable," "strong," and "well established" despite decades of conflicting reports and widely recognized methodological limitations. In this systematic review and meta-analysis, we evaluate the evidence for and against the serotonin deficiency hypothesis of human aggression across 4 methods of assessing serotonin: (a) cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (CSF 5-HIAA), (b) acute tryptophan depletion, (c) pharmacological challenge, and (d) endocrine challenge. Results across 175 independent samples and over 6,500 total participants were heterogeneous, but, in aggregate, revealed a small, inverse correlation between serotonin functioning and aggression, anger, and hostility (r = -.12). Pharmacological challenge studies had the largest mean weighted effect size (r = -.21), and CSF 5-HIAA studies had the smallest (r = -.06). Potential methodological and demographic moderators largely failed to account for variability in study outcomes. Notable exceptions included year of publication (effect sizes tended to diminish with time) and self- versus other-reported aggression (other-reported aggression was positively correlated to serotonin functioning). We discuss 4 possible explanations for the pattern of findings: unreliable measures, ambient correlational noise, an unidentified higher order interaction, and a selective serotonergic effect. Finally, we provide 4 recommendations for bringing much needed clarity to this important area of research: acknowledge contradictory findings and avoid selective reporting practices; focus on improving the reliability and validity of serotonin and aggression measures; test for interactions involving personality and/or environmental moderators; and revise the serotonin deficiency hypothesis to account for serotonin's functional complexity. PMID:23379963

  13. Serotonin promotes acinar dedifferentiation following pancreatitis-induced regeneration in the adult pancreas.

    Science.gov (United States)

    Saponara, Enrica; Grabliauskaite, Kamile; Bombardo, Marta; Buzzi, Raphael; Silva, Alberto B; Malagola, Ermanno; Tian, Yinghua; Hehl, Adrian B; Schraner, Elisabeth M; Seleznik, Gitta M; Zabel, Anja; Reding, Theresia; Sonda, Sabrina; Graf, Rolf

    2015-12-01

    The exocrine pancreas exhibits a distinctive capacity for tissue regeneration and renewal following injury. This regenerative ability has important implications for a variety of disorders, including pancreatitis and pancreatic cancer, diseases associated with high morbidity and mortality. Thus, understanding its underlying mechanisms may help in developing therapeutic interventions. Serotonin has been recognized as a potent mitogen for a variety of cells and tissues. Here we investigated whether serotonin exerts a mitogenic effect in pancreatic acinar cells in three regenerative models, inflammatory tissue injury following pancreatitis, tissue loss following partial pancreatectomy, and thyroid hormone-stimulated acinar proliferation. Genetic and pharmacological techniques were used to modulate serotonin levels in vivo. Acinar dedifferentiation and cell cycle progression during the regenerative phase were investigated over the course of 2 weeks. By comparing acinar proliferation in the different murine models of regeneration, we found that serotonin did not affect the clonal regeneration of mature acinar cells. Serotonin was, however, required for acinar dedifferentiation following inflammation-mediated tissue injury. Specifically, lack of serotonin resulted in delayed up-regulation of progenitor genes and delayed the formation of acinar-to-ductal metaplasia and defective acinar cell proliferation. We identified serotonin-dependent acinar secretion as a key step in progenitor-based regeneration, as it promoted acinar cell dedifferentiation and the recruitment of type 2 macrophages. Finally, we identified a regulatory Hes1-Ptfa axis in the uninjured adult pancreas, activated by zymogen secretion. Our findings indicated that serotonin plays a critical role in the regeneration of the adult pancreas following pancreatitis by promoting the dedifferentiation of acinar cells. PMID:26235267

  14. Serotonin Transporter and Receptor Expression in Osteocytic MLO-Y4 Cells

    OpenAIRE

    BLIZIOTES, M.; ESHLEMAN, A.; BURT-PICHAT, B.; Zhang, X.-W.; Hashimoto, J; WIREN, K.; C. Chenu

    2006-01-01

    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. Immunohistochemistr...

  15. Effects of serotonin on the internal anal sphincter: in vivo manometric study in rats.

    OpenAIRE

    Goldberg, M; Hanani, M.; Nissan, S

    1986-01-01

    The effects of serotonin (5-hydroxytryptamine, 5-HT) on the internal anal sphincter were studied in anaesthesized rats. Serotonin induced a dose dependent relaxation of the internal anal sphincter. Methysergide blocked this relaxation, but did not affect the rectoanal reflex. Methysergide did not antagonise the actions of cholinergic and adrenergic agonists on the internal anal sphincter. Other 5-HT antagonists such as cyproheptadine, ketanserin, chlorpromazine, amitriptyline and ergotamine f...

  16. The serotonin reuptake inhibitor citalopram suppresses activity in the neonatal rat barrel cortex in vivo.

    Science.gov (United States)

    Akhmetshina, Dinara; Zakharov, Andrei; Vinokurova, Daria; Nasretdinov, Azat; Valeeva, Guzel; Khazipov, Roustem

    2016-06-01

    Inhibition of serotonin uptake, which causes an increase in extracellular serotonin levels, disrupts the development of thalamocortical barrel maps in neonatal rodents. Previous in vitro studies have suggested that the disruptive effect of excessive serotonin on barrel map formation involves a depression at thalamocortical synapses. However, the effects of serotonin uptake inhibitors on the early thalamocortical activity patterns in the developing barrel cortex in vivo remain largely unknown. Here, using extracellular recordings of the local field potentials and multiple unit activity (MUA) we explored the effects of the selective serotonin reuptake inhibitor (SSRI) citalopram (10-20mg/kg, intraperitoneally) on sensory evoked activity in the barrel cortex of neonatal (postnatal days P2-5) rats in vivo. We show that administration of citalopram suppresses the amplitude and prolongs the delay of the sensory evoked potentials, reduces the power and frequency of the early gamma oscillations, and suppresses sensory evoked and spontaneous neuronal firing. In the adolescent P21-29 animals, citalopram affected neither sensory evoked nor spontaneous activity in barrel cortex. We suggest that suppression of the early thalamocortical activity patterns contributes to the disruption of the barrel map development caused by SSRIs and other conditions elevating extracellular serotonin levels. PMID:27016034

  17. Lack of Association between the Serotonin Transporter (5-HTT) and Serotonin Receptor (5-HT2A) Gene Polymorphisms with Smoking Behavior among Malaysian Malays

    OpenAIRE

    Rozak, Nur Iwani A; Ahmad, Imran; Gan, Siew Hua; Abu Bakar, Ruzilawati

    2014-01-01

    Abstract An insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) and a polymorphism (rs6313) in the serotonin 2A receptor gene (5-HT2A) have previously been linked to smoking behavior. The objective of this study was to determine the possible association of the 5-HTTLPR and 5-HT2A gene polymorphisms with smoking behavior within a population of Malaysian male smokers (n=248) and non-smokers (n=248). The 5-HTTLPR genotypes were determined using the...

  18. Novel Azido-Iodo Photoaffinity Ligands for the Human Serotonin Transporter Based on the Selective Serotonin Reuptake Inhibitor (S)-Citalopram

    OpenAIRE

    Kumar, Vivek; Yarravarapu, Nageswari; Lapinsky, David J.; Perley, Danielle; Felts, Bruce; Tomlinson, Michael J.; Vaughan, Roxanne A.; Henry, L. Keith; Lever, John R.; Newman, Amy Hauck

    2015-01-01

    Three photoaffinity ligands (PALs) for the human serotonin transporter (hSERT) were synthesized based on the selective serotonin reuptake inhibitor (SSRI), (S)-citalopram (1). The classic 4-azido-3-iodo-phenyl group was appended to either the C-1 or C-5 position of the parent molecule, with variable-length linkers, to generate ligands 15, 22, and 26. These ligands retained high to moderate affinity binding (K i = 24–227 nM) for hSERT, as assessed by [3H]5-HT transport inhibition. When tested ...

  19. Physical Interactions and Functional Relationships of Neuroligin 2 and Midbrain Serotonin Transporters

    Directory of Open Access Journals (Sweden)

    Ran eYe

    2016-01-01

    Full Text Available The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT modulates many key brain functions including those subserving sensation, emotion, reward and cognition. Efficient clearance of 5-HT after release is achieved by the antidepressant-sensitive 5-HT transporter (SERT, SLC6A4. To identify novel SERT regulators, we pursued a proteomic analysis of mouse midbrain SERT complexes, evaluating findings in the context of prior studies that established a SERT-linked transcriptome. Remarkably, both efforts converged on a relationship of SERT with the synaptic adhesion protein neuroligin 2 (NLGN2, a postsynaptic partner for presynaptic neurexins, and a protein well known to organize inhibitory GABAergic synapses. Western blots of midbrain reciprocal immunoprecipitations confirmed SERT/NLGN2 associations, and also extended to other NLGN2 associated proteins (e.g. -neurexin (NRXN, gephyrin. Midbrain SERT/NLGN2 interactions were found to be Ca2+-independent, supporting cis versus trans-synaptic interactions, and were absent in hippocampal preparations, consistent with interactions arising in somatodendritic compartments. Dual color in situ hybridization confirmed co-expression of Tph2 and Nlgn2 mRNA in the dorsal raphe, with immunocytochemical studies confirming SERT:NLGN2 co-localization in raphe cell bodies but not axons. Consistent with correlative mRNA expression studies, loss of NLGN2 expression in Nlgn2 null mice produced significant reductions in midbrain and hippocampal SERT expression and function. Additionally, dorsal raphe 5-HT neurons from Nlgn2 null mice exhibit reduced excitability, a loss of GABAA receptor-mediated IPSCs, and increased 5-HT1A autoreceptor sensitivity. Finally, Nlgn2 null mice display significant changes in behaviors known to be responsive to SERT and/or 5-HT receptor manipulations. We discuss our findings in relation to the possible coordination of intrinsic and extrinsic regulation afforded by somatodendritic SERT:NLGN2

  20. Physical Interactions and Functional Relationships of Neuroligin 2 and Midbrain Serotonin Transporters.

    Science.gov (United States)

    Ye, Ran; Quinlan, Meagan A; Iwamoto, Hideki; Wu, Hsiao-Huei; Green, Noah H; Jetter, Christopher S; McMahon, Douglas G; Veestra-VanderWeele, Jeremy; Levitt, Pat; Blakely, Randy D

