WorldWideScience

Sample records for altered serotonin physiology

  1. Two Distinct Central Serotonin Receptors with Different Physiological Functions

    Science.gov (United States)

    Peroutka, Stephen J.; Lebovitz, Richard M.; Snyder, Solomon H.

    1981-05-01

    Two distinct serotonin (5-hydroxytryptamine) receptors designated serotonin 1 and serotonin 2 bind tritium-labeled serotonin and tritium-labeled spiroperidol, respectively. Drug potencies at serotonin 2 sites, but not at serotonin 1 sites, predict their effects on the ``serotonin behavioral syndrome,'' indicating that serotonin 2 sites mediate these behaviors. The limited correlation of drug effects with regulation by guanine nucleotides suggests that serotonin 1 sites might be linked to adenylate cyclase. Drug specificities of serotonin-elicited synaptic inhibition and excitation may reflect serotonin 1 and serotonin 2 receptor interactions, respectively.

  2. Serotonin 1A receptors alter expression of movement representations.

    Science.gov (United States)

    Scullion, Kathleen; Boychuk, Jeffery A; Yamakawa, Glenn R; Rodych, Justin T G; Nakanishi, Stan T; Seto, Angela; Smith, Victoria M; McCarthy, Ryan W; Whelan, Patrick J; Antle, Michael C; Pittman, Quentin J; Teskey, G Campbell

    2013-03-13

    Serotonin has a myriad of central functions involving mood, appetite, sleep, and memory and while its release within the spinal cord is particularly important for generating movement, the corresponding role on cortical movement representations (motor maps) is unknown. Using adult rats we determined that pharmacological depletion of serotonin (5-HT) via intracerebroventricular administration of 5,7 dihydroxytryptamine resulted in altered movements of the forelimb in a skilled reaching task as well as higher movement thresholds and smaller maps derived using high-resolution intracortical microstimulation (ICMS). We ruled out the possibility that reduced spinal cord excitability could account for the serotonin depletion-induced changes as we observed an enhanced Hoffman reflex (H-reflex), indicating a hyperexcitable spinal cord. Motor maps derived in 5-HT1A receptor knock-out mice also showed higher movement thresholds and smaller maps compared with wild-type controls. Direct cortical application of the 5-HT1A/7 agonist 8-OH-DPAT lowered movement thresholds in vivo and increased map size in 5-HT-depleted rats. In rats, electrical stimulation of the dorsal raphe lowered movement thresholds and this effect could be blocked by direct cortical application of the 5-HT1A antagonist WAY-100135, indicating that serotonin is primarily acting through the 5-HT1A receptor. Next we developed a novel in vitro ICMS preparation that allowed us to track layer V pyramidal cell excitability. Bath application of WAY-100135 raised the ICMS current intensity to induce action potential firing whereas the agonist 8-OH-DPAT had the opposite effect. Together our results demonstrate that serotonin, acting through 5-HT1A receptors, plays an excitatory role in forelimb motor map expression.

  3. Alterations in physiology and anatomy during pregnancy.

    Science.gov (United States)

    Tan, Eng Kien; Tan, Eng Loy

    2013-12-01

    Pregnant women undergo profound anatomical and physiological changes so that they can cope with the increased physical and metabolic demands of their pregnancies. The cardiovascular, respiratory, haematological, renal, gastrointestinal and endocrine systems all undergo important physiological alterations and adaptations needed to allow development of the fetus and to allow the mother and fetus to survive the demands of childbirth. Such alterations in anatomy and physiology may cause difficulties in interpreting signs, symptoms, and biochemical investigations, making the clinical assessment of a pregnant woman inevitably confusing but challenging. Understanding these changes is important for every practicing obstetrician, as the pathological deviations from the normal physiological alterations may not be clear-cut until an adverse outcome has resulted. Only with a sound knowledge of the physiology and anatomy changes can the care of an obstetric parturient be safely optimized for a better maternal and fetal outcome.

  4. 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.)

  5. Alterations to embryonic serotonin change aggression and fearfulness

    Science.gov (United States)

    Prenatal environment, including maternal hormones, affects the development of the serotonin (5-HT) system, with long-lasting effects on mood and behavioral exhibition in children and adults. The chicken provides a unique animal model to study the effects of embryonic development on childhood and ado...

  6. Platelet serotonin transporter (5HTt): physiological influences on kinetic characteristics in a large human population.

    Science.gov (United States)

    Banović, Miroslav; Bordukalo-Niksić, Tatjana; Balija, Melita; Cicin-Sain, Lipa; Jernej, Branimir

    2010-01-01

    The present study had two goals: first, to give a detailed description of a reliable method for full kinetic analysis of serotonin transporter (5HTt) on the membrane of human platelets, and second, as a main issue, to report on physiological influences on kinetic characteristics of this transmembrane transport on a large population of healthy individuals. Full kinetic analyses of platelet serotonin uptake were performed on 334 blood donors of both sexes by the use of 14C-radioisotopic method, which was first optimized according to assumptions of enzyme kinetic analyses, with regard to platelet concentration, duration of uptake, concentration of substrate as well as important technical parameters (underpressure of filtration, blanks, incubating temperature, etc). Kinetic parameters of platelet serotonin uptake in the whole population were for V(max): 142 +/- 25.3 pmol 5HT/10(8) platelets/minute and for K(m): 0.404 +/- 0.089 microM 5HT. Besides the report on kinetic values of 5HT transporter protein, we have also described major physiological influences on the mentioned parameters, V(max), K(m) and their derivative, V(max)/K(m) (transporter efficiency): range and frequency distribution of normal values, intraindividual stability over time, lack of age influence, gender dependence and seasonal variations. The report on kinetic values and main physiological influences on platelet serotonin transport kinetics, obtained by the use of thoroughly reassessed methodology, and on by far the largest human population studied until now, offers a reliable frame of reference for pathophysiological studies of this parameter in various clinical fields.

  7. 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.

  8. Serotonin as a physiological substrate for myeloperoxidase and its superoxide-dependent oxidation to cytotoxic tryptamine-4,5-dione.

    Science.gov (United States)

    Ximenes, Valdecir F; Maghzal, Ghassan J; Turner, Rufus; Kato, Yoji; Winterbourn, Christine C; Kettle, Anthony J

    2009-12-14

    During inflammatory events, neutrophils and platelets interact to release a variety of mediators. Neutrophils generate superoxide and hydrogen peroxide, and also discharge the haem enzyme myeloperoxidase. Among numerous other mediators, platelets liberate serotonin (5-hydroxytryptamine), which is a classical neurotransmitter and vasoactive amine that has significant effects on inflammation and immunity. In the present study, we show that serotonin is a favoured substrate for myeloperoxidase because other physiological substrates for this enzyme, including chloride, did not affect its rate of oxidation. At low micromolar concentrations, serotonin enhanced hypochlorous acid production by both purified myeloperoxidase and neutrophils. At higher concentrations, it almost completely blocked the formation of hypochlorous acid. Serotonin was oxidized to a dimer by myeloperoxidase and hydrogen peroxide. It was also converted into tryptamine-4,5-dione, especially in the presence of superoxide. This toxic quinone was produced by stimulated neutrophils in a reaction that required myeloperoxidase. In plasma, stimulated human neutrophils oxidized serotonin to its dimer using the NADPH oxidase and myeloperoxidase. We propose that myeloperoxidase will oxidize serotonin at sites of inflammation. In doing so, it will impair its physiological functions and generate a toxic metabolite that will exacerbate inflammatory tissue damage. Consequently, oxidation of serotonin by myeloperoxidase may profoundly influence inflammatory processes.

  9. Serotonin alterations in anorexia and bulimia nervosa: new insights from imaging studies.

    Science.gov (United States)

    Kaye, Walter H; Frank, Guido K; Bailer, Ursula F; Henry, Shannan E; Meltzer, Carolyn C; Price, Julie C; Mathis, Chester A; Wagner, Angela

    2005-05-19

    Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders with relatively homogenous presentations such as age of onset and gender distribution. In addition, they share symptoms, such as extremes of food consumption, body image distortion, anxiety and obsessions, and ego-syntonic neglect, raises the possibility that these symptoms reflect disturbed brain function that contributes to the pathophysiology of this illness. Recent brain imaging studies have identified altered activity in frontal, cingulate, temporal, and parietal cortical regions in AN and BN. Importantly, such disturbances are present when subjects are ill and persist after recovery, suggesting that these may be traits that are independent of the state of the illness. Emerging data point to a dysregulation of serotonin pathways in cortical and limbic structures that may be related to anxiety, behavioral inhibition, and body image distortions. In specific, recent studies using PET with serotonin specific radioligands implicate alterations of 5-HT1A and 5-HT2A receptors and the 5-HT transporter. Alterations of these circuits may affect mood and impulse control as well as the motivating and hedonic aspects of feeding behavior. Such imaging studies may offer insights into new pharmacology and psychotherapy approaches.

  10. Hypothalamic serotonin-insulin signaling cross-talk and alterations in a type 2 diabetic model.

    Science.gov (United States)

    Papazoglou, Ioannis; Berthou, Flavien; Vicaire, Nicolas; Rouch, Claude; Markaki, Eirini M; Bailbe, Danielle; Portha, Bernard; Taouis, Mohammed; Gerozissis, Kyriaki

    2012-03-05

    Serotonin and insulin are key regulators of homeostatic mechanisms in the hypothalamus. However, in type 2 diabetes, the hypothalamic responsiveness to serotonin is not clearly established. We used a diabetic model, the Goto Kakizaki (GK) rats, to explore insulin receptor expression, insulin and serotonin efficiency in the hypothalamus and liver by means of Akt phosphorylation. Insulin or dexfenfluramine (stimulator of serotonin) treatment induced Akt phosphorylation in Wistar rats but not in GK rats that exhibit down-regulated insulin receptor. Studies in a neuroblastoma cell line showed that serotonin-induced Akt phosphorylation is PI3-kinase dependent. Finally, in response to food intake, hypothalamic serotonin release was reduced in GK rats, indicating impaired responsiveness of this neurotransmitter. In conclusion, hypothalamic serotonin as insulin efficiency is impaired in diabetic GK rats. The insulin-serotonin cross-talk and impairment observed is one potential key modification in the brain during the onset of diabetes.

  11. 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.

  12. Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze

    Science.gov (United States)

    Hernández-Pérez, J. Jesús; Gutiérrez-Guzmán, Blanca E.; López-Vázquez, Miguel Á.; Olvera-Cortés, María E.

    2015-01-01

    Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS), which includes mesencephalic and diencephalic relays. The supramamillary nucleus (SUMn) is located between the reticularis pontis oralis and the medial septum (MS), in close relation with the posterior hypothalamic nucleus (PHn), all of which are part of this ascending system. It has been proposed that the SUMn plays a role in the modulation of hippocampal theta-frequency; this could occur through direct connections between the SUMn and the hippocampus or through the influence of the SUMn on the MS. Serotonergic raphe neurons prominently innervate the hippocampus and several components of the SAS, including the SUMn. Serotonin desynchronizes hippocampal theta activity, and it has been proposed that serotonin may regulate learning through the modulation of hippocampal synchrony. In agreement with this hypothesis, serotonin depletion in the SUMn/PHn results in deficient spatial learning and alterations in CA1 theta activity-related learning in a Morris water maze. Because it has been reported that SUMn inactivation with lidocaine impairs the consolidation of reference memory, we asked whether changes in hippocampal theta activity related to learning would occur through serotonin depletion in the SUMn, together with deficiencies in memory. We infused 5,7-DHT bilaterally into the SUMn in rats and evaluated place learning in the standard Morris water maze task. Hippocampal (CA1 and dentate gyrus), septal and SUMn EEG were recorded during training of the test. The EEG power in each region and the coherence between the different regions were evaluated. Serotonin depletion in the SUMn induced deficient spatial learning and altered the expression of hippocampal high-frequency theta activity. These results provide evidence in

  13. Constitutive and Acquired Serotonin Deficiency Alters Memory and Hippocampal Synaptic Plasticity.

    Science.gov (United States)

    Fernandez, Sebastian P; Muzerelle, Aude; Scotto-Lomassese, Sophie; Barik, Jacques; Gruart, Agnès; Delgado-García, José M; Gaspar, Patricia

    2017-01-01

    Serotonin (5-HT) deficiency occurs in a number of brain disorders that affect cognitive function. However, a direct causal relationship between 5-HT hypo-transmission and memory and underlying mechanisms has not been established. We used mice with a constitutive depletion of 5-HT brain levels (Pet1KO mice) to analyze the contribution of 5-HT to different forms of learning and memory. Pet1KO mice exhibited a striking deficit in novel object recognition memory, a hippocampal-dependent task. No alterations were found in tasks for social recognition, procedural learning, or fear memory. Viral delivery of designer receptors exclusively activated by designer drugs was used to selectively silence the activity of 5-HT neurons in the raphe. Inhibition of 5-HT neurons in the median raphe, but not the dorsal raphe, was sufficient to impair object recognition in adult mice. In vivo electrophysiology in behaving mice showed that long-term potentiation in the hippocampus of 5-HT-deficient mice was altered, and administration of the 5-HT1A agonist 8-OHDPAT rescued the memory deficits. Our data suggest that hyposerotonergia selectively affects declarative hippocampal-dependent memory. Serotonergic projections from the median raphe are necessary to regulate object memory and hippocampal synaptic plasticity processes, through an inhibitory control mediated by 5-HT1A receptors.

  14. The use of animal models to decipher physiological and neurobiological alterations of Anorexia Nervosa patients.

    Directory of Open Access Journals (Sweden)

    Mathieu eMéquinion

    2015-05-01

    Full Text Available Extensive studies were performed to decipher the mechanisms regulating feeding due to the worldwide obesity pandemy and its complications. The data obtained might be adapted to another disorder related to alteration of food intake, the restrictive anorexia nervosa. This multifactorial disease with a complex and unknown etiology is considered as an awful eating disorder since the chronic refusal to eat leads to severe and sometimes irreversible complications for the whole organism, until death. There is an urgent need to better understand the different aspects of the disease to develop novel approaches complementary to the usual psychological therapies. For this purpose, the use of pertinent animal models becomes a necessity. We present here the various rodent models described in the literature that might be used to dissect central and peripheral mechanisms involved in the adaptation to deficient energy supplies and/or the maintenance of physiological alterations on the long term. Data obtained from the spontaneous or engineered genetic models permit to better apprehend the implication of one signaling system (hormone, neuropeptides, neurotransmitter in the development of several symptoms observed in anorexia nervosa. As example, mutations in the ghrelin, serotonin, dopamine pathways lead to alterations that mimic the phenotype, but compensatory mechanisms often occur rendering necessary the used of more selective gene strategies. Until now, environmental animal models based on one or several inducing factors like diet restriction, stress or physical activity mimicked more extensively central and peripheral alterations decribed in anorexia nervosa. They bring significant data on feeding behavior, energy expenditure and central circuit alterations. Animal models are described and criticized on the basis of the criteria of validity for anorexia nervosa.

  15. Risk of prenatal depression and stress treatment: alteration on serotonin system of offspring through exposure to Fluoxetine

    Science.gov (United States)

    Pei, Siran; Liu, Li; Zhong, Zhaomin; Wang, Han; Lin, Shuo; Shang, Jing

    2016-01-01

    Fluoxetine is widely used to treat depression, including depression in pregnant and postpartum women. Studies suggest that fluoxetine may have adverse effects on offspring, presumably through its action on various serotonin receptors (HTRs). However, definitive evidence and the underlying mechanisms are largely unavailable. As initial steps towards establishing a human cellular and animal model, we analyzed the expression patterns of several HTRs through the differentiation of human induced pluripotent stem (hiPS) cells into neuronal cells, and analyzed expression pattern in zebrafish embryos. Treatment of zebrafish embryos with fluoxetine significantly blocked the expression of multiple HTRs. Furthermore, fluoxetine gave rise to a change in neuropsychology. Embryos treated with fluoxetine continued to exhibit abnormal behavior upto 12 days post fertilization due to changes in HTRs. These findings support a possible long-term risk of serotonin pathway alteration, possibly resulting from the “placental drug transfer”. PMID:27703173

  16. Alterations in serotonin receptors and transporter immunoreactivities in the hippocampus in the rat unilateral hypoxic-induced epilepsy model.

    Science.gov (United States)

    An, Sung-Jin; Kim, Duk-Soo

    2011-11-01

    Unilateral hypoxic-ischemia results in the frequent occurrence of interictal spikes, and occasionally sustained ictal discharges accompanied by a reduction in paired-pulse inhibition within the non-lesioned dentate gyrus. To elucidate the roles of serotonin (5-hydroxytryptamine [5-HT]) in an epileptogenic insult, we investigated the changes in 5-HT receptors and serotonin transporter (5-HTT) immunoreactivities within the lesioned and contralateral hippocampus following unilateral hypoxic-ischemia. During epileptogenic periods following hypoxic-ischemia, both 5-HT(1A) and 5HT(1B) receptor immunoreactivities were decreased within the lesioned and the non-lesioned hippocampus. However, 5-HTT immunoreactivity was transiently increased within the hippocampus bilaterally. These findings indicate that alteration of the 5-HT system results in a "diaschisis" pattern, and may contribute to neuronal death and the development of emotional disorders in epileptic patients accompanied by psychological stress.

  17. Serotonin syndrome

    Science.gov (United States)

    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... two medicines that affect the body's level of serotonin are taken together at the same time. The ...

  18. Root bacterial endophytes alter plant phenotype, but not physiology

    Directory of Open Access Journals (Sweden)

    Jeremiah A. Henning

    2016-11-01

    Full Text Available Plant traits, such as root and leaf area, influence how plants interact with their environment and the diverse microbiota living within plants can influence plant morphology and physiology. Here, we explored how three bacterial strains isolated from the Populus root microbiome, influenced plant phenotype. We chose three bacterial strains that differed in predicted metabolic capabilities, plant hormone production and metabolism, and secondary metabolite synthesis. We inoculated each bacterial strain on a single genotype of Populus trichocarpa and measured the response of plant growth related traits (root:shoot, biomass production, root and leaf growth rates and physiological traits (chlorophyll content, net photosynthesis, net photosynthesis at saturating light–Asat, and saturating CO2–Amax. Overall, we found that bacterial root endophyte infection increased root growth rate up to 184% and leaf growth rate up to 137% relative to non-inoculated control plants, evidence that plants respond to bacteria by modifying morphology. However, endophyte inoculation had no influence on total plant biomass and photosynthetic traits (net photosynthesis, chlorophyll content. In sum, bacterial inoculation did not significantly increase plant carbon fixation and biomass, but their presence altered where and how carbon was being allocated in the plant host.

  19. Oxidative stress alters physiological and morphological neuronal properties.

    Science.gov (United States)

    Hasan, Sonia M; Joe, Mary; Alshuaib, Waleed B

    2007-07-01

    We investigated the effects of H(2)O(2)-induced oxidative stress on the delayed-rectifier current (IK(DR)), neuronal physiological and morphological properties. Measurements were obtained from hippocampal CA1 neurons in control solution and from the same neurons after exposure to oxidative stress (short- and long-term H(2)O(2) external applications at 0.1, 1, and 10 mM). With short-term (6 min) H(2)O(2) (1 mM) treatment, IK(DR) measured in the H(2)O(2)-containing solution (778 +/- 23 pA, n=20), was smaller than that measured in the control Ca(2+)-free Hepes solution (1,112 +/- 38 pA, n=20). Coenzyme Q(10) (0.1 mM) pretreatment prevented the H(2)O(2)-induced inhibition of IK(DR). With long-term (40, 80 min) H(2)O(2) (0.1, 10 mM) treatment, the neuron lost its distinctive shape (rounded up) and the neurite almost disappeared. These results suggest that oxidative stress, which inhibits IK(DR), can alter neural activity. The morphological changes caused by H(2)O(2) support the idea that oxidative stress causes intracellular damage and compromises neural function.

  20. Altered Resting and Exercise Respiratory Physiology in Obesity

    Science.gov (United States)

    Sood, Akshay

    2009-01-01

    Synopsis Obesity, particularly severe obesity, affects both resting and exercise-related respiratory physiology. Severe obesity classically produces a restrictive ventilatory abnormality, characterized by reduced expiratory reserve volume. However, obstructive ventilatory abnormality may also be associated with abdominal obesity. Decreased peak work rates are usually seen among obese subjects in a setting of normal or decreased ventilatory reserve and normal cardiovascular response to exercise. Weight loss may reverse many adverse physiological consequences of severe obesity on the respiratory system. PMID:19700043

  1. Lack of serotonin reuptake during brain development alters rostral raphe-prefrontal network formation

    Directory of Open Access Journals (Sweden)

    Josefine Storm Witteveen

    2013-10-01

    Full Text Available Besides its ‘classical’ neurotransmitter function, serotonin (5-HT has been found to also act as a neurodevelopmental signal. During development, the 5-HT projection system represents one of the earliest neurotransmitter systems to innervate the brain. One of the targets of the 5-HT projection system, originating in the brainstem raphe nuclei, is the medial prefrontal cortex (mPFC, an area involved in higher cognitive functions and important in the etiology of many neurodevelopmental disorders. Little is known however about the exact role of 5-HT and its signaling molecules in the formation of the raphe-prefrontal network. Using explant essays, we here studied the role of the 5-HT transporter (5-HTT, an important modulator of the 5-HT signal, in rostral raphe-prefrontal network formation. We found that the chemotrophic nature of the interaction between the origin (rostral raphe cluster and a target (mPFC of the 5-HT projection system was affected in rats lacking the 5-HTT (5-HTT-/-. While 5-HTT deficiency did not affect the dorsal raphe 5-HT-positive outgrowing neurites, the median raphe 5-HT neurites switched from a strong repulsive to an attractive interaction when co-cultured with the mPFC. Furthermore, the fasciculation of the mPFC outgrowing neurites was dependent on the amount of 5-HTT. In the mPFC of 5-HTT-/- pups, we observed clear differences in 5-HT innervation and the identity of a class of projection neurons of the mPFC. In the absence of the 5-HTT, the 5-HT innervation in all subareas of the early postnatal mPFC increased dramatically and the number of Satb2-positive callosal projection neurons was decreased. Together, these results suggest a 5-HTT dependency during early development of these brain areas and in the formation of the raphe-prefrontal network. The tremendous complexity of the 5-HT projection system and its role in several neurodevelopmental disorders highlights the need for further research in this largely

  2. Root bacterial endophytes alter plant phenotype, but not physiology

    DEFF Research Database (Denmark)

    Henning, Jeremiah A.; Weston, David J.; Pelletier, Dale A.;

    2016-01-01

    (root:shoot, biomass production, root and leaf growth rates) and physiological traits (chlorophyll content, net photosynthesis, net photosynthesis at saturating light-Asat, and saturating CO2-Amax). Overall, we found that bacterial root endophyte infection increased root growth rate up to 184% and leaf...

  3. 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.

  4. Root bacterial endophytes alter plant phenotype, but not physiology

    DEFF Research Database (Denmark)

    Henning, Jeremiah A.; Weston, David J.; Pelletier, Dale A.

    2016-01-01

    Plant traits, such as root and leaf area, influence how plants interact with their environment and the diverse microbiota living within plants can influence plant morphology and physiology. Here, we explored how three bacterial strains isolated from the Populus root microbiome, influenced plant...... phenotype. We chose three bacterial strains that differed in predicted metabolic capabilities, plant hormone production and metabolism, and secondary metabolite synthesis. We inoculated each bacterial strain on a single genotype of Populus trichocarpa and measured the response of plant growth related traits...... (root:shoot, biomass production, root and leaf growth rates) and physiological traits (chlorophyll content, net photosynthesis, net photosynthesis at saturating light-Asat, and saturating CO2-Amax). Overall, we found that bacterial root endophyte infection increased root growth rate up to 184% and leaf...

  5. Can Architectural Design alter the Physiological reaction to Psychosocial Stress ?

    DEFF Research Database (Denmark)

    Brorson Fich, Lars; Jönsson, Peter; Kirkegaard, Poul Henning

    2014-01-01

    Is has long been established, that views to natural scenes can a have a dampening effect on physiological stress responses. However, as people in Europe, Canada and North America today spent 50-85% of their time indoors, attention might also be paid to how the artificial man-made indoor environment...... is computer generated and properties of the space therefore can be systematically varied, we measured saliva cortisol and heart rate variability in participants in a closed room versus a room with openings. As shown by a significant linear contrast interaction between groups and TSST conditions, participants...

  6. Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain

    Science.gov (United States)

    Ngai, Ying Fai; Sulistyoningrum, Dian C.; O'Neill, Ryan; Innis, Sheila M.; Weinberg, Joanne

    2015-01-01

    Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE. PMID:26180184

  7. Polyploidy in aspen alters plant physiology and drought sensitivity

    Science.gov (United States)

    Greer, B.; Still, C. J.; Brooks, J. R.; Meinzer, F. C.

    2015-12-01

    Polyploids of quaking aspen (Populus tremuloides) may be better suited to dry climatic conditions than diploids. However, the expression of diploid and polyploid functional traits, including water use efficiency, an important component of drought avoidance and tolerance, are not well understood in quaking aspen. In this study diploid and triploid aspen clones' leaf, ramet, and stand functional traits were measured near the Rocky Mountain Biological Laboratory in Gothic, Colorado. The physiology of diploid and triploid aspen, including leaf size, chlorophyll content, stomatal size and density and stomatal conductance, as well as growth rates and carbon isotope discrimination in response to climate (measured in tree rings), were found to be significantly different between ploidy levels. These findings demonstrate different sensitivities of diploid and triploid clones to drought related climate stressors which may impact strategies for aspen forest management and conservation.

  8. High-fat diet alters gut microbiota physiology in mice.

    Science.gov (United States)

    Daniel, Hannelore; Gholami, Amin Moghaddas; Berry, David; Desmarchelier, Charles; Hahne, Hannes; Loh, Gunnar; Mondot, Stanislas; Lepage, Patricia; Rothballer, Michael; Walker, Alesia; Böhm, Christoph; Wenning, Mareike; Wagner, Michael; Blaut, Michael; Schmitt-Kopplin, Philippe; Kuster, Bernhard; Haller, Dirk; Clavel, Thomas

    2014-02-01

    The intestinal microbiota is known to regulate host energy homeostasis and can be influenced by high-calorie diets. However, changes affecting the ecosystem at the functional level are still not well characterized. We measured shifts in cecal bacterial communities in mice fed a carbohydrate or high-fat (HF) diet for 12 weeks at the level of the following: (i) diversity and taxa distribution by high-throughput 16S ribosomal RNA gene sequencing; (ii) bulk and single-cell chemical composition by Fourier-transform infrared- (FT-IR) and Raman micro-spectroscopy and (iii) metaproteome and metabolome via high-resolution mass spectrometry. High-fat diet caused shifts in the diversity of dominant gut bacteria and altered the proportion of Ruminococcaceae (decrease) and Rikenellaceae (increase). FT-IR spectroscopy revealed that the impact of the diet on cecal chemical fingerprints is greater than the impact of microbiota composition. Diet-driven changes in biochemical fingerprints of members of the Bacteroidales and Lachnospiraceae were also observed at the level of single cells, indicating that there were distinct differences in cellular composition of dominant phylotypes under different diets. Metaproteome and metabolome analyses based on the occurrence of 1760 bacterial proteins and 86 annotated metabolites revealed distinct HF diet-specific profiles. Alteration of hormonal and anti-microbial networks, bile acid and bilirubin metabolism and shifts towards amino acid and simple sugars metabolism were observed. We conclude that a HF diet markedly affects the gut bacterial ecosystem at the functional level.

  9. Simultaneous alterations of brain and plasma serotonin concentrations and liver cytochrome P450 in rats fed on a tryptophan-free diet.

    Science.gov (United States)

    Kot, Marta; Pilc, Andrzej; Daniel, Władysława A

    2012-10-01

    Our previous study suggested involvement of the brain serotonergic system in the regulation of liver cytochrome P450 (CYP). The aim of the present study was to demonstrate simultaneous responsiveness of liver CYP and the peripheral and brain serotonergic systems to a tryptophan deficient diet during three days and one or three weeks of ingestion. The concentrations of serotonin, noradrenaline, dopamine and their metabolites were measured in blood plasma, the hypothalamus and brain stem of male rats. The enzyme activity and protein levels in the liver were determined for isoforms CYP1A, CYP2A, CYP2B, CYP2C6, CYP2C11, CYP2D and CYP3A. A three-day tryptophan-free diet increased serotonin content in the hypothalamus (but not in the brain stem or plasma). After one week, the level of serotonin was not changed in the brain, but was markedly increased in the plasma. A three week tryptophan restriction significantly reduced the concentration of serotonin in the brain and plasma. Changes in CYP2C6 and CYP2C11 (an increase and a decrease, respectively) were maintained throughout the experiment, while those found in other CYP isoforms varied, which usually resulted in a gradual increase in the enzyme activity within three weeks. The observed alterations in liver CYPs suggest involvement of both central and peripheral serotonin in the regulation of liver CYP expression whose mechanism is discussed. In conclusion, a deficit in tryptophan in the diet may be responsible for very serious food-cytochrome P450 and food-drug metabolism interactions. Interactions of this type may also refer to drugs acting via serotonergic system.

  10. Suppression of serotonin hyperinnervation does not alter the dysregulatory influences of dopamine depletion on striatal neuropeptide gene expression in rodent neonates.

    Science.gov (United States)

    Basura, G J; Walker, P D

    1999-10-15

    Sixty days following neonatal dopamine depletion (>98%) with 6-hydroxydopamine, preprotachykinin and preprodynorphin mRNA levels were significantly reduced (67 and 78% of vehicle controls, respectively) in the anterior striatum as determined by in situ hybridization while preproenkephalin mRNA expression was elevated (133% of vehicle controls). Suppression of the serotonin hyperinnervation phenomenon in the dopamine-depleted rat with 5,7-dihydroxytryptamine yielded no significant alterations in reduced striatal preprotachykinin (66%) or preprodynorphin (64%) mRNA levels, while preproenkephalin mRNA expression remained significantly elevated (140%). These data suggest that striatal serotonin hyperinnervation does not contribute to the development of dysregulated striatal neuropeptide transmission in either direct or indirect striatal output pathways following neonatal dopamine depletion.

  11. Alteration of plant physiology by glyphosate and its by-product aminomethylphosphonic acid: an overview.

    Science.gov (United States)

    Gomes, Marcelo P; Smedbol, Elise; Chalifour, Annie; Hénault-Ethier, Louise; Labrecque, Michel; Lepage, Laurent; Lucotte, Marc; Juneau, Philippe

    2014-09-01

    It is generally claimed that glyphosate kills undesired plants by affecting the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme, disturbing the shikimate pathway. However, the mechanisms leading to plant death may also be related to secondary or indirect effects of glyphosate on plant physiology. Moreover, some plants can metabolize glyphosate to aminomethylphosphonic acid (AMPA) or be exposed to AMPA from different environmental matrices. AMPA is a recognized phytotoxin, and its co-occurrence with glyphosate could modify the effects of glyphosate on plant physiology. The present review provides an overall picture of alterations of plant physiology caused by environmental exposure to glyphosate and its metabolite AMPA, and summarizes their effects on several physiological processes. It particularly focuses on photosynthesis, from photochemical events to C assimilation and translocation, as well as oxidative stress. The effects of glyphosate and AMPA on several plant physiological processes have been linked, with the aim of better understanding their phytotoxicity and glyphosate herbicidal effects.

  12. Pharmacological and genetic interventions in serotonin (5-HT)(2C) receptors to alter drug abuse and dependence processes

    NARCIS (Netherlands)

    Filip, Malgorzata; Spampinato, Umberto; McCreary, Andrew C.; Przegalinski, Edmund

    2012-01-01

    The present review provides an overview on serotonin (5-hydroxytryptamine; 5-HT)(2C) receptors and their relationship to drug dependence. We have focused our discussion on the impact of 5-HT2C receptors on the effects of different classes of addictive drugs, illustrated by reference to data using ph

  13. Altered Circulating Levels of Serotonin and Immunological Changes in Laying Hens Divergently Selected for Feather Pecking Behavior

    DEFF Research Database (Denmark)

    Buitenhuis, Albert Johannes; Kjaer, Jørgen B.; Labouriau, Rodrigo

    2006-01-01

    The aim of this study was to investigate the changes in immunological parameters as well as changes with respect to plasma levels of serotonin and tryptophan in lines selected for and against feather pecking (FP) behavior [high FP (HP) line and low FP (LP) line] for 5 generations. The hens from...

  14. Studying the altered timing of physiological events during development: it's about time…or is it?

    Science.gov (United States)

    Spicer, John I; Rundle, Simon D; Tills, Oliver

    2011-08-31

    The investigation of the altered timing of developmental events is key to understanding evolution. Most empirical investigations of event timing are biased towards studying morphological variation. Recent reviews, however, have attempted to marshal the evidence for the importance of altered timing of physiological events, focusing on such timing shifts between species (physiological heterochrony) and within species (physiological heterokairy). Here we update these reviews. We firstly take a comparative developmental physiology approach to explore how recent studies have furthered our understanding of the links between physiological event timing shifts at different levels of biological organisation (i.e. individual, population and species). The alternative strategy of concentrating effort on one model system is then considered, in particular focussing on substantial recent advances in our understanding of fetal haemoglobin expression in humans. We conclude that, while the fetal haemoglobin model may be appropriate as a model for some questions, it can never be the model study system. We also discuss the different quantitative analyses available for investigating event timing alterations. We consider the efficacy of the terms heterochrony and heterokairy.

  15. Age-related alterations in behavioral and cerebral metabolic responses to the serotonin agonist meta-chlorophenylpiperazine in rats.

    Science.gov (United States)

    Freo, U; Rapoport, S I; Soncrant, T T

    1991-01-01

    To determine the functional relevance of the age-related neurochemical changes that occur in brain serotonin systems during aging, we measured the effects of the serotonin receptor agonist meta-chlorophenylpiperazine (MCPP) on behavior and on regional cerebral metabolic rates for glucose (rCMRglc) in awake rats. rCMRglc was determined in 74 regions of Fischer-344 rats aged 3, 12 and 24 months, at 15 and 90 min after MCPP 2.5 mg/kg IP, using the quantitative, autoradiographic [14C]2-deoxy-D-glucose technique. The time-course of motor performance following MCPP was assessed with a rotating rod. MCPP impaired motor performance in all ages maximally at 15-30 min. Three-month-old rats recovered completely within 60 min, whereas 12-month-old animals exhibited partial recovery and 24-month-old rats did not recover by 120 min. At 15 min after MCPP, rCMRglc was reduced in 51 of the 74 studied regions (overall decrease, 20%) of 3-month-old rats, in 21 regions (13% decrease) of 12-month-old rats and in 14 regions (2% decrease) of 24-month-old animals. Similar MCPP brain concentrations were achieved at 15 min in rats of all ages. The results suggest that the functional integrity of serotonergic transmission is reduced in aged rats and that the dysregulation is presynaptic.

  16. High serotonin levels during brain development alter the structural input-output connectivity of neural networks in the rat somatosensory layer IV

    Directory of Open Access Journals (Sweden)

    Stéphanie eMiceli

    2013-06-01

    Full Text Available Homeostatic regulation of serotonin (5-HT concentration is critical for normal topographical organization and development of thalamocortical (TC afferent circuits. Down-regulation of the serotonin transporter (SERT and the consequent impaired reuptake of 5-HT at the synapse, results in a reduced terminal branching of developing TC afferents within the primary somatosensory cortex (S1. Despite the presence of multiple genetic models, the effect of high extracellular 5-HT levels on the structure and function of developing intracortical neural networks is far from being understood. Here, using juvenile SERT knockout (SERT-/- rats we investigated, in vitro, the effect of increased 5-HT levels on the structural organization of (i the thalamocortical projections of the ventroposteromedial thalamic nucleus towards S1, (ii the general barrel-field pattern and (iii the electrophysiological and morphological properties of the excitatory cell population in layer IV of S1 (spiny stellate and pyramidal cells. Our results confirmed previous findings that high levels of 5-HT during development lead to a reduction of the topographical precision of TCA projections towards the barrel cortex. Also, the barrel pattern was altered but not abolished in SERT-/- rats. In layer IV, both excitatory spiny stellate and pyramidal cells showed a significantly reduced intracolumnar organization of their axonal projections. In addition, the layer IV spiny stellate cells gave rise to a prominent projection towards the infragranular layer Vb. Our findings point to a structural and functional reorganization, of TCAs, as well as early stage intracortical microcircuitry, following the disruption of 5-HT reuptake during critical developmental periods. The increased projection pattern of the layer IV neurons suggests that the intracortical network changes are not limited to the main entry layer IV but may also affect the subsequent stages of the canonical circuits of the barrel

  17. Parasitic infection alters the physiological response of a marine gastropod to ocean acidification.

    Science.gov (United States)

    Macleod, C D; Poulin, R

    2016-09-01

    Increased hydrogen ion concentration and decreased carbonate ion concentration in seawater are the most physiologically relevant consequences of ocean acidification (OA). Changes to either chemical species may increase the metabolic cost of physiological processes in marine organisms, and reduce the energy available for growth, reproduction and survival. Parasitic infection also increases the energetic demands experienced by marine organisms, and may reduce host tolerance to stressors associated with OA. This study assessed the combined metabolic effects of parasitic infection and OA on an intertidal gastropod, Zeacumantus subcarinatus. Oxygen consumption rates and tissue glucose content were recorded in snails infected with one of three trematode parasites, and an uninfected control group, maintained in acidified (7·6 and 7·4 pH) or unmodified (8·1 pH) seawater. Exposure to acidified seawater significantly altered the oxygen consumption rates and tissue glucose content of infected and uninfected snails, and there were clear differences in the magnitude of these changes between snails infected with different species of trematode. These results indicate that the combined effects of OA and parasitic infection significantly alter the energy requirements of Z. subcarinatus, and that the species of the infecting parasite may play an important role in determining the tolerance of marine gastropods to OA.

  18. Fluoxetine, a selective inhibitor of serotonin uptake, potentiates morphine analgesia without altering its discriminative stimulus properties or affinity for opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Hynes, M.D.; Lochner, M.A.; Bemis, K.G.; Hymson, D.L.

    1985-06-17

    The analgesic effect of morphine in the rat tail jerk assay was enhanced by the serotonin uptake inhibitor, fluoxetine. Tail jerk latency was not affected by fluoxetine alone. Morphine's affinity for opioid receptors labeled in vitro with /sup 3/H-naloxone or /sup 3/H-D-Ala/sup 2/-D-Leu/sup 5/-enkephalin was not altered by fluoxetine, which has no affinity for these sites at concentrations as high as 1000 nM. In rats trained to discriminate morphine from saline, fluoxetine at doses of 5 or 10 mg/kg were recognized as saline. Increasing the fluoxetine dose to 20 mg/kg did not result in generalization to either saline or morphine. The dose response curve for morphine generalization was not significantly altered by fluoxetine doses of 5 or 10 mg/kg. Those rats treated with the combination of morphine and 20 mg/kg of fluoxetine did not exhibit saline or morphine appropriate responding. Fluoxetine potentiates the analgesic properties of morphine without enhancing its affinity for opioid receptors or its discriminative stimulus properties. 30 references, 2 figures, 2 tables.

  19. Combined neonicotinoid pesticide and parasite stress alter honeybee queens’ physiology and survival

    Science.gov (United States)

    Dussaubat, Claudia; Maisonnasse, Alban; Crauser, Didier; Tchamitchian, Sylvie; Bonnet, Marc; Cousin, Marianne; Kretzschmar, André; Brunet, Jean-Luc; Le Conte, Yves

    2016-01-01

    Honeybee colony survival strongly relies on the queen to overcome worker losses exposed to combined stressors like pesticides and parasites. Queen’s capacity to withstand these stressors is however very little known. The effects of the common neonicotinoid pesticide imidacloprid in a chronic and sublethal exposure together with the wide distributed parasite Nosema ceranae have therefore been investigated on queen’s physiology and survivorship in laboratory and field conditions. Early physiological changes were observed on queens, particularly the increase of enzyme activities (catalase [CAT] and glutathione-S-transferase [GST] in the heads) related to protective responses to xenobiotics and oxidative stress against pesticide and parasite alone or combined. Stressors also alter the activity of two other enzymes (carboxylesterase alpha [CaE α] and carboxylesterase para [CaE p] in the midguts) involved in metabolic and detoxification functions. Furthermore, single and combined effects of pesticide and parasite decrease survivorship of queens introduced into mating hives for three months. Because colony demographic regulation relies on queen’s fertility, the compromise of its physiology and life can seriously menace colony survival under pressure of combined stressors. PMID:27578396

  20. Combined neonicotinoid pesticide and parasite stress alter honeybee queens' physiology and survival.

    Science.gov (United States)

    Dussaubat, Claudia; Maisonnasse, Alban; Crauser, Didier; Tchamitchian, Sylvie; Bonnet, Marc; Cousin, Marianne; Kretzschmar, André; Brunet, Jean-Luc; Le Conte, Yves

    2016-01-01

    Honeybee colony survival strongly relies on the queen to overcome worker losses exposed to combined stressors like pesticides and parasites. Queen's capacity to withstand these stressors is however very little known. The effects of the common neonicotinoid pesticide imidacloprid in a chronic and sublethal exposure together with the wide distributed parasite Nosema ceranae have therefore been investigated on queen's physiology and survivorship in laboratory and field conditions. Early physiological changes were observed on queens, particularly the increase of enzyme activities (catalase [CAT] and glutathione-S-transferase [GST] in the heads) related to protective responses to xenobiotics and oxidative stress against pesticide and parasite alone or combined. Stressors also alter the activity of two other enzymes (carboxylesterase alpha [CaE α] and carboxylesterase para [CaE p] in the midguts) involved in metabolic and detoxification functions. Furthermore, single and combined effects of pesticide and parasite decrease survivorship of queens introduced into mating hives for three months. Because colony demographic regulation relies on queen's fertility, the compromise of its physiology and life can seriously menace colony survival under pressure of combined stressors.

  1. Sexual Dimorphism in Circadian Physiology Is Altered in LXRα Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Céline Feillet

    Full Text Available The mammalian circadian timing system coordinates key molecular, cellular and physiological processes along the 24-h cycle. Accumulating evidence suggests that many clock-controlled processes display a sexual dimorphism. In mammals this is well exemplified by the difference between the male and female circadian patterns of glucocorticoid hormone secretion and clock gene expression. Here we show that the non-circadian nuclear receptor and metabolic sensor Liver X Receptor alpha (LXRα which is known to regulate glucocorticoid production in mice modulates the sex specific circadian pattern of plasma corticosterone. Lxrα(-/- males display a blunted corticosterone profile while females show higher amplitude as compared to wild type animals. Wild type males are significantly slower than females to resynchronize their locomotor activity rhythm after an 8 h phase advance but this difference is abrogated in Lxrα(-/- males which display a female-like phenotype. We also show that circadian expression patterns of liver 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 and Phosphoenolpyruvate carboxykinase (Pepck differ between sexes and are differentially altered in Lxrα(-/- animals. These changes are associated with a damped profile of plasma glucose oscillation in males but not in females. Sex specific alteration of the insulin and leptin circadian profiles were observed in Lxα(-/- females and could be explained by the change in corticosterone profile. Together this data indicates that LXRα is a determinant of sexually dimorphic circadian patterns of key physiological parameters. The discovery of this unanticipated role for LXRα in circadian physiology underscores the importance of addressing sex differences in chronobiology studies and future LXRα targeted therapies.

  2. Alterations in serotonin receptor-induced contractility of bovine lateral saphenous vein in cattle grazing endophyte-infected tall fescue

    Science.gov (United States)

    As part of a large 2-year study documenting the physiologic impact of grazing endophyte-infected tall fescue on growing cattle, 2 experiments were conducted to characterize and evaluate the effects of grazing 2 levels of toxic endophyte-infected tall fescue pastures on vascular contractility and ser...

  3. Brain Microstructural Abnormalities Are Related to Physiological Alterations in End-Stage Renal Disease.

    Directory of Open Access Journals (Sweden)

    Zhigang Bai

    Full Text Available To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD and examine the relationship between brain microstructure and physiological indictors in the disease.Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18-61 years and 40 age- and gender-matched healthy controls (HCs, 32 men, 22-58 years. A voxel-wise analysis was then used to identify microstructural alterations over the whole brain in the ESRD patients compared with the HCs. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability and dialysis duration were correlated with microstructural integrity for the patients.Compared to the HCs, the ESRD patients exhibited disrupted microstructural integrity in not only white matter (WM but also gray matter (GM regions, as characterized by decreased fractional anisotropy (FA and increased mean diffusivity (MD, axial diffusivity (AD and radial diffusivity (RD. Further correlation analyses revealed that the in MD, AD and RD values showed significantly positive correlations with the blood urea nitrogen in the left superior temporal gyrus and significantly negative correlations with the calcium levels in the left superior frontal gyrus (orbital part in the patients.Our findings suggest that ESRD is associated with widespread diffusion abnormalities in both WM and GM regions in the brain, and microstructural integrity of several GM regions are related to biochemical alterations in the disease.

  4. The resonant component of human physiological hand tremor is altered by slow voluntary movements.

    Science.gov (United States)

    Lakie, Martin; Vernooij, Carlijn A; Osborne, Timothy M; Reynolds, Raymond F

    2012-05-15

    Limb resonance imparts a characteristic spectrum to hand tremor. Movement will alter the resonance. We have examined the consequences of this change. Rectified forearm extensor muscle EMG and physiological hand tremor were recorded. In postural conditions the EMG spectrum is relatively flat whereas the acceleration spectrum is sharply peaked. Consequently, the gain between EMG and acceleration is maximal at the frequency where the tremor is largest (∼8 Hz). The shape of the gain curve implies mechanical resonance. Substantial alterations in posture do not significantly change the characteristics of the tremor or the shape or size of the gain curve. By contrast, slow or moderately paced voluntary wrist flexion–extension movements dramatically increase the hand tremor size and lower its peak frequency. These changes in size and frequency of the tremor cannot be attributed to changes in the EMG. Instead they reflect a very large change in the size and shape of the gain curve relating EMG to acceleration. The gain becomes larger and the peak moves to a lower frequency (∼6 Hz). We suggest that a movement-related (thixotropic) alteration in resonant properties of the wrist provides a simple explanation for these changes. The mechanism is illustrated by a model. Our new findings confirm that resonance plays a major role in wrist tremor. We also demonstrate that muscles operate very differently under postural and dynamic conditions. The different coupling between EMG and movement in posture and when moving must pose a considerable challenge for neural predictive control of skeletal muscles.

  5. The role of serotonin in irritable bowel syndrome: implications for management.

    Science.gov (United States)

    Garvin, Brian; Wiley, John W

    2008-08-01

    Irritable bowel syndrome (IBS) is a poorly understood, common, chronic condition characterized by -abdominal discomfort associated with altered bowel habits in the absence of structural or biochemical abnormalities. Despite the significant economic and personal burden associated with IBS, treatment options remain limited. Serotonin is recognized as a key neurotransmitter in intestinal secretory, sensory, and motor function. Although the pathophysiology of IBS is incompletely understood, there is evidence that abnormalities in brain-gut signaling and serotonin metabolism play a role. This article reviews the evidence that serotonin, one of the better-understood neurotransmitters with respect to its role in human central and intestinal physiology, plays a role in IBS. Serotonin signaling is discussed, with a focus on receptor subtypes and the therapeutic agents that target these receptors. Evidence that IBS is associated with perturbations in serotonin metabolism at various steps in the signaling pathway is also addressed, along with the limitations on alteration in serotonin metabolism as the sole explanation for the constellation of symptoms observed in patients with IBS.

  6. Conservation of 5-HT1A receptor-mediated autoinhibition of serotonin (5-HT neurons in mice with altered 5-HT homeostasis

    Directory of Open Access Journals (Sweden)

    Naozumi eAraragi

    2013-08-01

    Full Text Available Firing activity of serotonin (5-HT neurons in the dorsal raphe nucleus (DRN is controlled by inhibitory somatodendritic 5-HT1A autoreceptors. This autoinhibitory mechanism is implicated in the etiology of disorders of emotion regulation, such as anxiety disorders and depression, as well as in the mechanism of antidepressant action. Here, we investigated how persistent alterations in brain 5-HT availability affect autoinhibition in two genetically modified mouse models lacking critical mediators of serotonergic transmission: 5-HT transporter knockout (Sert -/- and tryptophan hydroxylase-2 knockout (Tph2 -/- mice. The degree of autoinhibition was assessed by loose-seal cell-attached recording in DRN slices. First, application of the 5-HT1A-selective agonist R(+-8-hydroxy-2-(di-n-propylaminotetralin showed mild sensitization and marked desensitization of 5-HT1A receptors in Tph2 -/- mice and Sert -/- mice, respectively. While 5-HT neurons from Tph2 -/- mice did not display autoinhibition in response to L-tryptophan, autoinhibition of these neurons was unaltered in Sert -/- mice despite marked desensitization of their 5-HT1A autoreceptors. When the Tph2-dependent 5-HT synthesis step was bypassed by application of 5-hydroxy-L-tryptophan (5-HTP, neurons from both Tph2 -/- and Sert -/- mice decreased their firing rates at significantly lower concentrations of 5-HTP compared to wildtype controls. Our findings demonstrate that, as opposed to the prevalent view, sensitivity of somatodendritic 5-HT1A receptors does not predict the magnitude of 5-HT neuron autoinhibition. Changes in 5-HT1A receptor sensitivity may rather be seen as an adaptive mechanism to keep autoinhibition functioning in response to extremely altered levels of extracellular 5-HT resulting from targeted inactivation of mediators of serotonergic signaling.

  7. [Serotonin syndrome].

    Science.gov (United States)

    Lheureux, P; Penaloza, A; De Cottenier, V; Ullmann, U; Gris, M

    2002-10-01

    The serotonin syndrome is a hyperserotoninergic state resulting from an excess of intrasynaptic 5-hydroxytryptamine, induced by multiple psychotropic agents, but also non psychiatric drugs. It is a potentially dangerous and sometimes lethal condition. The clinical manifestations usually include cognitive, neuromuscular and autonomic features and are mediated by the action of serotonin on various subtypes of receptors. The main differential diagnosis is the neuroleptic malignant syndrome. Treatment is mainly supportive. No pharmacological agent has been definitely demonstrated really effective. However, reports of cases treated with the 5-HT2 blockers, including cyproheptadine or chlorpromazine have suggested that these agents could have some efficacy. Serotonin syndrome is a toxic condition which requires heightened clinical awareness among physicians in order to prevent, recognize, and treat the condition promptly.

  8. Physiology

    Science.gov (United States)

    Kay, Ian

    2008-01-01

    Underlying recent developments in health care and new treatments for disease are advances in basic medical sciences. This edition of "Webwatch" focuses on sites dealing with basic medical sciences, with particular attention given to physiology. There is a vast amount of information on the web related to physiology. The sites that are included here…

  9. Automated mass spectrometric analysis of urinary and plasma serotonin

    NARCIS (Netherlands)

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

    2010-01-01

    Serotonin emerges as crucial neurotransmitter and hormone in a growing number of different physiologic processes. Besides extensive serotonin production previously noted in patients with metastatic carcinoid tumors, serotonin now is implicated in liver cell regeneration and bone formation. The aim w

  10. Alteration of complex sphingolipid composition and its physiological significance in yeast Saccharomyces cerevisiae lacking vacuolar ATPase.

    Science.gov (United States)

    Tani, Motohiro; Toume, Moeko

    2015-12-01

    In the yeast Saccharomyces cerevisiae, complex sphingolipids have three types of polar head group and five types of ceramide; however, the physiological significance of the structural diversity is not fully understood. Here, we report that deletion of vacuolar H+-ATPase (V-ATPase) in yeast causes dramatic alteration of the complex sphingolipid composition, which includes decreases in hydroxylation at the C-4 position of long-chain bases and the C-2 position of fatty acids in the ceramide moiety, decreases in inositol phosphorylceramide (IPC) levels, and increases in mannosylinositol phosphorylceramide (MIPC) and mannosyldiinositol phosphorylceramide [M(IP)2C] levels. V-ATPase-deleted cells exhibited slow growth at pH 7.2, whereas the increase in MIPC levels was significantly enhanced when V-ATPase-deleted cells were incubated at pH 7.2. The protein expression levels of MIPC and M(IP)2C synthases were significantly increased in V-ATPase-deleted cells incubated at pH 7.2. Loss of MIPC synthesis or an increase in the hydroxylation level of the ceramide moiety of sphingolipids on overexpression of Scs7 and Sur2 sphingolipid hydroxylases enhanced the growth defect of V-ATPase-deleted cells at pH 7.2. On the contrary, the growth rate of V-ATPase-deleted cells was moderately increased on the deletion of SCS7 and SUR2. In addition, supersensitivities to Ca2+, Zn2+ and H2O2, which are typical phenotypes of V-ATPase-deleted cells, were enhanced by the loss of MIPC synthesis. These results indicate the possibility that alteration of the complex sphingolipid composition is an adaptation mechanism for a defect of V-ATPase.

  11. High temperatures alter physiological properties of pyramidal cells and inhibitory interneurons in hippocampus

    Directory of Open Access Journals (Sweden)

    Jennifer eKim

    2012-07-01

    Full Text Available Temperature has multiple effects on neurons, yet little is known about the effects of high temperature on the physiology of mammalian central neurons. Hyperthermia can influence behavior and cause febrile seizures. We studied the effects of acute hyperthermia on the immature hippocampus in vitro by recording from pyramidal neurons and inhibitory oriens-lacunosum moleculare (O-LM interneurons (identified by green fluorescent protein expression in the GIN mouse line. Warming to 41°C caused depolarization, spontaneous action potentials, reduced input resistance and membrane time constant, and increased spontaneous synaptic activity of most pyramidal cells and O-LM interneurons. Pyramidal neurons of area CA3 were more strongly excited by hyperthermia than those of area CA1. About 90% of O-LM interneurons in both CA1 and CA3 increased their firing rates at hyperthermic temperatures; interneurons in CA3 fired faster than those in CA1 on average. Blockade of fast synaptic transmission did not abolish the effect of hyperthermia on neuronal excitability. Our results suggest that hyperthermia increases hippocampal excitability, particularly in seizure-prone area CA3, by altering the intrinsic membrane properties of pyramidal cells and interneurons.

  12. High temperatures alter physiological properties of pyramidal cells and inhibitory interneurons in hippocampus.

    Science.gov (United States)

    Kim, Jennifer A; Connors, Barry W

    2012-01-01

    Temperature has multiple effects on neurons, yet little is known about the effects of high temperature on the physiology of mammalian central neurons. Hyperthermia can influence behavior and cause febrile seizures. We studied the effects of acute hyperthermia on the immature hippocampus in vitro by recording from pyramidal neurons and inhibitory oriens-lacunosum moleculare (O-LM) interneurons (identified by green fluorescent protein (GFP) expression in the GIN mouse line). Warming to 41°C caused depolarization, spontaneous action potentials, reduced input resistance and membrane time constant, and increased spontaneous synaptic activity of most pyramidal cells and O-LM interneurons. Pyramidal neurons of area CA3 were more strongly excited by hyperthermia than those of area CA1. About 90% of O-LM interneurons in both CA1 and CA3 increased their firing rates at hyperthermic temperatures; interneurons in CA3 fired faster than those in CA1 on average. Blockade of fast synaptic transmission did not abolish the effect of hyperthermia on neuronal excitability. Our results suggest that hyperthermia increases hippocampal excitability, particularly in seizure-prone area CA3, by altering the intrinsic membrane properties of pyramidal cells and interneurons.

  13. Acid mist and soil Ca and Al alter the mineral nutrition and physiology of red spruce

    Energy Technology Data Exchange (ETDEWEB)

    Schaberg, P. G.; Murakami, P. F. [Northeastern Research Station, Burlington, VT (United States); Dehayes, D. H.; Hawley, G. J.; Strimbeck, G. R.; Borer, C. H. [Vermont Univ., School of Natural Resources, Burlington, VT (United States); Cumming, J. R. [West Virginia Univ, Dept. of Biology, Morgantown, WV (United States)

    2000-01-01

    The effects and potential interactions of acid mist and soil solutions of calcium and aluminium treatments on foliar cation concentrations, membrane-associated calcium leaching, growth, carbon exchange and cold tolerance in red spruce saplings was investigated. Results showed that soil solution calcium addition increased foliar calcium and zinc concentrations and increased the rate of respiration early in the growing season. Soil aluminium treatment reduced foliar concentrations of calcium, manganese, magnesium, phosphorus and zinc, which in turn, produced smaller stem diameters and shoot lengths. On the whole, aluminium -induced alterations in growth or physiology appeared to be independent of foliar calcium status. As a general rule, reduction in cation concentration associated with aluminium addition were greater for pH 5.0-treated saplings than for pH 3.0-treated saplings. This observation led the investigators to conclude that the mechanism underlying acid-induced reductions in foliar cold tolerance in red spruce is hydrogen ion-induced leaching of membrane-associated calcium from mesophyll cells. 93 refs., 6 tabs., 1 fig.

  14. GABA concentration and GABAergic neuron populations in limbic areas are differentially altered by brain serotonin deficiency in Tph2 knockout mice.

    Science.gov (United States)

    Waider, Jonas; Proft, Florian; Langlhofer, Georg; Asan, Esther; Lesch, Klaus-Peter; Gutknecht, Lise

    2013-02-01

    While tryptophan hydroxylase-2 (Tph2) null mutant (Tph2(-/-)) mice are completely deficient in brain serotonin (5-HT) synthesis, the formation of serotonergic neurons and pathfinding of their projections are not impaired. However, 5-HT deficiency, during development and in the adult, might affect morphological and functional parameters of other neural systems. To assess the influence of 5-HT deficiency on γ-amino butyric acid (GABA) systems, we carried out measurements of GABA concentrations in limbic brain regions of adult male wildtype (wt), heterozygous (Tph2(+/-)) and Tph2(-/-) mice. In addition, unbiased stereological estimation of GABAergic interneuron numbers and density was performed in subregions of amygdala and hippocampus. Amygdala and prefrontal cortex displayed significantly increased and decreased GABA concentrations, respectively, exclusively in Tph2(+/-) mice while no changes were detected between Tph2(-/-) and wt mice. In contrast, in the hippocampus, increased GABA concentrations were found in Tph2(-/-) mice. While total cell density in the anterior basolateral amygdala did not differ between genotypes, the number and density of the GABAergic interneurons were significantly decreased in Tph2(-/-) mice, with the group of parvalbumin (PV)-immunoreactive (ir) interneurons contributing somewhat less to the decrease than that of non-PV-ir GABAergic interneurons. Major morphological changes were also absent in the dorsal hippocampus, and only a trend toward reduced density of PV-ir cells was observed in the CA3 region of Tph2(-/-) mice. Our findings are the first to document that life-long reduction or complete lack of brain 5-HT transmission causes differential changes of GABA systems in limbic regions which are key players in emotional learning and memory processes. The changes likely reflect a combination of developmental alterations and functional adaptations of emotion circuits to balance the lack of 5-HT, and may underlie altered emotional

  15. Physiological and molecular alterations in plants exposed to high [CO2] under phosphorus stress.

    Science.gov (United States)

    Pandey, Renu; Zinta, Gaurav; AbdElgawad, Hamada; Ahmad, Altaf; Jain, Vanita; Janssens, Ivan A

    2015-01-01

    Atmospheric [CO2] has increased substantially in recent decades and will continue to do so, whereas the availability of phosphorus (P) is limited and unlikely to increase in the future. P is a non-renewable resource, and it is essential to every form of life. P is a key plant nutrient controlling the responsiveness of photosynthesis to [CO2]. Increases in [CO2] typically results in increased biomass through stimulation of net photosynthesis, and hence enhance the demand for P uptake. However, most soils contain low concentrations of available P. Therefore, low P is one of the major growth-limiting factors for plants in many agricultural and natural ecosystems. The adaptive responses of plants to [CO2] and P availability encompass alterations at morphological, physiological, biochemical and molecular levels. In general low P reduces growth, whereas high [CO2] enhances it particularly in C3 plants. Photosynthetic capacity is often enhanced under high [CO2] with sufficient P supply through modulation of enzyme activities involved in carbon fixation such as ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). However, high [CO2] with low P availability results in enhanced dry matter partitioning towards roots. Alterations in below-ground processes including root morphology, exudation and mycorrhizal association are influenced by [CO2] and P availability. Under high P availability, elevated [CO2] improves the uptake of P from soil. In contrast, under low P availability, high [CO2] mainly improves the efficiency with which plants produce biomass per unit P. At molecular level, the spatio-temporal regulation of genes involved in plant adaptation to low P and high [CO2] has been studied individually in various plant species. Genome-wide expression profiling of high [CO2] grown plants revealed hormonal regulation of biomass accumulation through complex transcriptional networks. Similarly, differential transcriptional regulatory networks are involved in P

  16. Exposure to acetylcholinesterase inhibitors alters the physiology and motor function of honeybees

    Directory of Open Access Journals (Sweden)

    Sally M Williamson

    2013-02-01

    Full Text Available Cholinergic signalling is fundamental to neuro-muscular function in most organisms. Sub-lethal doses of neurotoxic pesticides that target cholinergic signalling can alter the behaviour of insects in subtle ways; their influence on non-target organisms may not be readily apparent in simple mortality studies. Beneficial arthropods such as honeybees perform sophisticated behavioural sequences during foraging that, if influenced by pesticides, could impair foraging success and reduce colony health. Here, we investigate the behavioural effects on honeybees of exposure to a selection of pesticides that target cholinergic signalling by inhibiting acetylcholinesterase (AChE. To examine how continued exposure to AChE inhibitors affected motor function, we fed adult foraging worker honeybees sub-lethal concentrations of these compounds in sucrose solution for 24 h. Using an assay for locomotion in bees, we scored walking, stopped, grooming, and upside down behaviour continuously for 15 min. At a 10nM concentration, all the AChE inhibitors caused similar effects on behaviour, notably increased grooming activity and changes in the frequency of bouts of behaviour such as head grooming. Coumaphos caused dose-dependent effects on locomotion as well as grooming behaviour, and a 1µM concentration of coumaphos induced symptoms of malaise such as abdomen grooming and defecation. Biochemical assays confirmed that the 4 compounds we assayed (coumaphos, aldicarb, chlorpyrifos, and donepezil or their metabolites acted as AChE inhibitors in bees. Furthermore, we show that transcript expression levels of two honeybee acetylcholinesterase inhibitors were selectively upregulated in the brain and in gut tissues in response to AChE inhibitor exposure. The results of our study imply that the effects of pesticides that rely on this mode of action have subtle yet profound effects on physiological effects on behaviour that could lead to reduced survival.

  17. Lasting syndrome of depression produced by reduction in serotonin uptake during postnatal development: evidence from sleep, stress, and behavior.

    Science.gov (United States)

    Popa, Daniela; Léna, Clément; Alexandre, Chloé; Adrien, Joëlle

    2008-04-02

    Dysfunction of the serotonin system is implicated in sleep and emotional disorders. To test whether these impairments could arise during development, we studied the impact of early-life, transient versus genetic, permanent alterations of serotonin reuptake on sleep-wakefulness patterns, depression-related behavior, and associated physiological features. Here, we show that female mice treated neonatally with a highly selective serotonin reuptake inhibitor, escitalopram, exhibited signs of depression in the form of sleep anomalies, anhedonia, increased helplessness reversed by chronic antidepressant treatment, enhanced response to acute stress, and increased serotoninergic autoinhibitory feedback. This syndrome was not reproduced by treatment in naive adults but resembled the phenotype of mutant mice lacking the serotonin transporter, except that these exhibited decreased serotonin autoreceptor sensitivity and additional anxiety-like behavior. Thus, alteration of serotonin reuptake during development, whether induced by external or genetic factors, causes a depressive syndrome lasting into adulthood. Such early-life impairments might predispose individuals to sleep and/or mood disorders.

  18. 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.

  19. 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.

  20. Chronic treatment with meta-chlorophenylpiperazine (m-CPP) alters behavioral and cerebral metabolic responses to the serotonin agonists m-CPP and quipazine but not 8-hydroxy-2(di-N-propylamino)tetralin.

    Science.gov (United States)

    Freo, U; Holloway, H W; Greig, N H; Soncrant, T T

    1992-01-01

    The effects of the serotonin (5-HT) agonists meta-chlorophenylpiperazine (m-CPP), quipazine and 8-hydroxy-2(di-n-propylamino)tetralin (DPAT) on behavior and on regional cerebral metabolic rates for glucose (rCMRglc) were measured in control rats or in rats pretreated for 2 weeks with continuous infusion of saline or m-CPP (2.5 mg/kg/day, subcutaneously). rCMRglc was measured in 71 brain regions, using the quantitative autoradiographic [14C]2-deoxy-D-glucose technique, at 15 min after acute administration of m-CPP 2.5 mg/kg, 60 min after quipazine 20 mg/kg, or 10 min after DPAT 1 mg/kg. Behavioral effects were assessed for m-CPP with an activity monitor, for quipazine by counting head shakes and for DPAT by scoring the serotonin syndrome. Chronic m-CPP pretreatment produced tolerance to hypolocomotion induced by acute m-CPP and to head shakes caused by acute quipazine, but did not alter the serotonin syndrome produced by DPAT. m-CPP 2.5 mg/kg IP produced widespread rCMRglc reductions in control rats but failed to modify rCMRglc in any region after chronic m-CPP pretreatment. Quipazine increased rCMRglc in 4 regions in control rats, but reduced rCMRglc in 14 brain areas of chronically m-CPP-pretreated animals. DPAT altered rCMRglc to the same degree in control (25 regions affected) and in chronically m-CPP-pretreated rats (28 regions affected). Reduced behavioral and metabolic effects of acute m-CPP in chronically m-CPP-pretreated rats were not due to pharmacokinetic alterations. These results demonstrate that chronic administration of m-CPP produces behavioral and metabolic tolerance to acute administration of m-CPP, but not of DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Modulation of motoneuron activity by serotonin.

    Science.gov (United States)

    Perrier, Jean-François

    2016-02-01

    Serotonin is a major neuromodulator in the central nervous system involved in most physiological functions including appetite regulation, sexual arousal, sleep regulation and motor control. The activity of neurons from the raphe spinal tract, which release serotonin on motoneurons, is positively correlated with motor behaviour. During moderate physical activity, serotonin is released from synaptic terminals onto the dendrites and cell bodies of motoneurons. Serotonin increases the excitability of motoneurons and thereby facilitate muscle contraction by acting on several parallel intracellular pathways. By activating 5-HT1A receptors, serotonin inhibits TWIK-related acid-sensitive potassium channels and small conductance calcium-activated potassium channels. In parallel, serotonin binds to 5-HT2 receptors, which promotes the low-threshold L-type Ca(2+) channels. During intense physical activity, more serotonin is released. The reuptake systems saturate and serotonin spills over to reach extrasynaptic 5-HT1A receptors located on the axon initial segment of motoneurons. This in turn induces the inhibition of the Na(+) channels responsible for the initiation of action potentials. Fewer nerve impulses are generated and muscle contraction becomes weaker. By decreasing the gain of motoneurons, serotonin triggers central fatigue.

  2. Both stimulatory and inhibitory effects of dietary 5-hydroxytryptophan and tyrosine are found on urinary excretion of serotonin and dopamine in a large human population

    Directory of Open Access Journals (Sweden)

    George J Trachte

    2009-04-01

    Full Text Available George J Trachte1, Thomas Uncini2, Marty Hinz31Department of Physiology and Pharmacology, University of MN Medical School Duluth, Duluth, MN, USA; 2Chief Medical Examiner, St. Louis County, Hibbing, MN, USA; 3Clinical Research, NeuroResearch Clinics, Inc., Duluth, MN, USA Abstract: Amino acid precursors of dopamine and serotonin have been administered for decades to treat a variety of clinical conditions including depression, anxiety, insomnia, obesity, and a host of other illnesses. Dietary administration of these amino acids is designed to increase dopamine and serotonin levels within the body, particularly the brain. Convincing evidence exists that these precursors normally elevate dopamine and serotonin levels within critical brain tissues and other organs. However, their effects on urinary excretion of neurotransmitters are described in few studies and the results appear equivocal. The purpose of this study was to define, as precisely as possible, the influence of both 5-hydroxytryptophan (5-HTP and tyrosine on urinary excretion of serotonin and dopamine in a large human population consuming both 5-HTP and tyrosine. Curiously, only 5-HTP exhibited a marginal stimulatory influence on urinary serotonin excretion when 5-HTP doses were compared to urinary serotonin excretion; however, a robust relationship was observed when alterations in 5-HTP dose were compared to alterations in urinary serotonin excretion in individual patients. The data indicate three statistically discernible components to 5-HTP responses, including inverse, direct, and no relationships between urinary serotonin excretion and 5-HTP doses. The response to tyrosine was more consistent but primarily yielded an unexpected reduction in urinary dopamine excretion. These data indicate that the urinary excretion pattern of neurotransmitters after consumption of their precursors is far more complex than previously appreciated. These data on urinary neurotransmitter excretion might

  3. High temperatures alter physiological properties of pyramidal cells and inhibitory interneurons in hippocampus

    OpenAIRE

    Kim, Jennifer A; Barry W Connors

    2012-01-01

    Temperature has multiple effects on neurons, yet little is known about the effects of high temperature on the physiology of mammalian central neurons. Hyperthermia can influence behavior and cause febrile seizures. We studied the effects of acute hyperthermia on the immature hippocampus in vitro by recording from pyramidal neurons and inhibitory oriens-lacunosum moleculare (O-LM) interneurons (identified by green fluorescent protein (GFP) expression in the GIN mouse line). Warming to 41°C cau...

  4. Altered male physiologic function after surgery for prostate cancer: couple perspective

    Directory of Open Access Journals (Sweden)

    Matvey Tsivian

    2009-12-01

    Full Text Available Purpose: Both the diagnosis of prostate cancer (PCa and the physiologic outcomes of surgical treatment impact the male’s psychological sphere. However, current research advocates a refocusing of outcomes directed to the PCa “couple”. Herein we acquire insight into perspective and concordance regarding male physiological function from the standpoint of a couple recovering from PCa surgery. Materials and methods: Couples whereby the male partner had undergone primary surgical treatment for PCa were mailed a Retrospective Sexual Survey (RSS packet consisting of male and female partner questionnaires. RSS questions surveyed physiological changes in libido, foreplay, erection and arousal, orgasm and ejaculation in addition to perceived psychological impact. Patients’ and partners’ scores were evaluated to determine the concordance of both individual items as well as domain sums. Results: Twenty-eight couples completed the questionnaires. Only about 40% of men and women were happy with their levels of sexual interest with 82% concordance. Urine loss during orgasm was reported by 43% of men; the majority of participants were bothered by it. Ejaculation changes were observed by 96% of men (concordance 96% with most reporting anejaculation. A change in orgasm experience was noted by 86% of men (and 36% of their female partners, p < 0.0001. Despite the change, the majority of men and women reported being satisfied with their ability to climax. Conclusion: Our results indicate that patients and their female partners may interpret differently the same physiological outcomes of PCa surgery. This information could be useful to better counsel the PCa couple and help patients and partners adjust after surgery.

  5. Suppression of serotonin neuron firing increases aggression in mice.

    Science.gov (United States)

    Audero, Enrica; Mlinar, Boris; Baccini, Gilda; Skachokova, Zhiva K; Corradetti, Renato; Gross, Cornelius

    2013-05-15

    Numerous studies link decreased serotonin metabolites with increased impulsive and aggressive traits. However, although pharmacological depletion of serotonin is associated with increased aggression, interventions aimed at directly decreasing serotonin neuron activity have supported the opposite association. Furthermore, it is not clear if altered serotonin activity during development may contribute to some of the observed associations. Here, we used two pharmacogenetic approaches in transgenic mice to selectively and reversibly reduce the firing of serotonin neurons in behaving animals. Conditional overexpression of the serotonin 1A receptor (Htr1a) in serotonin neurons showed that a chronic reduction in serotonin neuron firing was associated with heightened aggression. Overexpression of Htr1a in adulthood, but not during development, was sufficient to increase aggression. Rapid suppression of serotonin neuron firing by agonist treatment of mice expressing Htr1a exclusively in serotonin neurons also led to increased aggression. These data confirm a role of serotonin activity in setting thresholds for aggressive behavior and support a direct association between low levels of serotonin homeostasis and increased aggression.

  6. Genetic variations alter physiological responses following heat stress in 2 strains of laying hens.

    Science.gov (United States)

    Felver-Gant, J N; Mack, L A; Dennis, R L; Eicher, S D; Cheng, H W

    2012-07-01

    Heat stress (HS) is a major problem experienced by the poultry industry during high-temperature conditions. The ability to manage the detrimental effects of HS can be attributed to multiple factors, including genetic background of flocks. The objective of the present study was to determine the genetic variation in HS effects on laying hens' physiological homeostasis. Ninety 28-wk-old White Leghorn hens of 2 strains were used: a commercial line of individually selected hens for high egg production, DeKalb XL (DXL), and a line of group-selected hens for high productivity and survivability, named kind gentle bird (KGB). Hens were randomly paired by strain and assigned to hot or control treatment for 14 d. Physical and physiological parameters were analyzed at d 8 and 14 posttreatment. Compared with controls, HS increased hen's core body temperature (P hens exposed to HS (P hens, KGB hens had higher heat shock protein 70 concentrations (P hens' liver weight decreased following HS, with less of a response in the KGB line (P hens due to genetic variations. These data provide evidence that is valuable for determining genetic interventions for laying hens under HS.

  7. Can architectural design alter the physiological reaction to psychosocial stress? A virtual TSST experiment.

    Science.gov (United States)

    Fich, Lars Brorson; Jönsson, Peter; Kirkegaard, Poul Henning; Wallergård, Mattias; Garde, Anne Helene; Hansen, Åse

    2014-08-01

    Is has long been established, that views to natural scenes can a have a dampening effect on physiological stress responses. However, as people in Europe, Canada and North America today spent 50-85% of their time indoors, attention might also be paid to how the artificial man-made indoor environment influences these mechanisms. The question that this study attempts to start addressing is therefore whether certain design, characteristics of indoor spaces can make a difference to the physiological stress response as well. Using a virtual version of the Trier Social Stress Test, in which the space is computer generated and properties of the space therefore can be systematically varied, we measured saliva cortisol and heart rate variability in participants in a closed room versus a room with openings. As shown by a significant linear contrast interaction between groups and TSST conditions, participants in the closed room responded with more pronounced cortisol reactivity to stress induction, and continued to show higher levels throughout recovery, compared to participants in the open room. No differences were found regarding any part of the autonomic nervous system.

  8. Physiologic and pathophysiologic consequences of altered sialylation and glycosylation on ion channel function.

    Science.gov (United States)

    Baycin-Hizal, Deniz; Gottschalk, Allan; Jacobson, Elena; Mai, Sunny; Wolozny, Daniel; Zhang, Hui; Krag, Sharon S; Betenbaugh, Michael J

    2014-10-17

    Voltage-gated ion channels are transmembrane proteins that regulate electrical excitability in cells and are essential components of the electrically active tissues of nerves, muscle and the heart. Potassium channels are one of the largest subfamilies of voltage sensitive channels and are among the most-studied of the voltage-gated ion channels. Voltage-gated channels can be glycosylated and changes in the glycosylation pattern can affect ion channel function, leading to neurological and neuromuscular disorders and congenital disorders of glycosylation (CDG). Alterations in glycosylation can also be acquired and appear to play a role in development and aging. Recent studies have focused on the impact of glycosylation and sialylation on ion channels, particularly for voltage-gated potassium and sodium channels. The terminal step of sialylation often affects channel activation and inactivation kinetics. The presence of sialic acids on O or N-glycans can alter the gating mechanism and cause conformational changes in the voltage-sensing domains due to sialic acid's negative charges. This manuscript will provide an overview of sialic acids, potassium and sodium channel function, and the impact of sialylation on channel activation and deactivation.

  9. Serotonin transporter and memory.

    Science.gov (United States)

    Meneses, Alfredo; Perez-Garcia, Georgina; Ponce-Lopez, Teresa; Tellez, Ruth; Castillo, Carlos

    2011-09-01

    The serotonin transporter (SERT) has been associated to diverse functions and diseases, though seldom to memory. Therefore, we made an attempt to summarize and discuss the available publications implicating the involvement of the SERT in memory, amnesia and anti-amnesic effects. Evidence indicates that Alzheimer's disease and drugs of abuse like d-methamphetamine (METH) and (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") have been associated to decrements in the SERT expression and memory deficits. Several reports have indicated that memory formation and amnesia affected the SERT expression. The SERT expression seems to be a reliable neural marker related to memory mechanisms, its alterations and potential treatment. The pharmacological, neural and molecular mechanisms associated to these changes are of great importance for investigation.

  10. Neuroendocrine disruption in the shore crab Carcinus maenas: Effects of serotonin and fluoxetine on chh- and mih-gene expression, glycaemia and ecdysteroid levels.

    Science.gov (United States)

    Robert, Alexandrine; Monsinjon, Tiphaine; Delbecque, Jean-Paul; Olivier, Stéphanie; Poret, Agnès; Foll, Frank Le; Durand, Fabrice; Knigge, Thomas

    2016-06-01

    Serotonin, a highly conserved neurotransmitter, controls many biological functions in vertebrates, but also in invertebrates. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are commonly used in human medication to ease depression by affecting serotonin levels. Their residues and metabolites can be detected in the aquatic environment and its biota. They may also alter serotonin levels in aquatic invertebrates, thereby perturbing physiological functions. To investigate whether such perturbations can indeed be expected, shore crabs (Carcinus maenas) were injected either with serotonin, fluoxetine or a combination of both. Dose-dependent effects of fluoxetine ranging from 250 to 750nM were investigated. Gene expression of crustacean hyperglycemic hormone (chh) as well as moult inhibiting hormone (mih) was assessed by RT-qPCR at 2h and 12h after injection. Glucose and ecdysteroid levels in the haemolymph were monitored in regular intervals until 12h. Serotonin led to a rapid increase of chh and mih expression. On the contrary, fluoxetine only affected chh and mih expression after several hours, but kept expression levels significantly elevated. Correspondingly, serotonin rapidly increased glycaemia, which returned to normal or below normal levels after 12h. Fluoxetine, however, resulted in a persistent low-level increase of glycaemia, notably during the period when negative feedback regulation reduced glycaemia in the serotonin treated animals. Ecdysteroid levels were significantly decreased by serotonin and fluoxetine, with the latter showing less pronounced and less rapid, but longer lasting effects. Impacts of fluoxetine on glycaemia and ecdysteroids were mostly observed at higher doses (500 and 750nM) and affected principally the response dynamics, but not the amplitude of glycaemia and ecdysteroid-levels. These results suggest that psychoactive drugs are able to disrupt neuroendocrine control in decapod crustaceans, as they interfere with the

  11. Physiological, biochemical and histological alterations induced by administration of imidacloprid in female albino rats.

    Science.gov (United States)

    Vohra, Prerna; Khera, Kuldeep Singh; Sangha, Gurinder Kaur

    2014-03-01

    Imidacloprid, a neonicotinoid the newest class of major insecticide has outstanding potency and systemic action for crop protection against piercing and sucking insects pests and also highly effective for control of flea on cats and dogs. The effect of oral administration of two doses of imidacloprid 10 and 20mg/kg/day for 60 days on biochemical parameters, histopathology and protein profile of female albino rat was assessed. Average feed intake was significantly reduced (Pimidacloprid treated groups. There was significant decrease (Pimidacloprid treated groups. Microscopically, liver tissue of rats treated with higher dose of imidacloprid showed marked dilation and congestion of central vein and degeneration of hepatocytes. The exposure to imidacloprid produced histopathological changes that could be correlated with changes in the biochemical profile of female albino rats. The blood plasma proteins were examined by SDS PAGE. There was no diagnostic difference in the pattern of plasma protein profile of control and treated rats. Based on the present physiological, biochemical and histological studies it is evident that imidacloprid did not produce any significant effects at 10mg/kg/day dose but induced toxicological effects at 20mg/kg/day to female rats.

  12. Transcriptomic underpinning of toxicant-mediated physiological function alterations in three terrestrial invertebrate taxa: A review

    Energy Technology Data Exchange (ETDEWEB)

    Brulle, Franck [Univ Lille Nord de France, F59000 Lille (France); LGCgE-Lille 1, Ecologie Numerique et Ecotoxicologie, F-59650 Villeneuve d' Ascq (France); Morgan, A. John [Cardiff School of Biosciences, Cardiff University, P.O. Box 915, Cardiff, CF10 3US Wales (United Kingdom); Cocquerelle, Claude [Univ Lille Nord de France, F59000 Lille (France); LGCgE-Lille 1, Ecologie Numerique et Ecotoxicologie, F-59650 Villeneuve d' Ascq (France); Vandenbulcke, Franck, E-mail: franck.vandenbulcke@univ-lille1.f [Univ Lille Nord de France, F59000 Lille (France); LGCgE-Lille 1, Ecologie Numerique et Ecotoxicologie, F-59650 Villeneuve d' Ascq (France)

    2010-09-15

    Diverse anthropogenic activities often lead to the accumulation of inorganic and organic residues in topsoils. Biota living in close contact with contaminated soils may experience stress at different levels of biological organisation throughout the continuum from the molecular-genetic to ecological and community levels. To date, the relationship between changes at the molecular (mRNA expression) and biochemical/physiological levels evoked by exposures to chemical compounds has been partially established in a limited number of terrestrial invertebrate species. Recently, the advent of a family of transcriptomic tools (e.g. Real-time PCR, Subtractive Suppressive Hybridization, Expressed Sequence Tag sequencing, pyro-sequencing technologies, Microarray chips), together with supporting informatic and statistical procedures, have permitted the robust analyses of global gene expression changes within an ecotoxicological context. This review focuses on how transcriptomics is enlightening our understanding of the molecular-genetic responses of three contrasting terrestrial macroinvertebrate taxa (nematodes, earthworms, and springtails) to inorganics, organics, and agrochemicals. - Environmental toxicology and transcriptomics in soil macroinvertebrates.

  13. Olfactory perception in women with physiologically altered hormonal status (during pregnancy and postmenopause

    Directory of Open Access Journals (Sweden)

    Savović Slobodan N.

    2002-01-01

    Full Text Available Introduction Olfaction is considered to be the ability to: perceive, conduct and recognize scents and odors. With its numerous connections to the limbic system and reticular formation, the olfactory system affects regulation of numerous vegetative functions, visceral functions and sexual behavior. Since estrogen and progesterone protect the olfactory function, changes in their levels in particular physiological states in women (in pregnancy and postmenopause exert an influence on the ability to feel and recognize smells. It has its role in creating emotions and adjustment of visceral and vegetative response to particular emotional states. Also, it represents the connection between higher cortical functions and the endocrine system. Material and methods Our investigation was performed at the Ear, Nose and Throat Clinic in Novi Sad. The research included 80 healthy women classified into 4 groups; 20 women aged between 20 and 30; 20 women in the first trimester of pregnancy aged between 20 and 30; 20 premenopausal women aged between 41 and 50; and 20 women at least 3 years in postmenopause, aged between 41 and 50. For our research we used an olfactometer and the Fortunato-Niccolini method. Results and discussion In pregnancy the thresholds of perception (TP and identification (TI of examined substances were slightly lower in comparison to nonpregnant women of the same ages, but without any statistical significance (p>0.05. In climacteric-postmenopausal women there was a significant decrease of olfactory ability in comparison to nonmenopausal women of the same ages (p<0.01. Conclusion All changes of the olfactory function in pregnancy are explained by mental changes of pregnant women as well as their hormonal status. Significant decrease of olfactory ability in postmenopause is explained by decline in sexual hormone levels.

  14. Single sublethal dose of microcystin-LR is responsible for different alterations in biochemical, histological and physiological renal parameters.

    Science.gov (United States)

    Lowe, J; Souza-Menezes, J; Freire, D S; Mattos, L J; Castiglione, R C; Barbosa, C M L; Santiago, L; Ferrão, F M; Cardoso, L H D; da Silva, R T; Vieira-Beiral, H J; Vieyra, A; Morales, M M; Azevedo, S M F O; Soares, R M

    2012-05-01

    Microcystins (MCYSTs) are very stable cyclic peptidic toxins produced by cyanobacteria. Their effects on hepatic tissue have been studied extensively, and they are considered to be a potent hepatotoxin. However, several effects of MCYST on other organs have also been described, but generally in studies using higher doses of MCYST. In the present work, we investigated the effect of a single sublethal dose of MCYST-LR (55 μg/kg) in Wistar rats and analyzed different aspects that influenced renal physiology, including toxin accumulation, excretion, histological morphology, biochemical responses and oxidative damage in the kidney. After 24 h of exposure to MCYST-LR, it was possible to observe an increased glomerular filtration rate (6.28 ± 1.56 vs 2.16 ± 0.48 μl/min per cm(2)) compared with the control group. Increase of interstitial space and collagen deposition corresponded to a fibrotic response to the increased production of reactive oxygen species. The observed decrease of Na(+) reabsorption was due to inhibition of the activity of both Na(+) pumps in proximal tubules cells. We suggested that this modulation is mediated by the effect of MCYST as a phosphatase protein inhibitor that maintains the sustained kinase-mediated regulatory phosphorylation of the ATPases. The observed alteration of Na(+) active transporters lead to damage of renal function, since are involved in regulation of water and solute reabsorption in proximal tubules. The results of this report reinforce the importance of understanding the molecular effects of a single sublethal dose of MCYST-LR, which, in this study, was responsible for macro-alterations found in the renal parenchyma and renal physiology in rats.

  15. Effect of grapeseed oil on diazinon-induced physiological and histopathological alterations in rats.

    Science.gov (United States)

    Al-Attar, Atef Mohammed

    2015-05-01

    The pollution of environment by toxic chemicals is a global and chronic problem. Human health risk due to exposure to chemical pollutants is constantly increasing. Pesticides form major toxic chemicals in environment. Scientifically, there is an obviously correlation between the exposure to pesticides and appearance of many diseases. Currently, the significance of natural products for health and medicine has been formidable. The present study investigated the effect of grapeseed oil in male rats exposed to diazinon. The experimental rats were divided into five groups. The rats of the first group were served as control. The experimental animals of the second group were exposed to diazinon (DZN). The animals of the third group were supplemented with grapeseed oil and treated with DZN. The rats of the fourth group were supplemented with grapeseed oil. The experimental rats of the fifth group were supplemented with corn oil. Hematobiochemical and histopathological evaluations were chosen as indicators of DZN toxicity and protective role of grapeseed oil. In rats exposed only to DZN, the levels of serum glucose, triglycerides, cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, creatinine, urea nitrogen, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase and lactate dehydrogenase were statistically increased, while the level of serum total protein was significantly decreased. Moreover, the histopathological evaluations of the liver, kidney and testis showed that DZN causes several severe alterations. Pretreatment with grapeseed oil exhibited a protective role against DZN toxicity which confirmed by the inhibition of hematobiochemical and histopathological changes due to DZN exposure. Additionally, the present study suggests that the effect of grapeseed oil supplementation against DZN toxicity may be attributed to the antioxidant role of its constituents.

  16. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contrac......The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro......-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase In frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile...

  17. 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

  18. Human Beta Cells Produce and Release Serotonin to Inhibit Glucagon Secretion from Alpha Cells

    OpenAIRE

    Joana Almaça; Judith Molina; Danusa Menegaz; Pronin, Alexey N.; Alejandro Tamayo; Vladlen Slepak; Per-Olof Berggren; Alejandro Caicedo

    2016-01-01

    In the pancreatic islet, serotonin is an autocrine signal increasing beta cell mass during metabolic challenges such as those associated with pregnancy or high-fat diet. It is still unclear whether serotonin is relevant for regular islet physiology and hormone secretion. Here, we show that human beta cells produce and secrete serotonin when stimulated with increases in glucose concentration. Serotonin secretion from beta cells decreases cyclic AMP (cAMP) levels in neighboring alpha cells via ...