    2015-01-01

    The neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] modulates many key brain functions including those subserving sensation, emotion, reward, and cognition. Efficient clearance of 5-HT after release is achieved by the antidepressant-sensitive 5-HT transporter (SERT, SLC6A4). To identify novel SERT regulators, we pursued a proteomic analysis of mouse midbrain SERT complexes, evaluating findings in the context of prior studies that established a SERT-linked transcriptome. Remarkably, both efforts converged on a relationship of SERT with the synaptic adhesion protein neuroligin 2 (NLGN2), a post-synaptic partner for presynaptic neurexins, and a protein well-known to organize inhibitory GABAergic synapses. Western blots of midbrain reciprocal immunoprecipitations confirmed SERT/NLGN2 associations, and also extended to other NLGN2 associated proteins [e.g., α-neurexin (NRXN), gephyrin]. Midbrain SERT/NLGN2 interactions were found to be Ca(2+)-independent, supporting cis vs. trans-synaptic interactions, and were absent in hippocampal preparations, consistent with interactions arising in somatodendritic compartments. Dual color in situ hybridization confirmed co-expression of Tph2 and Nlgn2 mRNA in the dorsal raphe, with immunocytochemical studies confirming SERT:NLGN2 co-localization in raphe cell bodies but not axons. Consistent with correlative mRNA expression studies, loss of NLGN2 expression in Nlgn2 null mice produced significant reductions in midbrain and hippocampal SERT expression and function. Additionally, dorsal raphe 5-HT neurons from Nlgn2 null mice exhibit reduced excitability, a loss of GABAA receptor-mediated IPSCs, and increased 5-HT1A autoreceptor sensitivity. Finally, Nlgn2 null mice display significant changes in behaviors known to be responsive to SERT and/or 5-HT receptor manipulations. We discuss our findings in relation to the possible coordination of intrinsic and extrinsic regulation afforded by somatodendritic SERT:NLGN2 complexes

  1. Two cases of mild serotonin toxicity via 5-hydroxytryptamine 1A receptor stimulation

    Directory of Open Access Journals (Sweden)

    Nakayama H

    2014-02-01

    Full Text Available Hiroto Nakayama,1,* Sumiyo Umeda,2,* Masashi Nibuya,3 Takeshi Terao,4 Koichi Nisijima,5 Soichiro Nomura3 1Yamaguchi Prefecture Mental Health Medical Center, Yamaguchi, Japan; 2Department of Psychiatry, NTT West Osaka Hospital, Osaka, Japan; 3Department of Psychiatry, National Defense Medical College, Saitama, Japan; 4Department of Neuropsychiatry, Oita University Faculty of Medicine, Oita, Japan; 5Department of Psychiatry, Jichi University School of Medicine, Tochigi, Japan  *These authors contributed equally to this work Abstract: We propose the possibility of 5-hydroxytryptamine (5-HT1A receptor involvement in mild serotonin toxicity. A 64-year-old woman who experienced hallucinations was treated with perospirone (8 mg/day. She also complained of depressed mood and was prescribed paroxetine (10 mg/day. She exhibited finger tremors, sweating, coarse shivering, hyperactive knee jerks, vomiting, diarrhea, tachycardia, and psychomotor agitation. After the discontinuation of paroxetine and perospirone, the symptoms disappeared. Another 81-year-old woman, who experienced delusions, was treated with perospirone (8 mg/day. Depressive symptoms appeared and paroxetine (10 mg/day was added. She exhibited tachycardia, finger tremors, anxiety, agitation, and hyperactive knee jerks. The symptoms disappeared after the cessation of paroxetine and perospirone. Recently, the effectiveness of coadministrating 5-HT1A agonistic psychotropics with selective serotonin reuptake inhibitors (SSRIs has been reported, and SSRIs with 5-HT1A agonistic activity have been newly approved in the treatment of depression. Perospirone is a serotonin–dopamine antagonist and agonistic on the 5-HT1A receptors. Animal studies have indicated that mild serotonin excess induces low body temperature through 5-HT1A, whereas severe serotonin excess induces high body temperature through 5-HT2A activation. Therefore, it could be hypothesized that mild serotonin excess induces side effects

  2. Determinação simultânea de precursores de serotonina - triptofano e 5-hidroxitriptofano - em café Simultaneous determination of serotonin precursors - tryptophan and 5-hidroxytryptophan - in coffee

    Directory of Open Access Journals (Sweden)

    Ana Carolina C. L. Martins

    2010-01-01

    Full Text Available Epidemiological studies attributed positive effects in the central nervous system (CNS to coffee. Among possible active constituents, serotonin, a neurotransmitter in the CNS, is present; but dietary sources do not cross the blood-brain barrier. Tryptophan and 5-hidroxytryptophan (5-HTP are serotonin precursors and can affect brain concentrations. An ion-pair-HPLC, post-column derivatization with o-phthalaldehyde and fluorimetric detection before and after hydrolysis with NaOH and extraction with methanol:water was developed for the simultaneous determination of these compounds. It was selective, sensitive (LOD = 0.3 and 0.2 μg/mL, precise (91.3 and 94.2% recovery for tryptophan and 5-HTP, respectively, and linear from 0.3 to 40 μg/mL for both compounds. It was applied to green and roasted arabica and robusta coffees.

  3. The Selective Serotonin Reuptake Inhibitor Paroxetine Does Not Alter Consummatory Concentration-Dependent Licking of Prototypical Taste Stimuli by Rats

    OpenAIRE

    Mathes, Clare M.; Spector, Alan C.

    2011-01-01

    Serotonin and the 5HT1A receptor are expressed in a subset of taste receptor cells, and the 5HT3 receptor is expressed on afferent fibers innervating taste buds. Exogenous administration of the selective serotonin reuptake inhibitor, paroxetine, has been shown to increase taste sensitivity to stimuli described by humans as sweet and bitter. Serotonergic agonists also decrease food and fluid intake, and it is possible that modulations of serotonin may alter taste-based hedonic responsiveness; ...

  4. Serotonin and Histamine Therapy Increases Tetanic Forces of Myoblasts, Reduces Muscle Injury, and Improves Grip Strength Performance of Dmd(mdx) Mice.

    Science.gov (United States)

    Gurel, Volkan; Lins, Jeremy; Lambert, Kristyn; Lazauski, Joan; Spaulding, James; McMichael, John

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a recessive X-linked fatal disorder caused by a mutation in the dystrophin gene. Although several therapeutic approaches have been studied, none has led to substantial long-term effects in patients. The aim of this study was to test a serotonin and histamine (S&H) combination on human skeletal myoblasts and Dmd(mdx) mice for its effects on muscle strength and injury. Normal human bioartificial muscles (BAMs) were treated, and muscle tetanic forces and muscle injury tests were performed using the MyoForce Analysis System. Dmd(mdx) mice, the murine model of DMD, were administered serotonin, histamine, or S&H combination twice daily for 6 weeks, and functional performance tests were conducted once a week. The S&H combination treatment caused significant increases in tetanic forces at all time points and concentrations tested as compared to the saline controls. Dose response of the BAMs to the treatment demonstrated a significant increase in force generation at all concentrations compared to the controls after 3 to 4 days of drug treatment. The highest 3 concentrations had a significant effect on lowering contractile-induced injury as measured by a reduction in the release of adenylate kinase. Histamine-only and S&H treatments improved grip strength of Dmd(mdx) mice, whereas serotonin-only treatment resulted in no significant improvement in muscle strength. The results of this study indicate that S&H therapy might be a promising new strategy for muscular dystrophies and that the mechanism should be further investigated. PMID:26740813

  5. In vivo Monitoring of Serotonin by Nanomaterial Functionalized Acupuncture Needle

    Science.gov (United States)

    Li, Yu-Tao; Tang, Li-Na; Ning, Yong; Shu, Qing; Liang, Feng-Xia; Wang, Hua; Zhang, Guo-Jun

    2016-06-01

    Acupuncture treatment is amazing but controversial. Up to now, the mechanism of treating diseases by acupuncture and moxibustion is still unclear, especially the occurrence of the molecular events in local acupoints. Herein, we report an extremely stable microsensor by modifying carbon nanotube (CNT) to the tip surface of acupuncture needle and applying this CNT-modified acupuncture needle for real time monitoring of serotonin (5-HT) in vivo. To stabilize CNT modification on the needle tip surface, poly(3,4-ethylenedioxythiophene)(PEDOT) was employed as glue water to stick CNT on the needle. The detection limit of the CNT-modified needle was found to be approximately 50 nM and 78 nM in the PBS and the cell medium, respectively. In addition, the needle showed good selectivity to some inflammatory mediators and some electroactive molecules. For the first time, the CNT-modified needle could be directly probed into rat body for real time monitoring of 5-HT in vivo, showing a great potential for better understanding the mechanism of acupuncture treatment.

  6. Alterations to embryonic serotonin change aggression and fearfulness.

    Science.gov (United States)

    Dennis, Rachel L; Fahey, Alan G; Cheng, Heng W

    2013-01-01

    Prenatal stress can alter the serotonin (5-HT) system in the developing and adult brain and lead to mood and behavioral disorders in children and adults. The chicken provides a unique animal model to study the effects of embryonic stressors on childhood and adolescent behavior. Manipulations to the egg can be made in the absence of confounding maternal effects from treatment. Eggs were injected with 50 μL of excess 5-HT (10 μg/egg), 8-OH-DPAT (a 5-HT1A receptor agonist; 16 μg/egg), or saline on day 0 prior to the 21 days incubation. Injections were performed at 0.5 cm below the shell. Behavior was analyzed at 9 weeks of age and again at the onset of sexual maturity (18 weeks). Hens treated with excess embryonic 5-HT exhibited significantly less aggressive behaviors at 9 weeks of age compared to both 5-HT1A agonist treated and saline hens (P early embryonic stages may create a developmental instability, causing phenotypic variations. These results showed that modification of the serotonergic system during early embryonic development alters its functions in mediating aggressive and fearful or anxious behaviors. Prenatal modification of the serotonergic system has long lived implications on both physiology and behavior, especially aggressive and fearful behaviors. PMID:23386480

  7. Gender differences in association between serotonin transporter gene polymorphism and resting-state EEG activity.

    Science.gov (United States)

    Volf, N V; Belousova, L V; Knyazev, G G; Kulikov, A V

    2015-01-22

    Human brain oscillations represent important features of information processing and are highly heritable. Gender has been observed to affect association between the 5-HTTLPR (serotonin-transporter-linked polymorphic region) polymorphism and various endophenotypes. This study aimed to investigate the effects of 5-HTTLPR on the spontaneous electroencephalography (EEG) activity in healthy male and female subjects. DNA samples extracted from buccal swabs and resting EEG recorded at 60 standard leads were collected from 210 (101 men and 109 women) volunteers. Spectral EEG power estimates and cortical sources of EEG activity were investigated. It was shown that effects of 5-HTTLPR polymorphism on electrical activity of the brain vary as a function of gender. Women with the S/L genotype had greater global EEG power compared to men with the same genotype. In men, current source density was markedly different among genotype groups in only alpha 2 and alpha 3 frequency ranges: S/S allele carriers had higher current source density estimates in the left inferior parietal lobule in comparison with the L/L group. In women, genotype difference in global power asymmetry was found in the central-temporal region. Contrasting L/L and S/L genotype carriers also yielded significant effects in the right hemisphere inferior parietal lobule and the right postcentral gyrus with L/L genotype carriers showing lower current source density estimates than S/L genotype carriers in all but gamma bands. So, in women, the effects of 5-HTTLPR polymorphism were associated with modulation of the EEG activity in a wide range of EEG frequencies. The significance of the results lies in the demonstration of gene by sex interaction with resting EEG that has implications for understanding sex-related differences in affective states, emotion and cognition. PMID:25450956