  19. HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications.

    Science.gov (United States)

    Janik, S; Schiefer, A I; Bekos, C; Hacker, P; Haider, T; Moser, J; Klepetko, W; Müllauer, L; Ankersmit, H J; Moser, B

    2016-01-01

    Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated.

  20. HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications

    Science.gov (United States)

    Janik, S.; Schiefer, A. I.; Bekos, C.; Hacker, P.; Haider, T.; Moser, J.; Klepetko, W.; Müllauer, L.; Ankersmit, H. J.; Moser, B.

    2016-01-01

    Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated. PMID:27097982

  1. Effects of early serotonin programming on behavior and central monoamine concentrations in an avian model

    Science.gov (United States)

    Serotonin (5-HT) acts as a neurogenic compound in the developing brain; however serotonin altering drugs such as SSRIs are often prescribed to pregnant and lactating mothers. Early agonism of 5-HT receptors could alter the development of serotonergic circuitry, altering neurotransmission and behavio...

  2. Resting state networks and consciousness.Alterations of multiple resting state network connectivity in physiological, pharmacological and pathological consciousness states.

    Directory of Open Access Journals (Sweden)

    Lizette eHeine

    2012-08-01

    Full Text Available In order to better understand the functional contribution of resting state activity to conscious cognition, we aimed to review increases and decreases in fMRI functional connectivity under physiological (sleep, pharmacological (anesthesia and pathological altered states of consciousness, such as brain death, coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. The reviewed RSNs were the DMN, left and right executive control, salience, sensorimotor, auditory and visual networks. We highlight some methodological issues concerning resting state analyses in severely injured brains mainly in terms of hypothesis-driven seed-based correlation analysis and data-driven independent components analysis approaches. Finally, we attempt to contextualize our discussion within theoretical frameworks of conscious processes. We think that this lesion approach allows us to better determine the necessary conditions under which normal conscious cognition takes place. At the clinical level, we acknowledge the technical merits of the resting state paradigm. Indeed, fast and easy acquisitions are preferable to activation paradigms in clinical populations. Finally, we emphasize the need to validate the diagnostic and prognostic value of fMRI resting state measurements in non-communicating brain damaged patients.

  3. Resting state networks and consciousness: alterations of multiple resting state network connectivity in physiological, pharmacological, and pathological consciousness States.

    Science.gov (United States)

    Heine, Lizette; Soddu, Andrea; Gómez, Francisco; Vanhaudenhuyse, Audrey; Tshibanda, Luaba; Thonnard, Marie; Charland-Verville, Vanessa; Kirsch, Murielle; Laureys, Steven; Demertzi, Athena

    2012-01-01

    In order to better understand the functional contribution of resting state activity to conscious cognition, we aimed to review increases and decreases in functional magnetic resonance imaging (fMRI) functional connectivity under physiological (sleep), pharmacological (anesthesia), and pathological altered states of consciousness, such as brain death, coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. The reviewed resting state networks were the DMN, left and right executive control, salience, sensorimotor, auditory, and visual networks. We highlight some methodological issues concerning resting state analyses in severely injured brains mainly in terms of hypothesis-driven seed-based correlation analysis and data-driven independent components analysis approaches. Finally, we attempt to contextualize our discussion within theoretical frameworks of conscious processes. We think that this "lesion" approach allows us to better determine the necessary conditions under which normal conscious cognition takes place. At the clinical level, we acknowledge the technical merits of the resting state paradigm. Indeed, fast and easy acquisitions are preferable to activation paradigms in clinical populations. Finally, we emphasize the need to validate the diagnostic and prognostic value of fMRI resting state measurements in non-communicating brain damaged patients.

  4. The Role of Serotonin in Hot Flashes after Breast Cancer

    Science.gov (United States)

    2009-03-01

    drink ingestion to 8 hours later. b Three hour period spanning 5 to 8 hours after drink ingestion. C Sum of all changes in skin conducta nce that...Psychiatry 1999;45:313-320. 10. Young SN, Leyton M. The role of serotonin in human mood and social interaction. Insight from altered tryptophan levels...dysphoria. Biol Psychiairy 1999;45:313-320. 65. Young SN, Ley ton M. The role of serotonin in human mood and social interaction. Insight from altered

  5. Reference intervals and physiologic alterations in hematologic and biochemical values of free-ranging desert tortoises in the Mojave Desert

    Science.gov (United States)

    Christopher, Mary M.; Berry, Kristin H.; Wallis, I.R.; Nagy, K.A.; Henen, B.T.; Peterson, C.C.

    1999-01-01

    Desert tortoise (Gopherus agassizii) populations have experienced precipitous declines resulting from the cumulative impact of habitat loss, and human and disease-related mortality. Evaluation of hematologic and biochemical responses of desert tortoises to physiologic and environmental factors can facilitate the assessment of stress and disease in tortoises and contribute to management decisions and population recovery. The goal of this study was to obtain and analyze clinical laboratory data from free-ranging desert tortoises at three sites in the Mojave Desert (California, USA) between October 1990 and October 1995, to establish reference intervals, and to develop guidelines for the interpretation of laboratory data under a variety of environmental and physiologic conditions. Body weight, carapace length, and venous blood samples for a complete blood count and clinical chemistry profile were obtained from 98 clinically healthy adult desert tortoises of both sexes at the Desert Tortoise Research Natural area (western Mojave), Goffs (eastern Mojave) and Ivanpah Valley (northeastern Mojave). Samples were obtained four times per year, in winter (February/March), spring (May/June), summer (July/August), and fall (October). Years of near-, above- and below-average rainfall were represented in the 5 yr period. Minimum, maximum and median values, and central 95 percentiles were used as reference intervals and measures of central tendency for tortoises at each site and/or season. Data were analyzed using repeated measures analysis of variance for significant (P < 0.01) variation on the basis of sex, site, season, and interactions between these variables. Significant sex differences were observed for packed cell volume, hemoglobin concentration, aspartate transaminase activity, and cholesterol, triglyceride, calcium, and phosphorus concentrations. Marked seasonal variation was observed in most parameters in conjunction with reproductive cycle, hibernation, or seasonal

  6. 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.

  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. Modulation of the genotoxicity of bleomycin by amines through noncovalent DNA interactions and alteration of physiological conditions in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, George R. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States)], E-mail: ghoffmann@holycross.edu; Gessner, Gabrielle S.; Hughes, Jennifer F.; Ronan, Matthew V.; Sylvia, Katelyn E.; Willett, Christine J. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States)

    2007-10-01

    noncovalent association with DNA, altered BLM access to DNA, and modulation of physiological conditions.

  9. Genetic and physiological alterations occurring in a yeast population continuously propagated at increasing temperatures with cell recycling.

    Science.gov (United States)

    Souza, Crisla S; Thomaz, Daniel; Cides, Elaine R; Oliveira, Karen F; Tognolli, João O; Laluce, Cecilia

    2007-12-01

    This work investigated the effects of increasing temperature from 30°C to 47°C on the physiological and genetic characteristics of Saccharomyces cerevisiae strain 63M after continuous fermentation with cell recycling in a system of five reactors in series. Steady state was attained at 30°C, and then the temperature of the system was raised so it ranged from 35°C in the last reactor to 43°C in the first reactor or feeding reactor with a 2°C difference between reactors. After 15 days at steady state, the temperature was raised from 37°C to 45°C for 25 days at steady state, then from 39°C to 47°C for 20 days at steady state. Starter strain 63M was a hybrid strain constructed to have a MAT a/α, LYS/lys, URA/ura genotype. This hybrid yeast showed vigorous growth on plates at 40°C, weak growth at 41°C, positive assimilation of melibiose, positive fermentation of galactose, raffinose and sucrose. Of 156 isolates obtained from this system at the end of the fermentation process, only 17.3% showed the same characteristics as starter strain 63M. Alterations in mating type reaction and in utilization of raffinose, melibiose, and sucrose were identified. Only 1.9% of the isolates lost the ability to grow at 40°C. Isolates showing requirements for lysine and uracil were also obtained. In addition, cell survival was observed at 39-47°C, but no isolates showing growth above 41°C were obtained.

  10. 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

  11. 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.

  12. Serotonin and emotion, learning and memory.

    Science.gov (United States)

    Meneses, Alfredo; Liy-Salmeron, Gustavo

    2012-01-01

    Serotonin (5-hydroxytryptamien, 5-HT) has been linked to emotional and motivational aspects of human behavior, including anxiety, depression, impulsivity, etc. Several clinically effective drugs exert effects via 5-HT systems. Growing evidence suggests that those effects play an important role in learning and memory. Whether the role of serotonin is related to memory and/or behavioral or emotional aspects remains an important question. A key question that remains is whether 5-HT markers (e.g., receptors) directly or indirectly participate and/or contribute to the physiological and pharmacological basis of memory and its pathogenesis. The major aim of this paper is to re-examine some recent advances regarding mammalian 5-HT receptors and transporter in light of their physiological, pathophysiological and therapeutic implications for memory. We particularly address evidence involving 5-HT systems in behavioral, pharmacological, molecular, genetic and imaging results and memory. Finally, this paper aims to summarize a portion of the evidence about serotonin, memory and emotion from animal and human studies and provide an overview of potential tools, markers and cellular and molecular candidate mechanisms. It should be noted that there are several subjects that this paper only briefly touches upon, presenting only what may be the most salient findings in the context of memory, emotion and serotonin.

  13. 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.

  14. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    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. PMID:22629209

  15. Serotonin receptors in hippocampus.

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    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.

  16. Rat dams exposed repeatedly to a daily brief separation from the pups exhibit increased maternal behavior, decreased anxiety and altered levels of receptors for estrogens (ERα, ERβ), oxytocin and serotonin (5-HT1A) in their brain.

    Science.gov (United States)

    Stamatakis, Antonios; Kalpachidou, Theodora; Raftogianni, Androniki; Zografou, Efstratia; Tzanou, Athanasia; Pondiki, Stavroula; Stylianopoulou, Fotini

    2015-02-01

    In the present study we investigated the neurobiological mechanisms underlying expression of maternal behavior. Increased maternal behavior was experimentally induced by a brief 15-min separation between the mother and the pups during postnatal days 1 to 22. On postnatal days (PND) 12 and 22, we determined in experimental and control dams levels of anxiety in the elevated plus maze (EPM) as well as the levels of receptors for estrogens (ERα, ERβ), oxytocin (OTR) and serotonin (5-HT1AR) in areas of the limbic system (prefrontal cortex-PFC, hippocampus, lateral septum-SL, medial preoptic area-MPOA, shell of nucleus accumbens-nAc-Sh, central-CeA and basolateral-BLA amygdala), involved in the regulation of maternal behavior. Experimental dams, which showed increased maternal behavior towards their offspring, displayed reduced anxiety in the EPM on both PND12 and PND22. These behavioral differences could be attributed to neurochemical alterations in their brain: On both PND12 and PND22, experimental mothers had higher levels of ERα and OTRs in the PFC, hippocampus, CeA, SL, MPOA and nAc-Sh. The experimental manipulation-induced increase in ERβ levels was less widespread, being localized in PFC, the hippocampal CA2 area, MPOA and nAc-Sh. In addition, 5-HT1ARs were reduced in the PFC, hippocampus, CeA, MPOA and nAc-Sh of the experimental mothers. Our results show that the experience of the daily repeated brief separation from the pups results in increased brain ERs and OTRs, as well as decreased 5-HT1ARs in the dam's brain; these neurochemical changes could underlie the observed increase in maternal behavior and the reduction of anxiety.

  17. Serotonin Receptors in Hippocampus

    OpenAIRE

    Laura Cristina Berumen; Angelina Rodríguez; Ricardo Miledi; Guadalupe García-Alcocer

    2012-01-01

    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 fu...

  18. 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.

  19. Effects of Postnatal Serotonin Agonism on Fear Response and Memory

    Science.gov (United States)

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

  20. Long-term physiological alterations and recovery in a mouse model of separation associated with time-restricted feeding: a tool to study anorexia nervosa related consequences.

    Directory of Open Access Journals (Sweden)

    Sara Zgheib

    Full Text Available BACKGROUND: Anorexia nervosa is a primary psychiatric disorder, with non-negligible rates of mortality and morbidity. Some of the related alterations could participate in a vicious cycle limiting the recovery. Animal models mimicking various physiological alterations related to anorexia nervosa are necessary to provide better strategies of treatment. AIM: To explore physiological alterations and recovery in a long-term mouse model mimicking numerous consequences of severe anorexia nervosa. METHODS: C57Bl/6 female mice were submitted to a separation-based anorexia protocol combining separation and time-restricted feeding for 10 weeks. Thereafter, mice were housed in standard conditions for 10 weeks. Body weight, food intake, body composition, plasma levels of leptin, adiponectin, IGF-1, blood levels of GH, reproductive function and glucose tolerance were followed. Gene expression of several markers of lipid and energy metabolism was assayed in adipose tissues. RESULTS: Mimicking what is observed in anorexia nervosa patients, and despite a food intake close to that of control mice, separation-based anorexia mice displayed marked alterations in body weight, fat mass, lean mass, bone mass acquisition, reproductive function, GH/IGF-1 axis, and leptinemia. mRNA levels of markers of lipogenesis, lipolysis, and the brown-like adipocyte lineage in subcutaneous adipose tissue were also changed. All these alterations were corrected during the recovery phase, except for the hypoleptinemia that persisted despite the full recovery of fat mass. CONCLUSION: This study strongly supports the separation-based anorexia protocol as a valuable model of long-term negative energy balance state that closely mimics various symptoms observed in anorexia nervosa, including metabolic adaptations. Interestingly, during a recovery phase, mice showed a high capacity to normalize these parameters with the exception of plasma leptin levels. It will be interesting therefore to

  1. An approach for serotonin depletion in pigs: effects on serotonin receptor binding

    DEFF Research Database (Denmark)

    Ettrup, Anders; Kornum, Birgitte R; Weikop, Pia

    2011-01-01

    concentrations of 5-HT in seven distinct brain structures from one hemisphere: frontal and occipital cortex, striatum, hippocampus, cerebellum, rostral, and caudal brain stem, were determined. The other hemisphere was processed for receptor autoradiography. Treatments with 50 mg/kg and 100 mg/kg pCPA caused...... is increasingly used as an experimental animal model especially in neuroscience research. Here, we present an approach for serotonin depletion in the pig brain. Central serotonin depletion in Danish Landrace pigs was achieved following 4 days treatment with para-chlorophenylalanine (pCPA). On day 5, tissue...... average decreases in 5-HT concentrations of 61% ± 14% and 66% ± 16%, respectively, and a substantial loss of 5-HT immunostaining was seen throughout the brain. The serotonin depletion significantly increased 5-HT₄ receptor binding in nucleus accumbens, but did not alter 5-HT(1A) and 5-HT(2A) receptor...

  2. An approach for serotonin depletion in pigs: effects on serotonin receptor binding

    DEFF Research Database (Denmark)

    Ettrup, Anders; Kornum, Birgitte R; Weikop, Pia

    2011-01-01

    concentrations of 5-HT in seven distinct brain structures from one hemisphere: frontal and occipital cortex, striatum, hippocampus, cerebellum, rostral, and caudal brain stem, were determined. The other hemisphere was processed for receptor autoradiography. Treatments with 50 mg/kg and 100 mg/kg pCPA caused...... is increasingly used as an experimental animal model especially in neuroscience research. Here, we present an approach for serotonin depletion in the pig brain. Central serotonin depletion in Danish Landrace pigs was achieved following 4 days treatment with para-chlorophenylalanine (pCPA). On day 5, tissue...... average decreases in 5-HT concentrations of 61% ± 14% and 66% ± 16%, respectively, and a substantial loss of 5-HT immunostaining was seen throughout the brain. The serotonin depletion significantly increased 5-HT4 receptor binding in nucleus accumbens, but did not alter 5-HT(1A) and 5-HT(2A) receptor...

  3. Yeast cell wall supplementation alters the physiological and acute phase responses of crossbred heifers to an endotoxin challenge

    Science.gov (United States)

    A study was conducted to determine the effect of feeding yeast cell wall (YCW) products on the physiological and acute phase responses of crossbred newly-received heifers to an endotoxin challenge. Heifers (n = 24; 219 ± 2.4 kg) were separated into treatment groups receiving a Control diet (n = 8), ...

  4. Altered physiological conditions of the terrestrial isopod Porcellio scaber as a measure of subchronic TiO2 effects.

    Science.gov (United States)

    Srpčič, Anja Menard; Drobne, Damjana; Novak, Sara

    2015-03-01

    Titanium dioxide nanoparticles (nano-TiO2) show low toxic potential against a variety of environmental organisms when measured by conventional toxicity endpoints. However, the question is whether the conventional measures of toxicity can define the adverse effects of nanoparticles. The aim of this study was to asses the potential toxic and cytotoxic effects of the ingested nano-TiO2 (anatase, Porcellio scaber. In addition to conventional toxicity parameters, the physiological condition of the animals was assessed. Following 28-day feeding exposure to nano-TiO2 at concentrations up to 5,000 μg nano-TiO2/g leaf dry weight, no toxic or cytotoxic effects were demonstrated. However, the physiological condition of the animals was affected in a dose-dependent manner. The physiological state of organisms is an important parameter to assess the potential population implications due to the exposure to nanomaterials. Therefore, we suggest that only if both, the physiological state of the animals exposed to nano-TiO2 and the conventional toxicity markers show no effects, the exposure dose can be interpreted as non-hazardous.

  5. 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...

  6. Serotonin, amygdala and fear: assembling the puzzle

    Directory of Open Access Journals (Sweden)

    Marco eBocchio

    2016-04-01

    Full Text Available The fear circuitry orchestrates defense mechanisms in response to environmental threats. This circuitry is evolutionarily crucial for survival, but its dysregulation is thought to play a major role in the pathophysiology of psychiatric conditions in humans. The amygdala is a key player in the processing of fear. This brain area is prominently modulated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT. The 5-HT input to the amygdala has drawn particular interest because genetic and pharmacological alterations of the 5-HT transporter (5-HTT affect amygdala activation in response to emotional stimuli. Nonetheless, the impact of 5-HT on fear processing remains poorly understood.The aim of this review is to elucidate the physiological role of 5-HT in fear learning via its action on the neuronal circuits of the amygdala. Since 5-HT release increases in the BLA during both fear memory acquisition and expression, we examine whether and how 5-HT neurons encode aversive stimuli and aversive cues. Next, we describe pharmacological and genetic alterations of 5-HT neurotransmission that, in both rodents and humans, lead to altered fear learning.To explore the mechanisms through which 5-HT could modulate conditioned fear, we focus on the rodent basolateral amygdala (BLA. We propose that a circuit-based approach taking into account the localization of specific 5-HT receptors on neurochemically-defined neurons in the BLA may be essential to decipher the role of 5-HT in emotional behavior. In keeping with a 5-HT control of fear learning, we review electrophysiological data suggesting that 5-HT regulates synaptic plasticity, spike synchrony and theta oscillations in the BLA via actions on different subcellular compartments of principal neurons and distinct GABAergic interneuron populations. Finally, we discuss how recently developed optogenetic tools combined with electrophysiological recordings and behavior could progress the knowledge of the

  7. 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...

  8. Serotonin and Aggression.

    Science.gov (United States)

    Brown, Serena-Lynn; And Others

    1994-01-01

    Decreased serotonin function has consistently been shown to be highly correlated with impulsive aggression across a number of different experimental paradigms. Such lowered serotonergic indices appear to correlate with the dimension of aggression dyscontrol and/or impulsivity rather than with psychiatric diagnostic categories per se. Implications…

  9. Exposure to extremely low frequency electromagnetic fields alters the behaviour, physiology and stress protein levels of desert locusts.

    Science.gov (United States)

    Wyszkowska, Joanna; Shepherd, Sebastian; Sharkh, Suleiman; Jackson, Christopher W; Newland, Philip L

    2016-11-03

    Electromagnetic fields (EMFs) are present throughout the modern world and are derived from many man-made sources including overhead transmission lines. The risks of extremely-low frequency (ELF) electromagnetic fields are particularly poorly understood especially at high field strengths as they are rarely encountered at ground level. Flying insects, however, can approach close to high field strength transmission lines prompting the question as to how these high levels of exposure affect behaviour and physiology. Here we utilise the accessible nervous system of the locust to ask how exposure to high levels of ELF EMF impact at multiple levels. We show that exposure to ELF EMFs above 4 mT leads to reduced walking. Moreover, intracellular recordings from an identified motor neuron, the fast extensor tibiae motor neuron, show increased spike latency and a broadening of its spike in exposed animals. In addition, hind leg kick force, produced by stimulating the extensor tibiae muscle, was reduced following exposure, while stress-protein levels (Hsp70) increased. Together these results suggest that ELF EMF exposure has the capacity to cause dramatic effects from behaviour to physiology and protein expression, and this study lays the foundation to explore the ecological significance of these effects in other flying insects.

  10. Differential dynamics of the serotonin1A receptor in membrane bilayers of varying cholesterol content revealed by all atom molecular dynamics simulation.

    Science.gov (United States)

    Patra, Swarna M; Chakraborty, Sudip; Shahane, Ganesh; Prasanna, Xavier; Sengupta, Durba; Maiti, Prabal K; Chattopadhyay, Amitabha

    2015-01-01

    The serotonin1A receptor belongs to the superfamily of G protein-coupled receptors (GPCRs) and is a potential drug target in neuropsychiatric disorders. The receptor has been shown to require membrane cholesterol for its organization, dynamics and function. Although recent work suggests a close interaction of cholesterol with the receptor, the structural integrity of the serotonin1A receptor in the presence of cholesterol has not been explored. In this work, we have carried out all atom molecular dynamics simulations, totaling to 3 μs, to analyze the effect of cholesterol on the structure and dynamics of the serotonin1A receptor. Our results show that the presence of physiologically relevant concentration of membrane cholesterol alters conformational dynamics of the serotonin1A receptor and, on an average lowers conformational fluctuations. Our results show that, in general, transmembrane helix VII is most affected by the absence of membrane cholesterol. These results are in overall agreement with experimental data showing enhancement of GPCR stability in the presence of membrane cholesterol. Our results constitute a molecular level understanding of GPCR-cholesterol interaction, and represent an important step in our overall understanding of GPCR function in health and disease.

  11. Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities.

    Directory of Open Access Journals (Sweden)

    Cornelle W Noorlander

    Full Text Available BACKGROUND: Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. In the treatment of depression and anxiety disorders, selective serotonin reuptake inhibitors (SSRIs are the most frequently prescribed drugs, while it is largely unknown whether this medication affects the development of the central nervous system of the fetus. The possible effects are the product of placental transfer efficiency, time of administration and dose of the respective SSRI. METHODOLOGY/PRINCIPAL FINDINGS: In order to attain this information we have setup a study in which these parameters were measured and the consequences in terms of physiology and behavior are mapped. The placental transfer of fluoxetine and fluvoxamine, two commonly used SSRIs, was similar between mouse and human, indicating that the fetal exposure of these SSRIs in mice is comparable with the human situation. Fluvoxamine displayed a relatively low placental transfer, while fluoxetine showed a relatively high placental transfer. Using clinical doses of fluoxetine the mortality of the offspring increased dramatically, whereas the mortality was unaffected after fluvoxamine exposure. The majority of the fluoxetine-exposed offspring died postnatally of severe heart failure caused by dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed long-term alterations in serotonin transporter levels in the raphe nucleus. Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety-related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not show alterations in behavior and serotonin transporter levels. Decreasing the dose of fluoxetine resulted in higher survival rates and less dramatic effects on the long-term behavior in the offspring. CONCLUSIONS: These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy

  12. Discoloured seeds of amaranth plant infected by Alternaria alternata: physiological, histopathological alterations and fungal secondary metabolites associated or registered

    Directory of Open Access Journals (Sweden)

    Noelting María Cristina

    2016-07-01

    Full Text Available In the present study the aspects of discolouration that could influence both the production and consumption of amaranth were analyzed with the objectives to identify the presence of Alternaria alternata on seeds, to analyze possible changes in the anatomy of seed tissues and to detect the presence of fungal secondary metabolites. Component plating, histopathological and mycological analyses on discoloured seeds allowed i location of propagules of A. alternata in all seminal components; ii observation of hypertrophies in perisperm and embryo and iii determination of several fungal secondary metabolites, mainly high concentrations of tenuazonic acid. To our knowledge, the information presented in this paper, related to physiological, histopathological changes and fungal secondary metabolites on discoloured seeds of (Amaranthus mantegazzianus syn. A. caudatus subsp. mantegazzianus (Pass Hanelt affected by A. alternata, is the first worldwide record.

  13. Nutraceutical up-regulation of serotonin paradoxically induces compulsive behavior

    Science.gov (United States)

    The role of diet in either the etiology or treatment of complex mental disorder is highly controversial in psychiatry. However, physiological mechanisms by which diet can influence brain chemistry – particularly that of serotonin – are well established. Here we show that dietary up-regulation of br...

  14. Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin.

    Science.gov (United States)

    Kronenberg, Golo; Mosienko, Valentina; Gertz, Karen; Alenina, Natalia; Hellweg, Rainer; Klempin, Friederike

    2016-04-01

    The interplay between BDNF signaling and the serotonergic system remains incompletely understood. Using a highly sensitive enzyme-linked immunosorbent assay, we studied BDNF concentrations in hippocampus and cortex of two mouse models of altered serotonin signaling: tryptophan hydroxylase (Tph)2-deficient (Tph2 (-/-)) mice lacking brain serotonin and serotonin transporter (SERT)-deficient (SERT(-/-)) mice lacking serotonin re-uptake. Surprisingly, hippocampal BDNF was significantly elevated in Tph2 (-/-) mice, whereas no significant changes were observed in SERT(-/-) mice. Furthermore, BDNF levels were increased in the prefrontal cortex of Tph2 (-/-) but not of SERT(-/-) mice. Our results emphasize the interaction between serotonin signaling and BDNF. Complete lack of brain serotonin induces BDNF expression.

  15. 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.

  16. Serotonin of mast cell origin contributes to hippocampal function.

    Science.gov (United States)

    Nautiyal, Katherine M; Dailey, Christopher A; Jahn, Jaquelyn L; Rodriquez, Elizabeth; Son, Nguyen Hong; Sweedler, Jonathan V; Silver, Rae

    2012-08-01

    In the central nervous system, serotonin, an important neurotransmitter and trophic factor, is synthesized by both mast cells and neurons. Mast cells, like other immune cells, are born in the bone marrow and migrate to many tissues. We show that they are resident in the mouse brain throughout development and adulthood. Measurements based on capillary electrophoresis with native fluorescence detection indicate that a significant contribution of serotonin to the hippocampal milieu is associated with mast cell activation. Compared with their littermates, mast cell-deficient C57BL/6 Kit(W-sh/W-sh) mice have profound deficits in hippocampus-dependent spatial learning and memory and in hippocampal neurogenesis. These deficits are associated with a reduction in cell proliferation and in immature neurons in the dentate gyrus, but not in the subventricular zone - a neurogenic niche lacking mast cells. Chronic treatment with fluoxetine, a selective serotonin reuptake inhibitor, reverses the deficit in hippocampal neurogenesis in mast cell-deficient mice. In summary, the present study demonstrates that mast cells are a source of serotonin, that mast cell-deficient C57BL/6 Kit(W-sh/W-sh) mice have disrupted hippocampus-dependent behavior and neurogenesis, and that elevating serotonin in these mice, by treatment with fluoxetine, reverses these deficits. We conclude that mast cells contribute to behavioral and physiological functions of the hippocampus and note that they play a physiological role in neuroimmune interactions, even in the absence of inflammatory responses.

  17. Abnormal physiological properties and altered cell wall composition in Streptococcus pneumoniae grown in the presence of clavulanic acid.

    Science.gov (United States)

    Severin, A; Severina, E; Tomasz, A

    1997-01-01

    Subinhibitory concentrations of clavulanate caused premature induction of stationary-phase autolysis, sensitization to lysozyme, and reductions in the MICs of deoxycholate and penicillin for Streptococcus pneumoniae. In the range of clavulanate concentrations producing these effects, this beta-lactam compound was selectively bound to PBP 3. Cell walls isolated from pneumococci grown in the presence of clavulanate showed increased sensitivity to the hydrolytic action of purified pneumococcal autolysin in vitro. High-performance liquid chromatography analysis of the peptidoglycan isolated from the clavulanate-grown cells showed major qualitative and quantitative changes in stem peptide composition, the most striking feature of which was the accumulation of peptide species carrying intact D-alanyl-D-alanine residues at the carboxy termini. The altered biological and biochemical properties of the clavulanate-grown pneumococci appear to be the consequences of suppressed D,D-carboxypeptidase activity. PMID:9055983

  18. Noninvasive measurement of lung carbon-11-serotonin extraction in man

    Energy Technology Data Exchange (ETDEWEB)

    Coates, G.; Firnau, G.; Meyer, G.J.; Gratz, K.F. (McMaster Univ. Medical Centre, Hamilton, Ontario (Canada))

    1991-04-01

    The fraction of serotonin extracted on a single passage through the lungs is being used as an early indicator of lung endothelial damage but the existing techniques require multiple arterial blood samples. We have developed a noninvasive technique to measure lung serotonin uptake in man. We utilized the double indicator diffusion principle, a positron camera, {sup 11}C-serotonin as the substrate, and {sup 11}CO-erythrocytes as the vascular marker. From regions of interest around each lung, we recorded time-activity curves in 0.5-sec frames for 30 sec after a bolus injection of first the vascular marker {sup 11}CO-erythrocytes and 10 min later {sup 11}C-serotonin. A second uptake measurement was made after imipramine 25-35 mg was infused intravenously. In three normal volunteers, the single-pass uptake of {sup 11}C-serotonin was 63.9% +/- 3.6%. This decreased in all subjects to a mean of 53.6% +/- 1.4% after imipramine. The rate of lung washout of {sup 11}C was also significantly prolonged after imipramine. This noninvasive technique can be used to measure lung serotonin uptake to detect early changes in a variety of conditions that alter the integrity of the pulmonary endothelium.

  19. The serotonin system in autism spectrum disorder: From biomarker to animal models.

    Science.gov (United States)

    Muller, C L; Anacker, A M J; Veenstra-VanderWeele, J

    2016-05-03

    Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker.

  20. Pseudouridine synthase 1 deficient mice, a model for Mitochondrial Myopathy with Sideroblastic Anemia, exhibit muscle morphology and physiology alterations

    Science.gov (United States)

    Mangum, Joshua E.; Hardee, Justin P.; Fix, Dennis K.; Puppa, Melissa J.; Elkes, Johnathon; Altomare, Diego; Bykhovskaya, Yelena; Campagna, Dean R.; Schmidt, Paul J.; Sendamarai, Anoop K.; Lidov, Hart G. W.; Barlow, Shayne C.; Fischel-Ghodsian, Nathan; Fleming, Mark D.; Carson, James A.; Patton, Jeffrey R.

    2016-01-01

    Mitochondrial myopathy with lactic acidosis and sideroblastic anemia (MLASA) is an oxidative phosphorylation disorder, with primary clinical manifestations of myopathic exercise intolerance and a macrocytic sideroblastic anemia. One cause of MLASA is recessive mutations in PUS1, which encodes pseudouridine (Ψ) synthase 1 (Pus1p). Here we describe a mouse model of MLASA due to mutations in PUS1. As expected, certain Ψ modifications were missing in cytoplasmic and mitochondrial tRNAs from Pus1−/− animals. Pus1−/− mice were born at the expected Mendelian frequency and were non-dysmorphic. At 14 weeks the mutants displayed reduced exercise capacity. Examination of tibialis anterior (TA) muscle morphology and histochemistry demonstrated an increase in the cross sectional area and proportion of myosin heavy chain (MHC) IIB and low succinate dehydrogenase (SDH) expressing myofibers, without a change in the size of MHC IIA positive or high SDH myofibers. Cytochrome c oxidase activity was significantly reduced in extracts from red gastrocnemius muscle from Pus1−/− mice. Transmission electron microscopy on red gastrocnemius muscle demonstrated that Pus1−/− mice also had lower intermyofibrillar mitochondrial density and smaller mitochondria. Collectively, these results suggest that alterations in muscle metabolism related to mitochondrial content and oxidative capacity may account for the reduced exercise capacity in Pus1−/− mice. PMID:27197761

  1. Association between As and Cu renal cortex accumulation and physiological and histological alterations after chronic arsenic intake

    Energy Technology Data Exchange (ETDEWEB)

    Rubatto Birri, Paolo N. [Instituto de Biologia Celular, Facultad de Ciencias Medicas (FCM), Universidad Nacional de Cordoba (UNC), Ciudad Universitaria, Cordoba (Argentina); Perez, Roberto D. [Facultad de Matematica, Astronomia y Fisica (FAMAF-UNC), Ciudad Universitaria, Cordoba (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Buenos Aires (Argentina); Cremonezzi, David [Catedra Anatomia Patologica, Hospital Nacional de Clinicas (FCM-UNC), Cordoba (Argentina); Perez, Carlos A. [Laboratorio Nacional de Luz Sincrotron (LNLS), Linha D09B-XRF, Campinas SP (Brazil); Rubio, Marcelo [Facultad de Matematica, Astronomia y Fisica (FAMAF-UNC), Ciudad Universitaria, Cordoba (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Buenos Aires (Argentina); Bongiovanni, Guillermina A., E-mail: gbongiovanni@conicet.gov.ar [Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Buenos Aires (Argentina); Laboratorio de Investigaciones Bioquimicas, Quimicas y de Medio Ambiente (LIBIQUIMA), Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Universidad Nacional del Comahue, Buenos Aires 1400, CP 8300 Neuquen (Argentina)

    2010-07-15

    Arsenic (As) is one of the most abundant hazards in the environment and it is a human carcinogen. Related to excretory functions, the kidneys in humans, animal models or naturally exposed fauna, are target organs for As accumulation and deleterious effects. Previous studies carried out using X-ray fluorescence spectrometry by synchrotron radiation (SR-{mu}XRF) showed a high concentration of As in the renal cortex of chronically exposed rats, suggesting that this is a suitable model for studies on renal As accumulation. This accumulation was accompanied by a significant increase in copper (Cu) concentration. The present study focused on the localization of these elements in the renal cortex and their correlation with physiological and histological As-related renal effects. Experiments were performed on nine male Wistar rats, divided into three experimental groups. Two groups received 100 {mu}g/ml sodium arsenite in drinking water for 60 and 120 consecutive days, respectively. The control group received water without sodium arsenite (<50 ppb As). For histological analysis, 5-{mu}m-thick sections of kidneys were stained with hematoxylin and eosin. Biochemical analyses were used to determine concentrations of plasma urea and creatinine. The As and Cu mapping were carried out by SR-{mu}XRF using a collimated white synchrotron spectrum (300 {mu}mx300 {mu}m) on kidney slices (2 mm thick) showing As and Cu co-distribution in the renal cortex. Then, renal cortical slices (100 {mu}m thick) were scanned with a focused white synchrotron spectrum (30 {mu}mx30 {mu}m). Peri-glomerular accumulation of As and Cu at 60 and 120 days was found. The effects of 60 days of arsenic consumption were seen in a decreased Bowman's space as well as a decreased plasma blood urea nitrogen (BUN)/creatinine ratio. Major deleterious effects; however, were seen on tubules at 120 days of exposition. This study supports the hypothesis that tubular accumulation of As-Cu may have some bearing on

  2. 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

  3. Brief Report: Platelet-Poor Plasma Serotonin in Autism

    Science.gov (United States)

    Anderson, George M.; Hertzig, Margaret E.; McBride, P. A.

    2012-01-01

    Possible explanations for the well-replicated platelet hyperserotonemia of autism include an alteration in the platelet's handling of serotonin (5-hydroxyserotonin, 5-HT) or an increased exposure of the platelet to 5-HT. Measurement of platelet-poor plasma (PPP) levels of 5-HT appears to provide the best available index of in vivo exposure of the…

  4. Kinetic and physiological effects of alterations in homologous isocitrate-binding sites of yeast NAD(+)-specific isocitrate dehydrogenase.

    Science.gov (United States)

    Lin, A P; McCammon, M T; McAlister-Henn, L

    2001-11-27

    Yeast NAD(+)-specific isocitrate dehydrogenase is an allosterically regulated octameric enzyme composed of four each of two homologous but nonidentical subunits designated IDH1 and IDH2. Models based on the crystallographic structure of Escherichia coli isocitrate dehydrogenase suggest that both yeast subunits contain isocitrate-binding sites. Identities in nine residue positions are predicted for the IDH2 site whereas four of the nine positions differ between the IDH1 and bacterial enzyme sites. Thus, we speculate that the IDH2 site is catalytic and that the IDH1 site may bind but not catalytically alter isocitrate. This was examined by kinetic analyses of enzymes with independent and concerted replacement of residues in each yeast IDH subunit site with the residues that differ in the other subunit site. Mutant enzymes were expressed in a yeast strain containing disrupted IDH1 and IDH2 loci and affinity-purified for kinetic analyses. The primary effects of various residue replacements in IDH2 were reductions of 30->300-fold in V(max) values, consistent with the catalytic function of this subunit. In contrast, replacement of all four residues in IDH1 produced a 17-fold reduction in V(max) under the same assay conditions, suggesting that the IDH1 site is not the primary catalytic site. However, single or multiple residue replacements in IDH1 uniformly increased half-saturation concentrations for isocitrate, implying that isocitrate can be bound at this site. Both subunits appear to contribute to cooperativity with respect to isocitrate, but AMP activation is lost only with residue replacements in IDH1. Overall, results are consistent with isocitrate binding by IDH2 for catalysis and with isocitrate binding by IDH1 being a prerequisite for allosteric activation by AMP. The effects of residue substitutions on enzyme function in vivo were assessed by analysis of various growth phenotypes. Results indicate a positive correlation between the level of IDH catalytic

  5. Effects of 60-Hz electric fields on serotonin metabolism in the rat pineal gland

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, L.E.; Hilton, D.I.; Phillips, R.D.; Wilson, B.W.; Chess, E.K.

    1982-06-01

    Serotonin and two of its metabolites, melatonin and 5-methoxytryptophol, exhibit circadian rhythmicity in the pineal gland. We recently reported a marked reduction in the normal night-time increase in melatonin concentration in the pineal glands of rats exposed to 60-Hz electric fields. Concomitant with the apparent abolition of melatonin rhythmicity, serotonin-N-acetyl transferase (SNAT) activity was suppressed. We have now conducted studies to determine if abolition of the rhythm in melatonin production in electric-field-exposed rats arises solely from interference in SNAT activity, or if the availability of pineal serotonin is a factor that is affected by exposure. Pineal serotonin concentrations were compared in rats that were either exposed or sham exposed to 65 kV/m for 30 days. Sham-exposed animals exhibited normal diurnal rhythmicity for pineal concentrations of both melatonin and serotonin; melatonin levels increased markedly during the dark phase with a concurrent decrease in serotonin levels. In the exposed animals, however, normal serotonin rhythmicity was abolished; serotonin levels in these animals did not increase during the light period. The conclusion that electric field exposure results in a biochemical alteration in SNAT enzyme activity can be inferred from the loss of both serotonin and melatonin rhythmicity, as well as by direct measurement of SNAT activity itself. 35 references, 3 figures, 1 table.

  6. Serotonin syndrome caused by fentanyl and methadone in a burn injury.

    Science.gov (United States)

    Hillman, Ashley D; Witenko, Corey J; Sultan, Said M; Gala, Gary

    2015-01-01

    Serotonin syndrome is a syndrome identified by a triad of altered mental status, neuromuscular overactivity, and autonomic instability caused by the overstimulation of serotonin in the central nervous system and periphery. Serotonin syndrome may be provoked with the addition or increase in serotonergic agents such as selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors as well as other agents with serotonergic properties. Some narcotics, including fentanyl and methadone, have these properties and may be associated with the development of serotonin syndrome when used in conjunction with other agents. Currently, there are no identified case reports of narcotics as the sole agent causing serotonin syndrome. This report provides a brief overview of serotonin syndrome, particularly with cases involving administration of narcotics such as fentanyl and methadone. The case described is the first report associated with fentanyl and methadone without the coadministration of other serotonergic agents, and a possible drug interaction with voriconazole is discussed. This raises awareness of using multiple serotonergic narcotics and the potential precipitation of serotonin syndrome.

  7. 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.

  8. Serotonin transporter gene polymorphisms: Relation with platelet serotonin level in patients with primary Sjogren's syndrome.

    Science.gov (United States)

    Markeljevic, J; Sarac, H; Bozina, N; Henigsberg, N; Simic, M; Cicin Sain, L

    2015-05-15

    Significantly lower platelet serotonin level (PSL) in patients with primary Sjogren's syndrome (pSS) than in healthy controls has been reported in our prior studies. In the present report, we demonstrated effect of functional polymorphisms in the serotonin transporter gene (5-HTT) on PSL. We describe a group of 61 pSS patients and 100 healthy individuals subjects, who received PSL measurement in our prior study. All subjects were genotyped for the promoter 5-HTTLPR (L/S), rs25531 (A/G) and intronic 5-HTTVNTRin2 (l/s) polymorphisms. Overall, the presence of 5-HTTVNTRin2 ss genotype was associated with significantly lower PSL in pSS patients, not in healthy controls. Reduced PSL in pSS patients is in line with hypothesis of association between chronic immunoinflammation and 5-HT system dysregulation, identifying additional mechanisms such as altered 5-HT transport as potential genetic factor contributing to PSL depletion.

  9. Serotonin enhances the impact of health information on food choice.

    Science.gov (United States)

    Vlaev, Ivo; Crockett, Molly J; Clark, Luke; Müller, Ulrich; Robbins, Trevor W

    2017-01-23

    Serotonin has been implicated in promoting self-control, regulation of hunger and physiological homeostasis, and regulation of caloric intake. However, it remains unclear whether the effects of serotonin on caloric intake reflect purely homeostatic mechanisms, or whether serotonin also modulates cognitive processes involved in dietary decision making. We investigated the effects of an acute dose of the serotonin reuptake inhibitor citalopram on choices between food items that differed along taste and health attributes, compared with placebo and the noradrenaline reuptake inhibitor atomoxetine. Twenty-seven participants attended three sessions and received single doses of atomoxetine, citalopram, and placebo in a double-blind randomised cross-over design. Relative to placebo, citalopram increased choices of more healthy foods over less healthy foods. Citalopram also increased the emphasis on health considerations in decisions. Atomoxetine did not affect decision making relative to placebo. The results support the hypothesis that serotonin may influence food choice by enhancing a focus on long-term goals. The findings are relevant for understanding decisions about food consumption and also for treating health conditions such as eating disorders and obesity.

  10. Plasma anti-serotonin and serotonin anti-idiotypic antibodies are elevated in panic disorder.

    Science.gov (United States)

    Coplan, J D; Tamir, H; Calaprice, D; DeJesus, M; de la Nuez, M; Pine, D; Papp, L A; Klein, D F; Gorman, J M

    1999-04-01

    The psychoneuroimmunology of panic disorder is relatively unexplored. Alterations within brain stress systems that secondarily influence the immune system have been documented. A recent report indicated elevations of serotonin (5-HT) and ganglioside antibodies in patients with primary fibromyalgia, a condition with documented associations with panic disorder. In line with our interest in dysregulated 5-HT systems in panic disorder (PD), we wished to assess if antibodies directed at the 5-HT system were elevated in patients with PD in comparison to healthy volunteers. Sixty-three patients with panic disorder and 26 healthy volunteers were diagnosed by the SCID. Employing ELISA, we measured anti-5-HT and 5-HT anti-idiotypic antibodies (which are directed at 5-HT receptors). To include all subjects in one experiment, three different batches were run during the ELISA. Plasma serotonin anti-idiotypic antibodies: there was a significant group effect [patients > controls (p = .007)] and batch effect but no interaction. The mean effect size for the three batches was .76. Following Z-score transformation of each separate batch and then combining all scores, patients demonstrated significantly elevated levels of plasma serotonin anti-idiotypic antibodies. Neither sex nor age as covariates affected the significance of the results. There was a strong correlation between anti-serotonin antibody and serotonin anti-idiotypic antibody measures. Plasma anti-serotonin antibodies: there was a significant diagnosis effect [patients > controls (p = .037)]. Mean effect size for the three batches was .52. Upon Z-score transformation, there was a diagnosis effect with antibody elevations in patients. Covaried for sex and age, the result falls below significance to trend levels. The data raise the possibility that psychoimmune dysfunction, specifically related to the 5-HT system, may be present in PD. Potential interruption of 5-HT neurotransmission through autoimmune mechanisms may be of

  11. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity

    Science.gov (United States)

    Kane, Maureen A.; Folias, Alexandra E.; Wang, Chao; Napoli, Joseph L.

    2010-01-01

    All-trans-retinoic acid (atRA) supports embryonic development, central nervous system function, and the immune response. atRA initiates neurogenesis and dendritic growth in the hippocampus and is required for spatial memory; superphysiological atRA inhibits neurogenesis, causes teratology and/or embryo toxicity, and alters cognitive function and behavior. Because abnormal atRA shares pathological conditions with alcoholism, inhibition of retinol (vitamin A) activation into atRA has been credited widely as a mechanism of ethanol toxicity. Here, we analyze the effects of ethanol on retinoid concentrations in vivo during normal vitamin A nutriture, using sensitive and analytically robust assays. Ethanol either increased or had no effect on atRA, regardless of changes in retinol and retinyl esters. Acute ethanol (3.5 g/kg) increased atRA in adult hippocampus (1.6-fold), liver (2.4-fold), and testis (1.5-fold). Feeding dams a liquid diet with 6.5% ethanol from embryonic day 13 (e13) to e19 increased atRA in fetal hippocampus (up to 20-fold) and cortex (up to 50-fold), depending on blood alcohol content. One-month feeding of the 6.5% ethanol diet increased atRA in adult hippocampus (20-fold), cortex (2-fold), testis (2-fold), and serum (10-fold). Tissue-specific increases in retinoid dehydrogenase mRNAs and activities, extrahepatic retinol concentrations, and atRA catabolism combined to produce site-specific effects. Because a sustained increase in atRA has deleterious effects on the central nervous system and embryo development, these data suggest that superphysiological atRA contributes to ethanol pathological conditions, including cognitive dysfunction and fetal alcohol syndrome.—Kane, M. A., Folias, A. E., Wang, C., Napoli, J. L. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity. PMID:19890016

  12. Behavioral, hormonal and central serotonin modulating effects of injected leptin.

    Science.gov (United States)

    Haleem, Darakhshan J; Haque, Zeba; Inam, Qurrat-ul-Aen; Ikram, Huma; Haleem, Muhammad Abdul

    2015-12-01

    Leptin is viewed as an important target for developing novel therapeutics for obesity, depression/anxiety and cognitive dysfunctions. The present study therefore concerns behavioral, hormonal and central serotonin modulating effects of systemically injected leptin. Pharmacological doses (100 and 500 μg/kg) of leptin injected systemically decreased 24h cumulative food intake and body weight in freely feeding rats and improved acquisition and retention of memory in Morris water maze test. Potential anxiety reducing, hormonal and serotonin modulating effects of the peptide hormone were determined in a separate experiment. Animals injected with 100 or 500 μg/kg leptin were tested for anxiety in an elevated plus maze test 1h later. A significant increase in the number of entries and time passed in open arm of the elevated plus maze in leptin injected animals suggested pronounced anxiety reducing effect. Moreover, circulating levels of leptin correlated significantly with anxiety reducing effects of the peptide hormone. Serum serotonin increased and ghrelin decreased in leptin injected animals and correlated, positively and negatively respectively, with circulating leptin. Corticosterone increased at low dose and levels were normal at higher dose. Serotonin metabolism in the hypothalamus and hippocampus decreased only at higher dose of leptin. The results support a role of leptin in the treatment of obesity, anxiety and cognitive dysfunctions. It is suggested that hormonal and serotonin modulating effects of leptin can alter treatment efficacy in particularly comorbid conditions.

  13. [Serotonin dysfunctions in the background of the seven deadly sins].

    Science.gov (United States)

    Janka, Zoltán

    2003-11-20

    The symbolic characters of the Seven Deadly Sins can be traced from time to time in the cultural history of human mankind, being directly specified in certain artistic products. Such are, among others, the painting entitled "The Seven Deadly Sins and the Four Lost Things" by Hieronymus Bosch and the poems Divina Commedia and The Foerie Queene by Dante Alighieri and Edmund Spenser, respectively. However, there are several paragraphs referring to these behaviours of the Seven Deadly Sins in the Bible and in the dramas of William Shakespeare. The objective of the present review is to propose that dysfunctions in the central serotonergic system might be involved in the neurobiology of these 'sinful' behaviour patterns. Evidences indicate that behaviour traits such as Accidia (Sloth), Luxuria (Lust, Lechery), Superbia (Pride), Ira (Wrath, Anger), Invidia (Envy), Avaritia (Greed, Avarice), and Gula (Gluttony) can relate to the functional alterations of serotonin in the brain. Results of biochemical and molecular genetic (polymorphism) studies on the human serotonergic system (receptor, transporter, enzyme), findings of functional imaging techniques, effects of depletion (or supplementation) of the serotonin precursor tryptophan, data of challenge probe investigations directed to testing central serotonergic functions, alterations in the peripheral serotonin measures (platelet), and the changes in the CSF 5-hydroxy-indoleacetic acid content indicate such serotonergic involvement. Furthermore, results of animal experiments on behaviour change (aggressive, dominant or submissive, appetite, alcohol preference) attributed to serotonin status modification and the clinically evidenced therapeutic efficacy of pharmacological interventions, based on the modulation and perturbation of the serotonergic system (e.g. selective serotonin reuptake inhibitors), in treating the 'sinful' behaviour forms and analogous pathological states reaching the severity of psychiatric disorders

  14. Diurnal and seasonal variation of the brain serotonin system in healthy male subjects.

    Science.gov (United States)

    Matheson, Granville J; Schain, Martin; Almeida, Rita; Lundberg, Johan; Cselényi, Zsolt; Borg, Jacqueline; Varrone, Andrea; Farde, Lars; Cervenka, Simon

    2015-05-15

    The mammalian circadian clock underlies both diurnal and seasonal changes in physiology, and its function is thought to be disturbed in both seasonal and non-seasonal depression. In humans, molecular imaging studies have reported seasonal changes in the serotonin system. Despite the role of the circadian clock in generating seasonal physiological changes, however, diurnal variation of serotonin receptors and transporters has never been directly studied in humans. We used positron emission tomography to examine diurnal and seasonal changes in the serotonin 5-HT1A receptor and serotonin transporter in two large cohorts of healthy male subjects, employing a cross-sectional design. In 56 subjects measured with [(11)C]WAY-100635, we observed diurnal increases in the availability of 5-HT1A receptors in the cortex. In 40 subjects measured with [(11)C]MADAM, a decrease in 5-HTT was observed in the midbrain across the day. We also found seasonal changes in the 5-HT1A receptor in serotonin projection regions, with higher availability on days with a longer duration of daylight. Our observation that serotonin receptor and transporter levels may change across the day in humans is corroborated by experimental research in rodents. These findings have important implications for understanding the relationship between the circadian and serotonin systems in both the healthy brain and in affective disorders, as well as for the design of future molecular imaging studies.

  15. Fibromyalgia and the serotonin pathway.

    Science.gov (United States)

    Juhl, J H

    1998-10-01

    Fibromyalgia syndrome is a musculoskeletal pain and fatigue disorder manifested by diffuse myalgia, localized areas of tenderness, fatigue, lowered pain thresholds, and nonrestorative sleep. Evidence from multiple sources support the concept of decreased flux through the serotonin pathway in fibromyalgia patients. Serotonin substrate supplementation, via L-tryptophan or 5-hydroxytryptophan (5-HTP), has been shown to improve symptoms of depression, anxiety, insomnia and somatic pains in a variety of patient cohorts. Identification of low serum tryptophan and serotonin levels may be a simple way to identify persons who will respond well to this approach.

  16. Altered Respiratory Physiology in Obesity

    Directory of Open Access Journals (Sweden)

    Krishnan Parameswaran

    2006-01-01

    Full Text Available The major respiratory complications of obesity include a heightened demand for ventilation, elevated work of breathing, respiratory muscle inefficiency and diminished respiratory compliance. The decreased functional residual capacity and expiratory reserve volume, with a high closing volume to functional residual capacity ratio of obesity, are associated with the closure of peripheral lung units, ventilation to perfusion ratio abnormalities and hypoxemia, especially in the supine position. Conventional respiratory function tests are only mildly affected by obesity except in extreme cases. The major circulatory complications are increased total and pulmonary blood volume, high cardiac output and elevated left ventricular end-diastolic pressure. Patients with obesity commonly develop hypoventilation and sleep apnea syndromes with attenuated hypoxic and hypercapnic ventilatory responsiveness. The final result is hypoxemia, pulmonary hypertension and progressively worsening disability. Obese patients have increased dyspnea and decreased exercise capacity, which are vital to quality of life. Decreased muscle, increased joint pain and skin friction are important determinants of decreased exercise capacity, in addition to the cardiopulmonary effects of obesity. The effects of obesity on mortality in heart failure and chronic obstructive pulmonary disease have not been definitively resolved. Whether obesity contributes to asthma and airway hyper-responsiveness is uncertain. Weight reduction and physical activity are effective means of reversing the respiratory complications of obesity.

  17. Histamine H3 receptor-mediated inhibition of serotonin release in the rat brain cortex.

    Science.gov (United States)

    Schlicker, E; Betz, R; Göthert, M

    1988-05-01

    Rat brain cortex slices preincubated with 3H-serotonin were superfused with physiological salt solution (containing citalopram, an inhibitor of serotonin uptake) and the effect of histamine on the electrically (3 Hz) evoked 3H overflow was studied. Histamine decreased the evoked overflow in a concentration-dependent manner. The inhibitory effect of histamine was antagonized by impromidine and burimamide, but was not affected by pheniramine, ranitidine, metitepine and phentolamine. Given alone, impromidine facilitated the evoked overflow, whereas burimamide, pheniramine and ranitidine had no effect. The results suggest that histamine inhibits serotonin release in the rat brain cortex via histamine H3 receptors, which may be located presynaptically.

  18. Fish on Prozac: a simple, noninvasive physiology laboratory investigating the mechanisms of aggressive behavior in Betta splendens.

    Science.gov (United States)

    Lynn, Sharon E; Egar, Joseph M; Walker, Brian G; Sperry, Todd S; Ramenofsky, Marilyn

    2007-12-01

    The neuromodulator serotonin is an important regulator of aggressive behavior in vertebrates. Experimentally increasing synaptic levels of serotonin with fluoxetine, a selective serotonin reuptake inhibitor, has been shown to reliably decrease the expression of aggressive behavior. Here, we describe a method by which fluoxetine can be noninvasively administered to male Betta splendens (an attractive model for the study of aggressive behavior) and describe a simple laboratory exercise that allows students to experimentally investigate the physiological mechanisms of aggressive behavior. We demonstrate that relatively short-term exposure (3 h) of male bettas to as little as 3 microg/ml of fluoxetine-treated aquarium water is sufficient to reduce the expression of specific aggressive behaviors. We emphasize the physiological concepts that can be addressed with this exercise, including the role of the serotonergic system in regulating aggression, and the interplay of environmental contaminants and physiology in regulating the expression of behavior. We also highlight important aspects of experimental design. This exercise can be flexibly altered to accommodate one or several laboratory periods. It is also low cost, is low impact to the animals, and requires minimal preparation time for instructors.

  19. 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

    Tracking serotonergic pathways in the brain through immunodetection of serotonin has widely been used for the anatomical characterization of the serotonergic system. Immunostaining for serotonin is also frequently applied for the visualization of individual serotonin containing fibers and quantif......Tracking serotonergic pathways in the brain through immunodetection of serotonin has widely been used for the anatomical characterization of the serotonergic system. Immunostaining for serotonin is also frequently applied for the visualization of individual serotonin containing fibers...

  20. Serotonin and decision making processes.

    NARCIS (Netherlands)

    Homberg, J.R.

    2012-01-01

    Serotonin (5-HT) is an important player in decision making. Serotonergic antidepressant, anxiolytic and antipsychotic drugs are extensively used in the treatment of neuropsychiatric disorders characterized by impaired decision making, and exert both beneficial and harmful effects in patients. Detail

  1. 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.

  2. Serotonin-1A receptor imaging in recurrent depression: replication and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Drevets, Wayne C. [Mood and Anxiety Disorders Program, MINH Molecular Imaging Branch, Bethesda, MD 20892 (United States); Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Radiology, University of Pittsburgh, Pittsburgh, PA 19213 (United States)], E-mail: drevetsw@mail.nih.gov; Thase, Michael E. [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Psychiatry, University of Pennsylvania, School of Medicine and Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104 (United States); Moses-Kolko, Eydie L. [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Price, Julie [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Radiology, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Frank, Ellen; Kupfer, David J. [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Mathis, Chester [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Radiology, University of Pittsburgh, Pittsburgh, PA 19213 (United States)

    2007-10-15

    Introduction: Serotonin-1A receptor (5-HT{sub 1A}R) function appears to be decreased in major depressive disorder (MDD) based on physiological responses to 5-HT{sub 1A}R agonists in vivo and to 5-HT{sub 1A}R binding in brain tissues postmortem or antemortem. We have previously assessed 5-HT{sub 1A}R binding potential (BP) in depression using positron emission tomography (PET) and [carbonyl-{sup 11}C]WAY-100635, and we have demonstrated reduced 5-HT{sub 1A}R BP in the mesiotemporal cortex (MTC) and raphe in depressives with primary recurrent familial mood disorders (n=12) versus controls (n=8) [Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 1999;46(10):1375-87]. These findings were replicated by some, but not other, studies performed in depressed samples that were more generally selected using criteria for MDD. In the current study, we attempted to replicate our previous findings in an independent sample of subjects selected according to the criteria for primary recurrent depression applied in our prior study. Methods: Using PET and [carbonyl-{sup 11}C]WAY-100635, 5-HT{sub 1A}R BP was assessed in 16 depressed subjects and 8 healthy controls. Results: Mean 5-HT{sub 1A}R BP was reduced by 26% in the MTC (P < .005) and by 43% in the raphe (P < .001) in depressives versus controls. Conclusions: These data replicate our original findings, which showed that BP was reduced by 27% in the MTC (P < .025) and by 42% in the raphe (P < .02) in depression. The magnitudes of these reductions in 5-HT{sub 1A}R binding were similar to those found postmortem in 5-HT{sub 1A}R mRNA concentrations in the hippocampus in MDD [Lopez JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547-73] and in 5-HT{sub 1A

  3. 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.

  4. Effects of Early Serotonin Programming on Fear Response, Memory and Aggression

    Science.gov (United States)

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

  5. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; de Bruin, A.

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver regeneratio

  6. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration.

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; Bruin, A. de

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver regeneratio

  7. 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.

  8. Serotonin reuptake inhibitors and cardiovascular disease

    OpenAIRE

    Belcher, P.R.; Drake-Holland, A.J.; Noble, M.

    2005-01-01

    Selective serotonin re-uptake inhibiting drugs (SSRIs) are widely used for endogenous depression. In addition to depleting the nerve terminals of serotonin they also lower blood platelet serotonin levels. Platelet aggregation is a major component of acute coronary syndromes, including sudden death, and also of limb ischaemia. Platelet-released serotonin causes constriction of diseased blood vessels. The recent literature has revealed a number of reports of association between the treatment of...

  9. Repeated, Intermittent Social Defeat across the Entire Juvenile Period Resulted in Behavioral, Physiological, Hormonal, Immunological, and Neurochemical Alterations in Young Adult Male Golden Hamsters.

    Science.gov (United States)

    Yu, Wei-Chun; Liu, Ching-Yi; Lai, Wen-Sung

    2016-01-01

    The developing brain is vulnerable to social defeat during the juvenile period. As complements of human studies, animal models of social defeat provide a straightforward approach to investigating the functional and neurobiological consequences of social defeats. Taking advantage of agonist behavior and social defeat in male golden hamster, a set of 6 experiments was conducted to investigate the consequences at multiple levels in young adulthood resulting from repeated, intermittent social defeats or "social threats" across the entire juvenile period. Male hamsters at postnatal day 28 (P28) were randomly assigned to either the social defeat, "social threat", or arena control group, and they correspondingly received a series of nine social interaction trials (i.e., either social defeat, "social threat", or arena control conditions) from P33 to P66. At the behavioral level (Experiment 1), we found that repeated social defeats (but not "social threats") significantly impacted locomotor activity in the familiar context and social interaction in the familiar/unfamiliar social contexts. At the physiological and hormonal levels (Experiments 2 and 3), repeated social defeat significantly enhanced the cortisol and norepinephrine concentrations in blood. Enlargement of the spleen was also found in the social defeat and "social threat" groups. At the immunological level (Experiment 4), the social defeat group showed lower levels of pro-inflammatory cytokines in the hypothalamus and hippocampus but higher concentration of IL-6 in the striatum compared to the other two groups. At the neurochemical level (Experiment 5), the socially defeated hamsters mainly displayed reductions of dopamine, dopamine metabolites, and 5-HT levels in the striatum and decreased level of 5-HT in the hippocampus. In Experiment 6, an increase in the spine density of hippocampal CA1 pyramidal neurons was specifically observed in the "social threat" group. Collectively, our findings indicate that repeated

  10. Gene structure and expression of serotonin receptor HTR2C in hypothalamic samples from infanticidal and control sows

    Directory of Open Access Journals (Sweden)

    Quilter Claire R

    2012-04-01

    Full Text Available Abstract Background The serotonin pathways have been implicated in behavioural phenotypes in a number of species, including human, rat, mouse, dog and chicken. Components of the pathways, including the receptors, are major targets for drugs used to treat a variety of physiological and psychiatric conditions in humans. In our previous studies we have identified genetic loci potentially contributing to maternal infanticide in pigs, which includes a locus on the porcine X chromosome long arm. The serotonin receptor HTR2C maps to this region, and is therefore an attractive candidate for further study based on its function and its position in the genome. Results In this paper we describe the structure of the major transcripts produced from the porcine HTR2C locus using cDNA prepared from porcine hypothalamic and pooled total brain samples. We have confirmed conservation of sites altered by RNA editing in other mammalian species, and identified polymorphisms in the gene sequence. Finally, we have analysed expression and editing of HTR2C in hypothalamus samples from infanticidal and control animals. Conclusions The results confirm that although the expression of the long transcriptional variant of HTR2C is raised in infanticidal animals, the overall patterns of editing in the hypothalamus are similar between the two states. Sequences associated with the cDNA and genomic structures of HTR2C reported in this paper are deposited in GenBank under accession numbers FR720593, FR720594 and FR744452.

  11. Novel biochemical manipulation of brain serotonin reveals a role of serotonin in the circadian rhythm of sleep-wake cycles.

    Science.gov (United States)

    Nakamaru-Ogiso, Eiko; Miyamoto, Hiroyuki; Hamada, Kozo; Tsukada, Koji; Takai, Katsuji

    2012-06-01

    Serotonin (5-HT) neurons have been implicated in the modulation of many physiological functions, including mood regulation, feeding, and sleep. Impaired or altered 5-HT neurotransmission appears to be involved in depression and anxiety symptoms, as well as in sleep disorders. To investigate brain 5-HT functions in sleep, we induced 5-HT deficiency through acute tryptophan depletion in rats by intraperitoneally injecting a tryptophan-degrading enzyme called tryptophan side chain oxidase I (TSOI). After the administration of TSOI (20 units), plasma tryptophan levels selectively decreased to 1-2% of those of controls within 2 h, remained under 1% for 12-24 h, and then recovered between 72 and 96 h. Following plasma tryptophan levels, brain 5-HT levels decreased to ∼30% of the control level after 6 h, remained at this low level for 20-30 h, and returned to normal after 72 h. In contrast, brain norepinephreine and dopamine levels remained unchanged. After TSOI injection, the circadian rhythms of the sleep-wake cycle and locomotive activity were lost and broken into minute(s) ultradian alternations. The hourly slow-wave sleep (SWS) time significantly increased at night, but decreased during the day, whereas rapid eye movement sleep was significantly reduced during the day. However, daily total (cumulative) SWS time was retained at the normal level. As brain 5-HT levels gradually recovered 48 h after TSOI injection, the circadian rhythms of sleep-wake cycles and locomotive activity returned to normal. Our results suggest that 5-HT with a rapid turnover rate plays an important role in the circadian rhythm of sleep-wake cycles.

  12. Acute melatonin and para-chloroamphetamine interactions on pineal, brain and serum serotonin levels as well as stress hormone levels.

    Science.gov (United States)

    Manzana, E J; Chen, W J; Champney, T H

    2001-08-03

    para-Chloroamphetamine, an amphetamine analog, alters serotonergic neurochemistry. In previous reports, melatonin (MEL), when administered with other amphetamine analogs, altered the decline in serotonin content produced by these analogs. The present studies assessed the effects of various doses of melatonin and p-chloroamphetamine on serotonin levels in numerous brain regions in male rats. Melatonin (10, 25 or 50 mg/kg, s.c.) and p-chloroamphetamine (3 or 5 mg/kg, s.c.) were administered and, 3 h later, brain samples and serum were collected. Serotonin levels in the serum and various regions of the brain were assayed using high-performance liquid chromatography. Melatonin in combination with a high dose of p-chloroamphetamine (5 mg/kg) produced cumulative deficits in serotonin levels in the serum. However, serotonin levels in the pineal, cortex or brain stem in all combined melatonin and p-chloroamphetamine groups were not significantly different from groups that received p-chloroamphetamine alone. Serum adrenocorticotropin (ACTH) and corticosterone levels were significantly elevated in the melatonin and p-chloroamphetamine combined groups, suggesting that animals receiving both treatments were more stressed than control animals or animals receiving melatonin or p-chloroamphetamine alone. These results indicate that melatonin does not alter p-chloroamphetamine-induced deficits in central serotonin levels. The increased serum adrenocorticotropic hormone, corticosterone and serotonin levels observed following melatonin and p-chloroamphetamine treatment suggest that this combination may have adverse peripheral effects.

  13. Serotonin and Aggressiveness in Chickens

    Science.gov (United States)

    Serotonin (5-HT) regulates aggressive behavior in animals. This study examined if 5-HT regulation of aggressiveness is gene-dependent. Chickens from two divergently selected lines KGB and MBB (Kind Gentle Birds and Mean Bad Birds displaying low and high aggressiveness, respectively) and DXL (Dekalb ...

  14. 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

  15. Selective serotonin reuptake inhibitor exposure.

    Science.gov (United States)

    Fitzgerald, Kevin T; Bronstein, Alvin C

    2013-02-01

    Many antidepressants inhibit serotonin or norepinephrine reuptake or both to achieve their clinical effect. The selective serotonin reuptake inhibitor class of antidepressants (SSRIs) includes citalopram, escitalopram (active enantiomer of citalopram), fluoxetine, fluvoxamine, paroxetine, and sertraline. The SSRIs are as effective as tricyclic antidepressants in treatment of major depression with less significant side effects. As a result, they have become the largest class of medications prescribed to humans for depression. They are also used to treat obsessive-compulsive disorder, panic disorders, alcoholism, obesity, migraines, and chronic pain. An SSRI (fluoxetine) has been approved for veterinary use in treatment of canine separation anxiety. SSRIs act specifically on synaptic serotonin concentrations by blocking its reuptake in the presynapse and increasing levels in the presynaptic membrane. Clinical signs of SSRI overdose result from excessive amounts of serotonin in the central nervous system. These signs include nausea, vomiting, mydriasis, hypersalivation, and hyperthermia. Clinical signs are dose dependent and higher dosages may result in the serotonin syndrome that manifests itself as ataxia, tremors, muscle rigidity, hyperthermia, diarrhea, and seizures. Current studies reveal no increase in appearance of any specific clinical signs of serotonin toxicity with regard to any SSRI medication. In people, citalopram has been reported to have an increased risk of electrocardiographic abnormalities. Diagnosis of SSRI poisoning is based on history, clinical signs, and response to therapy. No single clinical test is currently available to confirm SSRI toxicosis. The goals of treatment in this intoxication are to support the animal, prevent further absorption of the drug, support the central nervous system, control hyperthermia, and halt any seizure activity. The relative safety of the SSRIs in overdose despite the occurrence of serotonin syndrome makes them

  16. 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.

  17. A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism

    Science.gov (United States)

    Palamiuc, Lavinia; Noble, Tallie; Witham, Emily; Ratanpal, Harkaranveer; Vaughan, Megan; Srinivasan, Supriya

    2017-01-01

    Serotonin, a central neuromodulator with ancient ties to feeding and metabolism, is a major driver of body fat loss. However, mechanisms by which central serotonin action leads to fat loss remain unknown. Here, we report that the FLP-7 neuropeptide and its cognate receptor, NPR-22, function as the ligand-receptor pair that defines the neuroendocrine axis of serotonergic body fat loss in Caenorhabditis elegans. FLP-7 is secreted as a neuroendocrine peptide in proportion to fluctuations in neural serotonin circuit functions, and its release is regulated from secretory neurons via the nutrient sensor AMPK. FLP-7 acts via the NPR-22/Tachykinin2 receptor in the intestine and drives fat loss via the adipocyte triglyceride lipase ATGL-1. Importantly, this ligand-receptor pair does not alter other serotonin-dependent behaviours including food intake. For global modulators such as serotonin, the use of distinct neuroendocrine peptides for each output may be one means to achieve phenotypic selectivity. PMID:28128367

  18. Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary.

    Science.gov (United States)

    Dosi, Rupal; Ambaliya, Annirudh; Joshi, Harshal; Patell, Rushad

    2014-06-23

    Serotonin syndrome and neuroleptic malignant syndrome are two drug toxidromes that have often overlapping and confusing clinical pictures. We report a case of a young man who presented with alteration of mental status, autonomic instability and neuromuscular hyperexcitability following ingestion of multiple psychiatric and antiepileptic medications. The patient satisfied criteria for serotonin syndrome and neuroleptic malignant syndrome, and based on the characteristic clinical features, laboratory findings and clinical course it was concluded that the patient had both toxidromes. The patient was managed with cyproheptadine and supportive measures, and recovered over the course of 3 weeks. A brief review of literature highlighting the diagnostic clues as well as the importance of recognising and distinguishing the often missed and confounding diagnoses follows.

  19. 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...

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

    Science.gov (United States)

    Sanchez, C L; Biskup, C S; Herpertz, S; Gaber, T J; Kuhn, C M; Hood, S H; Zepf, F D

    2015-05-19

    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 with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.

  1. 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.

  2. Serotonin-induced down-regulation of cell surface serotonin transporter

    DEFF Research Database (Denmark)

    Jørgensen, Trine Nygaard; Christensen, Peter Møller; Gether, Ulrik

    2014-01-01

    The serotonin transporter (SERT) terminates serotonergic signaling and enables refilling of synaptic vesicles by mediating reuptake of serotonin (5-HT) released into the synaptic cleft. The molecular and cellular mechanisms controlling SERT activity and surface expression are not fully understood...

  3. Immunomodulatory Effects Mediated by Serotonin

    OpenAIRE

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

    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...

  4. 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.

  5. 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.

  6. Expression of serotonin receptors in human lower esophageal sphincter

    OpenAIRE

    Li, He-Fei; Liu, Jun-Feng; Zhang, Ke; Feng, Yong

    2014-01-01

    Serotonin (5-HT) is a neurotransmitter and vasoactive amine that is involved in the regulation of a large number of physiological functions. The wide variety of 5-HT-mediated functions is due to the existence of different classes of serotonergic receptors in the mammalian gastrointestinal tract and nervous system. The aim of this study was to explore the expression of multiple types of 5-HT receptor (5-HT1AR, 5-HT2AR, 5-HT3AR, 5-HT4R, 5-HT5AR, 5-HT6R and 5-HT7R) in sling and clasp fibers from...

  7. 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

  8. 5-HT systems: emergent targets for memory formation and memory alterations.

    Science.gov (United States)

    Meneses, Alfredo

    2013-01-01

    Drugs acting through 5-hydroxytryptamine (serotonin or 5-HT) systems modulate memory and its alterations, although the mechanisms involved are poorly understood. 5-HT drugs may present promnesic and/or antiamnesic (or even being amnesic) effects. Key questions regarding 5-HT markers include whether receptors directly or indirectly participate and/or contribute to the physiological and pharmacological basis of memory and its pathogenesis; hence, the major aim of this article was to examine recent advances in emergent targets of the 5-HT systems for memory formation and memory alterations. Recent reviews and findings are summarized, mainly in the context of the growing notion of memory deficits in brain disorders (e.g., posttraumatic stress disorder, mild cognitive impairment, consumption of drugs, poststroke cognitive dysfunctions, schizophrenia, Parkinson disease, and infection-induced memory impairments). Mainly, mammalian and (some) human data were the focus. At least agonists and antagonists for 5-HT1A/1B, 5-HT2A/2B/2C, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors as well as serotonin uptake inhibitors seem to have a promnesic and/or antiamnesic effect in different conditions and 5-HT markers seem to be associated to neural changes. Available evidence offers clues about the possibilities, but the exact mechanisms remain unclear. For instance, 5-HT transporter expression seems to be a reliable neural marker related to memory mechanisms and its alterations.

  9. Analysis and prediction of the physiological effects of altered coenzyme specificity in xylose reductase and xylitol dehydrogenase during xylose fermentation by Saccharomyces cerevisiae.

    Science.gov (United States)

    Krahulec, Stefan; Klimacek, Mario; Nidetzky, Bernd

    2012-04-30

    An advanced strategy of Saccharomyces cerevisiae strain development for fermentation of xylose applies tailored enzymes in the process of metabolic engineering. The coenzyme specificities of the NADPH-preferring xylose reductase (XR) and the NAD⁺-dependent xylitol dehydrogenase (XDH) have been targeted in previous studies by protein design or evolution with the aim of improving the recycling of NADH or NADPH in their two-step pathway, converting xylose to xylulose. Yeast strains expressing variant pairs of XR and XDH that according to in vitro kinetic data were suggested to be much better matched in coenzyme usage than the corresponding pair of wild-type enzymes, exhibit widely varying capabilities for xylose fermentation. To achieve coherence between enzyme properties and the observed strain performance during fermentation, we explored the published kinetic parameters for wild-type and engineered forms of XR and XDH as possible predictors of xylitol by-product formation (Y(xylitol)) in yeast physiology. We found that the ratio of enzymatic reaction rates using NADP(H) and NAD(H) that was calculated by applying intracellular reactant concentrations to rate equations derived from bi-substrate kinetic analysis, succeeded in giving a statistically reliable forecast of the trend effect on Y(xylitol). Prediction based solely on catalytic efficiencies with or without binding affinities for NADP(H) and NAD(H) were not dependable, and we define a minimum demand on the enzyme kinetic characterization to be performed for this purpose. An immediate explanation is provided for the typically lower Y(xylitol) in the current strains harboring XR engineered for utilization of NADH as compared to strains harboring XDH engineered for utilization of NADP⁺. The known XDH enzymes all exhibit a relatively high K(m) for NADP⁺ so that physiological boundary conditions are somewhat unfavorable for xylitol oxidation by NADP⁺. A criterion of physiological fitness is developed for

  10. Activity of etv5a and etv5b genes in the hypothalamus of fasted zebrafish is influenced by serotonin.

    Science.gov (United States)

    Mechaly, Alejandro S; Richardson, Ebony; Rinkwitz, Silke

    2016-12-29

    Serotonin has been implicated in the inhibition of food intake in vertebrates. However, the mechanisms through which serotonin acts has yet to be elucidated. Recently, ETV5 (ets variant gene 5) has been associated with obesity and food intake control mechanisms in mammals. We have analyzed a putative physiological function of the two etv5 paralogous genes (etv5a and etv5b) in neuronal food intake control in adult zebrafish that have been exposed to different nutritional conditions. A feeding assay was established and fluoxetine, a selective serotonin re-uptake inhibitor (SSRI), was applied. Gene expression changes in the hypothalamus were determined using real-time PCR. Fasting induced an up-regulation of etv5a and etv5b in the hypothalamus, whereas increased serotonin levels in the fasted fish counteracted the increase in expression. To investigate potential mechanisms the expression of further food intake control genes was determined. The results show that an increase of serotonin in fasting fish causes a reduction in the activity of genes stimulating food intake. This is in line with a previously demonstrated anorexigenic function of serotonin. Our results suggest that obesity-associated ETV5 has a food intake stimulating function and that this function is modulated through serotonin.

  11. The role of serotonin and its receptors in activation of immune responses and inflammation.

    Science.gov (United States)

    Shajib, M S; Khan, W I

    2015-03-01

    Serotonin or 5-hydroxytryptamine (5-HT) is a neurotransmitter and hormone that contributes to the regulation of various physiological functions by its actions in the central nervous system (CNS) and in the respective organ systems. Peripheral 5-HT is predominantly produced by enterochromaffin (EC) cells of the gastrointestinal (GI) tract. These gut-resident cells produce much more 5-HT than all neuronal and other sources combined, establishing EC cells as the main source of this biogenic amine in the human body. Peripheral 5-HT is also a potent immune modulator and affects various immune cells through its receptors and via the recently identified process of serotonylation. Alterations in 5-HT signalling have been described in inflammatory conditions of the gut, such as inflammatory bowel disease. The association between 5-HT and inflammation, however, is not limited to the gut, as changes in 5-HT levels have also been reported in patients with allergic airway inflammation and rheumatoid arthritis. Based on searches for terms such as '5-HT', 'EC cell', 'immune cells' and 'inflammation' in pubmed.gov as well as by utilizing pertinent reviews, the current review aims to provide an update on the role of 5-HT in biological functions with a particular focus on immune activation and inflammation.

  12. Genetics of serotonin receptors and depression: state of the art.

    Science.gov (United States)

    Fabbri, Chiara; Marsano, Agnese; Serretti, Alessandro

    2013-05-01

    Major depression (MD) is a major health problem, partly due to the incomplete understanding of the pathogenic mechanisms of the disease. Research efforts have mainly focused on alterations in monoaminergic neurotransmission, especially in relation to the serotonergic system, due to its key role in the regulation of mood and related biological functions. Given the high heritability of MD (estimated between 31% and 42% for unipolar depression), genes coding for key regulators of the serotonergic neurotransmission have been considered as optimal candidates. The present review is focused on the role of genes coding for serotonin receptors in MD pathogenesis, since the serotonin transporter and enzymes involved in serotonin metabolism have been reviewed elsewhere. Despite the large number of candidate gene studies focusing on genes coding for serotonin receptors, results have been inconsistent. The most replicated findings are the associations between rs6295 (HTR1A gene) G allele or G/G genotype and rs6311 (HTR2A gene) A allele or A/A genotype and MD or depressive symptoms. Preclinical and imaging/post-mortem studies in humans provide strong support for the involvement of HTR1A and HTR2A genes in MD. Nevertheless, the inconsistency across previous studies clearly suggests that innovative approaches should be designed in order to overcome the limitations of candidate gene studies. To date, the most appealing methodologies seem to be full exome or genome sequencing, genome-wide pathway analyses, endophenotypes, and epigenetic biomarkers. The reported tools may assist in the detection of multiple-loci models, which could potentially explain the high percentage of MD susceptibility ascribed to genetic factors.

  13. Serotonin modulates insect hemocyte phagocytosis via two different serotonin receptors.

    Science.gov (United States)

    Qi, Yi-Xiang; Huang, Jia; Li, Meng-Qi; Wu, Ya-Su; Xia, Ren-Ying; Ye, Gong-Yin

    2016-03-14

    Serotonin (5-HT) modulates both neural and immune responses in vertebrates, but its role in insect immunity remains uncertain. We report that hemocytes in the caterpillar, Pieris rapae are able to synthesize 5-HT following activation by lipopolysaccharide. The inhibition of a serotonin-generating enzyme with either pharmacological blockade or RNAi knock-down impaired hemocyte phagocytosis. Biochemical and functional experiments showed that naive hemocytes primarily express 5-HT1B and 5-HT2B receptors. The blockade of 5-HT1B significantly reduced phagocytic ability; however, the blockade of 5-HT2B increased hemocyte phagocytosis. The 5-HT1B-null Drosophila melanogaster mutants showed higher mortality than controls when infected with bacteria, due to their decreased phagocytotic ability. Flies expressing 5-HT1B or 5-HT2B RNAi in hemocytes also showed similar sensitivity to infection. Combined, these data demonstrate that 5-HT mediates hemocyte phagocytosis through 5-HT1B and 5-HT2B receptors and serotonergic signaling performs critical modulatory functions in immune systems of animals separated by 500 million years of evolution.

  14. 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

  15. Serotonin: Modulator of a Drive to Withdraw

    Science.gov (United States)

    Tops, Mattie; Russo, Sascha; Boksem, Maarten A. S.; Tucker, Don M.

    2009-01-01

    Serotonin is a fundamental neuromodulator in both vertebrate and invertebrate nervous systems, with a suspected role in many human mental disorders. Yet, because of the complexity of serotonergic function, researchers have been unable to agree on a general theory. One function suggested for serotonin systems is the avoidance of threat. We propose…

  16. Nasal Physiology

    Science.gov (United States)

    ... Caregivers Contact ARS HOME ANATOMY Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ... Patient Education About this Website Font Size + - Home > ANATOMY > Nasal Physiology Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy ...

  17. The effect of melanocortin (Mc3 and Mc4) antagonists on serotonin-induced food and water intake of broiler cockerels.

    Science.gov (United States)

    Zendehdel, Morteza; Hamidi, Farshid; Babapour, Vahab; Mokhtarpouriani, Kasra; Fard, Ramin Mazaheri Nezhad

    2012-09-01

    The current study was designed to examine the effects of intracerebroventricular injections of SHU9119 [a nonselective melanocortin receptor (McR) antagonist] and MCL0020 (a selective McR antagonist) on the serotonin-induced eating and drinking responses of broiler cockerels deprived of food for 24 h (FD24). For Experiment 1, the chickens were intracerebroventricularly injected with 2.5, 5, and 10 µg serotonin. In Experiment 2, the chickens received 2 nmol SHU9119 before being injected with 10 µg serotonin. For Experiment 3, the chickens were given 10 µg serotonin after receiving 2 nmol MCL0020, and the level of food and water intake was determined 3 h post-injection. Results of this study showed that serotonin decreased food intake but increased water intake among the FD24 broiler cockerels and that these effects occurred in a dose-dependent manner. The inhibitory effect of serotonin on food intake was significantly attenuated by pretreatment with SHU9119 and MCL0020. However, the stimulatory effect of serotonin on water intake was not altered by this pretreatment. These results suggest that serotonin hypophagia and hyperdipsia were mediated by different mechanisms in the central nervous system, and that serotonin required downstream activation of McRs to promote hypophagia but not hyperdipsia in the FD24 chickens.

  18. Development and application of assays for serotonin

    Energy Technology Data Exchange (ETDEWEB)

    Gow, I.F.

    1987-01-01

    In this thesis, two assays for serotonin were developed, validated, and used to investigate the relationship between platelet aggregation, serotonin levels and sodium status and serotonin levels and platelet function in patients with cardiovascular disease. A radioimmunoassay (RIA) using an (/sup 125/I)-labelled tracer was developed and validated for the measurement of serotonin in human platelet-rich plasma (PRP) and rat serum. Antisera were raised against N-succinamylserotonin conjugated to bovine albumin and, to improve assay sensitivity, the analyte was made chemically similar to the immunogen by conversion to N-acetylserotonin prior to assay, using the specific amino reagent N-acetoxysuccinimide. An assay for serotonin using high-pressure liquid chromatography with electrochemical detection (HPLC-ECD) was developed, and used to validate the RIA. The RIA can be used to assay up to 100 samples/day compared with 10-20/day by the HPLC-ECD assay.

  19. Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

    Directory of Open Access Journals (Sweden)

    Watson Cheryl S

    2010-10-01

    Full Text Available Abstract Background Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens. Methods We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone at 10 pM (representing pre-development levels, and 1 nM (representing higher cycle-dependent and pregnancy levels in combinations with the same levels of xenoestrogens in GH3/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2 phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively. Results All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses. Conclusions Responses mediated by endogenous estrogens representing different life stages are

  20. Selective labeling of serotonin uptake sites in rat brain by (/sup 3/H)citalopram contrasted to labeling of multiple sites by (/sup 3/H)imipramine

    Energy Technology Data Exchange (ETDEWEB)

    D' Amato, R.J.; Largent, B.L.; Snowman, A.M.; Snyder, S.H.

    1987-07-01

    Citalopram is a potent and selective inhibitor of neuronal serotonin uptake. In rat brain membranes (/sup 3/H)citalopram demonstrates saturable and reversible binding with a KD of 0.8 nM and a maximal number of binding sites (Bmax) of 570 fmol/mg of protein. The drug specificity for (/sup 3/H)citalopram binding and synaptosomal serotonin uptake are closely correlated. Inhibition of (/sup 3/H)citalopram binding by both serotonin and imipramine is consistent with a competitive interaction in both equilibrium and kinetic analyses. The autoradiographic pattern of (/sup 3/H)citalopram binding sites closely resembles the distribution of serotonin. By contrast, detailed equilibrium-saturation analysis of (/sup 3/H)imipramine binding reveals two binding components, i.e., high affinity (KD = 9 nM, Bmax = 420 fmol/mg of protein) and low affinity (KD = 553 nM, Bmax = 8560 fmol/mg of protein) sites. Specific (/sup 3/H)imipramine binding, defined as the binding inhibited by 100 microM desipramine, is displaced only partially by serotonin. Various studies reveal that the serotonin-sensitive portion of binding corresponds to the high affinity sites of (/sup 3/H)imipramine binding whereas the serotonin-insensitive binding corresponds to the low affinity sites. Lesioning of serotonin neurons with p-chloroamphetamine causes a large decrease in (/sup 3/H)citalopram and serotonin-sensitive (/sup 3/H)imipramine binding with only a small effect on serotonin-insensitive (/sup 3/H)imipramine binding. The dissociation rate of (/sup 3/H)imipramine or (/sup 3/H)citalopram is not altered by citalopram, imipramine or serotonin up to concentrations of 10 microM. The regional distribution of serotonin sensitive (/sup 3/H)imipramine high affinity binding sites closely resembles that of (/sup 3/H)citalopram binding.

  1. Regulatory roles of serotonin and melatonin in abiotic stress tolerance in plants.

    Science.gov (United States)

    Kaur, Harmeet; Mukherjee, Soumya; Baluska, Frantisek; Bhatla, Satish C

    2015-01-01

    Understanding the physiological and biochemical basis of abiotic stress tolerance in plants has always been one of the major aspects of research aiming to enhance plant productivity in arid and semi-arid cultivated lands all over the world. Growth of stress-tolerant transgenic crops and associated agricultural benefits through increased productivity, and related ethical issues, are also the major concerns of current research in various laboratories. Interesting data on the regulation of abiotic stress tolerance in plants by serotonin and melatonin has accumulated in the recent past. These two indoleamines possess antioxidative and growth-inducing properties, thus proving beneficial for stress acclimatization. Present review shall focus on the modes of serotonin and melatonin-induced regulation of abiotic stress tolerance in plants. Complex molecular interactions of serotonin and auxin-responsive genes have suggested their antagonistic nature. Data from genomic and metabolomic analyses of melatonin-induced abiotic stress signaling have lead to an understanding of the regulation of stress tolerance through the modulation of transcription factors, enzymes and various signaling molecules. Melatonin, nitric oxide (NO) and calmodulin interactions have provided new avenues for research on the molecular aspects of stress physiology in plants. Investigations on the characterization of receptors associated with serotonin and melatonin responses, are yet to be undertaken in plants. Patenting of biotechnological inventions pertaining to serotonin and melatonin formulations (through soil application or foliar spray) are expected to be some of the possible ways to regulate abiotic stress tolerance in plants. The present review, thus, summarizes the regulatory roles of serotonin and melatonin in modulating the signaling events accompanying abiotic stress in plants.