  8. The immobility produced by intermittent swim stress is not mediated by serotonin.

    Science.gov (United States)

    Christianson, John P; Rabbett, Sarah; Lyckland, Jennifer; Drugan, Robert C

    2008-05-01

    Exposure to uncontrollable stressors such as intermittent swim stress (ISS) produces a behavioral syndrome that resembles behavioral depression including immobility in a Forced Swim Test (FST) and escape learning deficits. The results of previous studies suggest that stress causes a temporary sensitization of the brain serotonin (5-HT) system that is necessary and sufficient for producing behavioral depression. If this hypothesis is true in the ISS paradigm, then enhancing or inhibiting 5-HT transmission during stress should exacerbate or block the development of behavioral depression, respectively. The selective 5-HT uptake inhibitor fluoxetine (FLX) was administered prior to ISS or confinement; 24 h later the FST was used to detect behavioral immobility. ISS, but not FLX, significantly increased immobility in the FST. The purported 5-HT uptake enhancer tianeptine (TPT) was administered in place of FLX. Again ISS increased immobility in the FST, but TPT had no effect. These results suggested that 5-HT is not a critical mediator of ISS induced behavioral depression. However, some authors have raised concern that TPT does not act directly on 5-HT. Therefore, the 5-HT synthesis inhibitor, para-chlorophenylaline (PCPA) was administered to deplete central 5-HT before stress. PCPA did not alter immobility in the FST. Finally, a sub-chronic regimen of FLX given after ISS, but before the FST, was without effect on reversing the ISS-induced immobility. Taken together, these experiments indicate that ISS produces a significant behavioral depression manifested as increased immobility but offer no support of the hypothesis that 5-HT is a critical mediator of these effects.

  9. CB-1 receptors modulate the effect of the selective serotonin reuptake inhibitor, citalopram on extracellular serotonin levels in the rat prefrontal cortex

    NARCIS (Netherlands)

    Kleijn, Jelle; Cremers, Thomas I. F. H.; Hofland, Corry M.; Westerink, Ben H. C.

    2011-01-01

    A large percentage of depressed individuals use drugs of abuse, like cannabis. This study investigates the impact of cannabis on the pharmacological effects of the antidepressant citalopram. Using microdialysis in the prefrontal cortex of rats we monitored serotonin levels before and after cannabino

  10. Seasonal Changes in Brain Serotonin Transporter Binding in Short Serotonin Transporter Linked Polymorphic Region-Allele Carriers but Not in Long-Allele Homozygotes

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Erritzoe, David; Holst, Klaus K;

    2010-01-01

    in the thalamus, whereas this association was not observed for the midbrain. Furthermore, in the putamen, an anatomic region with relatively dense serotonin innervation, we found a significant gene X daylight effect, such that there was a negative correlation between 5-HTT binding and daylight minutes in carriers...

  11. News/Press Releases

    Data.gov (United States)

    Office of Personnel Management — A press release, news release, media release, press statement is written communication directed at members of the news media for the purpose of announcing programs...

  12. Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate

    DEFF Research Database (Denmark)

    Hertel, Niels; Stoltenberg, Meredin; Juul, A;

    1993-01-01

    Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s......-PIIINP levels to height velocity in girls (r = 0.35; P <0.001 and r = 0.33; P <0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P <0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s...

  13. Assessment and management of serotonin syndrome in a simulated patient study of Australian community pharmacies

    Directory of Open Access Journals (Sweden)

    MacFarlane B

    2016-06-01

    Full Text Available Background: The incidence of serotonin syndrome is increasing due to the widening use of serotonergic drugs. Identification of serotonin syndrome is challenging as the manifestations are diverse. Misdiagnosis can lead to delay in care and inappropriate treatment. Objectives: The objectives of this study were to determine if staff of community pharmacies in Australia could identify the symptoms of serotonin syndrome in simulated patients and recommend an appropriate course of action. Methods: Agents acting on behalf of a simulated patient were trained on a patient scenario that reflected possible serotonin syndrome due to an interaction between duloxetine and recently prescribed tramadol. They entered 148 community pharmacies in Australia to ask for advice about a 60 year old male simulated patient who was ‘not feeling well’. The interaction was audio recorded and analysed for degree of access to the pharmacist, information gathered by pharmacy staff, management advice given and pharmacotherapy recommended. Results: The simulated patient’s agent was consulted by a pharmacist in 94.0% (139/148 of cases. The potential for serotonin syndrome was identified by 35.1% (52/148 of pharmacies. Other suggested causes of the simulated patient’s symptoms were viral (16.9%; 25/148 and cardiac (15.5%; 23/148. A total of 33.8% (50/148 of pharmacies recommended that the simulated patient should cease taking tramadol. This advice always came from the pharmacist. Immediate cessation of tramadol was advised by 94.2% (49/52 of pharmacists correctly identifying serotonin syndrome. The simulated patient was advised to seek urgent medical care in 14.2% (21/148 of cases and follow up with a doctor when possible in 68.2% (101/148 of cases. The majority of pharmacies (87.8%; 130/148 did not recommend non-prescription medicines. Conclusion: While not identifying the cause of the simulated patient’s symptoms in the majority of cases, community pharmacies

  14. Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter.

    Science.gov (United States)

    Cozzi, Nicholas V; Gopalakrishnan, Anupama; Anderson, Lyndsey L; Feih, Joel T; Shulgin, Alexander T; Daley, Paul F; Ruoho, Arnold E

    2009-12-01

    N,N-dimethyltryptamine (DMT) is a potent plant hallucinogen that has also been found in human tissues. When ingested, DMT and related N,N-dialkyltryptamines produce an intense hallucinogenic state. Behavioral effects are mediated through various neurochemical mechanisms including activity at sigma-1 and serotonin receptors, modification of monoamine uptake and release, and competition for metabolic enzymes. To further clarify the pharmacology of hallucinogenic tryptamines, we synthesized DMT, N-methyl-N-isopropyltryptamine (MIPT), N,N-dipropyltryptamine (DPT), and N,N-diisopropyltryptamine. We then tested the abilities of these N,N-dialkyltryptamines to inhibit [(3)H]5-HT uptake via the plasma membrane serotonin transporter (SERT) in human platelets and via the vesicle monoamine transporter (VMAT2) in Sf9 cells expressing the rat VMAT2. The tryptamines were also tested as inhibitors of [(3)H]paroxetine binding to the SERT and [(3)H]dihydrotetrabenazine binding to VMAT2. Our results show that DMT, MIPT, DPT, and DIPT inhibit [(3)H]5-HT transport at the SERT with K ( I ) values of 4.00 +/- 0.70, 8.88 +/- 4.7, 0.594 +/- 0.12, and 2.32 +/- 0.46 microM, respectively. At VMAT2, the tryptamines inhibited [(3)H]5-HT transport with K ( I ) values of 93 +/- 6.8, 20 +/- 4.3, 19 +/- 2.3, and 19 +/- 3.1 muM, respectively. On the other hand, the tryptamines were very poor inhibitors of [(3)H]paroxetine binding to SERT and of [(3)H]dihydrotetrabenazine binding to VMAT2, resulting in high binding-to-uptake ratios. High binding-to-uptake ratios support the hypothesis that the tryptamines are transporter substrates, not uptake blockers, at both SERT and VMAT2, and also indicate that there are separate substrate and inhibitor binding sites within these transporters. The transporters may allow the accumulation of tryptamines within neurons to reach relatively high levels for sigma-1 receptor activation and to function as releasable transmitters. PMID:19756361

  15. A characterization of the Manduca sexta serotonin receptors in the context of olfactory neuromodulation.

    Directory of Open Access Journals (Sweden)

    Andrew M Dacks

    Full Text Available Neuromodulation, the alteration of individual neuron response properties, has dramatic consequences for neural network function and is a phenomenon observed across all brain regions and taxa. However, the mechanisms underlying neuromodulation are made complex by the diversity of neuromodulatory receptors expressed within a neural network. In this study we begin to examine the receptor basis for serotonergic neuromodulation in the antennal lobe of Manduca sexta. To this end we cloned all four known insect serotonin receptor types from Manduca (the Ms5HTRs. We used phylogenetic analyses to classify the Ms5HTRs and to establish their relationships to other insect serotonin receptors, other insect amine receptors and the vertebrate serotonin receptors. Pharmacological assays demonstrated that each Ms5HTR was selective for serotonin over other endogenous amines and that serotonin had a similar potency at all four Ms5HTRs. The pharmacological assays also identified several agonists and antagonists of the different Ms5HTRs. Finally, we found that the Ms5HT1A receptor was expressed in a subpopulation of GABAergic local interneurons suggesting that the Ms5HTRs are likely expressed heterogeneously within the antennal lobe based on functional neuronal subtype.

  16. Chronic citalopram administration causes a sustained suppression of serotonin synthesis in the mouse forebrain.

    Directory of Open Access Journals (Sweden)

    Gerard Honig

    Full Text Available BACKGROUND: Serotonin (5-HT is a neurotransmitter with important roles in the regulation of neurobehavioral processes, particularly those regulating affect in humans. Drugs that potentiate serotonergic neurotransmission by selectively inhibiting the reuptake of serotonin (SSRIs are widely used for the treatment of psychiatric disorders. Although the regulation of serotonin synthesis may be an factor in SSRI efficacy, the effect of chronic SSRI administration on 5-HT synthesis is not well understood. Here, we describe effects of chronic administration of the SSRI citalopram (CIT on 5-HT synthesis and content in the mouse forebrain. METHODOLOGY/PRINCIPAL FINDINGS: Citalopram was administered continuously to adult male C57BL/6J mice via osmotic minipump for 2 days, 14 days or 28 days. Plasma citalopram levels were found to be within the clinical range. 5-HT synthesis was assessed using the decarboxylase inhibition method. Citalopram administration caused a suppression of 5-HT synthesis at all time points. CIT treatment also caused a reduction in forebrain 5-HIAA content. Following chronic CIT treatment, forebrain 5-HT stores were more sensitive to the depleting effects of acute decarboxylase inhibition. CONCLUSIONS/SIGNIFICANCE: Taken together, these results demonstrate that chronic citalopram administration causes a sustained suppression of serotonin synthesis in the mouse forebrain. Furthermore, our results indicate that chronic 5-HT reuptake inhibition renders 5-HT brain stores more sensitive to alterations in serotonin synthesis. These results suggest that the regulation of 5-HT synthesis warrants consideration in efforts to develop novel antidepressant strategies.