  2. Serotonin, neural markers, and memory.

    Science.gov (United States)

    Meneses, Alfredo

    2015-01-01

    Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals' species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors as well as SERT (serotonin transporter) seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence.

  3. Serotonin, neural markers and memory

    Directory of Open Access Journals (Sweden)

    Alfredo eMeneses

    2015-07-01

    Full Text Available Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals’ species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptors as well as SERT (serotonin transporter seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence

  4. The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3,4-methylenedioxymethamphetamine ('Ecstasy') in healthy volunteers.

    Science.gov (United States)

    Liechti, M E; Vollenweider, F X

    2000-01-01

    MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' is a widely used recreational drug that produces a state of heightened mood but also cardiovascular and vegetative side-effects. In animals, MDMA releases serotonin and, to a lesser extent, dopamine and norepinephrine. The release of serotonin can be blocked by serotonin uptake inhibitors such as citalopram. It is unknown to what extent this mechanism is also responsible for the physiological side-effects of MDMA seen in humans. We investigated the effect of citalopram pretreatment (40 mg i.v.) on vegetative and cardiovascular effects of MDMA (1.5 mg/kg p.o.) in a double-blind placebo-controlled study in 16 healthy volunteers. MDMA moderately increased blood pressure and heart rate, slightly elevated body temperature and produced a broad range of acute and short-term side-effects. Citalopram reduced all these MDMA-induced physiological changes except for body temperature. These findings suggest that physiological effects of MDMA in humans are partially due to an interaction of MDMA with the serotonin carrier and a subsequent release of serotonin.

  5. Lipidomic profiling of tryptophan hydroxylase 2 knockout mice reveals novel lipid biomarkers associated with serotonin deficiency.

    Science.gov (United States)

    Weng, Rui; Shen, Sensen; Burton, Casey; Yang, Li; Nie, Honggang; Tian, Yonglu; Bai, Yu; Liu, Huwei

    2016-04-01

    Serotonin is an important neurotransmitter that regulates a wide range of physiological, neuropsychological, and behavioral processes. Consequently, serotonin deficiency is involved in a wide variety of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, schizophrenia, and depression. The pathophysiological mechanisms underlying serotonin deficiency, particularly from a lipidomics perspective, remain poorly understood. This study therefore aimed to identify novel lipid biomarkers associated with serotonin deficiency by lipidomic profiling of tryptophan hydroxylase 2 knockout (Tph2-/-) mice. Using a high-throughput normal-/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (NP/RP 2D LC-QToF-MS) method, 59 lipid biomarkers encompassing glycerophospholipids (glycerophosphocholines, lysoglycerophosphocholines, glycerophosphoethanolamines, lysoglycerophosphoethanolamines glycerophosphoinositols, and lysoglycerophosphoinositols), sphingolipids (sphingomyelins, ceramides, galactosylceramides, glucosylceramides, and lactosylceramides) and free fatty acids were identified. Systemic oxidative stress in the Tph2-/- mice was significantly elevated, and a corresponding mechanism that relates the lipidomic findings has been proposed. In summary, this work provides preliminary findings that lipid metabolism is implicated in serotonin deficiency.

  6. Diastolic function alteration mechanisms in physiologic hypertrophy versus pathologic hypertrophy are elucidated by model-based Doppler E-wave analysis

    Directory of Open Access Journals (Sweden)

    Simeng Zhu

    2014-12-01

    Full Text Available Athletic training can result in increased left ventricular (LV wall thickness, termed physiologic hypertrophy (PhH. By contrast, pathologic hypertrophy (PaH can be due to hypertension, aortic stenosis, or genetic mutation causing hypertrophic cardiomyopathy (HCM. Because morphologic (LV dimension, wall thickness, mass, etc. and functional index similarities (LV ejection fraction, cardiac output, peak filling rate, etc. limit diagnostic specificity, ability to differentiate between PhH and PaH is important. Conventional echocardiographic diastolic function (DF indexes have limited ability to differentiate between PhH and PaH and cannot provide information on chamber property (stiffness and relaxation. We hypothesized that kinematic model-based DF assessment can differentiate between PhH and PaH and, by providing chamber properties, has even greater value compared with conventional metrics. For validation, we assessed DF in the following three age-matched groups: pathologic (HCM hypertrophy (PaH, n = 14, PhH (Olympic rowers, PhH, n = 21, and controls (n = 21. Magnetic resonance imaging confirmed presence of both types of hypertrophy and determined LV mass and chamber size. Model-based indexes, chamber stiffness (k, relaxation/viscoelasticity (c, and load (xo and conventional indexes, Epeak (peak of E-wave, ratio of Epeak to Apeak (E/A, E-wave acceleration time (AT, and E-wave deceleration time (DT were computed. We analyzed 1588 E waves distributed as follows: 328 (PaH, 672 (athletes, and 588 (controls. Among conventional indexes, Epeak and E-wave DT were similar between PaH and PhH, whereas E/A and E-wave AT were lower in PaH. Model-based analysis showed that PaH had significantly higher relaxation/viscoelasticity (c and chamber stiffness (k than PhH. The physiologic equation of motion for filling-based derivation of the model provides a mechanistic understanding of the differences between PhH and PaH.

  7. 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

  8. 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...... 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...... with low neuroticism. This finding was confirmed with an independent voxel-based whole-brain analysis. Other personality traits did not correlate with 5-HT1A receptor BPP. Previous observations have reported lower serotonin 5-HT1A receptor density in major depression. This neurobiological finding may...

  9. Effect of Pre-treatment of α-Ketoglutarate on Cyanide-induced Toxicity and Alterations in Various Physiological Variables in Rodents

    Institute of Scientific and Technical Information of China (English)

    RAJKUMAR TULSAWANI; DEO KUMAR; R. BHATTACHARYA

    2007-01-01

    Objective To investigate the effects of pre-treatment of α-ketoglutarate (αt-KG) on cyanide-induced lethality and changes in various physiological parameters in rodents. Methods The LD50 of potassium cyanide (KCN) given orally (po),intraperitoneally (ip), subcutaneously (sc) or intravenously (iv) was determined in male mice, in the presence or absence α-KG given po, ip or iv. α-KG was administered 10, 20 or 40 min prior to KCN at 0.50, 1.0 or 2.0 g/kg by po or ip route, and at 0.10,0.20 or 0.40 g/kg by iv route. Protection index (PI) was calculated as the ratio of LD50 of KCN in the presence of α-KG (protected animals) and LD50 of KCN in the absence of α-KG (unprotected animals). In a separate experiment, several physiological variables viz. mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), neuromuscular transmission (NMT) and rectal temperature (RT) were measured in anesthetized female rats pre-treated (-10 min) with po (2.0 g/kg) or iv (0.125 g/kg) α-KG and then administered sub-lethal (0.75 LD50) or lethal (2.0, 4.0 or 8.0 LD50) doses of KCN (po). Results PI of 4.52, 6.40 and 7.60 at -10 min, 3.20, 5.40 and 6.40 at -20 min, and 1.40, 3.20 and 5.40 at -40 min of po administration with α-KG was observed for 0.50, 1.0 and 2.0 g/kg doses, respectively, against KCN given by po route. When KCN was given ip, a PI of 3.38, 4.79 and 5.70 was observed for 0.50, 1.0 and 2.0 g/kg α-KG given ip (-10 min), respectively. A lower PI of 3.37,2.83 and 2.38 was observed when KCN given sc was challenged by 2.0 g/kg α-KG given ip at -10, -20 or -40 min, respectively.Similarly, a PI of 3.37, 2.83 and 2.0 was noted when KCN given sc was antagonized by 2.0 g/kg α-KG given po at -10, -20 or -40 min, respectively. No appreciable protection was observed when lower doses of α-KG (ip or po) challenged KCN given by sc route. Pre-treatment of iv or po administration of α-KG did not afford any protection against KCN given po or iv route. Oral treatment of 0

  10. 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.

  11. 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)

  12. Serotonin: A New Hope in Alzheimer's Disease?

    Science.gov (United States)

    Claeysen, Sylvie; Bockaert, Joël; Giannoni, Patrizia

    2015-07-15

    Alzheimer's disease (AD) is the most common form of dementia affecting 35 million individuals worldwide. Current AD treatments provide only brief symptomatic relief. It is therefore urgent to replace this symptomatic approach with a curative one. Increasing serotonin signaling as well as developing molecules that enhance serotonin concentration in the synaptic cleft have been debated as possible therapeutic strategies to slow the progression of AD. In this Viewpoint, we discuss exciting new insights regarding the modulation of serotonin signaling for AD prevention and therapy.

  13. Serotonin Syndrome With Fluoxetine: Two Case Reports

    Science.gov (United States)

    Patel, Dipen Dineshkumar

    2016-01-01

    Background: Serotonin syndrome is a rare but serious complication of treatment with serotonergic agents. In its severe manifestations, death can ensue. Early recognition and aggressive management are crucial to mitigating the syndrome. Often the presentation can be subtle and easy to miss. Case Reports: We present 2 cases of serotonin syndrome seen in the psychiatric consultation service of a busy academic hospital. Both patients had favorable outcomes because of early recognition and aggressive management. Conclusion: Physicians should carefully consider and rule out the clinical diagnosis of serotonin syndrome when presented with an agitated or confused patient who is taking serotonergic agents. PMID:27999518

  14. Alterações bioquímicas e fisiológicas em sementes de milho causadas pelo ao envelhecimento acelerado Biochemical and physiological alterations in corn seeds due to accelerated aging

    Directory of Open Access Journals (Sweden)

    Maria Cristina Mingues Spinola

    2000-06-01

    Full Text Available Para avaliar possíveis alterações bioquímicas (análises eletroforéticas de proteínas totais e das isoenzimas peroxidase, fosfatase ácida e malato desidrogenase e fisiológicas (germinação e vigor que ocorrem nas sementes de milho durante a permanência das mesmas nas condições recomendadas na metodologia do teste de envelhecimento acelerado (41ºC e 100% UR, foi realizada a presente pesquisa. Utilizaram-se sementes de milho, híbrido AG122, provenientes de quatro lotes. Os períodos 0, 24, 48, 72, 96 e 120 horas de permanência das sementes na incubadora (envelhecimento acelerado definiram os tratamentos. As alterações nos perfís isoenzimáticos (fosfatase ácida e peroxidase detectadas nas sementes, a partir do período 72h de envelhecimento acelerado, revelaram o provável efeito deteriorativo provocado pela exposição das sementes às condições do teste, independentemente da qualidade do lote, apesar de a maioria dos testes determinantes da qualidade fisiológica das sementes não terem sido sensíveis para detectar tal efeito.In order to evaluate biochemical (total protein, acid phosphatase, peroxidase and malate dehydrogenase electrophoresis and physiological (germination and seed vigor alterations occurring during corn seed accelerated aging (41°C and 100%UR, four corn seed lots of the double hybrid (AG122 were submitted to zero, 24, 48, 72, 96 and 120 hours of accelerated aging. The biochemical assays carried out (isozyme electrophoretical patterns of acid phosphatase e peroxidase are more sensitive than the physiological test used to monitorate corn seed physiological quality deterioration during corn seed accelerated aging.

  15. Decreased Serotonin Levels and Serotonin-Mediated Osteoblastic Inhibitory Signaling in Patients With Ankylosing Spondylitis.

    Science.gov (United States)

    Klavdianou, Kalliopi; Liossis, Stamatis-Nick; Papachristou, Dionysios J; Theocharis, Georgios; Sirinian, Chaido; Kottorou, Anastasia; Filippopoulou, Alexandra; Andonopoulos, Andrew P; Daoussis, Dimitrios

    2016-03-01

    Evidence suggests that serotonin is an inhibitor of bone formation. We aimed to assess: 1) serum serotonin levels in patients with ankylosing spondylitis (AS), a prototype bone-forming disease, compared with patients with rheumatoid arthritis (RA) and healthy subjects; 2) the effect(s) of TNFα blockers on serum serotonin levels in patients with AS and RA; and 3) the effect(s) of serum of AS patients on serotonin signaling. Serum serotonin levels were measured in 47 patients with AS, 28 patients with RA, and 40 healthy subjects by radioimmunoassay; t test was used to assess differences between groups. The effect of serum on serotonin signaling was assessed using the human osteoblastic cell line Saos2, evaluating levels of phospho-CREB by Western immunoblots. Serotonin serum levels were significantly lower in patients with AS compared with healthy subjects (mean ± SEM ng/mL 122.9 ± 11.6 versus 177.4 ± 24.58, p = 0.038) and patients with RA (mean ± SEM ng/mL 244.8 ± 37.5, p = 0.0004). Patients with AS receiving TNFα blockers had significantly lower serotonin levels compared with patients with AS not on such treatment (mean ± SEM ng/mL 95.8 ± 14.9 versus 149.2 ± 16.0, p = 0.019). Serotonin serum levels were inversely correlated with pCREB induction in osteoblast-like Saos-2 cells. Serotonin levels are low in patients with AS and decrease even further during anti-TNFα treatment. Differences in serotonin levels are shown to have a functional impact on osteoblast-like Saos-2 cells. Therefore, serotonin may be involved in new bone formation in AS.

  16. Acute selective serotonin reuptake inhibitors regulate the dorsal raphe nucleus causing amplification of terminal serotonin release

    OpenAIRE

    Dankoski, Elyse C.; Carroll, Susan; Wightman, Robert Mark

    2016-01-01

    Abstract Selective serotonin reuptake inhibitors (SSRIs) were designed to treat depression by increasing serotonin levels throughout the brain via inhibition of clearance from the extracellular space. Although increases in serotonin levels are observed after acute SSRI exposure, 3–6 weeks of continuous use is required for relief from the symptoms of depression. Thus, it is now believed that plasticity in multiple brain systems that are downstream of serotonergic inputs contributes to the ther...

  17. Serotonin Transporter Genotype Affects Serotonin 5-HT1A Binding in Primates

    OpenAIRE

    Christian, Bradley T; Wooten, Dustin W; Hillmer, Ansel T.; Tudorascu, Dana L.; Converse, Alexander K.; Moore, Colleen F.; Ahlers, Elizabeth O.; Barnhart, Todd E.; Kalin, Ned H.; Barr, Christina S.; Schneider, Mary L.

    2013-01-01

    Disruption of the serotonin system has been implicated in anxiety and depression and a related genetic variation has been identified that may predispose individuals for these illnesses. The relationship of a functional variation of the serotonin transporter promoter gene (5-HTTLPR) on serotonin transporter binding using in vivo imaging techniques have yielded inconsistent findings when comparing variants for short (s) and long (l) alleles. However, a significant 5-HTTLPR effect on receptor bi...

  18. Potassium physiology.

    Science.gov (United States)

    Thier, S O

    1986-04-25

    Potassium is the most abundant exchangeable cation in the body. It exists predominantly in the intracellular fluid at concentrations of 140 to 150 meq/liter and in the extracellular fluid at concentrations of 3.5 to 5 meq/liter. The maintenance of the serum potassium concentration is a complex bodily function and results from the balance between intake, excretion, and distribution between intracellular and extracellular space. Ingested potassium is virtually completely absorbed from and minimally excreted through the intestine under nonpathologic circumstances. Renal excretion of potassium, which is the major chronic protective mechanism against abnormalities in potassium balance, depends on filtration, reabsorption, and a highly regulated distal nephron secretory process. Factors regulating potassium secretion include prior potassium intake, intracellular potassium, delivery of sodium chloride and poorly reabsorbable anions to the distal nephron, the urine flow rate, hormones such as aldosterone and beta-catecholamines, and the integrity of the renal tubular cell. The maintenance of distribution between the inside and outside of cells depends on the integrity of the cell membrane and its pumps, osmolality, pH, and the hormones insulin, aldosterone, beta 2-catecholamines, alpha-catecholamines, and prostaglandins. Both distribution across cell membranes and/or renal excretion of potassium may be altered by pharmacologic agents such as diuretics, alpha- and beta-catechol antagonists and agonists, depolarizing agents, and digitalis. Problems with hypokalemia and hyperkalemia can be analyzed on the basis of potassium physiology and pharmacology; proper treatment depends on an accurate analysis.

  19. Induced thermal stress on serotonin levels in the blue swimmer crab, Portunus pelagicus

    Directory of Open Access Journals (Sweden)

    Saravanan Rajendiran

    2016-03-01

    Full Text Available The temperature of habitat water has a drastic influence on the behavioral, physiological and biochemical mechanisms of crustaceans. Hyperglycemia is a typical response of many aquatic animals to harmful physical and chemical environmental changes. In crustaceans increased circulating crustacean hyperglycemic hormone (CHH and hyperglycemia are reported to occur following exposure to several environmental stress. The biogenic amine, serotonin has been found to modulate the CHH levels and oxidation of serotonin into its metabolites is catalysed by monoamine oxidase. The blue swimmer crab, Portunus pelagicus is a dominant intertidal species utilized throughout the indo-pacific region and is a particularly important species of Palk bay. It has high nutritional value and delicious taste and hence their requirements of capture and cultivation of this species are constantly increasing. This species experiences varying and increasing temperature levels as it resides in an higher intertidal zone of Thondi coast. The present study examines the effect of thermal stress on the levels of serotonin and crustacean hyperglycemic hormone in the hemolymph of P. pelagicus and analyzes the effect of the monoamine oxidase inhibitor, pargyline on serotonin and CHH level after thermal stress. The results showed increased levels of glucose, CHH and serotonin on exposure to 26 °C in control animals. Pargyline injected crabs showed highly significant increase in the levels of CHH and serotonin on every 2 °C increase or decrease in temperature. A greater CHH level of 268.86±2.87 fmol/ml and a greater serotonin level of 177.69±10.10 ng/ml was observed at 24 °C. This could be due to the effect of in maintaining the level of serotonin in the hemolymph and preventing its oxidation, which in turn induces hyperglycemia by releasing CHH into hemolymph. Thus, the study demonstrates the effect of thermal stress on the hemolymph metabolites studied and the role of

  20. 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.

  1. The influence of serotonin on fear learning.

    Science.gov (United States)

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

    2012-01-01

    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.

  2. 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

  3. The serotonin 5-HT3 receptor: a novel neurodevelopmental target

    Directory of Open Access Journals (Sweden)

    Mareen eEngel

    2013-05-01

    Full Text Available Serotonin (5-HT, next to being an important neurotransmitter, recently gained attention as a key regulator of pre- and postnatal development in the mammalian central nervous system (CNS. Several receptors for 5-HT are expressed in the developing brain including a ligand-gated ion channel, the 5-HT3 receptor. Over the past years, evidence has been accumulating that 5-HT3 receptors are involved in the regulation of neurodevelopment by serotonin.Here, we review the spatial and temporal expression patterns of 5-HT3 receptors in the pre- and early postnatal rodent brain and its functional implications. First, 5-HT3 receptors are expressed on GABAergic interneurons in neocortex and limbic structures derived from the caudal ganglionic eminence. Mature inhibitory GABAergic interneurons fine-tune neuronal excitability and thus are crucial for the physiological function of the brain. Second, 5-HT3 receptors are expressed on specific glutamatergic neurons, Cajal-Retzius cells in the cortex and granule cells in the cerebellum, where they regulate morphology, positioning and connectivity of the local microcircuitry. Taken together, the 5-HT3 receptor emerges as a potential key-regulator of network formation and function in the CNS, which could have a major impact on our understanding of neurodevelopmental disorders in which 5-HT plays a role.

  4. [Serotonin now: Part 1. Neurobiology and developmental genetics].

    Science.gov (United States)

    Kriegebaum, C; Gutknecht, L; Schmitt, A; Lesch, K-P; Reif, A

    2010-06-01

    As soon as in the 1960's, the role of serotonin (5-Hydroxytryptamin, 5-HT) in psychiatric disorders was realized, which was further substantiated by several lines of evidence amounting to a huge body of knowledge. The indolamine 5-HT belongs to the class of monoamine transmitters and can be found in the serotonergic neurons of the raphe nuclei in the brain stem. In the periphery, it is mainly present in the gastrointestinal system and the pineal gland. 5-HT is implicated in a variety of cognitive, emotional and vegetative behaviors, as well as in the regulation of circadian rhythms. Apart from its role as a neurotransmitter, it has an important function in prenatal development, where its expression pattern is tightly regulated, and in adult neurogenesis. The numerous effects of 5-HT are mediated by specific pre- and postsynaptic receptors, whose localization and functions are further described here. The serotonin transporter (SERT), which accomplishes the re-uptake of 5-HT into the neuron following its release in the synaptic cleft, not only has an important role in the termination of serotonergic neurotransmission but is also an important drug target for antidepressant compounds. In this part of the review, the neurobiological underpinnings of 5-HT synthesis, metabolism, and neurotransmission as well as the corresponding physiological consequences are summarized, while in the second part, an overview on clinical findings is provided and critically discussed.

  5. Do selective serotonin reuptake inhibitors acutely increase frontal cortex levels of serotonin?

    NARCIS (Netherlands)

    Beyer, Chad E.; Cremers, Thomas I. F. H.

    2008-01-01

    Selective serotonin uptake inhibitors (SSRIs) exert their effects by inhibiting serotonin (5-HT) re-uptake. Although blockade occurs almost immediately, the neurochemical effects on 5-HT, as measured by in vivo microdialysis, have been a matter of considerable debate. In particular, literature repor

  6. 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

  7. 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.

  8. Interplay between serotonin and cannabinoid function in the amygdala in fear conditioning.

    Science.gov (United States)

    Nasehi, Mohammad; Davoudi, Kamelia; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2016-04-01

    The possible interactions between the cannabinoid and serotonin systems in the regions of the brain involved in emotional learning and memory formation have been studied by some researchers. In view of the key role of the amygdala in the acquisition and expression of fear memory, we investigated the involvement of basolateral amygdala (BLA) serotonin 5-HT4 receptors in arachidonylcyclopropylamide (ACPA; selective CB1 cannabinoid receptor agonist)-induced fear memory consolidation impairment. In our study, a context and tone fear conditioning apparatus was used for testing fear conditioning in adult male NMRI mice. The results showed that intraperitoneal administration of ACPA 0.5 or 0.05, 0.1 and 0.5mg/kg immediately after training decreased the percentage of freezing time in context or tone fear conditioning respectively, suggesting a context- or tone-dependent fear memory consolidation impairment. Post-training intra-BLA microinjections of RS67333, as 5-HT4 serotonin receptor agonist, at doses of 0.025 and 0.05 µg/mouse also impaired context or tone memory consolidation, while RS23597, as 5-HT4 serotonin receptor antagonist, did not produce a marked difference in both fear memories as compared with the control group. Moreover, a subthreshold dose of RS67333 did not alter ACPA response in both fear conditionings. Interestingly, a subthreshold dose of RS23597 potentiated or reversed ACPA response at the dose of 0.01 or 0.05 respectively. It is concluded that BLA serotonin 5-HT4 receptors are involved in tone-dependent fear memory consolidation impairment induced by CB1 activation using ACPA, suggesting a modulatory role for serotonin 5-HT4 receptor.

  9. Mapping neurotransmitter networks with PET: an example on serotonin and opioid systems.

    Science.gov (United States)

    Tuominen, Lauri; Nummenmaa, Lauri; Keltikangas-Järvinen, Liisa; Raitakari, Olli; Hietala, Jarmo

    2014-05-01

    All functions of the human brain are consequences of altered activity of specific neural pathways and neurotransmitter systems. Although the knowledge of "system level" connectivity in the brain is increasing rapidly, we lack "molecular level" information on brain networks and connectivity patterns. We introduce novel voxel-based positron emission tomography (PET) methods for studying internal neurotransmitter network structure and intercorrelations of different neurotransmitter systems in the human brain. We chose serotonin transporter and μ-opioid receptor for this analysis because of their functional interaction at the cellular level and similar regional distribution in the brain. Twenty-one healthy subjects underwent two consecutive PET scans using [(11)C]MADAM, a serotonin transporter tracer, and [(11)C]carfentanil, a μ-opioid receptor tracer. First, voxel-by-voxel "intracorrelations" (hub and seed analyses) were used to study the internal structure of opioid and serotonin systems. Second, voxel-level opioid-serotonin intercorrelations (between neurotransmitters) were computed. Regional μ-opioid receptor binding potentials were uniformly correlated throughout the brain. However, our analyses revealed nonuniformity in the serotonin transporter intracorrelations and identified a highly connected local network (midbrain-striatum-thalamus-amygdala). Regionally specific intercorrelations between the opioid and serotonin tracers were found in anteromedial thalamus, amygdala, anterior cingulate cortex, dorsolateral prefrontal cortex, and left parietal cortex, i.e., in areas relevant for several neuropsychiatric disorders, especially affective disorders. This methodology enables in vivo mapping of connectivity patterns within and between neurotransmitter systems. Quantification of functional neurotransmitter balances may be a useful approach in etiological studies of neuropsychiatric disorders and also in drug development as a biomarker-based rationale for targeted

  10. Brain serotonin concentration and crude synaptosomal uptake in mice with the Chediak-Higashi syndrome.

    Science.gov (United States)

    Meyers, K M; Chen, M

    1976-12-01

    The Chediak-Higashi syndrome is characterized by a serotonin platelet defect and neuronal dysfunction. Whole blood serotonin concentration, serotonin brain concentration, and synaptosomal uptake of serotonin were determined in mice with the syndrome. While brain serotonin uptake in the affected mice was not significantly different from that in nonaffected mice, whole blood serotonin concentration was markedly reduced. These data suggest that in human neuropathies with platelet serotonin defect, a parallel neuronal serotonin disorder may not be assumed.

  11. Brain serotonin transporter binding of [123I]ADAM: within-subject variation between summer and winter data.

    Science.gov (United States)

    Koskela, Anu; Kauppinen, Tomi; Keski-Rahkonen, Anna; Sihvola, Elina; Kaprio, Jaakko; Rissanen, Aila; Ahonen, Aapo

    2008-09-01

    The neurotransmitter serotonin (5-HT) controls several physiological functions, and a disturbance of the 5-HT system is implicated in many psychiatric conditions. Seasonal variation has been suggested in the 5-HT system. We investigated within-subject seasonal variation in brain serotonin transporter (SERT) binding with the SERT-ligand [(123)I]ADAM and single photon emission computed tomography (SPECT) in 12 healthy individuals. No systematic variation was found in the midbrain or thalamus areas between scans done in summer and winter. Our results suggest that factors other than season are more important in causing within-subject variation of brain SERT binding between summer and winter.

  12. Effect of local anesthetics on serotonin1A receptor function.

    Science.gov (United States)

    Rao, Bhagyashree D; Shrivastava, Sandeep; Chattopadhyay, Amitabha

    2016-12-01

    The fundamental mechanism behind the action of local anesthetics is still not clearly understood. Phenylethanol (PEtOH) is a constituent of essential oils with a pleasant odor and can act as a local anesthetic. In this work, we have explored the effect of PEtOH on the function of the hippocampal serotonin1A receptor, a representative neurotransmitter receptor belonging to the G protein-coupled receptor (GPCR) family. Our results show that PEtOH induces reduction in ligand binding to the serotonin1A receptor due to lowering of binding affinity, along with a concomitant decrease in the degree of G-protein coupling. Analysis of membrane order using the environment-sensitive fluorescent probe DPH revealed decrease in membrane order with increasing PEtOH concentration, as evident from reduction in rotational correlation time of the probe. Analysis of results obtained shows that the action of local anesthetics could be attributed to the combined effects of specific interaction of the receptor with anesthetics and alteration of membrane properties (such as membrane order). These results assume relevance in the perspective of anesthetic action and could be helpful to achieve a better understanding of the possible role of anesthetics in the function of membrane receptors.

  13. 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.

  14. Serotonin receptor 5-HT5A in rat hippocampus decrease by leptin treatment.

    Science.gov (United States)

    García-Alcocer, Guadalupe; Rodríguez, Angelina; Moreno-Layseca, Paulina; Berumen, Laura C; Escobar, Jesica; Miledi, Ricardo

    2010-12-17

    5-Hydroxytryptamine (5-HT) is involved in a variety of different physiological processes and behaviors through the activation of equally diverse receptors subtypes. In this work we studied the changes on the expression of 5-HT(5A) receptors in rat hippocampus induced by leptin, an adipocyte-derived hormone that has been reported to participate in the modulation of food intake and in adult hippocampal neurogenesis. To study the effect of leptin on the 5-HT(5A) receptor gene expression a qRT-PCR was used and the distribution of those receptors in the hippocampus was visualized by immunohistochemistry. Rats were separated in four groups: control (untreated rats), leptin-treated, serotonin-treated and leptin+serotonin treated. The results showed that even though the 5-HT(5A) gene expression did not change in the hippocampus of any of the treated groups, in the rats treated with leptin and serotonin, the specific immunostaining for the 5-HT(5A) serotonin receptor decreased significantly in the dentate gyrus.

  15. 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...

  16. Organizational effects of oxytocin on serotonin innervation.

    Science.gov (United States)

    Eaton, Jennifer L; Roache, Laura; Nguyen, Khanhbao N; Cushing, Bruce S; Troyer, Emma; Papademetriou, Eros; Raghanti, Mary Ann

    2012-01-01

    Oxytocin (OT) has an organizational effect within the central nervous system and can have long-lasting effects on the expression of social behavior. OT has recently been implicated in modulating the release of serotonin through activation of receptors in the raphe nuclei. Here we test the hypothesis that OT can have an organizational effect on the serotonergic system. Male prairie voles received an intraperitoneal injection on postnatal day 1 with 3.0 or .3 µg OT, an OT antagonist, or a saline control. Brains were collected on day 21 and immunostained for serotonin. Serotonin axons were quantified in the anterior hypothalamus, cortical amygdala, medial amygdala, paraventricular nucleus of the hypothalamus, and ventromedial hypothalamus. Males treated with 3.0 µg OT displayed significantly higher serotonin axon length densities in the anterior hypothalamus, cortical amygdala, and the ventromedial hypothalamus than control males. These results support the hypothesis that OT has an organizational effect on the serotonin system during the neonatal period, and that these effects are site-specific.

  17. Differences in food intake of tumour-bearing cachectic mice are associated with hypothalamic serotonin signalling

    OpenAIRE

    Dwarkasing, Jvalini T; Mark V Boekschoten; Argilès, Joseph M; van Dijk, Miriam; Busquets, Silvia; Penna, Fabio; Toledo, Miriam; Laviano, Alessandro; Witkamp, R F; van Norren, Klaske

    2015-01-01

    Background Anorexia is a common symptom among cancer patients and contributes to malnutrition and strongly impinges on quality of life. Cancer-induced anorexia is thought to be caused by an inability of food intake-regulating systems in the hypothalamus to respond adequately to negative energy balance during tumour growth. Here, we show that this impaired response of food-intake control is likely to be mediated by altered serotonin signalling and by failure in post-transcriptional neuropeptid...

  18. A PrP(C)-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor.

    Science.gov (United States)

    Hernandez-Rapp, Julia; Martin-Lannerée, Séverine; Hirsch, Théo Z; Pradines, Elodie; Alleaume-Butaux, Aurélie; Schneider, Benoît; Baudry, Anne; Launay, Jean-Marie; Mouillet-Richard, Sophie

    2014-05-08

    The cellular prion protein, PrP(C), is a glycosylphosphatidylinositol-anchored protein, abundant in lipid rafts and highly expressed in the brain. While PrP(C) is much studied for its involvement under its abnormal PrP(Sc) isoform in Transmissible Spongiform Encephalopathies, its physiological role remains unclear. Here, we report that GSK3β, a multifunctional kinase whose inhibition is neuroprotective, is a downstream target of PrP(C) signalling in serotonergic neuronal cells. We show that the PrP(C)-dependent inactivation of GSK3β is relayed by a caveolin-Lyn platform located on neuronal cell bodies. Furthermore, the coupling of PrP(C) to GSK3β potentiates serotonergic signalling by altering the distribution and activity of the serotonin 1B receptor (5-HT1BR), a receptor that limits neurotransmitter release. In vivo, our data reveal an increased GSK3β kinase activity in PrP-deficient mouse brain, as well as sustained 5-HT1BR activity, whose inhibition promotes an anxiogenic behavioural response. Collectively, our data unveil a new facet of PrP(C) signalling that strengthens neurotransmission.

  19. A mathematical model to explore the interdependence between the serotonin and orexin/hypocretin systems.

    Science.gov (United States)

    Joshi, Alok; Wong-Lin, KongFatt; McGinnity, T Martin; Prasad, Girijesh

    2011-01-01

    Among their multitude of physiological and behavioral effects, the neurochemicals serotonin (5-HT) and orexin (Ox) have been closely linked to major depressive disorders (MDD) and sleep alterations. The dorsal raphe nucleus (DRN) and the lateral hypothalamus area (LHA) are brain regions that are sources of 5-HT and Ox, and there is evidence that suggests a reciprocal interaction between them. This lends support to the hypothesis of a close relationship between MDD and sleep disorders. Based on various experimental data, and appropriate assumptions, we construct a mathematical model of the coupled DRN-LHA neural circuit. Our model relates the dynamics of four important variables that can be experimentally measured: (i) the firing rate of 5-HT-containing neurons in DRN, (ii) the firing rate of Ox-containing neurons in the LHA, (iii) 5-HT concentration level in LHA, and (iv) Ox concentration level in DRN. Simulations show that our model supports the co-existence of baseline activities and concentration levels as observed in various separate experiments. It also allows circuit-level exploration of various parameters not yet identified experimentally, e.g. the rise and decay of Ox concentration levels due to Ox neural activity, and the exact dependence of Ox neural activity on 5-HT level. Finally we have made some model predictions regarding the effects of the 5-HT antagonist on the circuit. Our model, which can be subjected to verification and refinement as new experimental data accumulates, provides unified quantitative relationships and predictions between two important connected brain regions strongly tied to MDD and sleep disorders.

  20. Impacts of brain serotonin deficiency following Tph2 inactivation on development and raphe neuron serotonergic specification.

    Directory of Open Access Journals (Sweden)

    Lise Gutknecht

    Full Text Available Brain serotonin (5-HT is implicated in a wide range of functions from basic physiological mechanisms to complex behaviors, including neuropsychiatric conditions, as well as in developmental processes. Increasing evidence links 5-HT signaling alterations during development to emotional dysregulation and psychopathology in adult age. To further analyze the importance of brain 5-HT in somatic and brain development and function, and more specifically differentiation and specification of the serotonergic system itself, we generated a mouse model with brain-specific 5-HT deficiency resulting from a genetically driven constitutive inactivation of neuronal tryptophan hydroxylase-2 (Tph2. Tph2 inactivation (Tph2-/- resulted in brain 5-HT deficiency leading to growth retardation and persistent leanness, whereas a sex- and age-dependent increase in body weight was observed in Tph2+/- mice. The conserved expression pattern of the 5-HT neuron-specific markers (except Tph2 and 5-HT demonstrates that brain 5-HT synthesis is not a prerequisite for the proliferation, differentiation and survival of raphe neurons subjected to the developmental program of serotonergic specification. Furthermore, although these neurons are unable to synthesize 5-HT from the precursor tryptophan, they still display electrophysiological properties characteristic of 5-HT neurons. Moreover, 5-HT deficiency induces an up-regulation of 5-HT(1A and 5-HT(1B receptors across brain regions as well as a reduction of norepinephrine concentrations accompanied by a reduced number of noradrenergic neurons. Together, our results characterize developmental, neurochemical, neurobiological and electrophysiological consequences of brain-specific 5-HT deficiency, reveal a dual dose-dependent role of 5-HT in body weight regulation and show that differentiation of serotonergic neuron phenotype is independent from endogenous 5-HT synthesis.

  1. Serotonin Signal Transduction in Two Groups of Autistic Patients

    Science.gov (United States)

    2013-12-01

    AD_________________ Award Number: W81XWH-11-1-0820 TITLE: Serotonin Signal Transduction in Two...Report 3. DATES COVERED 15 September 2011-14 September 2013 4. TITLE AND SUBTITLE Serotonin Signal Transduction in Two Groups of Autistic Patients...the arena of serotonin sensitivity, from those cells obtained from autistic subjects with normal serum serotonin . This was not the case, as the

  2. Serotonin regulates repolarization of the C. elegans pharyngeal muscle

    OpenAIRE

    Niacaris, Timothy; Avery, Leon

    2003-01-01

    Caenorhabditis elegans feeds by rhythmically contracting its pharynx to ingest bacteria. The rate of pharyngeal contraction is increased by serotonin and suppressed by octopamine. Using an electrophysiological assay, we show that serotonin and octopamine regulate two additional aspects of pharyngeal behavior. Serotonin decreases the duration of the pharyngeal action potential and enhances activity of the pharyngeal M3 motor neurons. Gramine, a competitive serotonin antagonist, and octopamine ...

  3. The serotonin transporter in psychiatric disorders

    DEFF Research Database (Denmark)

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

    2015-01-01

    , obsessive-compulsive disorder, and eating disorders. Few studies have shown changes in serotonin transporter activity in schizophrenia and attention deficit hyperactivity disorder. By showing the scarcity of data in these psychiatric disorders, we highlight the potential for further investigation......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...

  4. Physiological Networks: towards systems physiology

    Science.gov (United States)

    Bartsch, Ronny P.; Bashan, Amir; Kantelhardt, Jan W.; Havlin, Shlomo; Ivanov, Plamen Ch.

    2012-02-01

    The human organism is an integrated network where complex physiologic systems, each with its own regulatory mechanisms, continuously interact, and where failure of one system can trigger a breakdown of the entire network. Identifying and quantifying dynamical networks of diverse systems with different types of interactions is a challenge. Here, we develop a framework to probe interactions among diverse systems, and we identify a physiologic network. We find that each physiologic state is characterized by a specific network structure, demonstrating a robust interplay between network topology and function. Across physiologic states the network undergoes topological transitions associated with fast reorganization of physiologic interactions on time scales of a few minutes, indicating high network flexibility in response to perturbations. The proposed system-wide integrative approach may facilitate new dimensions to the field of systems physiology.

  5. 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

  6. Neuroticism and serotonin 5-HT1A receptors in healthy subjects.

    Science.gov (United States)

    Hirvonen, Jussi; Tuominen, Lauri; Någren, Kjell; Hietala, Jarmo

    2015-10-30

    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 with low neuroticism. This finding was confirmed with an independent voxel-based whole-brain analysis. Other personality traits did not correlate with 5-HT1A receptor BPP. Previous observations have reported lower serotonin 5-HT1A receptor density in major depression. This neurobiological finding may be a trait-like phenomenon and partly explained by higher neuroticism in patients with affective disorders. The link between personality traits and 5-HT1A receptors should be studied in patients with major depression.

  7. Serotonin modulation of cortical neurons and networks

    Directory of Open Access Journals (Sweden)

    Pau eCelada

    2013-04-01

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

  8. Salt stress-induced seedling growth inhibition coincides with differential distribution of serotonin and melatonin in sunflower seedling roots and cotyledons.

    Science.gov (United States)

    Mukherjee, Soumya; David, Anisha; Yadav, Sunita; Baluška, František; Bhatla, Satish Chander

    2014-12-01

    Indoleamines regulate a variety of physiological functions during the growth, morphogenesis and stress-induced responses in plants. Present investigations report the effect of NaCl stress on endogenous serotonin and melatonin accumulation and their differential spatial distribution in sunflower (Helianthus annuus) seedling roots and cotyledons using HPLC and immunohistochemical techniques, respectively. Exogenous serotonin and melatonin treatments lead to variable effect on hypocotyl elongation and root growth under NaCl stress. NaCl stress for 48 h increases endogenous serotonin and melatonin content in roots and cotyledons, thus indicating their involvement in salt-induced long distance signaling from roots to cotyledons. Salt stress-induced accumulation of serotonin and melatonin exhibits differential distribution in the vascular bundles and cortex in the differentiating zones of the primary roots, suggesting their compartmentalization in the growing region of roots. Serotonin and melatonin accumulation in oil body rich cells of salt-treated seedling cotyledons correlates with longer retention of oil bodies in the cotyledons. Present investigations indicate the possible role of serotonin and melatonin in regulating root growth during salt stress in sunflower. Effect of exogenous serotonin and melatonin treatments (15 μM) on sunflower seedlings grown in the absence or presence of 120 mM NaCl substantiates their role on seedling growth. Auxin and serotonin biosynthesis are coupled to the common precursor tryptophan. Salt stress-induced root growth inhibition, thus pertains to partial impairment of auxin functions caused by increased serotonin biosynthesis. In seedling cotyledons, NaCl stress modulates the activity of N-acetylserotonin O-methyltransferase (HIOMT; EC 2.1.1.4), the enzyme responsible for melatonin biosynthesis from N-acetylserotonin.

  9. Relationship between brain serotonin transporter binding, plasma concentration and behavioural effect of selective serotonin reuptake inhibitors

    OpenAIRE

    2005-01-01

    The present study was undertaken to characterise the relationship between in vivo brain serotonin transporter (SERT) binding, plasma concentration and pharmacological effect of selective serotonin reuptake inhibitors (SSRIs) in mice. Oral administration of fluvoxamine, fluoxetine, paroxetine and sertraline at pharmacologically relevant doses exerted dose- and time-dependent binding activity of brain SERT as revealed by significant increases in KD for specific [3H]paroxetine binding, and the i...

  10. 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.

  11. [Serotonin syndrome. Which treatment and when?].

    Science.gov (United States)

    Jaunay, E; Gaillac, V; Guelfi, J D

    2001-11-17

    A TOXIC REACTION: Prevalence of the serotonin syndrome is increasing and can be fatal. The physiopathological hypothesis is principally supported by excess stimulation of the central (5HT1a) serotonin receptors. There are various serotonin drugs and associations implied. Monoamine oxidase inhibitors appear to be the major culprits. RECENTLY REVISED CLINICAL DIAGNOSIS FACTORS: The classical triad of neuropsychiatric, neuromuscular and neurovegetative symptoms, described in 1991 by Sternbach, has recently been modified. The syndrome is however protein-like and differential diagnosis remains the neuroleptic malignant syndrome. FIRST-LINE THERAPEUTIC MEASURES: Prevention of the syndrome and its early discovery are essential. Withdrawal of the imputable drugs often resolves the symptoms within 24 hours. Symptomatic and supportive care remains the pillar to treatment. ORIENTATION TOWARDS SPECIFIC TREATMENTS: Several non-selective anti-serotonin treatments have been tested without much success. In the absence of prospective studies, current therapeutic strategies rely on case reports demonstrating the relative efficacy of cyproheptadine and chlorpromazine. The proposed treatment, as soon as severe or persisting symptoms are observed, is administration of 8 to 30 mg cyproheptadine per os, and in the case of failure or contraindication, followed by 50 to 100 mg of intramuscular chlorpromazine, renewed when necessary.

  12. Central serotonin metabolism and frequency of depression

    NARCIS (Netherlands)

    Praag, H.M. van; Haan, S. de

    1979-01-01

    Central serotonin (5-hydroxytryptamine; 5-HT) metabolism can be disturbed in a subgroup of patients with vital (endogenous, primary) depression. Presumably these disturbances do not result from the depression and have a predisposing rather than a causative relationship to it. This latter statement i

  13. Modulation of auditory brainstem responses by serotonin and specific serotonin receptors.

    Science.gov (United States)

    Papesh, Melissa A; Hurley, Laura M

    2016-02-01

    The neuromodulator serotonin is found throughout the auditory system from the cochlea to the cortex. Although effects of serotonin have been reported at the level of single neurons in many brainstem nuclei, how these effects correspond to more integrated measures of auditory processing has not been well-explored. In the present study, we aimed to characterize the effects of serotonin on far-field auditory brainstem responses (ABR) across a wide range of stimulus frequencies and intensities. Using a mouse model, we investigated the consequences of systemic serotonin depletion, as well as the selective stimulation and suppression of the 5-HT1 and 5-HT2 receptors, on ABR latency and amplitude. Stimuli included tone pips spanning four octaves presented over a forty dB range. Depletion of serotonin reduced the ABR latencies in Wave II and later waves, suggesting that serotonergic effects occur as early as the cochlear nucleus. Further, agonists and antagonists of specific serotonergic receptors had different profiles of effects on ABR latencies and amplitudes across waves and frequencies, suggestive of distinct effects of these agents on auditory processing. Finally, most serotonergic effects were more pronounced at lower ABR frequencies, suggesting larger or more directional modulation of low-frequency processing. This is the first study to describe the effects of serotonin on ABR responses across a wide range of stimulus frequencies and amplitudes, and it presents an important step in understanding how serotonergic modulation of auditory brainstem processing may contribute to modulation of auditory perception.

  14. Association of serotonin transporter gene (5HTT) polymorphism and juvenile myoclonic epilepsy: a case-control study.

    Science.gov (United States)

    Esmail, Eman H; Labib, Dalia M; Rabie, Walaa A

    2015-09-01

    Serotonin levels might alter susceptibility to seizures. Serotonin transporter (5HTT) gene polymorphisms were found to be associated with some forms of epilepsy. Here, we attempted to examine an association between 5HTT VNTR allele variants in a serotonin transporter gene and epileptogenesis in juvenile myoclonic epilepsy (JME) cases. We conducted a case-control candidate gene study evaluating the frequencies of 5HTT VNTR allele variants using SYBR green real-time PCR with melting curve analysis in JME patients and healthy subjects. Forty patients with JME were selected from the Epilepsy Outpatient Clinic of Kasr Al Ainy Hospital, Cairo University, who had been classified according to the electroclinical classification of the ILAE. The control group consisted of 40 healthy Egyptian subjects. The less efficient transcriptional genotypes for 5-HTT polymorphisms were more frequent in JME patients (OR 9.33, CI 2.85-30.60; p value epileptogenesis in JME.

  15. Serotonin modulates glutamatergic transmission to neurons in the lateral habenula.

    Science.gov (United States)

    Xie, Guiqin; Zuo, Wanhong; Wu, Liangzhi; Li, Wenting; Wu, Wei; Bekker, Alex; Ye, Jiang-Hong

    2016-04-01

    The lateral habenula (LHb) is bilaterally connected with serotoninergic raphe nuclei, and expresses high density of serotonin receptors. However, actions of serotonin on the excitatory synaptic transmission to LHb neurons have not been thoroughly investigated. The LHb contains two anatomically and functionally distinct regions: lateral (LHbl) and medial (LHbm) divisions. We compared serotonin's effects on glutamatergic transmission across the LHb in rat brains. Serotonin bi-directionally and differentially modulated glutamatergic transmission. Serotonin inhibited glutamatergic transmission in higher percentage of LHbl neurons but potentiated in higher percentage of LHbm neurons. Magnitude of potentiation was greater in LHbm than in LHbl. Type 2 and 3 serotonin receptor antagonists attenuated serotonin's potentiation. The serotonin reuptake blocker, and the type 2 and 3 receptor agonists facilitated glutamatergic transmission in both LHbl and LHbm neurons. Thus, serotonin via activating its type 2, 3 receptors, increased glutamate release at nerve terminals in some LHb neurons. Our data demonstrated that serotonin affects both LHbm and LHbl. Serotonin might play an important role in processing information between the LHb and its downstream-targeted structures during decision-making. It may also contribute to a homeostatic balance underlying the neural circuitry between the LHb and raphe nuclei.

  16. 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

  17. Effects of injection of serotonin into nucleus caudatus on food and water intake and body weight in albino rats.

    Science.gov (United States)

    Pal, G K; Kannan, N; Pal, Pravati

    2004-10-01

    Serotonin is known to inhibit food and water intake. However, the effect of its injection into nucleus caudatus on food and water intake is not known. In the present study, serotonin hydrochloride, buspirone (the serotonin 5-HT1A agonist) and ondensetron (the 5HT3 antagonist) were injected into nucleus caudatus through stereotaxically implanted cannulae in three different dosages (1, 2 and 5 microg) and their effects on 24 h food and water intake, and body weight were recorded. The injection of serotonin hydrochloride resulted in a dose- dependent decrease in food intake attaining maximum of 27.3% at 5 microg dose, whereas water intake and body weight were decreased 12% and 4.3% respectively only at the highest does. Buspirone elicited a dose dependent inhibition of food and water intake and body weight (22.3%, 19.8% and 5.1% respectively), whereas ondensetron elicited an increase in food and water intake (37.8% and 36.3% respectively) without significantly altering bodyweight. It was concluded that serotonin hydrochloride injected into nucleus caudatus inhibits food and water intake significantly. These effects are mediated via 5-HT1A and 5HT3 receptors. The effect of injections of 5-HT1A receptor agonist is more pronounced on water intake. The effect of injections of 5HT3 receptor antagonist is also more pronounced on water intake.

  18. Lethal effect of the serotonin-xylocaineR association in ganglion-blocked rats.

    Science.gov (United States)

    Valle, L B; Oliveira-Filho, R M; Armonia, P L; Saraceni, G; Nassif, M; De Lucia, R

    1976-12-01

    In rats anestetized with urethane and under ganglionic blockade by hexamethonium (20 mg/kg, i.v.), the i.v. injection of serotonin (60 mug/kg) determined apnea, ECG alterations and a brief hypotensive response which is similar to that as elicited when 5-HT is given to intact rats. During the hypertension which follows that initial response, apnea is still present along with more severe ECG changes. After that, blood pressure falls into a prolonged hypotension, which is invariably accompanied by death. Neither norepinephrine, nor respiratory analeptics (CoramineR, RemeflinF) were able to prevent the fatal outcome. Only artificial respiration was found to be useful in some instances. It was concluded that the association serotonin plus lidocaine becomes lethal when given to ganglion-blocked rate, and this toxic effect can be ascribed mainly to the respiratory depressor activity of the drugs.

  19. [Sensitization of bradycardia during final hypotension induced by serotonin in rats: effect of lidocaine].

    Science.gov (United States)

    Valle, L B; Oliveira-Filho, R M; Armonia, P L; Nassif, M; Saraceni, G

    1975-10-01

    It was studied the sensibilizing effect of lidocaine (8.5 mg/kg, i.v.) on the ECG (heart rate, P-R interval, QRS complex and Q-T interval) of both intact and bilaterally vagotomised rats, in the nadir of the final hypotension determined by serotonine (60 mug/kg, i.v.). The results showed (1) a certain degree of selectivity of the vagi, and (2) the effects of serotonine either isolated or associated to lidocaine on P-R interval and heart rate were reinforced when intact animals were used. Although no significant alterations of Q-T were elicited by the drugs, lidocaine surprisingly enlarged the QRS complex in a more significant fashion for the intact than for the vagotomised animals.

  20. Mathematical physiology

    CERN Document Server

    Sneyd, James

    2009-01-01

    There has been a long history of interaction between mathematics and physiology. This book looks in detail at a wide selection of mathematical models in physiology, showing how physiological problems can be formulated and studied mathematically, and how such models give rise to interesting and challenging mathematical questions. With its coverage of many recent models it gives an overview of the field, while many older models are also discussed, to put the modern work in context. In this second edition the coverage of basic principles has been expanded to include such topics as stochastic differential equations, Markov models and Gibbs free energy, and the selection of models has also been expanded to include some of the basic models of fluid transport, respiration/perfusion, blood diseases, molecular motors, smooth muscle, neuroendrocine cells, the baroreceptor loop, turboglomerular oscillations, blood clotting and the retina. Owing to this extensive coverage, the second edition is published in two volumes. ...

  1. 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.

  2. Physiological Control of Germline Development

    OpenAIRE

    Hubbard, E. Jane Albert; Korta, Dorota Z.; Dalfó, Diana

    2013-01-01

    The intersection between developmental programs and environmental conditions that alter physiology is a growing area of research interest. The C. elegans germ line is emerging as a particularly sensitive and powerful model for these studies. The germ line is subject to environmentally regulated diapause points that allow worms to withstand harsh conditions both prior to and after reproduction commences. It also responds to more subtle changes in physiological conditions. Recent studies demons...

  3. 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...

  4. Serotonin: a never-ending story.

    Science.gov (United States)

    Olivier, Berend

    2015-04-15

    The neurotransmitter serotonin is an evolutionary ancient molecule that has remarkable modulatory effects in almost all central nervous system integrative functions, such as mood, anxiety, stress, aggression, feeding, cognition and sexual behavior. After giving a short outline of the serotonergic system (anatomy, receptors, transporter) the author's contributions over the last 40 years in the role of serotonin in depression, aggression, anxiety, stress and sexual behavior is outlined. Each area delineates the work performed on animal model development, drug discovery and development. Most of the research work described has started from an industrial perspective, aimed at developing animals models for psychiatric diseases and leading to putative new innovative psychotropic drugs, like in the cases of the SSRI fluvoxamine, the serenic eltoprazine and the anxiolytic flesinoxan. Later this research work mainly focused on developing translational animal models for psychiatric diseases and implicating them in the search for mechanisms involved in normal and diseased brains and finding new concepts for appropriate drugs.

  5. 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.

  6. Serotonin syndrome presenting as pulmonary edema

    Science.gov (United States)

    Shah, Nilima Deepak; Jain, Ajay B.

    2016-01-01

    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. PMID:26997733

  7. Exercise physiology

    DEFF Research Database (Denmark)

    Kiens, Bente; Richter, Erik; Wojtaszewski, Jørgen

    2014-01-01

    The passing of Professor Bengt Saltin on September 12, 2014 truly marks the end of an era. As editor of the Journal of Applied Physiology and one of Bengt’s many collaborators and colleagues, I wanted the Journal to celebrate his many seminal contributions by means of an Editorial. Professor Bent...

  8. Reproductive physiology

    Science.gov (United States)

    Gee, G.F.; Russman, S.E.; Ellis, David H.; Gee, George F.; Mirande, Claire M.

    1996-01-01

    Conclusions: Although the general pattern of avian physiology applies to cranes, we have identified many physiological mechanisms (e.g., effects of disturbance) that need further study. Studies with cranes are expensive compared to those done with domestic fowl because of the crane's larger size, low reproductive rate, and delayed sexual maturity. To summarize, the crane reproductive system is composed of physiological and anatomical elements whose function is controlled by an integrated neural-endocrine system. Males generally produce semen at a younger age than when females lay eggs. Eggs are laid in clutches of two (1 to 3), and females will lay additional clutches if the preceding clutches are removed. Both sexes build nests and incubate the eggs. Molt begins during incubation and body molt may be completed annually in breeding pairs. However, remiges are replaced sequentially over 2 to 3 years, or abruptly every 2 to 3 years in other species. Most immature birds replace their juvenal remiges over a 2 to 3 year period. Stress interferes with reproduction in cranes by reducing egg production or terminating the reproductive effort. In other birds, stress elevates corticosterone levels and decreases LHRH release. We know little about the physiological response of cranes to stress.

  9. AGN-2979, an inhibitor of tryptophan hydroxylase activation, does not affect serotonin synthesis in Flinders Sensitive Line rats, a rat model of depression, but produces a significant effect in Flinders Resistant Line rats.

    Science.gov (United States)

    Kanemaru, Kazuya; Nishi, Kyoko; Diksic, Mirko

    2009-12-01

    The neurotransmitter, serotonin, is involved in several brain functions, including both normal, physiological functions, and pathophysiological functions. Alterations in any of the normal parameters of serotonergic neurotransmission can produce several different psychiatric disorders, including major depression. In many instances, brain neurochemical variables are not able to be studied properly in humans, thus making the use of good animal models extremely valuable. One of these animal models is the Flinders Sensitive Line (FSL) of rats, which has face, predictive and constructive validities in relation to human depression. The objective of this study was to quantify the effect of the tryptophan hydroxylase (TPH) activation inhibitor, AGN-2979, on the FSL rats (rats with depression-like behaviour), and compare it to the effect on the Flinders Resistant Line (FRL) of rats used as the control rats. The effect was evaluated by measuring changes in regional serotonin synthesis in the vehicle treated rats (FSL-VEH and FRL-VEH) relative to those measured in the AGN-2979 treated rats (FSL-AGN and FRL-AGN). Regional serotonin synthesis was measured autoradiographically in more than 30 brain regions. The measurements were performed using alpha-[(14)C]methyl-l-tryptophan as the tracer. The results indicate that AGN-2979 did not produce a significant reduction of TPH activity in the AGN-2979 group relative to the vehicle group (a reduction would have been observed if there had been an activation of TPH by the experimental setup) in the FSL rats. On the other hand, there was a highly significant reduction of synthesis in the FRL rats treated by AGN-2979, relative to the vehicle group. Together, the results demonstrate that in the FSL rats, AGN-2979 does not affect serotonin synthesis. This suggests that there was no activation of TPH in the FSL rats during the experimental procedure, but such activation did occur in the FRL rats. Because of this finding, it could be

  10. Serotonin, Amygdala and Fear: Assembling the Puzzle

    OpenAIRE

    Bocchio, Marco; McHugh, Stephen B.; Bannerman, David M; Sharp, Trevor; Capogna, Marco

    2016-01-01

    The fear circuitry orchestrates defense mechanisms in response to environmental threats. This circuitry is evolutionarily crucial for survival, but its dysregulation is thought to play a major role in the pathophysiology of psychiatric conditions in humans. The amygdala is a key player in the processing of fear. This brain area is prominently modulated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). The 5-HT input to the amygdala has drawn particular interest because genetic an...

  11. 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.

  12. MODULATION OF DEFENSIVE REFLEX CONDITIONING IN SNAILS BY SEROTONIN

    Directory of Open Access Journals (Sweden)

    Vyatcheslav V Andrianov

    2015-10-01

    Full Text Available We studied the role of serotonin in the mechanisms of learning in terrestrial snails. To produce a serotonin deficit, the neurotoxic analogues of serotonin, 5,6- or 5,7-dihydroxytryptamine (5,6/5,7-DHT were used. Injection of 5,6/5,7-DHT was found to disrupt defensive reflex conditioning. Within two weeks of neurotoxin application, the ability to learn had recovered. Daily injection of serotonin before a training session accelerated defensive reflex conditioning and daily injections of 5-HTP in snails with a deficiency of serotonin induced by 5,7-DHT restored the snail’s ability to learn. We discovered that injections of the neurotoxins 5,6/5,7-DHT as well as serotonin, caused a decrease in the resting and threshold potentials of the premotor interneurons LPa3 and RPa3.

  13. Oligonucleotide-induced alternative splicing of serotonin 2C receptor reduces food intake.

    Science.gov (United States)

    Zhang, Zhaiyi; Shen, Manli; Gresch, Paul J; Ghamari-Langroudi, Masoud; Rabchevsky, Alexander G; Emeson, Ronald B; Stamm, Stefan

    2016-08-01

    The serotonin 2C receptor regulates food uptake, and its activity is regulated by alternative pre-mRNA splicing. Alternative exon skipping is predicted to generate a truncated receptor protein isoform, whose existence was confirmed with a new antiserum. The truncated receptor sequesters the full-length receptor in intracellular membranes. We developed an oligonucleotide that promotes exon inclusion, which increases the ratio of the full-length to truncated receptor protein. Decreasing the amount of truncated receptor results in the accumulation of full-length, constitutively active receptor at the cell surface. After injection into the third ventricle of mice, the oligonucleotide accumulates in the arcuate nucleus, where it changes alternative splicing of the serotonin 2C receptor and increases pro-opiomelanocortin expression. Oligonucleotide injection reduced food intake in both wild-type and ob/ob mice. Unexpectedly, the oligonucleotide crossed the blood-brain barrier and its systemic delivery reduced food intake in wild-type mice. The physiological effect of the oligonucleotide suggests that a truncated splice variant regulates the activity of the serotonin 2C receptor, indicating that therapies aimed to change pre-mRNA processing could be useful to treat hyperphagia, characteristic for disorders like Prader-Willi syndrome.

  14. Functional Role of Serotonin in Insulin Secretion in a Diet-Induced Insulin-Resistant State

    OpenAIRE

    Kim, Kyuho; Oh, Chang-Myung; Ohara-Imaizumi, Mica; Park, Sangkyu; Namkung, Jun; Yadav, Vijay K.; Tamarina, Natalia A.; Roe, Michael W; Louis H Philipson; Karsenty, Gerard; Nagamatsu, Shinya; German, Michael S.; Kim, Hail

    2014-01-01

    The physiological role of serotonin, or 5-hydroxytryptamine (5-HT), in pancreatic β-cell function was previously elucidated using a pregnant mouse model. During pregnancy, 5-HT increases β-cell proliferation and glucose-stimulated insulin secretion (GSIS) through the Gαq-coupled 5-HT2b receptor (Htr2b) and the 5-HT3 receptor (Htr3), a ligand-gated cation channel, respectively. However, the role of 5-HT in β-cell function in an insulin-resistant state has yet to be elucidated. Here, we charact...

  15. Production and Peripheral Roles of 5-HTP, a Precursor of Serotonin

    OpenAIRE

    Kazuhiro Nakamura; Hiroyuki Hasegawa

    2009-01-01

    Serotonin (5-hydroxytryptamine [5-HT]) has been implicated in a variety of physiological and pathological functions. Multiple steps of enzyme reactions enable biosynthesis of 5-HT. The first and rate-limiting step of the reaction is the synthesis of 5-hydroxy-L-tryptophan (5-HTP) from L-tryptophan. This step is dictated by an enzyme, tryptophan hydroxylase (TPH). TPH requires 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) as a co-substrate of TPH. 5-HTP has been simply regarded as a precursor...

  16. 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.

  17. Serotonin and the regulation of mammalian energy balance

    OpenAIRE

    Michael H Donovan; 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...

  18. Venlafaxine-induced serotonin syndrome with relapse following amitriptyline

    OpenAIRE

    Perry, N

    2000-01-01

    A case of venlafaxine-induced serotonin syndrome is described with relapse following the introduction of amitriptyline, despite a 2-week period between the discontinuation of one drug and the commencement of the other. Electroencephalography may play an important part in diagnosis. With the increasing use of selective serotonin re-uptake inhibitors, greater awareness of the serotonin syndrome is necessary. Furthermore, the potential for drug interactions which may lead to the syndrome needs t...

  19. Methylene Blue Causing Serotonin Syndrome Following Cystocele Repair

    Directory of Open Access Journals (Sweden)

    Kailash Kapadia

    2016-11-01

    Full Text Available 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.

  20. The Face of Physiology

    Directory of Open Access Journals (Sweden)

    Paul White

    2008-10-01

    Full Text Available This article explores the relationship between the physiology of the emotions and the display of character in Victorian Britain. Charles Bell and others had begun to link certain physiological functions, such as respiration, with the expression of feelings such as fear, regarding the heart and other internal organs as instruments by which the emotions were made visible. But a purely functional account of the emotions, which emerged through the development of reflex physiology during the second half of the century, would dramatically alter the nature of feelings and the means of observing them. At the same time, instinctual or acquired sympathy, which had long underpinned the accurate reading of expressions, became a problem to be surmounted by new 'objectively'. Graphic recording instruments measuring a variety of physiological functions and used with increasing frequency in clinical diagnostics became of fundamental importance for tracing the movement of feelings during the period prior to the development of cinematography. They remained, in the form of devices such as the polygraph, a crucial and controversial means of measuring affective states, beneath the potentially deceptive surface of the body.

  1. Integrative Physiology of Fasting.

    Science.gov (United States)

    Secor, Stephen M; Carey, Hannah V

    2016-03-15

    Extended bouts of fasting are ingrained in the ecology of many organisms, characterizing aspects of reproduction, development, hibernation, estivation, migration, and infrequent feeding habits. The challenge of long fasting episodes is the need to maintain physiological homeostasis while relying solely on endogenous resources. To meet that challenge, animals utilize an integrated repertoire of behavioral, physiological, and biochemical responses that reduce metabolic rates, maintain tissue structure and function, and thus enhance survival. We have synthesized in this review the integrative physiological, morphological, and biochemical responses, and their stages, that characterize natural fasting bouts. Underlying the capacity to survive extended fasts are behaviors and mechanisms that reduce metabolic expenditure and shift the dependency to lipid utilization. Hormonal regulation and immune capacity are altered by fasting; hormones that trigger digestion, elevate metabolism, and support immune performance become depressed, whereas hormones that enhance the utilization of endogenous substrates are elevated. The negative energy budget that accompanies fasting leads to the loss of body mass as fat stores are depleted and tissues undergo atrophy (i.e., loss of mass). Absolute rates of body mass loss scale allometrically among vertebrates. Tissues and organs vary in the degree of atrophy and downregulation of function, depending on the degree to which they are used during the fast. Fasting affects the population dynamics and activities of the gut microbiota, an interplay that impacts the host's fasting biology. Fasting-induced gene expression programs underlie the broad spectrum of integrated physiological mechanisms responsible for an animal's ability to survive long episodes of natural fasting.

  2. 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.

  3. Role of a Serotonin Precursor in Development of Gut Microvilli

    OpenAIRE

    Nakamura, Kazuhiro; Sato, Taku; Ohashi, Akiko; Tsurui, Hiromichi; Hasegawa, Hiroyuki

    2008-01-01

    Monoamines exert diverse functions in various cells in peripheral organs as well as in the central nervous system. 5-Hydroxy-l-tryptophan (5-HTP) has been simply regarded as a precursor of serotonin, and it is believed that the biological significance of 5-HTP is essentially ascribable to the production of serotonin. Systemic treatment with 5-HTP is often applied to patients with low serotonin levels in the brain. Here we show that endogenous and exogenous 5-HTP but not serotonin induced the ...

  4. Tail biting in pigs: blood serotonin and fearfulness as pieces of the puzzle?

    Directory of Open Access Journals (Sweden)

    Winanda W Ursinus

    Full Text Available 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 and with their behavioural and physiological responses to novelty. Pigs (n = 480 were born in conventional farrowing pens and after weaning at four weeks of age they were either housed barren (B or in straw-enriched (E pens. Individual pigs were exposed to a back test and novel environment test before weaning, and after weaning to a novel object (i.e. bucket test in an unfamiliar arena. A Principal Component Analysis on behaviours during the tests and salivary cortisol (novel object test only revealed five factors for both housing systems, labeled 'Early life exploration', 'Near bucket', 'Cortisol', 'Vocalizations & standing alert', and 'Back test activity'. Blood samples were taken at 8, 9 and 22 weeks of age to determine blood platelet serotonin. In different phases of life, pigs were classified as tail biter/non-tail biter based on tail biting behaviour, and as victim/non-victim based on tail wounds. A combination of both classifications resulted in four pig types: biters, victims, biter/victims, and neutrals. Generally, only in phases of life during which pigs were classified as tail biters, they seemed to have lower blood platelet serotonin storage and higher blood platelet uptake velocities. Victims also seemed to have lower blood serotonin storage. Additionally, in B housing, tail biters seemed to consistently have lower scores of the factor 'Near bucket', possibly indicating a higher fearfulness in tail biters. Further research is needed to elucidate the nature of the relationship between peripheral 5-HT, fearfulness and tail biting, and to develop successful strategies and interventions to prevent and reduce tail biting.

  5. Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Visser, Anniek K.D.; Waarde, Aren van; Willemsen, Antoon T.M. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Bosker, Fokko J. [University of Groningen, University Medical Center Groningen, University Center of Psychiatry, Groningen (Netherlands); Luiten, Paul G.M. [University of Groningen, Center for Behavior and Neurosciences, Department of Molecular Neurobiology, Haren (Netherlands); Boer, Johan A. den [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, University Center of Psychiatry, Groningen (Netherlands); Kema, Ido P. [University of Groningen, University Medical Center Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Dierckx, Rudi A.J.O. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University Hospital Ghent, Department of Nuclear Medicine, Ghent (Belgium)

    2011-03-15

    The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors (each with their particular distribution patterns), specific reuptake mechanisms and synthetic processes. Many aspects of the functioning of the serotonergic system are still unclear, partially because of the difficulty of measuring physiological processes in the living brain. In this review we give an overview of the conventional methods of measuring serotonin synthesis and methods using positron emission tomography (PET) tracers, more specifically with respect to serotonergic function in affective disorders. Conventional methods are invasive and do not directly measure synthesis rates. Although they may give insight into turnover rates, a more direct measurement may be preferred. PET is a noninvasive technique which can trace metabolic processes, like serotonin synthesis. Tracers developed for this purpose are {alpha}-[{sup 11}C]methyltryptophan ([{sup 11}C]AMT) and 5-hydroxy-L-[{beta}-{sup 11}C]tryptophan ([{sup 11}C]5-HTP). Both tracers have advantages and disadvantages. [{sup 11}C]AMT can enter the kynurenine pathway under inflammatory conditions (and thus provide a false signal), but this tracer has been used in many studies leading to novel insights regarding antidepressant action. [{sup 11}C]5-HTP is difficult to produce, but trapping of this compound may better represent serotonin synthesis. AMT and 5-HTP kinetics are differently affected by tryptophan depletion and changes of mood. This may indicate that both tracers are associated with different enzymatic processes. In conclusion, PET with radiolabelled substrates for the serotonergic pathway is the only direct way to detect changes of serotonin synthesis in the living brain. (orig.)

  6. Recognition of familiar food activates feeding via an endocrine serotonin signal in Caenorhabditis elegans.

    Science.gov (United States)

    Song, Bo-Mi; Faumont, Serge; Lockery, Shawn; Avery, Leon

    2013-02-05

    Familiarity discrimination has a significant impact on the pattern of food intake across species. However, the mechanism by which the recognition memory controls feeding is unclear. Here, we show that the nematode Caenorhabditis elegans forms a memory of particular foods after experience and displays behavioral plasticity, increasing the feeding response when they subsequently recognize the familiar food. We found that recognition of familiar food activates the pair of ADF chemosensory neurons, which subsequently increase serotonin release. The released serotonin activates the feeding response mainly by acting humorally and directly activates SER-7, a type 7 serotonin receptor, in MC motor neurons in the feeding organ. Our data suggest that worms sense the taste and/or smell of novel bacteria, which overrides the stimulatory effect of familiar bacteria on feeding by suppressing the activity of ADF or its upstream neurons. Our study provides insight into the mechanism by which familiarity discrimination alters behavior.DOI:http://dx.doi.org/10.7554/eLife.00329.001.

  7. Serotonin and dopamine protect from hypothermia/rewarming damage through the CBS/H2S pathway.

    Directory of Open Access Journals (Sweden)

    Fatemeh Talaei

    Full Text Available Biogenic amines have been demonstrated to protect cells from apoptotic cell death. Herein we show for the first time that serotonin and dopamine increase H(2S production by the endogenous enzyme cystathionine-β-synthase (CBS and protect cells against hypothermia/rewarming induced reactive oxygen species (ROS formation and apoptosis. Treatment with both compounds doubled CBS expression through mammalian target of rapamycin (mTOR and increased H(2S production in cultured rat smooth muscle cells. In addition, serotonin and dopamine treatment significantly reduced ROS formation. The beneficial effect of both compounds was minimized by inhibition of their re-uptake and by pharmacological inhibition of CBS or its down-regulation by siRNA. Exogenous administration of H(2S and activation of CBS by Prydoxal 5'-phosphate also protected cells from hypothermic damage. Finally, serotonin and dopamine pretreatment of rat lung, kidney, liver and heart prior to 24 h of hypothermia at 3°C followed by 30 min of rewarming at 37°C upregulated the expression of CBS, strongly reduced caspase activity and maintained the physiological pH compared to untreated tissues. Thus, dopamine and serotonin protect cells against hypothermia/rewarming induced damage by increasing H(2S production mediated through CBS. Our data identify a novel molecular link between biogenic amines and the H(2S pathway, which may profoundly affect our understanding of the biological effects of monoamine neurotransmitters.

  8. Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation

    DEFF Research Database (Denmark)

    Santini, Martin; Klein, A B; El-Sayed, M

    2011-01-01

    Many psychiatric disorders are characterized by cognitive and emotional alterations that are related to abnormal function of the frontal cortex (FC). FC is involved in working memory and decision making and is activated following exposure to a novel environment. The serotonin 2A receptor (5-HT(2A...

  9. Serotonin Transporter Gene ("SLC6A4") Methylation Associates with Neonatal Intensive Care Unit Stay and 3-month-old Temperament in Preterm Infants

    Science.gov (United States)

    Montirosso, Rosario; Provenzi, Livio; Fumagalli, Monica; Sirgiovanni, Ida; Giorda, Roberto; Pozzoli, Uberto; Beri, Silvana; Menozzi, Giorgia; Tronick, Ed; Morandi, Francesco; Mosca, Fabio; Borgatti, Renato

    2016-01-01

    Preterm birth and Neonatal Intensive Care Unit (NICU) stay are early adverse stressful experiences, which may result in an altered temperamental profile. The serotonin transporter gene ("SLC6A4"), which has been linked to infant temperament, is susceptible to epigenetic regulation associated with early stressful experience. This study…

  10. Serotonin and the search for the anatomical substrate of aggression.

    Science.gov (United States)

    Alekseyenko, Olga V; Kravitz, Edward A

    2014-01-01

    All species of animals display aggression in order to obtain resources such as territories, mates, or food. Appropriate displays of aggression rely on the correct identification of a potential competitor, an evaluation of the environmental signals, and the physiological state of the animal. With a hard-wired circuitry involving fixed numbers of neurons, neuromodulators like serotonin offer adaptive flexibility in behavioral responses without changing the "hard-wiring". In a recent report, we combined intersectional genetics, quantitative behavioral assays and morphological analyses to identify single serotonergic neurons that modulate the escalation of aggression. We found anatomical target areas within the brain where these neurons appear to form synaptic contacts with 5HT1A receptor-expressing neurons, and then confirmed the likelihood of those connections on a functional level. In this Extra View article, we offer an extended discussion of these recent findings and elaborate on how they can link a cellular and functional mapping of an aggression-regulating circuit at a single-cell resolution level.

  11. Tryptophan-enriched cereal intake improves nocturnal sleep, melatonin, serotonin, and total antioxidant capacity levels and mood in elderly humans

    OpenAIRE

    Bravo, R; Matito, S.; Cubero, J.; Paredes, S.D.; De Franco, L.; Rivero, M.; Rodríguez, A. B.; Barriga, C.

    2012-01-01

    Melatonin and serotonin rhythms, which exhibit a close association with the endogenous circadian component of sleep, are attenuated with increasing age. This decrease seems to be linked to sleep alterations in the elderly. Chrononutrition is a field of chronobiology that establishes the principle of consuming foodstuffs at times of the day when they are more useful for health, improving, therefore, biorhythms and physical performance. Our aim was to analyze whether the consumption of cereals ...

  12. Changes in serotonin (5-HT) and brain-derived neurotrophic factor (BDFN) expression in frontal cortex and hippocampus of aged rat treated with high tryptophan diet.

    Science.gov (United States)

    Musumeci, Giuseppe; Castrogiovanni, Paola; Castorina, Sergio; Imbesi, Rosa; Szychlinska, Marta Anna; Scuderi, Soraya; Loreto, Carla; Giunta, Salvatore

    2015-10-01

    Age-related cognitive decline is accompanied by an alteration in neurotransmitter synthesis and a dysregulation of neuroplasticity-related molecules such as serotonin (5-HT) and brain-derived neurotrophic factor (BDFN). It has been previously demonstrated that hyperserotonemia induced by l-Tryptophan (TrP) enriched diet protect against memory deficits during physiological aging. Since 5-HT is closely associated to BDNF, we aimed to investigate the effect of high TrP diet on 5-HT levels and BDNF expression in Frontal Cortex (FC) and Hippocampus (Hp) of aged rats. We found that the raising of systemic 5-HT levels by chronic diet (1 month) containing high TrP significantly prevents age-related decline of BDNF protein expression in both brain areas as indicated by ELISA and Western Blot analyses. Interestingly, immunohistochemical analyses confirmed that high TrP diet significantly elevates the number of 5-HT immunoreactive fibers in both brain areas tested and this correlated with BDNF increase in the FC and hippocampal regions CA1, CA2, CA3 and a strikingly down-regulation of neurotrophin levels in the dentate gyrus (DG) of aged rats. Altogether, these finding provide evidence that enhanced TrP intake and the consequent increase in 5-HT neurotransmission may act as a modulator of BDNF system suggesting a possible mechanism for the protective role of serotonergic system on memory impairment occurring along normal aging process.

  13. Candidate-gene approach in posttraumatic stress disorder after urban violence: association analysis of the genes encoding serotonin transporter, dopamine transporter, and BDNF.

    Science.gov (United States)

    Valente, Nina Leão Marques; Vallada, Homero; Cordeiro, Quirino; Miguita, Karen; Bressan, Rodrigo Affonseca; Andreoli, Sergio Baxter; Mari, Jair Jesus; Mello, Marcelo Feijó

    2011-05-01

    Posttraumatic stress disorder (PTSD) is a prevalent, disabling anxiety disorder marked by behavioral and physiologic alterations which commonly follows a chronic course. Exposure to a traumatic event constitutes a necessary, but not sufficient, factor. There is evidence from twin studies supporting a significant genetic predisposition to PTSD. However, the precise genetic loci still remain unclear. The objective of the present study was to identify, in a case-control study, whether the brain-derived neurotrophic factor (BDNF) val66met polymorphism (rs6265), the dopamine transporter (DAT1) three prime untranslated region (3'UTR) variable number of tandem repeats (VNTR), and the serotonin transporter (5-HTTPRL) short/long variants are associated with the development of PTSD in a group of victims of urban violence. All polymorphisms were genotyped in 65 PTSD patients as well as in 34 victims of violence without PTSD and in a community control group (n = 335). We did not find a statistical significant difference between the BDNF val66met and 5-HTTPRL polymorphism and the traumatic phenotype. However, a statistical association was found between DAT1 3'UTR VNTR nine repeats and PTSD (OR = 1.82; 95% CI, 1.20-2.76). This preliminary result confirms previous reports supporting a susceptibility role for allele 9 and PTSD.

  14. Occupational physiology

    CERN Document Server

    Toomingas, Allan; Tornqvist, Ewa Wigaeus

    2011-01-01

    In a clear and accessible presentation, Occupational Physiology focuses on important issues in the modern working world. Exploring major public health problems-such as musculoskeletal disorders and stress-this book explains connections between work, well-being, and health based on up-to-date research in the field. It provides useful methods for risk assessment and guidelines on arranging a good working life from the perspective of the working individual, the company, and society as a whole.The book focuses on common, stressful situations in different professions. Reviewing bodily demands and r

  15. Alteração fisiológica da cana-de-açúcar pela aplicação de Glyphosate e Sulfumeturon-Methyl Physiological alteration in sugarcane influenced by Glyphosate and Sulfumeturon-Methyl application

    Directory of Open Access Journals (Sweden)

    D.K. Meschede

    2011-06-01

    inversamente proporcionais aos níveis Fe. A aplicação de sulfumeturon-methyl não interferiu nos teores de clorofila, no entanto os níveis de carotenoides se mostraram mais sensíveis e seus teores reduzidos. As alterações observadas nos níveis de clorofilas e carotenoides pela aplicação dos produtos podem afetar de maneira distinta o metabolismo da fotossíntese pela absorção e/ou conversão de energia.The partial blockage of the routes of action of herbicides, using low doses, may have important implications by altering the balance of the metabolic processes in plants. Thus, an experiment was conducted in cutting cane ratoon 2 at Cosan Group's Fazenda Jurema in Barra Bonita-SP, during the agricultural years 2006/2007, to verify the effects of glyphosate and sulfometuron methyl sub-doses on the physiological behavior of sugarcane based on the the levels of chlorophyll and carotenoids. The treatments consisted of applications of two herbicides: sulfometuron methyl (480 a.i. kg-1 and glyphosate (360 a.e. kg-1 in different doses and mixtures (Roundup and Curavial, respectively, plus a control treatment, without herbicide application. The doses used were: glyphosate pc ha-1 of 200 mL, 400 mL of glyphosate pc ha-1; pc ha-1 of 200 mL glyphosate + 10 g of pc ha-1 of sulfometuron methyl; pc ha-1 of 150 mL glyphosate + 12 g of pc ha-1 of sulfometuron methyl, sulfometuron methyl pc ha¹ of 20. The experiment was arranged in a randomized block design with four replications. The evaluations were carried out 15 and 30 days after planting (DAP and 30, 60, 90, 120, 150 and 180 days after harvest (DAH. The leaves were cut using the same standardized weight and leaf area. To determine the content of chlorophyll and carotenoids, samples of 0.2 g of fresh leaf tissue were prepared and the extracts were filtered, and spectrophotometer readings were conducted (663 and 645 nm for chlorophyll a and b, respectively. The application of glyphosate and sulfumeturon methyl at larger doses

  16. The tricks of the trait: neural implementation of personality varies with genotype-dependent serotonin levels.

    Science.gov (United States)

    Hahn, Tim; Heinzel, Sebastian; Notebaert, Karolien; Dresler, Thomas; Reif, Andreas; Lesch, Klaus-Peter; Jakob, Peter M; Windmann, Sabine; Fallgatter, Andreas J

    2013-11-01

    Gray's Reinforcement Sensitivity Theory (RST) has developed into one of the most prominent personality theories of the last decades. The RST postulates a Behavioral Inhibition System (BIS) modulating the reaction to stimuli indicating aversive events. A number of psychiatric disorders including depression, anxiety disorders, and psychosomatic illnesses have been associated with extreme BIS responsiveness. In recent years, neuroimaging studies have implicated the amygdala-septo-hippocampal circuit as an important neural substrate of the BIS. However, the neurogenetic basis of the regulation of this behaviorally and clinically essential system remains unclear. Investigating the effects of two functional genetic polymorphisms (tryptophan hydroxylase-2, G-703T, and serotonin transporter, serotonin transporter gene-linked polymorphic region) in 89 human participants, we find significantly different patterns of associations between BIS scores and amygdala-hippocampus connectivity during loss anticipation for genotype groups regarding both polymorphisms. Specifically, the correlation between amygdala-hippocampus connectivity and Gray's trait anxiety scores is positive in individuals homozygous for the TPH2 G-allele, while carriers of at least one T-allele show a negative association. Likewise, individuals homozygous for the 5-HTTLPR L(A) variant display a positive association while carriers of the S/L(G) allele show a trend towards a negative association. Thus, we show converging evidence of different neural implementation of the BIS depending on genotype-dependent levels of serotonin. We provide evidence suggesting that genotype-dependent serotonin levels and thus putative changes in the efficiency of serotonergic neurotransmission might not only alter brain activation levels directly, but also more fundamentally impact the neural implementation of personality traits. We outline the direct clinical implications arising from this finding and discuss the complex interplay

  17. 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,

  18. 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,

  19. 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-H......-(2-amino-4-methylphenylthio)benzylamine ([11C]MADAM). In secondary analyses, 5-HTT BPND was correlated with other TCI dimensions....

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

    NARCIS (Netherlands)

    van Riel, E; Meijer, OC; Veenema, AH; Joëls, 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

  1. Conservation physiology of animal migration.

    Science.gov (United States)

    Lennox, Robert J; Chapman, Jacqueline M; Souliere, Christopher M; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D; Cooke, Steven J

    2016-01-01

    Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains

  2. Alterations in rat hippocampal norepinephrine and serotonin levels under physical exercise and psychological stress%体力运动和心理应激对大鼠海马去甲肾上腺素和五-羟色胺水平的影响

    Institute of Scientific and Technical Information of China (English)

    马强; 王静; 陈学伟; 安改红; 刘洪涛

    2008-01-01

    目的:研究长期体力运动和慢性心理应激对大鼠中枢海马去甲肾上腺素(norepinephrine,NE)和五-羟色胺(serotonin,5-HT)水平的影响,并进一步探讨这2种神经递质在运动减缓应激性海马损伤效应中的作用.方法:采用了4周自愿跑轮运动(运动组)、3周束缚应激(应激组)和预先进行4周运动再施3周应激(运动-应激组)的实验动物模型,高效液相电化学法检测实验大鼠海马的NE和5-HT水平.结果:长期运动大鼠海马的NE和5-HT水平明显升高(P<0.01),慢性应激大鼠的5-HT水平明显降低(P<0.05);并且,先运动再应激组的海马NE水平维持正常并显著高于单纯应激组(P<0.01),而以上2组的5-HT水平并无显著差异,且均低于单纯运动组(P<0.05).结论:在运动益于海马的正性作用中,NE和5-HT可能是重要的调控因素;在应激损伤海马的负性作用中,5-HT可能是重要的调控因素;而在运动减缓应激性海马损伤的作用途径中,NE可能是更重要的调控因素;并且,海马NE可能对运动更敏感,而5-HT可能对应激更敏感.%AIM: This study is to determine changes of hippocampal norepinephrine (NE) and serotonin (5 -HT) in long term physical exercise and chronic psychological stress, and to study the roles of the two monoamine transmitters in the effect of exercise counteracting stress - induced hippocampal damages in brain. METHODS : Levels of hippocampal NE and 5 - HT in rats undergoing 4 - week voluntary wheel running exercise (exercise group) or 3 - week restraint stress (stress group) or 4 - week exercise and 3 - week stress (exercise - stress group) were detected by high - performance liquid chromatography using electrochemical detection. RESULTS: It is showed that levels of hippocampal NEand 5 - HT increased significantly (P < 0. 01) in the exercised rats, and in the stressed rats, hippocampal 5 - HT levelssignificantly decreased(P < 0. 05). Additionally, the NE levels maintained significant

  3. 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...... reflexes. Thermography is a reliable, non-invasive, and objective method for assessment in serotonin-induced itch model in rat....

  4. 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

  5. The Risk of Congenital Heart Anomalies Following Prenatal Exposure to Serotonin Reuptake Inhibitors—Is Pharmacogenetics the Key?

    Science.gov (United States)

    Daud, Aizati N. A.; Bergman, Jorieke E. H.; Kerstjens-Frederikse, Wilhelmina S.; Groen, Henk; Wilffert, Bob

    2016-01-01

    Serotonin reuptake inhibitors (SRIs) are often prescribed during pregnancy. Previous studies that found an increased risk of congenital anomalies, particularly congenital heart anomalies (CHA), with SRI use during pregnancy have created concern among pregnant women and healthcare professionals about the safety of these drugs. However, subsequent studies have reported conflicting results on the association between CHA and SRI use during pregnancy. These discrepancies in the risk estimates can potentially be explained by genetic differences among exposed individuals. In this review, we explore the potential pharmacogenetic predictors involved in the pharmacokinetics and mechanism of action of SRIs, and their relation to the risk of CHA. In general, the risk is dependent on the maternal concentration of SRIs and the foetal serotonin level/effect, which can be modulated by the alteration in the expression and/or function of the metabolic enzymes, transporter proteins and serotonin receptors involved in the serotonin signalling of the foetal heart development. Pharmacogenetics might be the key to understanding why some children exposed to SRIs develop a congenital heart anomaly and others do not. PMID:27529241

  6. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

    Directory of Open Access Journals (Sweden)

    Trisha A. Jenkins

    2016-01-01

    Full Text Available The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis.

  7. Possible role of serotonin and neuropeptide Y on the disruption of the reproductive axis activity by perfluorooctane sulfonate.