  17. Improvement of social adaptation in depression with serotonin and norepinephrine reuptake inhibitors

    Directory of Open Access Journals (Sweden)

    Mike Briley

    2010-09-01

    Full Text Available Mike Briley, Chantal MoretNeuroBiz Consulting and Communication, Castres, FranceAbstract: Depression is a disabling condition resulting in significant impairment in social functioning, involving the patient’s family, friends, work colleagues, and society at large. Although both psychologic and pharmacologic treatments generally improve many depressive symptoms, they do not always result in significant improvement in social functioning. The importance of recovery of social functioning in depressed patients is now widely appreciated, and studies are beginning to include it in evaluations of therapeutic efficacy. Among the various social adjustment evaluation rating scales, the Social Adaptation Self-Evaluation Scale, a social motivation and behavior scale, has been found to be simple to use and sensitive to change. Using this scale, the selective norepinephrine reuptake inhibitor, reboxetine, has been shown to be significantly more effective in improving social functioning than the selective serotonin reuptake inhibitor, fluoxetine. These findings are consistent with the notion that improvement in social adaptation involves functions depending primarily on noradrenergic neurotransmission. This hypothesis suggests that the serotonin and norepinephrine reuptake inhibitors, venlafaxine, duloxetine, and milnacipran, could be particularly helpful in improving social functioning. Preliminary studies with the serotonin and norepinephrine reuptake inhibitors suggest that they significantly improve social functioning. Comparative studies with selective serotonin reuptake inhibitors on the effects on social functioning should be encouraged.Keywords: Social Adaptation Self-Evaluation Scale, social functioning, depression, serotonin and norepinephrine reuptake inhibitors, noradrenergic neurotransmission

  18. Levomilnacipran extended release: first global approval.

    Science.gov (United States)

    Hair, Philip; Cameron, Fiona; Garnock-Jones, Karly P

    2013-09-01

    Pierre Fabre and Forest Laboratories are developing levomilnacipran extended release (ER) [FETZIMA™], an enantiomer of milnacipran, for the treatment of major depressive disorder (MDD). In addition, Pierre Fabre (the originator of the compound) is developing the drug to improve recovery in patients with ischaemic stroke. Levomilnacipran ER exerts its effects by selectively inhibiting the reuptake of norepinephrine and serotonin (two neurotransmitters known to play an essential role in regulating mood) without directly affecting the uptake of dopamine or other neurotransmitters. The agent is being developed as an extended-release capsule formulation for once-daily dosing. Levomilnacipran ER is approved and launched in the US for the treatment of MDD; phase III development in this indication was completed in the US and Canada. In Europe, a phase II trial for MDD was completed, and development is in progress for improving functional recovery of patients with ischaemic stroke. A completed phase II trial in the US investigated levomilnacipran ER for the treatment of fatigue associated with MDD. This article summarizes the milestones in the development of levomilnacipran ER leading to the first approval for major depressive disorder. PMID:24000002

  19. Selective serotonin reuptake inhibitors in the treatment of premature ejaculation

    Institute of Scientific and Technical Information of China (English)

    WANG Wei-fu; CHANG Le; Suks Minhas; David J Ralph

    2007-01-01

    Objective To review and assess the update studies regarding se lective serotonin reuptake inhibitors (SSRIs) in the treatment of premature ejaculation (PE) and then provide practical recommendations and possible mechanisms concerning state of the art knowledge for the use of SSRIs in alleviating PE.Data sources Using the Medline, 48 articles published from January 1st, 1996 to August 1st, 2006 concerning the use of SSRIs and their possible mechanisms in alleviating PE were found and reviewed.Study selection PE, rapid ejaculation, early ejaculation and SSRIs were employed as the keywords, and relevant articles about the use of SSRIs and their possible mechanisms in the treatment of PE were selected.Results Many kinds of SSRIs, such as fluoxetine, sertraline, paroxetine and citalopram, have widely been employed to treat PE. However, their effects are moderate and there is no a universal agreement about the kind, dose, protocol and duration. Dapoxetine, as the first prescription treatment of PE, may change this bottle-neck situation. SSRIs are suggested to be used in young men with lifelong PE, and acquired PE when etiological factors are removed but PE still exists. Phosphodiesterase 5 inhibitors (PDE5-Is) are suggested to be employed alone or combined with SSRIs when SSRIs fail to treat PE or sexual dysfunction associated with SSRIs occurs. The protocol of taking drugs on demand based on taking them daily for a suitable period is proposed to be chosen firstly. The possible mechanisms include increasing serotonergic neurotransmission and activating 5-hydroxytryptamine 2C (5-HT2C) receptors, then switching the ejaculatory threshold to a higher level, decreasing the penile sensitivity and their own effect of antidepression.Conclusion The efficacies of the current SSRIs are moderate in the treatment of PE and they have not been approved by the FDA, therefore new SSRI like dapoxetine needs to be further evaluated.

  20. Relative nutritional deficiencies associated with centrally acting monoamines

    Directory of Open Access Journals (Sweden)

    Hinz M

    2012-05-01

    Full Text Available Marty Hinz1, Alvin Stein2, Thomas Uncini31Clinical Research, NeuroResearch Clinics Inc, Cape Coral, 2Stein Orthopedic Associates, Plantation, FL, 3DBS Labs, Duluth, MN, USABackground: Two primary categories of nutritional deficiency exist. An absolute nutritional deficiency occurs when nutrient intake is not sufficient to meet the normal needs of the system, and a relative nutritional deficiency exists when nutrient intake and systemic levels of nutrients are normal, while a change occurs in the system that induces a nutrient intake requirement that cannot be supplied from diet alone. The purpose of this paper is to demonstrate that the primary component of chronic centrally acting monoamine (serotonin, dopamine, norepinephrine, and epinephrine disease is a relative nutritional deficiency induced by postsynaptic neuron damage.Materials and methods: Monoamine transporter optimization results were investigated, re-evaluated, and correlated with previous publications by the authors under the relative nutritional deficiency hypothesis. Most of those previous publications did not discuss the concept of a relative nutritional deficiency. It is the purpose of this paper to redefine the etiology expressed in these previous writings into the realm of relative nutritional deficiency, as demonstrated by monoamine transporter optimization. The novel and broad range of amino acid precursor dosing values required to address centrally acting monoamine relative nutritional deficiency properly is also discussed.Results: Four primary etiologies are described for postsynaptic neuron damage leading to a centrally acting monoamine relative nutritional deficiency, all of which require monoamine transporter optimization to define the proper amino acid dosing values of serotonin and dopamine precursors.Conclusion: Humans suffering from chronic centrally acting monoamine-related disease are not suffering from a drug deficiency; they are suffering from a relative

  1. Serotonin modulates immune function in T cells from HIV-seropositive subjects

    DEFF Research Database (Denmark)

    Eugen-Olsen, J; Afzelius, P; Andresen, L;

    1997-01-01

    We have shown earlier increased intracellular levels of cAMP in peripheral lymphocytes from HIV-seropositive subjects and that a chemically induced decrease in this level increases cell proliferation and cytotoxicity. Others have shown that serotonin indirectly decreases intracellular cAMP levels...... proliferation was most likely mediated through the serotonin 5HT1a receptor because similar results could be obtained by using DPAT, a specific activator of this receptor. Changes in the expression of 5HT1a receptors as judged by the expression of mRNA could not explain why serotonin in vitro had a stronger...... enhancing effect on cell proliferation in some HIV-seropositive individuals than in others....

  2. Serotonin syndrome due to fluoxetine and tramadol in renal impaired patient

    Directory of Open Access Journals (Sweden)

    Rajnish Raj

    2014-02-01

    Full Text Available Serotonin syndrome causes confusion or altered mental status; other symptoms include myoclonus, shivering, tremors, diaphoresis, hyperreflexia, incoordination, fever and diarrhoea. Tramadol possesses dual pharmacological effects i.e., a weak opiate agonist at mu, kappa and delta opiate receptors along with reuptake inhibition of norepinephrine and serotonin. Risk associated with tramadol increases when co-administered with serotonergic antidepressants or MAOIs (monoamine oxidase inhibitors and in renal impaired. The incidence of this syndrome is less than 1% as most of the cases remain unreported. The case highlights the fact that interaction between serotonergic agents like fluoxetine and tramadol especially in the presence of co-morbid medical illness can lead to serotonin syndrome. [Int J Basic Clin Pharmacol 2014; 3(1.000: 227-229

  3. Neuroticism and serotonin 5-HT1A receptors in healthy subjects

    DEFF Research Database (Denmark)

    Hirvonen, Jussi; Tuominen, Lauri; Någren, Kjell;

    2015-01-01

    Neuroticism is a personality trait associated with vulnerability for mood and anxiety disorders. Serotonergic mechanisms likely contribute to neuroticism. Serotonin 5-HT1A receptors are altered in mood and anxiety disorders, but whether 5-HT1A receptors are associated with neuroticism in healthy...... subjects is unclear. We measured brain serotonin 5-HT1A receptor in 34 healthy subjects in vivo using positron emission tomography (PET) and [carbonyl-(11)C]WAY-100635. Binding potential (BPP) was determined using the golden standard of kinetic compartmental modeling using arterial blood samples...... and radiometabolite determination. Personality traits were assessed using the Karolinska Scales of Personality. We found a strong negative association between serotonin 5-HT1A receptor BPP and neuroticism. That is, individuals with high neuroticism tended to have lower 5-HT1A receptor binding than individuals...

  4. The serotonin transporter undergoes constitutive internalization and is primarily sorted to late endosomes and lysosomal degradation

    DEFF Research Database (Denmark)

    Rahbek-Clemmensen, Troels; Bay, Tina; Eriksen, Jacob;

    2014-01-01

    The serotonin transporter (SERT) plays a critical role in regulating serotonin signaling by mediating reuptake of serotonin from the extracellular space. The molecular and cellular mechanisms controlling SERT levels in the membrane remain poorly understood. To study trafficking of surface resident...... SERT, two functional epitope tagged variants were generated. Fusion of a FLAG-tagged one-transmembrane segment protein Tac to the SERT N-terminus generated a transporter with an extracellular epitope suited for trafficking studies (TacSERT). Likewise, a construct with an extracellular antibody epitope...... was generated by introducing an HA-tag in the extracellular loop 2 of SERT (HA-SERT). By using TacSERT and HA-SERT in antibody-based internalization assays, we show that SERT undergoes constitutive internalization in a dynamin-dependent manner. Confocal images of constitutively internalized SERT demonstrated...

  5. Expression of hippocampal serotonin receptors 5-HT2C and 5-HT5A in a rat model of diet-induced obesity supplemented with tryptophan.