    Science.gov (United States)

    López-Doval, S; Salgado, R; Fernández-Pérez, B; Lafuente, A

    2015-03-04

    Perfluorooctane sulfonate (PFOS) is an endocrine disruptor, whose exposure can induce several alterations on the reproductive axis activity in males during adulthood. This study was undertaken to evaluate the possible role of serotonin and neuropeptide Y (NPY) on the disruption of the hypothalamic-pituitary-testicular (HPT) axis induced by PFOS in adult male rats. For that, adult male rats were orally treated with 0.5; 1.0; 3.0 and 6.0mg of PFOS/kg/day for 28 days. After PFOS exposure, serotonin concentration increased in the anterior and mediobasal hypothalamus as well as in the median eminence. The metabolism of this amine (expressed as the ratio 5-hydroxyindolacetic acid (5-HIAA)/serotonin) was diminished except in the anterior hypothalamus, with the doses of 3.0 and 6.0mg/kg/day, being this dose 0.5mg/kg/day in the median eminence. In general terms, PFOS-treated rats presented a decrease of the hypothalamic concentration of the gonadotropin releasing hormone (GnRH) and NPY. A diminution of the serum levels of the luteinizing hormone (LH), testosterone and estradiol were also shown. These results suggest that both serotonin and NPY could be involved in the inhibition induced by PFOS on the reproductive axis activity in adult male rats.

  8. Serotonin enhances solitariness in phase transition of the migratory locust

    Directory of Open Access Journals (Sweden)

    Xiaojiao eGuo

    2013-10-01

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

  9. Physiological Acoustics

    Science.gov (United States)

    Young, Eric D.

    The analysis of physiological sound in the peripheral auditory system solves three important problems. First, sound energy impinging on the head must be captured and presented to the transduction apparatus in the ear as a suitable mechanical signal; second, this mechanical signal needs to be transduced into a neural representation that can be used by the brain; third, the resulting neural representation needs to be analyzed by central neurons to extract information useful to the animal. This chapter provides an overview of some aspects of the first two of these processes. The description is entirely focused on the mammalian auditory system, primarily on human hearing and on the hearing of a few commonly used laboratory animals (mainly rodents and carnivores). Useful summaries of non-mammalian hearing are available [1]. Because of the large size of the literature, review papers are referenced wherever possible.

  10. 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...... the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes...... 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...

  11. [Interaction effect of serotonin transporter gene and brain-derived neurotrophic factor on the platelet serotonin content in stroke patients].

    Science.gov (United States)

    Golimbet, V E; Brusov, O S; Factor, M I; Zlobina, G P; Lezheĭko, T V; Lavrushina, O M; Petrova, E A; Savina, M A; Skvortsova, V I

    2010-01-01

    Platelet serotonin content in patients in the acute period of stroke is an important index of clinical changes during the post stroke period as well as a predictor of development of mental disorders. We studied the association between two polymorphisms (5-HTTLPR and Val66Met BDNF) and the platelet serotonin content in 47 patients with stroke. We also investigated the moderating effect of genetic variants on the association between platelet serotonin content and development of affective and anxiety disorders in stroke patients in the acute period of stroke. The interaction effect of two polymorphisms on levels of platelet serotonin was found. The lowest level was observed in patients with the diplotype LL*ValVal, the highest level--in the group of patients with the LL genotype and genotypes containing at least one copy of a Met allele. No moderating effect of genetic variants on the relationship between serotonin content and affective or anxiety disorder was found.

  12. The distribution and function of serotonin in the large milkweed bug, Oncopeltus fasciatus. a comparative study with the blood-feeding bug, Rhodnius prolixus.

    Science.gov (United States)

    Miggiani, L; Orchard, I; TeBrugge, V

    1999-11-01

    The blood-feeding hemipteran, Rhodnius prolixus, ingests a large blood meal at the end of each larval stage. To accommodate and process this meal, its cuticle undergoes plasticisation, and its gut and Malpighian tubules respectively absorb and secrete a large volume of water and salts for rapid diuresis. Serotonin has been found to be integral to the feeding process in this animal, along with a diuretic peptide(s). The large milkweed bug, Oncopeltus fasciatus, tends to feed in a more continuous and abstemious manner, and therefore may have different physiological requirements than the blood feeder. Unlike R. prolixus, O. fasciatus is lacking serotonin-like immunoreactive dorsal unpaired median neurons in the mesothoracic ganglionic mass, and lacks serotonin-like immunoreactive neurohaemal areas and processes on the abdominal nerves, integument, salivary glands, and anterior junction of the foregut and crop. The salivary glands and crop do, however, respond to serotonin with increased levels of cAMP, while the integument and Malpighian tubules do not. In addition, O. fasciatus Malpighian tubules respond to both O. fasciatus and R. prolixus partially purified CNS extracts, which are likely to contain any native diuretic peptides. Thus, while serotonin and diuretic peptides may be involved in tubule control in R. prolixus, the latter may be of greater importance in O. fasciatus.

  13. 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

  14. Selective serotonin reuptake inhibitors for fibromyalgia syndrome

    Directory of Open Access Journals (Sweden)

    Brian Walitt

    Full Text Available ABSTRACT 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: To assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs in the treatment of fibromyalgia. METHODS: 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

  15. Serotonin-dependent kinetics of feeding bursts underlie a graded response to food availability in C. elegans.

    Science.gov (United States)

    Lee, Kyung Suk; Iwanir, Shachar; Kopito, Ronen B; Scholz, Monika; Calarco, John A; Biron, David; Levine, Erel

    2017-02-01

    Animals integrate physiological and environmental signals to modulate their food uptake. The nematode C. elegans, whose food uptake consists of pumping bacteria from the environment into the gut, provides excellent opportunities for discovering principles of conserved regulatory mechanisms. Here we show that worms implement a graded feeding response to the concentration of environmental bacteria by modulating a commitment to bursts of fast pumping. Using long-term, high-resolution, longitudinal recordings of feeding dynamics under defined conditions, we find that the frequency and duration of pumping bursts increase and the duration of long pauses diminishes in environments richer in bacteria. The bioamine serotonin is required for food-dependent induction of bursts as well as for maintaining their high rate of pumping through two distinct mechanisms. We identify the differential roles of distinct families of serotonin receptors in this process and propose that regulation of bursts is a conserved mechanism of behaviour and motor control.

  16. Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD: implication for COPD-associated neuropathogenesis.

    Directory of Open Access Journals (Sweden)

    Isaac K Sundar

    Full Text Available The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d, sub-chronic (10 d or chronic (6 mo CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD.

  17. Chromatographic analysis of age-related changes in mucosal serotonin transmission in the murine distal ileum

    Directory of Open Access Journals (Sweden)

    Parmar Leena

    2012-04-01

    Full Text Available Abstract Background In the upper bowel, alterations in motility and absorption of key nutrients have been observed as part of the normal ageing process. Serotonin (5-HT is a key signalling molecule in the gastrointestinal tract and is known to influence motility, however little is known of how the ageing process alters 5-HT signalling processes in the bowel. Results An isocratic chromatographic method was able to detect all 5-HT precursors and metabolites. Using extracellular and intracellular sampling approaches, we were able to monitor all key parameters associated with the transmission process. There was no alteration in the levels of tryptophan and 5-HTP between 3 and 18 month old animals. There was a significant increase in the ratio of 5-HT:5-HTP and an increase in intracellular 5-HT between 3 and 18 month old animals suggesting an increase in 5-HT synthesis. There was also a significant increase in extracellular 5-HT with age, suggesting increased 5-HT release. There was an age-related decrease in the ratio of intracellular 5-HIAA:extracellular 5-HT, whilst the amount of 5-HIAA did not change with age. In the presence of an increase in extracellular 5-HT, the lack of an age-related change in 5-HIAA is suggestive of a decrease in re-uptake via the serotonin transporter (SERT. Conclusions We have used intracellular and extracellular sampling to provide more insight into alterations in the neurotransmission process of 5-HT during normal ageing. We observed elevated 5-HT synthesis and release and a possible decrease in the activity of SERT. Taken together these changes lead to increased 5-HT availability and may alter motility function and could lead to the changes in adsorption observed in the elderly.

  18. 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...

  19. Space Physiology within an Exercise Physiology Curriculum

    Science.gov (United States)

    Carter, Jason R.; West, John B.

    2013-01-01

    Compare and contrast strategies remain common pedagogical practices within physiological education. With the support of an American Physiological Society Teaching Career Enhancement Award, we have developed a junior- or senior-level undergraduate curriculum for exercise physiology that compares and contrasts the physiological adaptations of…

  20. Serotonin and the regulation of mammalian energy balance.

    Directory of Open Access Journals (Sweden)

    Michael H Donovan

    2013-03-01

    Full Text Available 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 through which serotonin impacts energy balance pathways within the hypothalamus. How upstream factors relevant to energy balance regulate the release of hypothalamic serotonin is less clear, but work addressing this issue is underway. Generally, investigation into the central serotonergic regulation of energy balance has had a predominantly hypothalamocentric focus, yet nonhypothalamic structures that have been implicated in energy balance regulation also receive serotonergic innervation and express multiple subtypes of serotonin receptors. Moreover, there is a growing appreciation of the diverse mechanisms through which peripheral serotonin impacts energy balance regulation. Clearly, the serotonergic regulation of energy balance is a field characterized by both rapid advances and by an extensive and diverse set of central and peripheral mechanisms yet to be delineated.

  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. 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.

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

    OpenAIRE

    2009-01-01

    Parkinson’s Disease (PD) is marked by prominent motor symptoms that reflect striatal dopamine insufficiency. However, non-motor symptoms, including depression, are common in PD. These changes have been suggested to reflect pathological involvement of non-dopaminergic systems. We examined regional changes in serotonin and norepinephrine systems in mice treated with two different 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment paradigms and that survived for 3 or 16 weeks after th...

  4. Serotonin-induced proliferation of pulmonary arterysmooth muscle cells is serotonin transporter and ERK pathway dependent

    Institute of Scientific and Technical Information of China (English)

    Huai-liangWANG

    2004-01-01

    AIM: To investigate the effect of serotonin transporter (5-HTT)inhibitor fluoxetine and antisense oligodeoxynucleotide (ODN)to extracelluar signal-regulated kinases (ERKs) on pulmonary arterial smooth muscle cells (PASMCs) proliferation induced by 5-HT. METHODS: Liposomal transfection was used to introduce ODNs to ERK1/2 into cultured rat PASMCs and the transfection efficiency was measured by observing the uptake of the

  5. Diphenyl diselenide elicits antidepressant-like activity in rats exposed to monosodium glutamate: A contribution of serotonin uptake and Na(+), K(+)-ATPase activity.

    Science.gov (United States)

    Quines, Caroline B; Rosa, Suzan G; Velasquez, Daniela; Da Rocha, Juliana T; Neto, José S S; Nogueira, Cristina W

    2016-03-15

    Depression is a disorder with symptoms manifested at the psychological, behavioral and physiological levels. Monosodium glutamate (MSG) is the most widely used additive in the food industry; however, some adverse effects induced by this additive have been demonstrated in experimental animals and humans, including functional and behavioral alterations. The aim of this study was to investigate the possible antidepressant-like effect of diphenyl diselenide (PhSe)2, an organoselenium compound with pharmacological properties already documented, in the depressive-like behavior induced by MSG in rats. Male and female newborn Wistar rats were divided in control and MSG groups, which received, respectively, a daily subcutaneous injection of saline (0.9%) or MSG (4g/kg/day) from the 1st to 5th postnatal day. At 60th day of life, animals received (PhSe)2 (10mg/kg, intragastrically) 25min before spontaneous locomotor and forced swimming tests (FST). The cerebral cortices of rats were removed to determine [(3)H] serotonin (5-HT) uptake and Na(+), K(+)-ATPase activity. A single administration of (PhSe)2 was effective against locomotor hyperactivity caused by MSG in rats. (PhSe)2 treatment protected against the increase in the immobility time and a decrease in the latency for the first episode of immobility in the FST induced by MSG. Furthermore, (PhSe)2 reduced the [(3)H] 5-HT uptake and restored Na(+), K(+)-ATPase activity altered by MSG. In the present study a single administration of (PhSe)2 elicited an antidepressant-like effect and decrease the synaptosomal [(3)H] 5-HT uptake and an increase in the Na(+), K(+)-ATPase activity in MSG-treated rats.

  6. Acute fluoxetine exposure alters crab anxiety-like behaviour, but not aggressiveness.

    Science.gov (United States)

    Hamilton, Trevor James; Kwan, Garfield T; Gallup, Joshua; Tresguerres, Martin

    2016-01-25

    Aggression and responsiveness to noxious stimuli are adaptable traits that are ubiquitous throughout the animal kingdom. Like vertebrate animals, some invertebrates have been shown to exhibit anxiety-like behaviour and altered levels of aggression that are modulated by the neurotransmitter serotonin. To investigate whether this influence of serotonin is conserved in crabs and whether these behaviours are sensitive to human antidepressant drugs; the striped shore crab, Pachygrapsus crassipes, was studied using anxiety (light/dark test) and aggression (mirror test) paradigms. Crabs were individually exposed to acute doses of the selective serotonin reuptake inhibitor, fluoxetine (5 or 25 mg/L), commonly known as Prozac®, followed by behavioural testing. The high dose of fluoxetine significantly decreased anxiety-like behaviour but had no impact on mobility or aggression. These results suggest that anxiety-like behaviour is more sensitive to modulation of serotonin than is aggressiveness in the shore crab.

  7. Behavioral and neuropharmacological evidence that serotonin crosses the blood-brain barrier in Coturnix japonica (Galliformes; Aves

    Directory of Open Access Journals (Sweden)

    PA. Polo

    Full Text Available This study was carried out aiming to reach behavioral and neuropharmacological evidence of the permeability of the blood-brain barrier (BBB to serotonin systemically administered in quails. Serotonin injected by a parenteral route (250-1000 µg.kg-1, sc elicited a sequence of behavioral events concerned with a sleeping-like state. Sleeping-like behaviors began with feather bristling, rapid oral movements, blinking and finally crouching and closure of the eyes. Previous administration of 5-HT2C antagonist, LY53857 (3 mg.kg-1, sc reduced the episodes of feather bristling and rapid oral movements significantly but without altering the frequency of blinking and closure of the eyes. Treatment with the 5-HT2A/2C antagonist, ketanserin (3 mg.kg-1, sc did not affect any of the responses evoked by the serotonin. Quipazine (5 mg.kg-1, sc a 5-HT2A/2C/3 agonist induced intense hypomotility, long periods of yawning-like and sleeping-like states. Previous ketanserin suppressed gaping responses and reduced hypomotility, rapid oral movements and bristling but was ineffective for remaining responses induced by quipazine. Results showed that unlike mammals, serotonin permeates the BBB and activates hypnogenic mechanisms in quails. Studies using serotoninergic agonist and antagonists have disclosed that among the actions of the serotonin, feather bristling, rapid oral movements and yawning-like state originated from activation of 5-HT2 receptors while blinking and closure of the eyes possibly require other subtypes of receptors.

  8. 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.

  9. 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.

  10. 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.

  11. Origins of serotonin innervation of forebrain structures

    Science.gov (United States)

    Kellar, K. J.; Brown, P. A.; Madrid, J.; Bernstein, M.; Vernikos-Danellis, J.; Mehler, W. R.

    1977-01-01

    The tryptophan hydroxylase activity and high-affinity uptake of (3H) serotonin ((3H)5-HT) were measured in five discrete brain regions of rats following lesions of the dorsal or median raphe nuclei. Dorsal raphe lesions reduced enzyme and uptake activity in the striatum only. Median raphe lesions reduced activities in the hippocampus, septal area, frontal cortex, and, to a lesser extent, in the hypothalamus. These data are consistent with the suggestion that the dorsal and median raphe nuclei are the origins of two separate ascending serotonergic systems - one innervating striatal structures and the other mesolimbic structures, predominantly. In addition, the data suggest that measurements of high-affinity uptake of (3H)5-HT may be a more reliable index of innervation than either 5-HT content or tryptophan hydroxylase activity.

  12. 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....

  13. [Physiology of the neuropeptides].

    Science.gov (United States)

    García-López, M J; Martínez-Martos, J M; Mayas, M D; Carrera, M P; Ramírez- Expósito, M J

    In the present review, the characteristics of mammalian neuropeptides have been studied. Neuropeptides are widely distributed not only in the nervous system but also in the periphery. They are synthesised by neurons as large precursor molecules (pre propeptides) which have to be cleaved and modified in order to form the mature neuropeptides. Neuropeptides may exert actions as neurotransmitters, neuromodulators and/or neurohormones. In the neurons, they coexist with classic transmitters and often with other peptides. After their releasing, they bind to especific receptors to exert their action in the target cell. Most of these receptors belongs to a family of G protein coupled receptors. Finally, peptidases are the enzymes involved in the degradation of neuropeptides. Conclusions. In the last years, the number of known neuropeptides and the understanding of their functions have been increased. With these data, present investigations are looking for the treatment of different pathologies associated with alterations in the physiology of neuropeptides.

  14. Selective serotonin reuptake inhibitor sertraline inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.

    Science.gov (United States)

    Kim, Han Sol; Li, Hongliang; Kim, Hye Won; Shin, Sung Eun; Choi, Il-Whan; Firth, Amy L; Bang, Hyoweon; Bae, Young Min; Park, Won Sun

    2016-12-01

    We examined the effects of the selective serotonin reuptake inhibitor (SSRI) sertraline on voltage-dependent K+ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using the voltage-clamp technique. Sertraline decreased the Kv channel current in a dose-dependent manner, with an IC50 value of 0.18 mu M and a slope value (Hill coefficient) of 0.61. Although the application of 1 mu M sertraline did not affect the steady-state activation curves, sertraline caused a significant, negative shift in the inactivation curves. Pretreatment with another SSRI, paroxetine, had no significant effect on Kv currents and did not alter the inhibitory effects of sertraline on Kv currents. From these results, we concluded that sertraline dose-dependently inhibited Kv currents independently of serotonin reuptake inhibition by shifting inactivation curves to a more negative potential.

  15. Selective serotonin reuptake inhibitor sertraline inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

    Indian Academy of Sciences (India)

    HAN SOL KIM; HONGLIANG LI; HYE WON KIM; SUNG EUN SHIN; IL-WHAN CHOI; AMY L FIRTH; HYOWEON BANG; YOUNG MIN BAE; WON SUN PARK

    2016-12-01

    We examined the effects of the selective serotonin reuptake inhibitor (SSRI) sertraline on voltage-dependent K+ (Kv)channels in freshly isolated rabbit coronary arterial smooth muscle cells using the voltage-clamp technique. Sertralinedecreased the Kv channel current in a dose-dependent manner, with an IC50 value of 0.18 μM and a slope value (Hillcoefficient) of 0.61. Although the application of 1 μM sertraline did not affect the steady-state activation curves,sertraline caused a significant, negative shift in the inactivation curves. Pretreatment with another SSRI, paroxetine,had no significant effect on Kv currents and did not alter the inhibitory effects of sertraline on Kv currents. From theseresults, we concluded that sertraline dose-dependently inhibited Kv currents independently of serotonin reuptakeinhibition by shifting inactivation curves to a more negative potential.

  16. Serotonin synthesis rate and the tryptophan hydroxylase-2

    DEFF Research Database (Denmark)

    Furmark, Tomas; Marteinsdottir, Ina; Frick, Andreas;

    2016-01-01

    It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort......, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron...... emission tomography and 5-hydroxy-L-[β -(11)C]tryptophan, [(11)C]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G...

  17. Selective serotonin reuptake inhibitorprescribing before, during and after pregnancy

    DEFF Research Database (Denmark)

    Charlton, Ra; Jordan, S; Pierini, A;

    2015-01-01

    OBJECTIVE: To explore the prescribing patterns of selective serotonin reuptake inhibitors (SSRIs) before, during and after pregnancy in six European population-based databases. DESIGN: Descriptive drug utilisation study. SETTING: Six electronic healthcare databases in Denmark, the Netherlands...

  18. 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.

  19. Encapsulation of serotonin in β-cyclodextrin nano-cavities: Fluorescence spectroscopic and molecular modeling studies

    Science.gov (United States)

    Chaudhuri, Sudip; Chakraborty, Sandipan; Sengupta, Pradeep K.

    2010-06-01

    Serotonin is a physiologically important biogenic amine, deficiency of which leads to mental disorders such as Alzheimer's disease, schizophrenia, infantile autism, and depression. Both β-cyclodextrin (β-CD) and its chemically substituted synthetic varieties (often possessing enhanced aqueous solubility and improved drug complexing abilities) are finding wide applications as drug delivery vehicles. Here we have studied the encapsulation of serotonin in β-CD and succinyl-2-hydroxypropyl β-cyclodextrin (SHP-β-CD) by exploiting the intrinsic serotonin fluorescence. Enhanced fluorescence emission intensity (which increases by ˜18% and 34% in β-CD and SHPβ-CD respectively) and anisotropy ( r) ( r = 0.075 and 0.1 in β-CD and SHPβ-CD respectively) are observed in presence of the cyclodextrins. From the fluorescence data host-guest interaction with 1:1 stoichiometry is evident, the association constants ( K) being 126.06 M -1 and 461.62 M -1 for β-CD and SHPβ-CD respectively. Additionally, molecular docking and semiempirical calculations have been carried out which provide, for the first time, detailed insights regarding the encapsulation process. In particular, it is evident that the indole ring is inserted within the β-CD cavity with the aliphatic amine side chain protruding towards the primary rim of the β-CD cavity. Docking calculations reveal that hydrogen bonding interactions are involved in the formation of the inclusion complex. Semiempirical calculations indicate that formation of the 1:1 inclusion complex is energetically favorable which is consistent with the fluorescence data.

  20. 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.

  1. Fatty acids, membrane viscosity, serotonin and ischemic heart disease

    OpenAIRE

    Cocchi Massimo; Tonello Lucio; Lercker Giovanni

    2010-01-01

    Abstract Novel markers for ischemic heart disease are under investigation by the scientific community at international level. This work focuses on a specific platelet membrane fatty acid condition of viscosity which is linked to molecular aspects such as serotonin and G proteins, factors involved in vascular biology. A suggestive hypothesis is considered about the possibility to use platelet membrane viscosity, in relation to serotonin or, indirectly, the fatty acid profile, as indicator of i...

  2. Increased hypothalamic serotonin turnover in inflammation-induced anorexia

    OpenAIRE

    Dwarkasing, J.T.; Witkamp, R F; Boekschoten, M.V.; Laak, ter, H.J.; Heins, M.S.; Norren, van, K.

    2016-01-01

    Background Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS....

  3. 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.

  4. [Tyramine and serotonin syndromes. Pharmacological, medical and legal remarks].

    Science.gov (United States)

    Toro-Martínez, Esteban

    2005-01-01

    The tyramine syndrome and the serotonin syndrome are a complex of signs and symptoms that are thought to be largely attributable to drug - drug interactions or drug - food interactions that enhances norepinephrine o serotonin activity. This article reviews: pharmacological basis of those syndromes; clinical features; forbidden foods, drug-drug interactions, and treatment options. Finally a set of legal recommendations are proposed to avoid liability litigations.

  5. Serotonin of mast cell origin contributes to hippocampal function

    OpenAIRE

    Nautiyal, Katherine M.; Dailey, Christopher A.; Jahn, Jaquelyn L.; Rodriquez, Elizabeth; Son, Nguyen Hong; Jonathan V. Sweedler; Silver, Rae

    2012-01-01

    In the CNS, serotonin, an important neurotransmitter and trophic factor, is synthesized by both mast cells and neurons. Mast cells, like other immune cells, are born in the bone marrow and migrate to many tissues. We show that they are resident in the mouse brain throughout development and adulthood. Measurements based on capillary electrophoresis with native fluorescence detection indicate that a significant contribution of serotonin to the hippocampal milieu is associated with mast cell act...

  6. [Human physiology: kidney].

    Science.gov (United States)

    Natochin, Iu V

    2010-01-01

    The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

  7. Lung damage and pulmonary uptake of serotonin in intact dogs

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, C.A.; Christensen, C.W.; Rickaby, D.A.; Linehan, J.H.; Johnston, M.R.

    1985-06-01

    The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of (/sup 3/H)serotonin and the extravascular volume accessible to (/sup 14/C)antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage.

  8. New perspective on the pathophysiology of panic: merging serotonin and opioids in the periaqueductal gray

    Directory of Open Access Journals (Sweden)

    F.G. Graeff

    2012-04-01

    Full Text Available Panic disorder patients are vulnerable to recurrent panic attacks. Two neurochemical hypotheses have been proposed to explain this susceptibility. The first assumes that panic patients have deficient serotonergic inhibition of neurons localized in the dorsal periaqueductal gray matter of the midbrain that organize defensive reactions to cope with proximal threats and of sympathomotor control areas of the rostral ventrolateral medulla that generate most of the neurovegetative symptoms of the panic attack. The second suggests that endogenous opioids buffer normal subjects from the behavioral and physiological manifestations of the panic attack, and their deficit brings about heightened suffocation sensitivity and separation anxiety in panic patients, making them more vulnerable to panic attacks. Experimental results obtained in rats performing one-way escape in the elevated T-maze, an animal model of panic, indicate that the inhibitory action of serotonin on defense is connected with activation of endogenous opioids in the periaqueductal gray. This allows reconciliation of the serotonergic and opioidergic hypotheses of panic pathophysiology, the periaqueductal gray being the fulcrum of serotonin-opioid interaction.

  9. Interplay between serotonin 5-HT1A and 5-HT7 receptors in depressive disorders.

    Science.gov (United States)

    Naumenko, Vladimir S; Popova, Nina K; Lacivita, Enza; Leopoldo, Marcello; Ponimaskin, Evgeni G

    2014-07-01

    Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter regulating a wide range of physiological and pathological functions via activation of heterogeneously expressed 5-HT receptors. Besides the important role of 5-HT receptors in the pathogenesis of depressive disorders and in their clinical medications, underlying mechanisms are far from being completely understood. This review focuses on possible cross talk between two serotonin receptors, 5-HT1A and the 5-HT7 . Although these receptors are highly co-expressed in brain regions implicated in depression, and most agonists developed for the 5-HT1A or 5-HT7 receptors have cross-reactivity, their functional interaction has not been yet established. It has been recently shown that 5-HT1A and 5-HT7 receptors form homo- and heterodimers both in vitro and in vivo. From the functional point of view, heterodimerization has been shown to play an important role in regulation of receptor-mediated signaling and internalization, suggesting the implication of heterodimerization in the development and maintenance of depression. Interaction between these receptors is also of clinical interest, because both receptors represent an important pharmacological target for the treatment of depression and anxiety.

  10. The impact of treatment with selective serotonin reuptake inhibitors on primate cardiovascular disease, behavior, and neuroanatomy.

    Science.gov (United States)

    Shively, Carol A; Silverstein-Metzler, Marnie; Justice, Jamie; Willard, Stephanie L

    2017-03-01

    Selective serotonin reuptake inhibitor (SSRI) use is ubiquitous because they are widely prescribed for a number of disorders in addition to depression. Depression increases the risk of coronary heart disease (CHD). Hence, treating depression with SSRIs could reduce CHD risk. However, the effects of long term antidepressant treatment on CHD risk, as well as other aspects of health, remain poorly understood. Thus, we undertook an investigation of multisystem effects of SSRI treatment with a physiologically relevant dose in middle-aged adult female cynomolgus monkeys, a primate species shown to be a useful model of both depression and coronary and carotid artery atherosclerosis. Sertraline had no effect on depressive behavior, reduced anxious behavior, increased affiliation, reduced aggression, changed serotonin neurotransmission and volumes of neural areas critical to mood disorders, and exacerbated coronary and carotid atherosclerosis. These data suggest that a conservative approach to prescribing SSRIs for cardiovascular or other disorders for long periods may be warranted, and that further study is critical given the widespread use of these medications.

  11. Sex differences in the serotonin 1A receptor and serotonin transporter binding in the human brain measured by PET.

    Science.gov (United States)

    Jovanovic, Hristina; Lundberg, Johan; Karlsson, Per; Cerin, Asta; Saijo, Tomoyuki; Varrone, Andrea; Halldin, Christer; Nordström, Anna-Lena

    2008-02-01

    Women and men differ in serotonin associated psychiatric conditions, such as depression, anxiety and suicide. Despite this, very few studies focus on sex differences in the serotonin system. Of the biomarkers in the serotonin system, serotonin(1A) (5-HT(1A)) receptor is implicated in depression, and anxiety and serotonin transporter (5-HTT) is a target for selective serotonin reuptake inhibitors, psychotropic drugs used in the treatment of these disorders. The objective of the present study was to study sex related differences in the 5-HT(1A) receptor and 5-HTT binding potentials (BP(ND)s) in healthy humans, in vivo. Positron emission tomography and selective radioligands [(11)C]WAY100635 and [(11)C]MADAM were used to evaluate binding potentials for 5-HT(1A) receptors (14 women and 14 men) and 5-HTT (8 women and 10 men). The binding potentials were estimated both on the level of anatomical regions and voxel wise, derived by the simplified reference tissue model and wavelet/Logan plot parametric image techniques respectively. Compared to men, women had significantly higher 5-HT(1A) receptor and lower 5-HTT binding potentials in a wide array of cortical and subcortical brain regions. In women, there was a positive correlation between 5-HT(1A) receptor and 5-HTT binding potentials for the region of hippocampus. Sex differences in 5-HT(1A) receptor and 5-HTT BP(ND) may reflect biological distinctions in the serotonin system contributing to sex differences in the prevalence of psychiatric disorders such as depression and anxiety. The result of the present study may help in understanding sex differences in drug treatment responses to drugs affecting the serotonin system.

  12. Serotonin signaling in Schistosoma mansoni: a serotonin-activated G protein-coupled receptor controls parasite movement.

    Directory of Open Access Journals (Sweden)

    Nicholas Patocka

    2014-01-01

    Full Text Available Serotonin is an important neuroactive substance in all the parasitic helminths. In Schistosoma mansoni, serotonin is strongly myoexcitatory; it potentiates contraction of the body wall muscles and stimulates motor activity. This is considered to be a critical mechanism of motor control in the parasite, but the mode of action of serotonin is poorly understood. Here we provide the first molecular evidence of a functional serotonin receptor (Sm5HTR in S. mansoni. The schistosome receptor belongs to the G protein-coupled receptor (GPCR superfamily and is distantly related to serotonergic type 7 (5HT7 receptors from other species. Functional expression studies in transfected HEK 293 cells showed that Sm5HTR is a specific serotonin receptor and it signals through an increase in intracellular cAMP, consistent with a 5HT7 signaling mechanism. Immunolocalization studies with a specific anti-Sm5HTR antibody revealed that the receptor is abundantly distributed in the worm's nervous system, including the cerebral ganglia and main nerve cords of the central nervous system and the peripheral innervation of the body wall muscles and tegument. RNA interference (RNAi was performed both in schistosomulae and adult worms to test whether the receptor is required for parasite motility. The RNAi-suppressed adults and larvae were markedly hypoactive compared to the corresponding controls and they were also resistant to exogenous serotonin treatment. These results show that Sm5HTR is at least one of the receptors responsible for the motor effects of serotonin in S. mansoni. The fact that Sm5HTR is expressed in nerve tissue further suggests that serotonin stimulates movement via this receptor by modulating neuronal output to the musculature. Together, the evidence identifies Sm5HTR as an important neuronal protein and a key component of the motor control apparatus in S. mansoni.

  13. Fluoxetine: clinical pharmacology and physiologic disposition

    Energy Technology Data Exchange (ETDEWEB)

    Lemberger, L.; Bergstrom, R.F.; Wolen, R.L.; Farid, N.A.; Enas, G.G.; Aronoff, G.R.

    1985-03-01

    Fluoxetine (30 mg), administered for 7 days to normal volunteers, produced a 66% inhibition of tritiated serotonin uptake into platelets. Plasma concentrations of fluoxetine correlated positively with inhibition of serotonin uptake. Fluoxetine is well absorbed after oral administration in both the fed and fasted states and demonstrates dose proportionality. Fluoxetine disappears from plasma with a half-life of 1-3 days; its metabolite norfluoxetine has a plasma half-life of 7-15 days. After administration of /sup 14/C-fluoxetine, approximately 65% of the administered dose of radioactivity is recovered in urine and about 15% in feces. Fluoxetine, given as a single dose or in multiple doses over 8 days, did not produce significant effects on the plasma disappearance of warfarin, diazepam, tolbutamide, or chlorothiazide. Coadministration of fluoxetine and ethanol did not result in an increase from control values in the blood ethanol levels, nor did it produce significant changes in physiologic, psychometric, or psychomotor activity. Pharmacokinetics of fluoxetine in the elderly and normal volunteers appear to be similar. In addition, pharmacokinetic analyses in patients with varying degrees of renal impairment did not show significant differences from healthy subjects.

  14. The selective serotonin reuptake inhibitor sertraline: its profile and use in psychiatric disorders.

    Science.gov (United States)

    MacQueen, G; Born, L; Steiner, M

    2001-01-01

    The naphthylamine derivative sertraline is a potent and selective inhibitor of serotonin reuptake into presynaptic terminals. Sertraline has a linear pharmacokinetic profile and a half-life of about 26 h. Its major metabolite, desmethylsertraline does not appear to inhibit serotonin reuptake. Sertraline mildly inhibits the CYP2D6 isoform of the cytochrome P450 system but has little effect on CYP1A2, CYP3A3/4, CYP2C9, or CYP2C19. It is, however, highly protein bound and may alter blood levels of other highly protein bound agents. Sertraline is a widely used serotonin reuptake inhibitor that has been shown to have both antidepressant and antianxiety effects. Many clinical trials have demonstrated its efficacy in depression compared with both placebo and other antidepressant drugs. Its efficacy has also been demonstrated in randomized, controlled trials of patients with obsessive-compulsive disorder, panic disorder, social phobia, and premenstrual dysphoric disorder. In short-term, open-label studies it has appeared efficacious and tolerable in children and adolescents and in the elderly, and data are positive for its use in pregnant or lactating women. Typical side effects include gastrointestinal and central nervous system effects as well as treatment-emergent sexual dysfunction; withdrawal reactions may be associated with abrupt discontinuation of the agent. The safety profile of sertraline in overdose is very favorable. Sertraline's efficacy for both mood and anxiety disorders, relatively weak effect on the cytochrome P450 system, and tolerability profile and safety in overdose are factors that contribute to make it a first-line agent for treatment in both primary and tertiary care settings.

  15. Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning.

    Science.gov (United States)

    Johnson, Philip L; Molosh, Andrei; Fitz, Stephanie D; Arendt, Dave; Deehan, Gerald A; Federici, Lauren M; Bernabe, Cristian; Engleman, Eric A; Rodd, Zachary A; Lowry, Christopher A; Shekhar, Anantha

    2015-11-01

    The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including conditioned fear and social anxiety. Based on previous studies demonstrating that enhanced serotonin release in the BLC leads to increased anxiety and fear responses, we hypothesized that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7-DHT) injections would lead to diminished anxiety and disrupted fear conditioning. To test this hypothesis, 5,7-DHT(a serotonin-depleting agent) was bilaterally injected into the BLC. Desipramine (a norepinephrine reuptake inhibitor) was systemically administered to prevent non-selective effects on norepinephrine. After 5days, 5-7-DHT-treated rats showed increases in the duration of social interaction (SI) time, suggestive of reduced anxiety-like behavior. We then used a cue-induced fear conditioning protocol with shock as the unconditioned stimulus and tone as the conditioned stimulus for rats pretreated with bilateral 5,7-DHT, or vehicle, injections into the BLC. Compared to vehicle-treated rats, 5,7-DHT rats had reduced acquisition of fear during conditioning (measured by freezing time during tone), also had reduced fear retrieval/recall on subsequent testing days. Ex vivo analyses revealed that 5,7-DHT reduced local 5-HT concentrations in the BLC by ~40% without altering local norepinephrine or dopamine concentrations. These data provide additional support for 5-HT playing a critical role in modulating anxiety-like behavior and fear-associated memories through its actions within the BLC.

  16. Serum Levels of Tryptophan, 5-Hydroxytryptophan and Serotonin in Patients Affected with Different Forms of Amenorrhea

    Directory of Open Access Journals (Sweden)

    S. Comai

    2010-06-01

    Full Text Available Tryptophan (Trp is present in the serum, partly bound to albumine and in the free form. The unbound portion of circulating tryptophan has the property of crossing the hematoencephalic barrier and being converted within the brain into serotonin (5-HT through the enzymatic processes of hydroxylation and decarboxylation. The serotoninergic system plays an important role in neuroendocrine control of reproductive hormone secretion, and in particular, it may influence GnRH pulsatility, a function essential for reproductive processes. In this study, we analysed serum levels of tryptophan, serotonin and 5-hydroxytryptophan (5-HTP in women with three different forms of amenorrhea: 16 patients were diagnosed with anorexia nervosa, 60 patients with functional hypothalamic amenorrhea, and 14 patients with hyperprolactinemia. Data were compared with those of a group of 25 healthy women. Serum Trp levels were significantly (P ≤ 0.05 lower in the anorexic (11.64 ± 0.53 µg/ml, mean ± S.E. than in the control (12.98 ± 0.37 µg/ml groups. In addition, in the anorexic group a statistical dispersion of Trp values was shown indicating a bimodal data distribution suggesting the existence of two different subgroups of patients. Regarding 5-HTP, an increase of its serum level was observed in all the groups with amenorrhea with the highest value in hyperprolactinemic patients. On the contrary, no statistical differences in serum 5-HT levels among the four analyzed groups were observed. This study shows that women affected by various forms of amenorrhea present an altered metabolism of tryptophan via serotonin and, in particular, markedly high differences are observed between the two subgroups of anorexic patients.

  17. Serotonin Deficiency Rescues Lactation on Day 1 in Mice Fed a High Fat Diet

    Science.gov (United States)

    Prichard, Allan S.; Perez, Paola K.; Streckenbach, Liana J.; Olson, Jake M.; Cook, Mark E.; Hernandez, Laura L.

    2016-01-01

    Obesity is an inflammatory state associated with delayed lactogenesis stage II and altered mammary gland morphology. Serotonin mediates inflammation and mammary gland involution. The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet. Twenty-six female mice were fed a high (HFD) or low fat (LFD) diet throughout pregnancy and lactation. Fourteen mice were genetically deficient for Tph1 (Tph1-/-), and twelve were wild type. Milk yield, pup mortality, and dam weights were recorded and milk samples were collected. On day 10 of lactation, dams were sacrificed and mammary glands were harvested for RT-PCR and histological evaluation. HFD dams weighed more than LFD dams at the onset of lactation. WT HFD dams were unable to lactate on day 1 of lactation and exhibited increased pup mortality relative to all other treatments, including Tph1-/- HFD dams. mRNA expression of immune markers C-X-C motif chemokine 5 and tumor necrosis factor alpha were elevated in WT HFD mammary glands. Mammary gland histology showed a reduced number of alveoli in WT compared to Tph1-/- dams, regardless of diet, and the alveoli of HFD dams were smaller than those of LFD dams. Finally, fatty acid profile in milk was dynamic in both early and peak lactation, with reduced de novo synthesis of fatty acids on day 10 of lactation in the HFD groups. Administration of a HFD to C57BL/6 dams produced an obese phenotype in the mammary gland, which was alleviated by a genetic deficiency of Tph1. Serotonin may modulate the effects of obesity on the mammary gland, potentially contributing to the delayed onset of lactogenesis seen in obese women. PMID:27603698

  18. Dual role of endogenous serotonin in 2,4,6-trinitrobenzene sulfonic acid-induced colitis

    Directory of Open Access Journals (Sweden)

    Alberto eRapalli

    2016-03-01

    Full Text Available Background and Aims: Changes in gut serotonin content have been described in Inflammatory Bowel Disease and in different experimental models of colitis: the critical role of this monoamine in the pathogenesis of chronic gastrointestinal inflammation is gradually emerging. Aim of the present study was to evaluate the contribution of endogenous serotonin through the activation of its specific receptor subtypes to the local and systemic inflammatory responses in an experimental model of Inflammatory Bowel Disease. Methods: Colitis was induced by intrarectal 2,4,6-TriNitroBenzene Sulfonic acid in mice subacutely treated with selective antagonists of 5-HT1A (WAY100135, 5-HT2A (Ketanserin, 5-HT3 (Ondansetron, 5-HT4 (GR125487, 5-HT7 (SB269970 receptors and with 5-HT1A agonist 8-Hydroxy-2-(di-n-propylaminotetralin. Results: Blockade of 5-HT1A receptors worsened TNBS-induced local and systemic neutrophil recruitment while 5-HT1A agonist delayed and mitigated the severity of colitis, counteracting the increase in colonic 5-HT content. On the contrary, blockade of 5-HT2A receptors improved global health conditions, reduced colonic morphological alterations, down-regulated neutrophil recruitment, inflammatory cytokines levels and colonic apoptosis. Antagonism of 5-HT3, 5-HT4 and 5-HT7 receptor sites did not remarkably affect the progression and outcome of the pathology or only slightly improved it.Conclusions: The prevailing deleterious contribution given by endogenous serotonin to inflammation in TNBS-induced colitis is seemingly mediated by 5-HT2A and, to a lesser extent, by 5-HT4 receptors and coexists with the weak beneficial effect elicited by 5-HT1A stimulation. These findings suggest how only a selective interference with 5-HT pro-inflammatory actions may represent an additional potential therapeutic option for intestinal inflammatory disorders.

  19. Effects of Selective Serotonin Reuptake Inhibitors on Interregional Relation of Serotonin Transporter Availability in Major Depression

    Science.gov (United States)

    James, Gregory M.; Baldinger-Melich, Pia; Philippe, Cecile; Kranz, Georg S.; Vanicek, Thomas; Hahn, Andreas; Gryglewski, Gregor; Hienert, Marius; Spies, Marie; Traub-Weidinger, Tatjana; Mitterhauser, Markus; Wadsak, Wolfgang; Hacker, Marcus; Kasper, Siegfried; Lanzenberger, Rupert

    2017-01-01

    Selective serotonin reuptake inhibitors (SSRIs) modulate serotonergic neurotransmission by blocking reuptake of serotonin from the extracellular space. Up to now, it remains unclear how SSRIs achieve their antidepressant effect. However, task-based and resting state functional magnetic resonance imaging studies, have demonstrated connectivity changes between brain regions. Here, we use positron emission tomography (PET) to quantify SSRI’s main target, the serotonin transporter (SERT), and assess treatment-induced molecular changes in the interregional relation of SERT binding potential (BPND). Nineteen out-patients with major depressive disorder (MDD) and 19 healthy controls (HC) were included in this study. Patients underwent three PET measurements with the radioligand [11C]DASB: (1) at baseline, (2) after a first SSRI dose; and (3) following at least 3 weeks of daily intake. Controls were measured once with PET. Correlation analyses were restricted to brain regions repeatedly implicated in MDD pathophysiology. After 3 weeks of daily SSRI administration a significant increase in SERT BPND correlations of anterior cingulate cortex and insula with the amygdala, midbrain, hippocampus, pallidum and putamen (p < 0.05; false discovery rate, FDR corrected) was revealed. No significant differences were found when comparing MDD patients and HC at baseline. These findings are in line with the clinical observation that treatment response to SSRIs is often achieved only after a latency of several weeks. The elevated associations in interregional SERT associations may be more closely connected to clinical outcomes than regional SERT occupancy measures and could reflect a change in the regional interaction of serotonergic neurotransmission during antidepressant treatment. PMID:28220069

  20. 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

    --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...... 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...

  1. 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...... and anxiety. In the present study we have undertaken a mutational scanning of human SERT in order to identify residues that are responsible for individual differences among related monoamine transporters. One mutant, G100A, was inactive in transport. However, ligand binding affinity was similar to wild...

  2. 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.