    Science.gov (United States)

    Lopez-Esparza, Sarahi; Berumen, Laura C; Padilla, Karla; Miledi, Ricardo; García-Alcocer, Guadalupe

    2015-05-01

    Food intake regulation is a complex mechanism that involves endogenous substances and central nervous system structures like hypothalamus or even hippocampus. The neurotransmitter serotonin is distinguished as food intake mediator; within its multiples receptors, the 5-HT2C type is characterized by its inhibitory appetite action but there is no information about 5-HT5A receptors involvement in obesity disease. It is also unknown if there are any changes in the receptors expression in rats hippocampus with induced obesity during development through a high energy diet (HED) supplemented with tryptophan (W). To appreciate the receptors expression pattern in the hippocampus, obesity was induced to young Sprague Dawley rats through a HED and supplemented with W. Immunocytochemical and western blot techniques were used to study the receptor distribution and quantify the protein expression. The rats with HED diet developed obesity until week 13 of treatment. The 5-HT2C receptor expression decreased in CA1, CA2, CA3 and DG of HED group; and also in CA2, CA3 and DG for HEDW group. The 5-HT5A receptor expression only decreased in DG for HED group. Variations of the two serotonin receptors subtypes support their potential role in obesity.

  6. Relevance of dorsal raphe nucleus firing in serotonin 5-HT2C receptor blockade-induced augmentation of SSRIs effects

    NARCIS (Netherlands)

    Sotty, Florence; Folgering, Joost H. A.; Brennum, Lise T.; Hogg, Sandra; Mork, Arne; Hertel, Peter; Cremers, Thomas I. F. H.

    2009-01-01

    Selective serotonin reuptake inhibitors are the most widely prescribed antidepressant drugs. However, they exhibit a slow onset of action, putatively due to the initial decrease in serotonin cell firing mediated via somato-dendritic autoreceptors. Interestingly, blockade of 5-HT2C receptors signific

  7. Transient expression of functional serotonin 5-HT3 receptors by glutamatergic granule cells in the early postnatal mouse cerebellum

    NARCIS (Netherlands)

    M. Oostland; J. Sellmeijer; J.A. van Hooft

    2011-01-01

    The serotonin 5-HT3 receptor is the only ligand-gated ion channel activated by serotonin and is expressed by GABAergic interneurons in many brain regions, including the cortex, amygdala and hippocampus. Furthermore, 5-HT3 receptors are expressed by glutamatergic Cajal-Retzius cells in the cerebral c

  8. Chemical release module facility

    Science.gov (United States)

    Reasoner, D. L.

    1980-01-01

    The chemical release module provides the capability to conduct: (1) thermite based metal vapor releases; (2) pressurized gas releases; (3) dispersed liquid releases; (4) shaped charge releases from ejected submodules; and (5) diagnostic measurements with pi supplied instruments. It also provides a basic R-F and electrical system for: (1) receiving and executing commands; (2) telemetering housekeeping data; (3) tracking; (4) monitoring housekeeping and control units; and (5) ultrasafe disarming and control monitoring.

  9. Serotonin/dopamine interactions in a hyperactive mouse: reduced serotonin receptor 1B activity reverses effects of dopamine transporter knockout.

    Directory of Open Access Journals (Sweden)

    Frank Scott Hall

    Full Text Available Knockout (KO mice that lack the dopamine transporter (SL6A3; DAT display increased locomotion that can be attenuated, under some circumstances, by administration of drugs that normally produce psychostimulant-like effects, such as amphetamine and methylphenidate. These results have led to suggestions that DAT KO mice may model features of attention deficit hyperactivity disorder (ADHD and that these drugs may act upon serotonin (5-HT systems to produce these unusual locomotor decreasing effects. Evidence from patterns of brain expression and initial pharmacologic studies led us to use genetic and pharmacologic approaches to examine the influence of altered 5-HT1B receptor activity on hyperactivity in DAT KO mice. Heterozygous 5-HT1B KO and pharmacologic 5-HT1B antagonism both attenuated locomotor hyperactivity in DAT KO mice. Furthermore, DAT KO mice with reduced, but not eliminated, 5-HT1B receptor expression regained cocaine-stimulated locomotion, which was absent in DAT KO mice with normal levels of 5-HT1B receptor expression. Further experiments demonstrated that the degree of habituation to the testing apparatus determined whether cocaine had no effect on locomotion in DAT KO or reduced locomotion, helping to resolve differences among prior reports. These findings of complementation of the locomotor effects of DAT KO by reducing 5-HT1B receptor activity underscore roles for interactions between specific 5-HT receptors and dopamine (DA systems in basal and cocaine-stimulated locomotion and support evaluation of 5-HT1B antagonists as potential, non-stimulant ADHD therapeutics.

  10. BDNF Val66met and 5-HTTLPR polymorphisms predict a human in vivo marker for brain serotonin levels

    DEFF Research Database (Denmark)

    Fisher, Patrick M; Holst, Klaus K; Adamsen, Dea;

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) has been implicated in multiple aspects of brain function including regulation of serotonin signaling. The BDNF val66met polymorphism (rs6265) has been linked to aspects of serotonin signaling in humans but its effects are not well understood. To address...... this, we evaluated whether BDNF val66met was predictive of a putative marker of brain serotonin levels, serotonin 4 receptor (5-HT4 ) binding assessed with [(11) C]SB207145 positron emission tomography, which has also been associated with the serotonin-transporter-linked polymorphic region (5-HTTLPR...... BDNF val66met significantly predicted a LV reflecting [(11) C]SB207145 binding across regions (P = 0.005). BDNF val66met met-carriers showed 2-9% higher binding relative to val/val homozygotes. In contrast, 5-HTTLPR did not predict the LV but S-carriers showed 7% lower neocortical binding relative...

  11. Meta-analysis: a functional polymorphism in the gene encoding for activity of the serotonin transporter protein is not associated with the irritable bowel syndrome.

    NARCIS (Netherlands)

    Kerkhoven, L.A.S. van; Laheij, R.J.F.; Jansen, J.B.M.J.

    2007-01-01

    BACKGROUND: Serotonin is associated with symptoms of the irritable bowel syndrome, its action is terminated by the serotonin transporter protein. AIM: To assess the association between a functional polymorphism in the gene encoding for activity of the serotonin transporter protein and the irritable

  12. A nonlinear relationship between cerebral serotonin transporter and 5-HT(2A) receptor binding: an in vivo molecular imaging study in humans

    DEFF Research Database (Denmark)

    Erritzoe, David; Holst, Klaus; Frokjaer, Vibe G.;

    2010-01-01

    Serotonergic neurotransmission is involved in the regulation of physiological functions such as mood, sleep, memory, and appetite. Within the serotonin transmitter system, both the postsynaptically located serotonin 2A (5-HT2A) receptor and the presynaptic serotonin transporter (SERT) are sensitive...

  13. Binding of the Multimodal Antidepressant Drug Vortioxetine to the Human Serotonin Transporter

    DEFF Research Database (Denmark)

    Andersen, Jacob; Ladefoged, Lucy Kate; Wang, Danyang;

    2015-01-01

    Selective inhibitors of the human serotonin transporter (hSERT) have been first-line treatment against depression for several decades. Recently, vortioxetine was approved as a new therapeutic option for the treatment of depression. Vortioxetine represents a new class of antidepressant drugs with ......-based drug discovery of novel multimodal drugs with fine-tuned selectivity across different transporter and receptor proteins in the human brain.......Selective inhibitors of the human serotonin transporter (hSERT) have been first-line treatment against depression for several decades. Recently, vortioxetine was approved as a new therapeutic option for the treatment of depression. Vortioxetine represents a new class of antidepressant drugs...

  14. Serotonin (2C) receptor regulation of cocaine-induced conditioned place preference and locomotor sensitization

    OpenAIRE

    Craige, Caryne P.; Unterwald, Ellen M.

    2012-01-01

    Previous studies have identified an inhibitory regulatory role of the 5-HT2C receptor in serotonin and dopamine neurotransmission. As cocaine is known to enhance serotonin and dopamine transmission, the ability of 5-HT2C receptors to modulate cocaine-induced behaviors was investigated. Alterations in cocaine reward behavior were assessed in the conditioned place preference (CPP) paradigm. Mice were injected with a selective 5-HT2C receptor agonist, Ro 60-0175 (0, 1, 3, 10 mg/kg, i.p.) prior t...

  15. Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease

    DEFF Research Database (Denmark)

    Marner, Lisbeth; Frøkjær, Vibe; Kalbitzer, Jan;

    2012-01-01

    In patients with Alzheimer's disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT(2A)) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT(2A) receptor...... = .0005). No change in [(11)C]DASB binding was found in the midbrain. We conclude that the prominent reduction in neocortical 5-HT(2A) receptor binding in early AD is not caused by a primary loss of serotonergic neurons or their projections....

  16. CORTICOTROPIN-RELEASING FACTOR INCREASES GABA SYNAPTIC ACTIVITY AND INDUCES INWARD CURRENT IN 5-HYDROXYTRYPTAMINE DORSAL RAPHE NEURONS

    OpenAIRE

    Kirby, Lynn G.; Freeman-Daniels, Emily; Lemos, Julia C; Nunan, John D.; Lamy, Christophe; Akanwa, Adaure; Beck, Sheryl G

    2008-01-01

    Stress-related psychiatric disorders such as anxiety and depression involve dysfunction of the serotonin (5-hydroxytryptamine; 5-HT) system. Previous studies have found that the stress neurohormone corticotropin-releasing factor (CRF) inhibits 5-HT neurons in the dorsal raphe nucleus (DRN) in vivo. The goals of the present study were to characterize the CRF receptor subtypes (CRF-R1 and R2) and cellular mechanisms underlying CRF-5-HT interactions. Visualized whole-cell patch clamp recording t...

  17. Endocannabinoids blunt the augmentation of synaptic transmission by serotonin 2A receptors in the nucleus tractus solitarii (nTS).

    Science.gov (United States)

    Austgen, James R; Kline, David D

    2013-11-01

    Serotonin (5-Hydroxytryptamine, 5-HT) and the 5-HT2 receptor modulate cardiovascular and autonomic function in part through actions in the nTS, the primary termination and integration point for cardiorespiratory afferents in the brainstem. In other brain regions, 5-HT2 receptors (5-HT2R) modify synaptic transmission directly, as well as through 5-HT2AR-induced endocannabinoid release. This study examined the role of 5-HT2AR as well as their interaction with endocannabinoids on neurotransmission in the nucleus tractus solitarii (nTS). Excitatory postsynaptic currents (EPSCs) in monosynaptic nTS neurons were recorded in the horizontal brainstem slice during activation and blockade of 5-HT2ARs. 5-HT2AR activation augmented solitary tract (TS) evoked EPSC amplitude whereas 5-HT2AR blockade depressed TS-EPSC amplitude at low and high TS stimulation rates. The 5-HT2AR-induced increase in neurotransmission was reduced by endocannabinoid receptor block and increased endogenous endocannabinoids in the synaptic cleft during high frequency, but not low, TS stimulation. Endocannabinoids did not tonically modify EPSCs. These data suggest 5-HT acting through the 5-HT2AR is an excitatory neuromodulator in the nTS and its effects are modulated by the endocannabinoid system.

  18. DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor.

    Science.gov (United States)

    Aldrin-Kirk, Patrick; Heuer, Andreas; Wang, Gang; Mattsson, Bengt; Lundblad, Martin; Parmar, Malin; Björklund, Tomas

    2016-06-01

    Transplantation of DA neurons is actively pursued as a restorative therapy in Parkinson's disease (PD). Pioneering clinical trials using transplants of fetal DA neuroblasts have given promising results, although a number of patients have developed graft-induced dyskinesias (GIDs), and the mechanism underlying this troublesome side effect is still unknown. Here we have used a new model where the activity of the transplanted DA neurons can be selectively modulated using a bimodal chemogenetic (DREADD) approach, allowing either enhancement or reduction of the therapeutic effect. We show that exclusive activation of a cAMP-linked (Gs-coupled) DREADD or serotonin 5-HT6 receptor, located on the grafted DA neurons, is sufficient to induce GIDs. These findings establish a mechanistic link between the 5-HT6 receptor, intracellular cAMP, and GIDs in transplanted PD patients. This effect is thought to be mediated through counteraction of the D2 autoreceptor feedback inhibition, resulting in a dysplastic DA release from the transplant.

  19. Serotonin antagonists fail to alter MDMA self-administration in rats.

    Science.gov (United States)

    Schenk, Susan; Foote, Jason; Aronsen, Dane; Bukholt, Natasha; Highgate, Quenten; Van de Wetering, Ross; Webster, Jeremy

    2016-09-01

    Acute exposure to ±3,4-methylenedioxymethamphetamine (MDMA) preferentially increases release of serotonin (5-HT), and a role of 5-HT in many of the behavioral effects of acute exposure to MDMA has been demonstrated. A role of 5-HT in MDMA self-administration in rats has not, however, been adequately determined. Therefore, the present study measured the effect of pharmacological manipulation of some 5-HT receptor subtypes on self-administration of MDMA. Rats received extensive experience with self-administered MDMA prior to tests with 5-HT ligands. Doses of the 5-HT1A antagonist, WAY 100635 (0.1-1.0mg/kg), 5-HT1B antagonist, GR 127935 (1.0-3.0mg/kg), and the 5-HT2A antagonist, ketanserin (1.0-3.0mg/kg) that have previously been shown to decrease self-administration of other psychostimulants and that decreased MDMA-produced hyperactivity in the present study did not alter MDMA self-administration. Experimenter-administered injections of MDMA (10.0mg/kg, ip) reinstated extinguished drug-taking behavior, but this also was not decreased by any of the antagonists. In contrast, both WAY 100635 and ketanserin, but not GR 127935, decreased cocaine-produced drug seeking in rats that had been trained to self-administered cocaine. The 5-HT1A agonist, 8-OH-DPAT (0.1-1.0mg/kg), but not the 5-HT1B/1A agonist, RU 24969 (0.3-3.0mg/kg), decreased drug-seeking produced by the reintroduction of a light stimulus that had been paired with self-administered MDMA infusions. These findings suggest a limited role of activation of 5-HT1A, 5-HT1B or 5-HT2 receptor mechanisms in MDMA self-administration or in MDMA-produced drug-seeking following extinction. The data suggest, however, that 5-HT1A agonists inhibit cue-induced drug-seeking following extinction of MDMA self-administration and might, therefore, be useful adjuncts to therapies to limit relapse to MDMA use. PMID:27264435

  20. Xenopus Vocalizations Are Controlled by a Sexually Differentiated Hindbrain Central Pattern Generator

    OpenAIRE

    Rhodes, Heather J.; Yu, Heather J.; YAMAGUCHI, ayako

    2007-01-01

    Male and female African clawed frogs (Xenopus laevis) produce rhythmic, sexually distinct vocalizations as part of courtship and mating. We found that Xenopus vocal behavior is governed by a sexually dimorphic central pattern generator (CPG) and that fictive vocalizations can be elicited from an in vitro brain preparation by application of serotonin or by electrical stimulation of a premotor nucleus. Male brains produced fictive vocal patterns representing two calls commonly produced by males...

  1. Ethanol intake and sup 3 H-serotonin uptake II: A study in alcoholic patients using platelets sup 3 H-paroxetine binding

    Energy Technology Data Exchange (ETDEWEB)

    Daoust, M.; Boucly, P. (U.F.R. de Medecine et Pharmacie, Saint Etienne du Rouvrary (France)); Ernouf, D. (Institut du Medicament, Tours (France)); Breton, P. (Centre National de Transfusion Sanguine de Rouen (France)); Lhuintre, J.P.

    1991-01-01

    The kinetic parameters of {sup 3}H-paroxetine binding and {sup 3}H-serotonin uptake were studied in platelets of alcoholic patients. There was no difference between alcoholic and non alcoholic subjects in {sup 3}H-paroxetine binding. When binding and {sup 3}H-serotonin uptake were studied, in the same plasma of the same subjects, the Vmax of serotonin uptake was increased in alcoholics. The data confirm the involvement of serotonin uptake system in alcohol dependance and suggest that serotonin uptake and paroxetine binding sites may be regulated independently in this pathology.

  2. Toxics Release Inventory (TRI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  3. Brain serotonin synthesis in adult males characterized by physical aggression during childhood: a 21-year longitudinal study.

    Directory of Open Access Journals (Sweden)

    Linda Booij

    Full Text Available BACKGROUND: Adults exhibiting severe impulsive and aggressive behaviors have multiple indices of low serotonin (5-HT neurotransmission. It remains unclear though whether low 5-HT mediates the behavior or instead reflects a pre-existing vulnerability trait. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, positron emission tomography with the tracer alpha-[(11C]methyl-L-tryptophan ((11C-AMT was used to compare 5-HT synthesis capacity in two groups of adult males from a 21-year longitudinal study (mean age +/- SD: 27.1+/-0.7: individuals with a history of childhood-limited high physical aggression (C-LHPA; N = 8 and individuals with normal (low patterns of physical aggression (LPA; N = 18. The C-LHPA males had significantly lower trapping of (11C-AMT bilaterally in the orbitofrontal cortex and self-reported more impulsiveness. Despite this, in adulthood there were no group differences in plasma tryptophan levels, genotyping, aggression, emotional intelligence, working memory, computerized measures of impulsivity, psychosocial functioning/adjustment, and personal and family history of mood and substance abuse disorders. CONCLUSIONS/SIGNIFICANCE: These results force a re-examination of the low 5-HT hypothesis as central in the biology of violence. They suggest that low 5-HT does not mediate current behavior and should be considered a vulnerability factor for impulsive-aggressive behavior that may or may not be expressed depending on other biological factors, experience, and environmental support during development.

  4. Effect of Selective Serotonin Reuptake Inhibitors and Immunomodulator on Cytokines Levels: An Alternative Therapy for Patients with Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    María Eugenia Hernandez

    2013-01-01

    Full Text Available Major depressive disorder (MDD is a psychiatric illness that presents as a deficit of serotonergic neurotransmission in the central nervous system. MDD patients also experience alterations in cortisol and cytokines levels. Treatment with selective serotonin reuptake inhibitors (SSRIs is the first-line antidepressant regimen for MDD. The aim of this study was to determine the effect of a combination of SSRIs and an immunomodulator—human dialyzable leukocyte extract (hDLE—on cortisol and cytokines levels. Patients received SSRIs or SSRIs plus hDLE. The proinflammatory cytokines IL-1β, IL-2, and IFN-γ; anti-inflammatory cytokines IL-13 and IL-10; and 24-h urine cortisol were measured at weeks (W 0, 5, 20, 36, and 52 of treatment. The reduction in cortisol levels in the SSRI-treated group was 30% until W52, in contrast, the combined treatment induced a 54% decrease at W36. The decline in cortisol in patients who were treated with SSRI plus hDLE correlated with reduction of anti-inflammatory cytokines and increases levels of proinflammatory cytokines at the study conclusion. These results suggest that the immune-stimulating activity of hDLE, in combination with SSRIs, restored the pro- and anti-inflammatory cytokine balance and cortisol levels in depressed patients versus those who were given SSRIs alone.

  5. Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users

    NARCIS (Netherlands)

    L. Reneman; T. Schilt; M.M. de Win; J. Booij; B. Schmand; W. van den Brink; O. Bakker

    2006-01-01

    Although 3,4-methytenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the tong-term consequences of MDMA-induced 5-HT neurotoxic Lesions on functions in which 5-HT is involved, such as cognitive func

  6. Recognition of Scared Faces and the Serotonin Transporter Gene in Young Children: The Generation R Study

    Science.gov (United States)

    Szekely, Eszter; Herba, Catherine M.; Arp, Pascal P.; Uitterlinden, Andre G.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; Hudziak, James J.; Tiemeier, Henning

    2011-01-01

    Background: Previous research highlights the significance of a functional polymorphism located in the promoter region (5-HTTLPR) of the serotonin transporter gene in emotional behaviour. This study examined the effect of the 5-HTTLPR polymorphism on emotion processing in a large number of healthy preschoolers. Methods: The 5-HTTLPR genotype was…

  7. Clinical Efficacy of Fluvoxamine and Functional Polymorphism in a Serotonin Transporter Gene on Childhood Autism

    Science.gov (United States)

    Sugie, Yoko; Sugie, Hideo; Fukuda,Tokiko; Ito, Masataka; Sasada, Yumiko; Nakabayashi, Mutsumi; Fukashiro, Kazunobu; Ohzeki, Takehiko

    2005-01-01

    We studied the correlation between response to fluvoxamine and serotonin transporter gene promoter region polymorphism (5-HTTLPR). Eighteen children with autistic disorder completed a 12-week double-blind, placebo-controlled, randomized crossover study of fluvoxamine. Behavioral assessments were obtained before and at 12 weeks of treatment.…

  8. SEROTONIN (5-HT) AND THE RATS EYE - SOME PILOT-STUDIES

    NARCIS (Netherlands)

    BOERRIGTER, RMM; SIERTSEMA, JV; KEMA, IP

    1992-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic amine which has a multitude of more or less clearly established effects on peripheral vessels. It influences blood viscosity, platelet aggregation, and vasoconstruction and -dilatation, it enhances capillary permeability, it is the precursor of mel

  9. Extrapyramidal syndromes associated with selective serotonin reuptake inhibitors : a case-control study using spontaneous reports

    NARCIS (Netherlands)

    Schillevoort, I; van Puijenbroek, E P; de Boer, A; Roos, R A C; Jansen, Paul A F; Leufkens, H G M

    2002-01-01

    The aim of this study was to assess whether use of selective serotonin reuptake inhibitors (SSRIs) is associated with extrapyramidal syndromes (EPS). We analysed the spontaneous reports of adverse drug reactions (ADRs) collected by The Netherlands Pharmacovigilance Foundation Lareb in the period 198

  10. Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia

    DEFF Research Database (Denmark)

    Santini, Martin A; Ratner, Cecilia Friis; Aznar, Susana;

    2013-01-01

    Prefrontal serotonin 2A receptors (5-HT2A Rs) have been linked to the pathogenesis and treatment of schizophrenia. Many antipsychotics fully occupy 5-HT2A R at clinical relevant doses, and activation of 5-HT2A receptors by lysergic acid diethylamide (LSD) and LSD-like drugs induces a schizophrenia...

  11. Effects of LSD on grooming behavior in serotonin transporter heterozygous (Sert⁺/⁻) mice.

    Science.gov (United States)

    Kyzar, Evan J; Stewart, Adam Michael; Kalueff, Allan V

    2016-01-01

    Serotonin (5-HT) plays a crucial role in the brain, modulating mood, cognition and reward. The serotonin transporter (SERT) is responsible for the reuptake of 5-HT from the synaptic cleft and regulates serotonin signaling in the brain. In humans, SERT genetic variance is linked to the pathogenesis of various psychiatric disorders, including anxiety, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Rodent self-grooming is a complex, evolutionarily conserved patterned behavior relevant to stress, ASD and OCD. Genetic ablation of mouse Sert causes various behavioral deficits, including increased anxiety and grooming behavior. The hallucinogenic drug lysergic acid diethylamide (LSD) is a potent serotonergic agonist known to modulate human and animal behavior. Here, we examined heterozygous Sert(+/-) mouse behavior following acute administration of LSD (0.32 mg/kg). Overall, Sert(+/-) mice displayed a longer duration of self-grooming behavior regardless of LSD treatment. In contrast, LSD increased serotonin-sensitive behaviors, such as head twitching, tremors and backwards gait behaviors in both Sert(+/+) and Sert(+/-) mice. There were no significant interactions between LSD treatment and Sert gene dosage in any of the behavioral domains measured. These results suggest that Sert(+/-) mice may respond to the behavioral effects of LSD in a similar manner to wild-type mice.

  12. Cerebral serotonin transporter binding is inversely related to body mass index

    DEFF Research Database (Denmark)

    Erritzoe, D; Frokjaer, V G; Haahr, M T;

    2010-01-01

    ) in animal models is inversely related to food intake and body weight and some effective anti-obesity agents involve blockade of the serotonin transporter (SERT). We investigated in 60 healthy volunteers body mass index (BMI) and regional cerebral SERT binding as measured with [(11)C]DASB PET. In a linear...

  13. The effect of selective serotonin reuptake inhibitors in healthy subjects. A systematic review

    DEFF Research Database (Denmark)

    Knorr, Ulla; Kessing, Lars Vedel

    2010-01-01

    BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) show antidepressant properties in many patients with a diagnosis of depression. An understanding of the underlying mechanisms of the effect of SSRIs in healthy patients may lead to an understanding of the yet unclear pathophysiology of d...

  14. Synthesis of Dopamine and Serotonin Derivatives for Immobilization on a Solid Support

    DEFF Research Database (Denmark)

    Funder, Erik Daa; Jensen, Anne Bjørnskov; Tørring, Thomas;

    2012-01-01

    The two important neurotransmitters dopamine and serotonin are synthesized with short PEG tethers and immobilized on a magnetic solid support. The tether is attached to the aromatic moiety of the neurotransmitters to conserve their original functional groups. This approach causes minimal alterati...

  15. Serotonin-producing pancreatic endocrine tumour. Histological, ultrastructural and immunohistochemical study of a case

    OpenAIRE

    Kanavaros, Panagiotis; Hoang, Catherine; Le Bodic, Marie Francoise; Polivka, Marc; Hautefeuille, Pierre

    1990-01-01

    Serotonin-producing pancreatic endocrine tumours are rare neoplasms which in most cases exhibit malignant biological behaviour. These tumours, in the majority of the well-documented cases, are composed of argyrophil- and argentaffin-positive cells which contain large pleomorphic neurosecretory granules. In contrast, argyrophilic non-argentaffin pancreatic endocrine tumours with tumour cells containing round neurosecretory granules are exceptional. In this study...

  16. Serotonin transporter gene polymorphisms in irritable bowel syndrome and their impact on tegaserod treatment

    Institute of Scientific and Technical Information of China (English)

    李瑜元

    2006-01-01

    Objective To investigate the serotonin reuptake transporter (SERT) genetic polymorphisms in the 5 -hydroxytryptamine (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) and the variable number tandem repeats (VNTRs) in intron 2 among Chinese people, and their relationship to the pathogenesis of irritable bowel syndrome (IBS);and to investigate the im-

  17. Síndrome serotoninérgica associada ao uso de paroxetina: relato de caso

    Directory of Open Access Journals (Sweden)

    CAVALLAZZI LUÍS OTÁVIO

    1999-01-01

    Full Text Available Relatamos um caso de síndrome serotoninérgica pelo uso de inibidor da recaptação da serotonina, a paroxetina. Tal síndrome por esta droga, sem combinações, ainda não tinha sido descrita na literatura.

  18. Lack of differential serotonin biosynthesis capacity in genetically selected low and high aggressive mice

    NARCIS (Netherlands)

    Natarajan, Deepa; de Boer, Sietse F.; Koolhaas, Jaap M.

    2009-01-01

    Reduced brain serotonin (5-HT) activity has been linked to impulsive and violent forms of aggression for decades. Despite a vast accumulation of data pertinent to the above observation, information about the possible mechanisms underlying such a decreased 5-HT functioning is virtually absent. Amongs

  19. Novel and high affinity fluorescent ligands for the serotonin transporter based on (s)-citalopram

    DEFF Research Database (Denmark)

    Kumar, Vivek; Rahbek-Clemmensen, Troels; Billesbølle, Christian B;

    2014-01-01

    Novel rhodamine-labeled ligands, based on (S)-citalopram, were synthesized and evaluated for uptake inhibition at the human serotonin, dopamine, and norepinephrine transporters (hSERT, hDAT, and hNET, respectively) and for binding at SERT, in transiently transfected COS7 cells. Compound 14 demons...

  20. Polymorphism in serotonin receptor 3B is associated with pain catastrophizing.

    Directory of Open Access Journals (Sweden)

    Emilia Horjales-Araujo

    Full Text Available Pain catastrophizing, a coping style characterized by excessively negative thoughts and emotions in relation to pain, is one of the psychological factors that most markedly predicts variability in the perception of pain; however, only little is known about the underlying neurobiology. The aim of this study was to test for associations between psychological variables, such as pain catastrophizing, anxiety and depression, and selected polymorphisms in genes related to monoaminergic neurotransmission, in particular serotonin pathway genes. Three hundred seventy-nine healthy participants completed a set of psychological questionnaires: the Pain Catastrophizing Scale (PCS, the State-Trait Anxiety Inventory and Beck's Depression Inventory, and were genotyped for 15 single nucleotide polymorphisms (SNPs in nine genes. The SNP rs1176744 located in the serotonin receptor 3B gene (5-HTR3B was found to be associated with pain catastrophizing scores: both the global score and the subscales of magnification and helplessness. This is the first study to show an association between 5-HTR3B and PCS scores, thus suggesting a role of the serotonin pathway in pain catastrophizing. Since 5-HTR3B has previously been associated with descending pain modulation pathways, future studies will be of great interest to elucidate the molecular pathways involved in the relation between serotonin, its receptors and pain catastrophizing.

  1. Emotional modulation of muscle pain is associated with polymorphisms in the serotonin transporter gene.

    Science.gov (United States)

    Horjales-Araujo, Emilia; Demontis, Ditte; Lund, Ellen Kielland; Vase, Lene; Finnerup, Nanna Brix; Børglum, Anders D; Jensen, Troels Staehelin; Svensson, Peter

    2013-08-01

    The perception of pain is determined by a combination of genetic, neurobiological, cultural, and emotional factors. Recent studies have demonstrated an association between specific genotypes and pain perception. Particular focus has been given to the triallelic polymorphism in the promoter region of the serotonin transporter gene in relation to pain perception. The aim of this study was to investigate whether the modulatory effect of emotions mediated by visual stimuli on muscular pain perception is genotype dependent. A total of 150 healthy subjects were selected on the basis of their polymorphism in the serotonin transporter gene. First, visual conditioning was performed with positive, negative, and neutral pictures from the International Affective Picture System, and the unpleasantness/pleasantness of the pictures was rated. Second, visual conditioning stimuli were presented while experimental jaw muscle pain was evoked by injection of hypertonic saline into the masseter muscle, and participants continuously rated pain intensity on an electronic visual analogue scale. The pictures induced similar changes in emotions across the 3 genotype groups, and hypertonic saline evoked moderate pain levels in all participants. However, in participants with a high expression of the serotonin transporter protein, conditioning with negative pictures increased pain intensity and positive pictures decreased pain intensity when compared with neutral pictures. In contrast, there were no significant effects of the pictures on pain perception in participants with either intermediate or low expression of the protein. These results suggest that polymorphisms in the serotonin transporter gene play an important role in emotions modulation of muscle pain.

  2. Perseverative instrumental and Pavlovian responding to conditioned stimuli in serotonin transporter knockout rats

    NARCIS (Netherlands)

    Nonkes, L.J.P.; Homberg, J.R.

    2013-01-01

    Environmental stimuli can influence behavior via the process of Pavlovian conditioning. Recent genetic research suggests that some individuals are more sensitive to environmental stimuli for behavioral guidance than others. One important mediator of this effect is serotonin transporter (5-HTT) genet

  3. Sertraline causes strong coronary vasodilation : Possible relevance for cardioprotection by selective serotonin reuptake inhibitors

    NARCIS (Netherlands)

    van Melle, JP; Buikema, H; van den Berg, MP; van Buiten, A; van Veldhuisen, DJ; Boonstra, PW; van Gilst, WH

    2004-01-01

    Objective: Although Selective Serotonin Reuptake Inhibitors (SSRIs) are important antidepressant drugs, knowledge of their vaso active effects is limited. Vaso active effects of the SSRI sertraline were studied in rings of rat aorta, human Internal Mammary Arteries (IMAs) and in Langendorff perfused

  4. Serotonin modulates immune function in T cells from HIV-seropositive subjects

    DEFF Research Database (Denmark)

    Eugen-Olsen, J; Afzelius, P; Andresen, L;

    1997-01-01

    response; e.g., these with the highest initial responses have the highest increases. An increase in IL-2 production may be a part of this mechanism since addition of serotonin to in vitro cultures of PHA-stimulated cells increases the expression of mRNA for IL-2 and IFN-gamma. The effect on lymphocyte...

  5. The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring

    NARCIS (Netherlands)

    Olivier, J D A; Akerud, H; Kaihola, H; Pawluski, J L; Skalkidou, A; Högberg, U; Sundström-Poromaa, I

    2013-01-01

    It has been estimated that 20% of pregnant women suffer from depression and it is well-documented that maternal depression can have long-lasting effects on the child. Currently, common treatment for maternal depression has been the selective serotonin reuptake inhibitor medications (SSRIs) which are

  6. Serotonin Transporter Knockout Rats Show Improved Strategy Set-Shifting and Reduced Latent Inhibition

    Science.gov (United States)

    Nonkes, Lourens J. P.; van de Vondervoort, Ilse I. G. M.; de Leeuw, Mark J. C.; Wijlaars, Linda P.; Maes, Joseph H. R.; Homberg, Judith R.

    2012-01-01

    Behavioral flexibility is a cognitive process depending on prefrontal areas allowing adaptive responses to environmental changes. Serotonin transporter knockout (5-HTT[superscript -/-]) rodents show improved reversal learning in addition to orbitofrontal cortex changes. Another form of behavioral flexibility, extradimensional strategy set-shifting…

  7. Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action

    DEFF Research Database (Denmark)

    Lucas, Guillaume; Rymar, Vladimir V; Du, Jenny;

    2007-01-01

    Current antidepressants are clinically effective only after several weeks of administration. Here, we show that serotonin(4) (5-HT(4)) agonists reduce immobility in the forced swimming test, displaying an antidepressant potential. Moreover, a 3 day regimen with such compounds modifies rat brain...

  8. Tryptophan as an evolutionarily conserved signal to brain serotonin : Molecular evidence and psychiatric implications

    NARCIS (Netherlands)

    Russo, Sascha; Kema, Ido P.; Bosker, Fokko; Haavik, Jan; Korf, Jakob

    2009-01-01

    The role of serotonin (5-HT) in psychopathology has been investigated for decades. Among others, symptoms of depression, panic, aggression and suicidality have been associated with serotonergic dysfunction. Here we summarize the evidence that low brain 5-HT signals a metabolic imbalance that is evol

  9. The effects of selective serotonin reuptake inhibitors on platelet function in whole blood and platelet concentrates.

    Science.gov (United States)

    Reikvam, Anne-Grete; Hustad, Steinar; Reikvam, Håkon; Apelseth, Torunn Oveland; Nepstad, Ina; Hervig, Tor Audun

    2012-01-01

    Several studies report that patients who are treated with selective serotonin reuptake inhibitors (SSRIs) for depression may have increased risk of bleeding, particularly from the gastrointestinal tract. This may be related to low intraplatelet serotonin concentrations. Several blood banks do not store platelets from donors using SSRIs for transfusion, although the possible effects of SSRIs on platelet storage are not documented. We conducted a case-control pilot study of apheresis platelet concentrates prepared from donors using SSRIs (n=8) and from donors without medication (n=10). The platelet concentrates were stored for 5 days. Light transmission aggregometry (LTA), thrombelastography (TEG), and flow cytometric analyses were preformed for in vitro measurements of platelet function. Platelet function and platelet serotonin content were investigated in whole blood and in platelet concentrates stored for up to 5 days. LTA, TEG, and flow cytometric analysis of glycoprotein expression did not reveal any significant differences between the two groups. All 18 platelet concentrates performed well according to the standards set for platelet quality in relation to transfusion. Blood donors using SSRIs had significantly lower platelet serotonin compared to blood donors without medication. The results from our pilot study indicate that platelets from donors using SSRIs may be suitable for transfusion after storage for 5 days, but further laboratory and clinical studies are necessary to confirm this.

  10. Serotonin and dopamine play complementary roles in gambling to recover losses

    DEFF Research Database (Denmark)

    Campbell-Meiklejohn, Daniel; Cooke, Jennifer; Wakeley, Judi;

    2011-01-01

    Continued gambling to recover losses - 'loss-chasing' - is a prominent feature of social and pathological gambling. However, little is known about which neuromodulators influence this behaviour. In 3 separate experiments, we investigated the role of serotonin activity, D2/D3 receptor activity, and...

  11. Oxazepam and temazepam attenuate paroxetine-induced elevation of serotonin levels in guinea-pig hippocampus

    NARCIS (Netherlands)

    Cremers, Thomas I. F. H.; Dremencov, Eliyahu; Bosker, Fokko J.; Westerink, Ben H. C.

    2010-01-01

    Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are used as a first-line treatment in depression. However, many depressed patients are also treated with benzodiazepines to alleviate increased anxiety and sleep disturbances normally associated with depression. Since benzodiazepines inhibit 5-H

  12. The effects of chronic ethanol self-administration on hippocampal serotonin transporter density in monkeys

    Directory of Open Access Journals (Sweden)

    Elizabeth J Burnett

    2012-04-01

    Full Text Available Evidence for an interaction between alcohol consumption and the serotonin system has been observed repeatedly in both humans and animal models yet the specific relationship between the two remains unclear. Research has focused primarily on the serotonin transporter (SERT due in part to its role in regulating extracellular levels of serotonin. The hippocampal formation is heavily innervated by ascending serotonin fibers and is a major component of the neurocircuitry involved in mediating the reinforcing effects of alcohol. The current study investigated the effects of chronic ethanol self-administration on hippocampal SERT in a layer and field specific manner using a monkey model of human alcohol consumption. [3H]Citalopram was used to measure hippocampal SERT density in male cynomolgus macaques that voluntarily self-administered ethanol for 18 months. Hippocampal [3H]citalopram binding was less dense in ethanol drinkers than in controls, with the greatest effect observed in the molecular layer of the dentate gyrus. SERT density was not correlated with measures of ethanol consumption or blood ethanol concentrations, suggesting the possibility that a threshold level of consumption had been met. The lower hippocampal SERT density observed suggests that chronic ethanol consumption is associated with altered serotonergic modulation of hippocampal neurotransmission.

  13. 5-HT1B receptors and serotonin function : microdialysis studies in rats and knockout mice

    NARCIS (Netherlands)

    Groote, Lotte de

    2002-01-01

    The serotonergic system is an important target in the treatment of psychiatric disorders. Selective serotonin reuptake inhibitors (SSRIs) are widely used in the treatment of depression and anxiety disorders, but a clinical problem is the delayed therapeutic effect. This delayed onset of action sugge

  14. Síndrome serotoninérgica associada ao uso de paroxetina: relato de caso

    OpenAIRE

    CAVALLAZZI LUÍS OTÁVIO; GREZESIUK ANDERSON K.

    1999-01-01

    Relatamos um caso de síndrome serotoninérgica pelo uso de inibidor da recaptação da serotonina, a paroxetina. Tal síndrome por esta droga, sem combinações, ainda não tinha sido descrita na literatura.

  15. Altered dopamine and serotonin metabolism in motorically asymptomatic R6/2 mice.

    Directory of Open Access Journals (Sweden)

    Fanny Mochel

    Full Text Available 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 of biogenic amines. Hence, in order to reliably characterize the regional and chronological profile of brain neurotransmitters in a HD mouse model, we used a microwave fixation system that preserves in vivo concentrations of dopaminergic and serotoninergic amines. DA was decreased in the striatum of R6/2 mice at 8 and 12 weeks of age while DA metabolites, 3-methoxytyramine and homovanillic acid, were already significantly reduced in 4-week-old motorically asymptomatic R6/2 mice. In the striatum, hippocampus and frontal cortex of 4, 8 and 12-week-old R6/2 mice, serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly decreased in association with a decreased turnover of serotonin. In addition, automated high-resolution behavioural analyses displayed stress-like behaviours such as jumping and grooming and altered spatial learning in R6/2 mice at age 4 and 6 weeks respectively. Therefore, we describe the earliest alterations of DA and serotonin metabolism in a HD murine model. Our findings likely underpin the neuropsychological symptoms at time of disease onset in HD.

  16. Larvae of small white butterfly, Pieris rapae, express a novel serotonin receptor

    Science.gov (United States)

    The biogenic amine serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter in vertebrates and invertebrates. It acts in regulation and modulation of many physiological and behavioral processes through G protein-coupled receptors. Insects express five 5-HT receptor subtypes that share high simila...

  17. Tail Biting in Pigs: Blood Serotonin and Fearfulness as Pieces of the Puzzle?

    NARCIS (Netherlands)

    Ursinus, W.W.; Reenen, van C.G.; Reimert, I.; Bolhuis, J.E.

    2014-01-01

    Tail biting in pigs is a widespread problem in intensive pig farming. The tendency to develop this damaging behaviour has been suggested to relate to serotonergic functioning and personality characteristics of pigs. We investigated whether tail biting in pigs can be associated with blood serotonin a

  18. Multiple actions of iontophoretically applied serotonin on motorneurones in the turtle spinal cord in vitro

    DEFF Research Database (Denmark)

    Skydsgaard, Morten Arnika; Hounsgaard, J

    1996-01-01

    The effects of focal activation of serotonergic receptors in motorneurones were investigated in a slice preparation of the turtle spinal cord. The test response to glutamate evoked from a dendrite by iontophoresis was attenuated by serotonin or 8-hydroxy-dipropyl-aminotetralin (8-OH-DPAT) applied...

  19. Filling the Gap : Relationship Between the Serotonin-Transporter-Linked Polymorphic Region and Amygdala Activation

    NARCIS (Netherlands)

    Bastiaansen, Jojanneke A.; Servaas, Michelle N.; Marsman, Jan-Bernard; Ormel, Johan; Nolte, Ilja M.; Riese, Harriette; Aleman, Andre

    2014-01-01

    The alleged association between the serotonin-transporter-linked polymorphic region (5-HTTLPR) and amygdala activation forms a cornerstone of the common view that carrying the short allele of this polymorphism is a potential risk factor for affective disorders. The authors of a recent meta-analysis

  20. The effect of serotonin 1A receptor polymorphism on the cognitive function of premenstrual dysphoric disorder.

    Science.gov (United States)

    Yen, Ju-Yu; Tu, Hung-Pin; Chen, Cheng-Sheng; Yen, Cheng-Fang; Long, Cheng-Yu; Ko, Chih-Hung

    2014-12-01

    Estrogen and serotonin play vital roles in the mechanism of premenstrual dysphoric disorder (PMDD). Cognitive deficit in the premenstrual phase contributes to impaired life function among women with PMDD. The aim of this study was to evaluate the difficulties in cognitive control and working memory (WM) in PMDD and to explore the effects of gonadotropic hormone and polymorphism of serotonin 1A receptor (HTR1A; rs6295) on cognitive deficit in PMDD. Women with PMDD completed diagnostic interviewing, questionnaire assessment, the Go/Nogo task, 2-back and 3-back tasks, and gonadotropic hormone analysis in the premenstrual and follicular phases. Further, they were followed up for two menstrual cycles to confirm two consecutive symptomatic cycles. A total of 59 subjects with PMDD and 74 controls completed all evaluation, fulfilled the criteria, and entered into the final analysis. The results demonstrated cognitive control and WM decline in the premenstrual among women with PMDD. The G/G genotype of HTR1A (rs6295) was found to be associated with impaired WM in the premenstrual phase and premenstrual decline of cognitive function. It also contributed to the vulnerability of cognitive function to the menstrual cycle effect and PMDD effect. As the G/G genotype of HTR1A (rs6295) involves in reducing serotonin neurotransmission, our results provide insight into the serotonin mechanism of cognitive function among women with PMDD. PMID:24158751