  3. The importance of serotonin for orbitofrontal function.

    Science.gov (United States)

    Roberts, Angela C

    2011-06-15

    The orbitofrontal cortex (OFC) receives a dense serotonin (5-hydroxytryptamine, or 5-HT) innervation from the dorsal raphe nucleus, with a smaller contribution from the median raphe nucleus. The reciprocal innervation from the OFC enables the OFC to regulate not only its own 5-HT input but the 5-HT input to the rest of the forebrain. This article reviews the evidence from studies in rodents and primates that implicate 5-HT in the OFC in the ability of animals to adapt their responding to changes in reward contingencies in the environment. A consensus is emerging that reductions in orbitofrontal 5-HT, whether the result of localized infusions of 5,7-dihydroxytryptamine (5,7-DHT), peripheral treatment with parachloroamphetamine (PCA) or para-chlorophenylalanine (PCPA), or chronic cold stress impairs this ability. Genetic variation in the 5-HT transporter can also affect this ability. An explanation regarding insensitivity to reward loss is ruled out by the finding that marmosets with 5-HT reductions in the OFC display a decline of responding as rapid as that of control animals when reward is withheld during extinction of a two-pattern discrimination task. The failure of these same animals to explore alternative stimuli during extinction, along with the recent electrophysiological evidence that dorsal raphe nucleus neurons encode future motivational outcomes, implicates orbitofrontal 5-HT in the process by which animals either exploit current resources or explore alternative resources based on current reward expectations.

  4. Myocardial serotonin exchange: negligible uptake by capillary endothelium

    Energy Technology Data Exchange (ETDEWEB)

    Moffett, T.C.; Chan, I.S.; Bassingthwaighte, J.B.

    1988-03-01

    The extraction of serotonin from the blood during transorgan passage through the heart was studied using Langendorff-perfused rabbit hearts. Outflow dilution curves of /sup 131/I- or /sup 125/I-labeled albumin, (/sup 14/C)sucrose, and (3H)serotonin injected simultaneously into the inflow were fitted with an axially distributed blood-tissue exchange model to examine the extraction process. The model fits of the albumin and sucrose outflow dilution curves were used to define flow heterogeneity, intravascular dispersion, capillary permeability, and the volume of the interstitial space, which reduced the degrees of freedom in fitting the model to the serotonin curves. Serotonin extractions, measured against albumin, during single transcapillary passage, ranged from 24 to 64%. The ratio of the capillary permeability-surface area products for serotonin and sucrose, based on the maximum instantaneous extraction, was 1.37 +/- 0.2 (n = 18), very close to the predicted value of 1.39, the ratio of free diffusion coefficients calculated from the molecular weights. This result shows that the observed uptake of serotonin can be accounted for solely on the basis of diffusion between endothelial cells into the interstitial space. Thus it appears that the permeability of the luminal surface of the endothelial cell is negligible in comparison to diffusion through the clefts between endothelial cells. In 18 sets of dilution curves, with and without receptor and transport blockers or competitors (ketanserin, desipramine, imipramine, serotonin), the extractions and estimates of the capillary permeability-surface area product were not reduced, nor were the volumes of distribution. The apparent absence of transporters and receptors in rabbit myocardial capillary endothelium contrasts with their known abundance in the pulmonary vasculature.

  5. Involvement of presynaptic H3 receptors in the inhibitory effect of histamine on serotonin release in the rat brain cortex.

    Science.gov (United States)

    Fink, K; Schlicker, E; Neise, A; Göthert, M

    1990-11-01

    Rat brain cortex slices or synaptosomes preincubated with 3H-serotonin were superfused with physiological salt solution (which, in the case of slices, contained citalopram, an inhibitor of serotonin uptake), and the effects of histamine and related drugs on the evoked tritium overflow were studied. The electrically (3 Hz) evoked tritium overflow from slices was inhibited by histamine and the H3 receptor agonists R-(-)-alpha-methylhistamine and N alpha-methylhistamine (pIC12.5 values: 6.41, 7.28 and 6.12, respectively), but not affected by the H1 receptor agonist 2-(2-thiazolyl)ethylamine and the H2 receptor agonist dimaprit (each at 10 mumol/l). The concentration-response curve for histamine was shifted to the right by the H3 receptor antagonists impromidine, burimamide and thioperamide (apparent pA2 values: 7.45, 5.97 and 7.88, respectively); the concentration-response curve of serotonin for its inhibitory effect on the electrically evoked overflow was not affected by the three drugs (apparent pA2 values: less than 5.5, less than 5.5 and less than 6.5). Given alone, impromidine, thioperamide and a low concentration of burimamide facilitated the electrically evoked overflow. In slices superfused with K(+)-rich, Ca2(+)-free solution containing tetrodotoxin throughout and in synaptosomes superfused with Ca2(+)-free solution, histamine inhibited the overflow evoked by introduction of Ca2+ (in synaptosomes, simultaneously with an increased amount of K+). In either tissue, the effect of histamine was counteracted by thioperamide. The results provide evidence that exogenous and probably also endogenous histamine inhibits serotonin release in the rat brain cortex via presynaptic histamine H3 receptors.

  6. Physiology of the fetal and transitional circulation.

    Science.gov (United States)

    Finnemore, Anna; Groves, Alan

    2015-08-01

    The fetal circulation is an entirely transient event, not replicated at any point in later life, and functionally distinct from the pediatric and adult circulations. Understanding of the physiology of the fetal circulation is vital for accurate interpretation of hemodynamic assessments in utero, but also for management of circulatory compromise in premature infants, who begin extrauterine life before the fetal circulation has finished its maturation. This review summarizes the key classical components of circulatory physiology, as well as some of the newer concepts of physiology that have been appreciated in recent years. The immature circulation has significantly altered function in all aspects of circulatory physiology. The mechanisms and significance of these differences are also discussed, as is the impact of these alterations on the circulatory transition of infants born prematurely.

  7. Serotonin, visceral sensation in irritable bowel syndrome

    Institute of Scientific and Technical Information of China (English)

    QIAN Jia-ming

    2007-01-01

    @@ Irritable bowel syndrome(IBS) is highly prevalent and can affect up to 20% of the population.1 It is a common gastrointestinal(GI) disorder associated with alterations in motility,secretion and visceral sensation.

  8. Brain Glycogen Decreases During Intense Exercise Without Hypoglycemia: The Possible Involvement of Serotonin.

    Science.gov (United States)

    Matsui, Takashi; Soya, Shingo; Kawanaka, Kentaro; Soya, Hideaki

    2015-07-01

    Brain glycogen stored in astrocytes, a source of lactate as a neuronal energy source, decreases during prolonged exercise with hypoglycemia. However, brain glycogen dynamics during exercise without hypoglycemia remain unknown. Since intense exercise increases brain noradrenaline and serotonin as known inducers for brain glycogenolysis, we hypothesized that brain glycogen decreases with intense exercise not accompanied by hypoglycemia. To test this hypothesis, we employed a well-established acute intense exercise model of swimming in rats. Rats swam for fourteen 20 s bouts with a weight equal to 8 % of their body mass and were sacrificed using high-power (10 kW) microwave irradiation to inactivate brain enzymes for accurate detection of brain glycogen and monoamines. Intense exercise did not alter blood glucose, but did increase blood lactate levels. Immediately after exercise, brain glycogen decreased and brain lactate increased in the hippocampus, cerebellum, cortex, and brainstem. Simultaneously, serotonin turnover in the hippocampus and brainstem mutually increased and were associated with decreased brain glycogen. Intense swimming exercise that does not induce hypoglycemia decreases brain glycogen associated with increased brain lactate, implying an importance of glycogen in brain energetics during intense exercise even without hypoglycemia. Activated serotonergic regulation is a possible underlying mechanism for intense exercise-induced glycogenolysis at least in the hippocampus and brainstem.

  9. Selective serotonin reuptake inhibitor antidepressants potentiate methylphenidate (Ritalin)-induced gene regulation in the adolescent striatum.

    Science.gov (United States)

    Van Waes, Vincent; Beverley, Joel; Marinelli, Michela; Steiner, Heinz

    2010-08-01

    The psychostimulant methylphenidate (Ritalin) is used in conjunction with selective serotonin reuptake inhibitors (SSRIs) in the treatment of medical conditions such as attention-deficit hyperactivity disorder with anxiety/depression comorbidity and major depression. Co-exposure also occurs in patients on SSRIs who use psychostimulant 'cognitive enhancers'. Methylphenidate is a dopamine/norepinephrine reuptake inhibitor that produces altered gene expression in the forebrain; these effects partly mimic gene regulation by cocaine (dopamine/norepinephrine/serotonin reuptake inhibitor). We investigated whether the addition of SSRIs (fluoxetine or citalopram; 5 mg/kg) modified gene regulation by methylphenidate (2-5 mg/kg) in the striatum and cortex of adolescent rats. Our results show that SSRIs potentiate methylphenidate-induced expression of the transcription factor genes zif268 and c-fos in the striatum, rendering these molecular changes more cocaine-like. Present throughout most of the striatum, this potentiation was most robust in its sensorimotor parts. The methylphenidate + SSRI combination also enhanced behavioral stereotypies, consistent with dysfunction in sensorimotor striatal circuits. In so far as such gene regulation is implicated in psychostimulant addiction, our findings suggest that SSRIs may enhance the addiction potential of methylphenidate.

  10. Sildenafil potentiates the proliferative effect of porcine pulmonary artery smooth muscle cells induced by serotonin in vitro

    Institute of Scientific and Technical Information of China (English)

    LI Bing-bing; JIANG Zhen; SHENG Jian-yin; YAO Kang

    2011-01-01

    Background Sildenafil is one of the selective phosphodiesterase 5 inhibitors that has been proven by many investigators to suppress growth factor stimulated (e.g.platelet-derived growth factor (PDGF) or epidermal growth factor (EGF)) proliferation and hypertrophy of pulmonary artery smooth muscle cells (PASMCs) via cGMP/cGKIα pathway.Serotonin promotes cell cycle progression leading to cell mitogenesis and plays a key role in the pathogenesis of pulmonary artery hypertension.The role of sildenafil in proliferation of PASMCs induced by serotonin has not been investigated so far.In this study we explored the underlying mechanism of the effect of sildenafil on serotonin induced proliferation of porcine PASMCs.Methods PASMCs were cells from primary cultures by the explant method from the pulmonary artery of swine and cells at passage 3-5 were used in this study.MTT colorimetric assay and flow cytometry analysis were used to evaluate the cell proliferation and alterations in cell cycle progression respectively.Western blotting analysis was applied to determine the expression of phosphorylated extracellular signal-regulated kinase (ERK),proliferating cell nuclear antigen (PCNA)and mitogen activated protein kinase (MAPK) phosphatase-1 (MKP-1).Results Serotonin (10 μmol/L) induced the upregulation of phosphorylation of ERK1/ERK2 and PCNA,an increase in the percentage of cells in S phase and subsequent cell proliferation.Pretreatment with 1 μmol/L sildenafil potentiated the phosphorylation of ERK1/ERK2,an increase in the percentage of cells in S phase and cell proliferation,compared with serotonin stimulation alone (P <0.05).Furthermore,30-minute pretreatment with 10 μmol/L U0126,specific antagonist for ERK kinase (MEK) prevented the increase in phosphorylation of ERK1/ERK2 and abolished cell cycle progression and the proliferation of PASMCs induced by sildenafil.Conclusion This study shows that sildenafil potentiated the proliferative effect of serotonin on PASMCs

  11. 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

  12. Linking the serotonin transporter gene, family environments, hippocampal volume and depression onset: A prospective imaging gene × environment analysis.

    Science.gov (United States)

    Little, Keriann; Olsson, Craig A; Youssef, George J; Whittle, Sarah; Simmons, Julian G; Yücel, Murat; Sheeber, Lisa B; Foley, Debra L; Allen, Nicholas B

    2015-11-01

    A single imaging gene-environment (IGxE) framework that is able to simultaneously model genetic, neurobiological, and environmental influences on psychopathology outcomes is needed to improve understanding of how complex interrelationships between allelic variation, differences in neuroanatomy or neuroactivity, and environmental experience affect risk for psychiatric disorder. In a longitudinal study of adolescent development we demonstrate the utility of such an IGxE framework by testing whether variation in parental behavior at age 12 altered the strength of an imaging genetics pathway, involving an indirect association between allelic variation in the serotonin transporter gene to variation in hippocampal volume and consequent onset of major depressive disorder by age 18. Results were consistent with the presence of an indirect effect of the serotonin transporter S-allele on depression onset via smaller left and right hippocampal volumes that was significant only in family environments involving either higher levels of parental aggression or lower levels of positive parenting. The previously reported finding of S-allele carriers' increased risk of depression in adverse environments may, therefore, be partly because of the effects of these environments on a neurobiological pathway from the serotonin transporter gene to depression onset that proceeds through variation in hippocampal volume.

  13. Alterações das características fisiológicas da bananeira sob condições de fertirrigação Alteration of the physiologic characteristics in banana under fertirrigation conditions

    Directory of Open Access Journals (Sweden)

    Alberto Soares de Melo

    2009-06-01

    Full Text Available A aplicação de fertilizantes via sistema de irrigação tem se tornado uma prática importante para o suprimento de nutrientes na fruticultura. No entanto, é necessário estudar o efeito dessa aplicação sobre a fisiologia da bananeira a fim de aumentar a eficiência do uso desses insumos. O objetivo deste trabalho foi estudar os efeitos de doses de nitrogênio e potássio, via água de irrigação, sobre as características fisiológicas da bananeira, cultivar 'Prata-Anã', nos tabuleiros costeiros do Estado de Sergipe. O experimento foi conduzido no campo, utilizando um fatorial 4x4 com quatro blocos casualizados, na Estação Experimental da Universidade Federal de Sergipe. Foram testados dois fatores: nitrogênio (0; 250; 500 e 750, em kg ha-1 de N, na forma de uréia e potássio (0; 290; 580 e 870, em kg ha-1 de K2O, na forma de cloreto de potássio. Foram determinadas: a taxa de assimilação de CO², a transpiração, a condutância estomática, a concentração interna de CO² e as eficiências no uso da água e da carboxilação. A condutância estomática foi reduzida, principalmente, na fertilização com 700kg ha-1 de N e na ausência de K, afetando as trocas gasosas e, conseqüentemente, o processo fotossintético. Em situações de maior disponibilidade de potássio, as bananeiras necessitam de menores quantidades de nitrogênio para manutenção da eficiência no uso da água, como conseqüência da melhoria no ajuste estomático.Fertilizer application through the irrigation system, has become an important way to supply nutrients to fruit trees. However, it is necessary to study its effects on the banana tree physiology, in order to improve fertilizer use efficiency. The objective of this study was to evaluate doses of nitrogen and potassium through irrigation water, on the physiological characteristics of the banana tree, cv. 'Prata-Anã', in the coastal tablelands of Sergipe State. The experiment was established in the field

  14. The molecular interactions of buspirone analogues with the serotonin transporter.

    Science.gov (United States)

    Jarończyk, Małgorzata; Chilmonczyk, Zdzisław; Mazurek, Aleksander P; Nowak, Gabriel; Ravna, Aina W; Kristiansen, Kurt; Sylte, Ingebrigt

    2008-10-15

    A major problem with the selective serotonin reuptake inhibitors (SSRIs) is the delayed onset of action. A reason for that may be that the initial SSRI-induced increase in serotonin levels activates somatodendritic 5-HT(1A) autoreceptors, causing a decrease in serotonin release in major forebrain areas. It has been suggested that compounds combining inhibition of the serotonin transport protein with antagonistic effects on the 5-HT(1A) receptor will shorten the onset time. The anxiolytic drug buspirone is known as 5-HT(1A) partial agonist. In the present work, we are studying the inhibition of the serotonin transporter protein by a series of buspirone analogues by molecular modelling and by experimental affinity measurements. Models of the transporter protein were constructed using the crystal structure of the Escherichia coli major facilitator family transporter-LacY and the X-ray structure of the neurotransmitter symporter family (NSS) transporter-LeuT(Aa) as templates. The buspirone analogues were docked into both SERT models and the interactions with amino acids within the protein were analyzed. Two putative binding sites were identified on the LeuT(Aa) based model, one suggested to be a high-affinity site, and the other suggested to be a low-affinity binding site. Molecular dynamic simulations of the LacY based model in complex with ligands did not induce a helical architecture of the LacY based model into an arrangement more similar to that of the LeuT(Aa) based model.

  15. A case of serotonin syndrome associated with methadone overdose.

    Science.gov (United States)

    Martinez, Terry T; Martinez, Daniel N

    2008-01-01

    A chronic pain patient prescribed 20 mg of methadone per day was seen at the Emergency Department within one hour following a witnessed intentional 200 mg ingestion. In addition, he was taking the serotonin re-uptake inhibitor antidepressant drugs, sertraline and venlafaxine as prescribed. Methadone is also a serotonin re-uptake inhibitor which has been involved in serotonin toxicity reactions. Initially, no symptoms of narcotic overdose (depressed central nervous system, respiration, or blood pressure) could be distinguished, and the standard narcotic urine screen was negative. No decontamination or antagonist therapy was given, and the patient was discharged to a psychiatric unit for observation. At 5 hours post-ingestion he presented in a panic with hallucinations and elevated blood pressure, pulse, and respiration. These symptoms are characteristic of serotonin syndrome which is often described as mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. At 10 hours post-ingestion the patient was found unconscious. He had aspirated stomach contents into his lungs. His respiration, blood pressure, and pulse were all severely depressed. He never regained conciousness, and he died 5 days later. The medical examiner's finding was probable acute methadone intoxication. In this case serotonin syndrome appears to have opposed and delayed typical narcotic symptoms. Methadone has additional pharmacologic and toxicologic properties which may complicate the assessment and treatment in overdose situations.

  16. 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.

  17. The serotonin 5-HT7 receptors: two decades of research.

    Science.gov (United States)

    Gellynck, Evelien; Heyninck, Karen; Andressen, Kjetil W; Haegeman, Guy; Levy, Finn Olav; Vanhoenacker, Peter; Van Craenenbroeck, Kathleen

    2013-10-01

    Like most neurotransmitters, serotonin possesses a simple structure. However, the pharmacological consequences are more complex and diverse. Serotonin is involved in numerous functions in the human body including the control of appetite, sleep, memory and learning, temperature regulation, mood, behavior, cardiovascular function, muscle contraction, endocrine regulation, and depression. Low levels of serotonin may be associated with several disorders, namely increase in aggressive and angry behaviors, clinical depression, Parkinson's disease, obsessive-compulsive disorder, eating disorders, migraine, irritable bowel syndrome, tinnitus, and bipolar disease. These effects are mediated via different serotonin (5-HT) receptors. In this review, we will focus on the last discovered member of this serotonin receptor family, the 5-HT7 receptor. This receptor belongs to the G protein-coupled receptor superfamily and was cloned two decades ago. Later, different splice variants were described but no major functional differences have been described so far. All 5-HT7 receptor variants are coupled to Gαs proteins and stimulate cAMP formation. Recently, several interacting proteins have been reported, which can influence receptor signaling and trafficking.

  18. 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.

  19. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    Directory of Open Access Journals (Sweden)

    René Klysner

    2014-01-01

    Full Text Available The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.

  20. 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.

  1. Physiological effects in aromatherapy

    OpenAIRE

    2004-01-01

    The effects of aromas on humans are divided into physiological and psychological effects. The physiological effect acts directly on the physical organism, the psychological effect acts via the sense of smell or olfactory system, which in turn may cause a physiological effect. This paper reviews on the physiological effects which are used for the evaluation of the effects of aromas. Physiological parameters, i.e. heart rate blood pressure, electrodermal activity, electroencephalogram, slow pot...

  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...... and serotonin signaling in vivo in humans. We suggest that higher synaptic serotonin concentration, here indexed by lower 5-HT4r binding, supports HPA-axis dynamics, which in healthy volunteers is reflected by a robust CAR....

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

    OpenAIRE

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

    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...

  4. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    DEFF Research Database (Denmark)

    Klysner, René; Bjerg Bendsen, Birgitte; Hansen, Maja Soon

    2014-01-01

    The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.......The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine....

  5. Serotonin reciprocally regulates melanocortin neurons to modulate food intake.

    Science.gov (United States)

    Heisler, Lora K; Jobst, Erin E; Sutton, Gregory M; Zhou, Ligang; Borok, Erzsebet; Thornton-Jones, Zoe; Liu, Hong Yan; Zigman, Jeffrey M; Balthasar, Nina; Kishi, Toshiro; Lee, Charlotte E; Aschkenasi, Carl J; Zhang, Chen-Yu; Yu, Jia; Boss, Olivier; Mountjoy, Kathleen G; Clifton, Peter G; Lowell, Bradford B; Friedman, Jeffrey M; Horvath, Tamas; Butler, Andrew A; Elmquist, Joel K; Cowley, Michael A

    2006-07-20

    The neural pathways through which central serotonergic systems regulate food intake and body weight remain to be fully elucidated. We report that serotonin, via action at serotonin1B receptors (5-HT1BRs), modulates the endogenous release of both agonists and antagonists of the melanocortin receptors, which are a core component of the central circuitry controlling body weight homeostasis. We also show that serotonin-induced hypophagia requires downstream activation of melanocortin 4, but not melanocortin 3, receptors. These results identify a primary mechanism underlying the serotonergic regulation of energy balance and provide an example of a centrally derived signal that reciprocally regulates melanocortin receptor agonists and antagonists in a similar manner to peripheral adiposity signals.

  6. 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...... has in several previous studies been linked to an increased risk to develop mood disorders. We argue that long-lasting fluctuations in the cerebral serotonin transmission, which is regulated via the 5-HTT, are responsible for mediating responses to environmental changes based on an assessment...... 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...

  7. 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.

  8. Suppressive effect of paroxetine, a selective serotonin uptake inhibitor, on tetrahydrobiopterin levels and dopamine as well as serotonin turnover in the mesoprefrontal system of mice.

    Science.gov (United States)

    Miura, Hideki; Kitagami, Tomitsune; Ozaki, Norio

    2007-09-01

    Tetrahydrobiopterin (BH(4)) is a coenzyme of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), which are rate-limiting enzymes of monoamine biosynthesis. According to the monoamine hypothesis of depression, antidepressants will restore the function of the brain monoaminergic system and the BH(4) concentration. In the present study, we investigated the effect of paroxetine, a selective serotonin reuptake inhibitor (SSRI), on the BH(4) levels and dopamine (DA) and serotonin (5-HT) turnover in the mesoprefrontal system, incorporating two risk factors of depression, social isolation and acute environmental change. Male ddY mice (8W) were divided into two housing groups, i.e., group-housing (eight animals per cage; 28 days), and isolation-housing (one per cage; 28 days), being p.o.-administered paroxetine (5 or 10 mg/kg; days 15-28), and exposed to a 20-min novelty stress (day 28). The levels of BH(4), DA, homovanilic acid (HVA), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the prefrontal cortex and midbrain. In both the regions, novelty stress significantly increased BH(4) levels under the isolation-housing condition, whereas these levels were decreased under the group-housing condition. Thus, social isolation altered the neurochemical response to novelty stress. Paroxetine significantly decreased BH(4) levels under the isolation-housing condition, whereas decreased HVA/DA and 5-HIAA/5-HT ratios were observed under the group-housing condition. Thus, social isolation may have influenced the suppressive effects of paroxetine on BH(4) levels as well as exerted an influence on DA and 5-HT turnover. We replicated our recent findings that SSRI, fluvoxamine, suppressed BH(4) levels, as well as DA and 5-HT turnover in the mouse mesoprefrontal system.

  9. Obesity is associated with high serotonin 4 receptor availability in the brain reward circuitry

    DEFF Research Database (Denmark)

    Haahr, M. E.; Rasmussen, Peter Mondrup; Madsen, K.;

    2012-01-01

    The neurobiology underlying obesity is not fully understood. The neurotransmitter serotonin (5-HT) is established as a satiety-generating signal, but its rewarding role in feeding is less well elucidated. From animal experiments there is now evidence that the 5-HT4 receptor (5-HT4R) is involved...... in food intake, and that pharmacological or genetic manipulation of the receptor in reward-related brain areas alters food intake.Here, we used positron emission tomography in humans to examine the association between cerebral 5-HT4Rs and common obesity.We found in humans a strong positive association......'s food intake. They also suggest that pharmacological stimulation of the cerebral 5-HT4R may reduce reward-related overeating in humans....

  10. Quantitative Circulatory Physiology: an integrative mathematical model of human physiology for medical education.

    Science.gov (United States)

    Abram, Sean R; Hodnett, Benjamin L; Summers, Richard L; Coleman, Thomas G; Hester, Robert L

    2007-06-01

    We have developed Quantitative Circulatory Physiology (QCP), a mathematical model of integrative human physiology containing over 4,000 variables of biological interactions. This model provides a teaching environment that mimics clinical problems encountered in the practice of medicine. The model structure is based on documented physiological responses within peer-reviewed literature and serves as a dynamic compendium of physiological knowledge. The model is solved using a desktop, Windows-based program, allowing students to calculate time-dependent solutions and interactively alter over 750 parameters that modify physiological function. The model can be used to understand proposed mechanisms of physiological function and the interactions among physiological variables that may not be otherwise intuitively evident. In addition to open-ended or unstructured simulations, we have developed 30 physiological simulations, including heart failure, anemia, diabetes, and hemorrhage. Additional stimulations include 29 patients in which students are challenged to diagnose the pathophysiology based on their understanding of integrative physiology. In summary, QCP allows students to examine, integrate, and understand a host of physiological factors without causing harm to patients. This model is available as a free download for Windows computers at http://physiology.umc.edu/themodelingworkshop.

  11. 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…

  12. Serotonin-promoted elevation of ROS levels may lead to cardiac pathologies in diabetic rat

    OpenAIRE

    Ali Tahir; Shaheen Farhat; Mahmud Madiha; Waheed Hina; Ishtiaq Muhammad; Javed Qamar; Murtaza Iram

    2015-01-01

    Patients with diabetes mellitus (DM) develop tendencies toward heart disease. Hyperglycemia induces the release of serotonin from enterochromaffin cells (EC). Serotonin was observed to elevate reactive oxygen species (ROS) and downregulate antioxidant enzymes. As a result, elevated levels of serotonin could contribute to diabetic complications, including cardiac hypertrophy. In the present study, diabetes mellitus was induced in rats by alloxan administrati...

  13. 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...... 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...

  14. Serotonin 1A receptor binding and treatment response in late-life depression.

    Science.gov (United States)

    Meltzer, Carolyn Cidis; Price, Julie C; Mathis, Chester A; Butters, Meryl A; Ziolko, Scott K; Moses-Kolko, Eydie; Mazumdar, Sati; Mulsant, Benoit H; Houck, Patricia R; Lopresti, Brian J; Weissfeld, Lisa A; Reynolds, Charles F

    2004-12-01

    Depression in late life carries an increased risk of dementia and brittle response to treatment. There is growing evidence to support a key role of the serotonin type 1A (5-HT(1A)) receptor as a regulator of treatment response, particularly the 5-HT(1A) autoreceptor in the dorsal raphe nucleus (DRN). We used [11C]WAY 100635 and positron emission tomography (PET) to test our hypothesis that 5-HT(1A) receptor binding in the DRN and prefrontal cortex is altered in elderly depressives and that these measures relate to treatment responsivity. We studied 17 elderly subjects with untreated (nonpsychotic, nonbipolar) major depression (four men, 13 women; mean age: 71.4+/-5.9) and 17 healthy control subjects (eight men, nine women; mean age: 70.0+/-6.7). Patients were subsequently treated with paroxetine as part of a clinical trial of maintenance therapies in geriatric depression. [11C]WAY 100635 PET imaging was acquired and binding potential (BP) values derived using compartmental modeling. We observed significantly diminished [11C]WAY 100635 binding in the DRN in depressed (BP = 2.31+/-0.90) relative to control (BP = 3.69+/-1.56) subjects (p = 0.0016). Further, the DRN BP was correlated with pretreatment Hamilton Depression Rating Scores (r = 0.60, p = 0.014) in the depressed cohort. A trend level correlation between DRN binding and time to remission (r = 0.52, p = 0.067) was observed in the 14 depressed patients for whom these data were available. Our finding of decreased [11C]WAY 100635 binding in the brainstem region of the DRN in elderly depressed patients supports evidence of altered 5-HT(1A) autoreceptor function in depression. Further, this work indicates that dysfunction in autoreceptor activity may play a central role in the mechanisms underlying treatment response to selective serotonin reuptake inhibitors in late-life depression.

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

    Science.gov (United States)

    Hasler, F; Studerus, E; Lindner, K; Ludewig, S; Vollenweider, F X

    2009-11-01

    Serotonin (5-HT) release is the primary pharmacological mechanism of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') action in the primate brain. Dopamine release and direct stimulation of dopamine D2 and serotonin 5-HT2A receptors also contributes to the overall action of MDMA. The role of 5-HT1A receptors in the human psychopharmacology of MDMA, however, has not yet been elucidated. In order to reveal the consequences of manipulation at the 5-HT1A receptor system on cognitive and subjective effects of MDMA, a receptor blocking study using the mixed beta-adrenoreceptor blocker/5-HT1A antagonist pindolol was performed. Using a double-blind, placebo-controlled within-subject design, 15 healthy male subjects were examined under placebo (PL), 20 mg pindolol (PIN), MDMA (1.6 mg/kg b.wt.), MDMA following pre-treatment with pindolol (PIN-MDMA). Tasks from the Cambridge Neuropsychological Test Automated Battery were used for the assessment of cognitive performance. Psychometric questionnaires were applied to measure effects of treatment on core dimensions of Altered States of Consciousness, mood and state anxiety. Compared with PL, MDMA significantly impaired sustained attention and visual-spatial memory, but did not affect executive functions. Pre-treatment with PIN did not significantly alter MDMA-induced impairment of cognitive performance and only exerted a minor modulating effect on two psychometric scales affected by MDMA treatment ('positive derealization' and 'dreaminess'). Our findings suggest that MDMA differentially affects higher cognitive functions, but does not support the hypothesis from animal studies, that some of the MDMA effects are causally mediated through action at the 5-HT1A receptor system.

  16. Smolt physiology and endocrinology

    Science.gov (United States)

    McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

    2013-01-01

    Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.

  17. Serotonin transporter occupancy in rats exposed to serotonin reuptake inhibitors in utero or via breast milk.

    Science.gov (United States)

    Capello, Catherine F; Bourke, Chase H; Ritchie, James C; Stowe, Zachary N; Newport, D Jeffrey; Nemeroff, Amanda; Owens, Michael J

    2011-10-01

    Rigorous data regarding fetal central nervous system (CNS) exposure after antidepressant exposure are sparse. The magnitude of serotonin reuptake inhibitor (SRI) CNS exposure was measured in three groups of rats using ex vivo autoradiography of the serotonin transporter (SERT): 1) in utero, 2) postnatal clearance after birth, and 3) exposure through lactation. Rats were exposed to one of five SRI-type antidepressants (escitalopram, fluoxetine, paroxetine, sertraline, and venlafaxine) administered continuously via osmotic minipumps to pregnant or nursing dams. Dam dosing was adjusted to reflect the 50th and 85th percentiles of serum concentrations observed in pregnant women. Embryonic day 21 rat pups exposed in utero exhibited >80% SERT occupancy in brain tissue, which is equivalent to that of the pregnant dam and similar to that reported for human pharmacotherapy. Venlafaxine was the exception with occupancies ranging from 61 to 92% across different litters. The magnitude of SERT occupancy is essentially equivalent between dams and fetuses. By postnatal day 4, high SERT occupancy was observed only in fluoxetine-exposed pups (41-92% occupancy). Significantly less, but measurable, exposure occurred via breast milk exposure even in the absence of detectable drug concentrations in nursing pup sera. Pups exposed to SRIs via breast milk for 3 or 7 days exhibited varying SERT occupancies (0-57% depending on the individual medication and dam dose). These data highlight the need for animal modeling of fetal and nursing infant drug exposure using clinically meaningful dosing strategies and appropriate CNS measures to develop rational treatment guidelines that systematically minimize fetal and neonatal medication exposure in humans.

  18. 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

  19. The serotonin transporter: Examination of the changes in transporter affinity induced by ligand binding

    Energy Technology Data Exchange (ETDEWEB)

    Humphreys, C.J.

    1989-01-01

    The plasmalemmal serotonin transporter uses transmembrane gradients of Na{sup +}, Cl{sup {minus}} and K{sup +} to accumulate serotonin within blood platelets. Transport is competitively inhibited by the antidepressant imipramine. Like serotonin transport, imipramine binding requires Na{sup +}. Unlike serotonin, however, imipramine does not appear to be transported. To gain insight into the mechanism of serotonin transport the author have analyzed the influences of Na{sup +} and Cl{sup {minus}}, the two ions cotransported with serotonin, on both serotonin transport and the interaction of imipramine and other antidepressant drugs with the plasmalemmal serotonin transporter of human platelets. Additionally, the author have synthesized, purified and characterized the binding of 2-iodoimipramine to the serotonin transporter. Finally, the author have conducted a preliminary study of the inhibition of serotonin transport and imipramine binding produced by dicyclohexylcarbodiimide. My results reveal many instances of positive heterotropic cooperativity in ligand binding to the serotonin transporter. Na{sup +} binding enhances the transporters affinity for imipramine and several other antidepressant drugs, and also increases the affinity for Cl{sup {minus}}. Cl{sup {minus}} enhances the transporters affinity for imipramine, as well as for Na{sup +}. At concentrations in the range of its K{sub M} for transport serotonin is a competitive inhibitor of imipramine binding. At much higher concentrations, however, serotonin also inhibits imipramines dissociation rate constant. This latter effect which is Na{sup +}-independent and species specific, is apparently produced by serotonin binding at a second, low affinity site on, or near, the transporter complex. Iodoimipramine competitively inhibit both ({sup 3}H)imipramine binding and ({sup 3}H)serotonin transport.

  20. Assessment of the Potential Role of Tryptophan as the Precursor of Serotonin and Melatonin for the Aged Sleep-wake Cycle and Immune Function: Streptopelia Risoria as a Model

    Directory of Open Access Journals (Sweden)

    Sergio D. Paredes

    2009-01-01

    Full Text Available In the present review we summarize the relationship between the amino acid, tryptophan, the neurotransmitter, serotonin, and the indole, melatonin, with the rhythms of sleep/wake and the immune response along with the possible connections between the alterations in these rhythms due to aging and the so-called “serotonin and melatonin deficiency state.” The decrease associated with aging of the brain and circulating levels of serotonin and melatonin seemingly contributes to the alterations of both the sleep/wake cycle and the immune response that typically accompany old age. The supplemental administration of tryptophan, e.g. the inclusion of tryptophan-enriched food in the diet, might help to remediate these age- related alterations due to its capacity of raise the serotonin and melatonin levels in the brain and blood. Herein, we also summarize a set of studies related to the potential role that tryptophan, and its derived product melatonin, may play in the restoration of the aged circadian rhythms of sleep/wake and immune response, taking the ringdove (Streptopelia risoria as a suitable model.

  1. 5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders.

    Science.gov (United States)

    Ciranna, Lucia; Catania, Maria Vincenza

    2014-01-01

    Serotonin type 7 receptors (5-HT7) are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD), including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD.

  2. 5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Lucia eCiranna

    2014-08-01

    Full Text Available Serotonin type 7 receptors (5-HT7 are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD, including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD.

  3. Potential of [{sup 11}C]DASB for measuring endogenous serotonin with PET: binding studies

    Energy Technology Data Exchange (ETDEWEB)

    Lundquist, Pinelopi [Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Uppsala University, SE-751 24 Uppsala (Sweden) and Hospital Pharmacy, University Hospital, SE-751 85 Uppsala (Sweden)]. E-mail: pinelopi.lundquist@farmbio.uu.se; Wilking, Helena [Uppsala Imanet, SE-751 09 Uppsala (Sweden); Hoeglund, A. Urban [Uppsala Imanet, SE-751 09 Uppsala (Sweden); Sandell, Johan [Uppsala Imanet, SE-751 09 Uppsala (Sweden); Bergstroem, Mats [Uppsala Imanet, SE-751 09 Uppsala (Sweden); Hartvig, Per [Hospital Pharmacy, University Hospital, SE-751 85 Uppsala (Sweden); Langstroem, Bengt [Uppsala Imanet, SE-751 09 Uppsala (Sweden)

    2005-02-01

    The serotonin transporter radioligand [{sup 11}C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, or [{sup 11}C]DASB, was examined in order to assess its potential for measuring fluctuations in endogenous serotonin concentrations with positron emission tomography. Binding characteristics of [{sup 11}C]DASB and the propensity for serotonin to displace the tracer were explored in rat brain homogenates. Experiments showed that serotonin displaced [{sup 11}C]DASB in vitro. Ex vivo experiments performed after tranylcypromine injection (3 or 15 mg/kg) showed a dose-dependent trend in radioactivity uptake and suggested that serotonin may compete with [{sup 11}C]DASB for transporter binding.

  4. Physiological Information Database (PID)

    Science.gov (United States)

    EPA has developed a physiological information database (created using Microsoft ACCESS) intended to be used in PBPK modeling. The database contains physiological parameter values for humans from early childhood through senescence as well as similar data for laboratory animal spec...

  5. Interferon-γ is increased in the gut of patients with irritable bowel syndrome and modulates serotonin metabolism.

    Science.gov (United States)

    Barbaro, Maria Raffaella; Di Sabatino, Antonio; Cremon, Cesare; Giuffrida, Paolo; Fiorentino, Michelangelo; Altimari, Annalisa; Bellacosa, Lara; Stanghellini, Vincenzo; Barbara, Giovanni

    2016-03-15

    Mucosal immune activation and altered serotonin metabolism participate in the pathophysiology of irritable bowel syndrome (IBS). However, the reciprocal interplay between these two systems remains unknown. We evaluated the expression and release of interferon (IFN)-γ from the colonic mucosa of patients with IBS and its impact on serotonin reuptake transporter (SERT) gene expression in Caco-2 cells. qPCR was used to evaluate IFN-γ gene expression in colonic mucosal biopsies, whereas IFN-γ protein amount was assessed by ELISA. Colonic T box expressed in T cells (T-bet) and phosphorylated signal transducer and activator of transcription 4 protein amount were evaluated by Western blot. The impact of colonic mucosal mediators on SERT gene expression was evaluated in Caco-2 cells using qPCR. IFN-γ receptor was silenced in Caco-2 cells to determine the effect of IFN-γ released by mucosal biopsies. Compared with asymptomatic controls (ACs), the expression of IFN-γ gene and its transcription factor T-bet were markedly increased in the colonic mucosa of patients with IBS. Compared with ACs, IFN-γ protein tissue levels and its release by mucosal biopsies were significantly increased in IBS. The exposure of Caco-2 cells to IBS supernatants induced a significant decrease in SERT gene expression, independently of IBS subtypes, compared with AC mucosal supernatants. In Caco-2 cells, IFN-γ receptor silencing reversed the reduction of SERT expression evoked by IBS supernatants vs. nonsilenced cell lines. IFN-γ gene, its transcription factor T-bet, IFN-γ protein expression, and its release are increased in the colonic mucosa of patients with IBS and downregulate SERT gene expression in vitro. These results suggest that IFN-γ downregulates SERT expression, hence likely playing a role in altered serotonin metabolism of patients with IBS.

  6. Stimulus generalization by fenfluramine in a quipazine-ketanserin drug discrimination is not dependent on indirect serotonin release.

    Science.gov (United States)

    Smith, Randy L; Gresch, Paul J; Barrett, Robert J; Sanders-Bush, Elaine

    2002-05-01

    The purpose of this study was to determine if animals trained to discriminate a serotonin2A (5-HT2A) receptor agonist from a 5-HT2A receptor antagonist would also be sensitive to alterations in serotonin neurotransmission brought about by 5-HT reuptake inhibitors and releasers. Previous work from our laboratory has shown that the quipazine-ketanserin discrimination is mediated solely by the 5-HT2A receptor, thus providing a behavioral continuum of 5-HT2A receptor function. Rats were trained to discriminate quipazine (0.35 mg/kg) from ketanserin (1.0 mg/kg) on a variable interval-30 schedule of reinforcement. Following acquisition, substitution tests were conducted with the training drug, quipazine, and agents that have been shown to alter the synaptic levels of 5-HT, including fenfluramine, norfenfluramine, 5-methoxy-6-methyl-2-aminoindan (MMAI) and fluoxetine. All compounds substituted, except fluoxetine. Antagonist tests with mianserin and MDL 100,907 indicated that fenfluramine's and MMAI's substitution for quipazine was mediated by the 5-HT2A receptor. Animals were pretreated with PCPA to determine whether 5-HT release or direct agonism mediated the discriminative stimulus effects of fenfluramine and MMAI. PCPA blocked the substitution of MMAI but not of fenfluramine for quipazine. Analysis of 3H-IP formation in cells showed that norfenfluramine dose-dependently stimulated phosphoinositide hydrolysis to levels similar to that of serotonin and quipazine. These results indicate that fenfluramine's substitution for quipazine in rats trained on a quipazine-ketanserin discrimination are due to direct agonism at the 5-HT2A receptor likely mediated by norfenfluramine, an active metabolite.

  7. Clinical use of the determination of serotonin in whole blood

    NARCIS (Netherlands)

    Kremer, HP; Goekoop, J G; Van Kempen, G M

    1990-01-01

    Whole blood serotonin (5-hydroxytryptamine, 5-HT) was assayed, and factors possibly influencing 5-HT content were investigated in healthy controls. No significant circadian rhythm or effect of dexamethasone or meals was observed. After use of fluvoxamine, a specific 5-HT reuptake inhibitor, the whol

  8. 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

  9. 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...

  10. Serotonin 2A Receptors, Citalopram and Tryptophan-Depletion

    DEFF Research Database (Denmark)

    Macoveanu, Julian; Hornboll, Bettina; Elliott, Rebecca;

    2013-01-01

    in serotonergic regulation of response inhibition. In 24 healthy adults, we used (18)F-altanserin positron emission tomography to assess cerebral 5-HT(2A) receptors, which have been related to impulsivity. We then investigated the impact of two acute manipulations of brain serotonin levels on behavioral...

  11. A role for serotonin in piglet preweaning mortality

    Science.gov (United States)

    Improving piglet survivability rate is of high priority for swine production as well as for piglet well-being. Dysfunction in the serotonin system has been associated with growth deficiencies, infant mortality or failure to thrive (FTT) in human infants. The aim of this study was to examine the role...

  12. Serotonin receptors: Subtypes, functional responses and therapeutic relevance

    NARCIS (Netherlands)

    P.R. Saxena (Pramod Ranjan)

    1995-01-01

    textabstractRecent, rapid progress in the molecular biology of serotonin (5-HT) receptors requires conceptual re-thinking with respect to receptor classification. Thus, based on operational criteria (agonist and antagonist rank order), as well as transduction mechanisms involved and the structure of

  13. Linezolid and Rasagiline - A culprit for serotonin syndrome

    Directory of Open Access Journals (Sweden)

    Mohamed Hisham

    2016-01-01

    Full Text Available A 65-year-old female patient was admitted to the hospital for cellulitis. She had a history of diabetes mellitus and parkinsonism on levodopa/carbidopa, rasagiline, ropinirole, trihexyphenidyl, amantadine, metformin, and glipizide. We present here a case of rare incidence of serotonin syndrome associated with linezolid and rasagiline.

  14. Increased hypothalamic serotonin turnover in inflammation-induced anorexia

    NARCIS (Netherlands)

    Dwarkasing, J.T.; Witkamp, R.F.; Boekschoten, M.V.; Laak, ter M.C.; Heins, M.S.; Norren, van K.

    2016-01-01

    Background: Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections b

  15. Serotonin transporter genotype, salivary cortisol, neuroticism and life events

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla; Kessing, Lars Vedel

    2014-01-01

    OBJECTIVE: To investigate if cortisol alone or in interaction with other risk factors (familial risk, the serotonin transporter genotype, neuroticism and life events (LEs)) predicts onset of psychiatric disorder in healthy individuals at heritable risk. MATRIAL AND METHODS: In a high-risk study...

  16. Pressure Suppresses Serotonin Release by Guinea Pig Striatal Synaptosomes

    Science.gov (United States)

    1988-01-01

    cuerpo estriado-de conejillos de Indias.-Undersea Biorned Res 19,98; 15(2):69-77. La exposici6n a presiones altas produce cambios neurol6gicos en...sistemna serotonin~rgico en estos sintortias, nuestro’itr~s residi6 en el estudic de Ia Iiberaci6n de serotonina a presiones altas. SC empleo

  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. 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

  19. Linezolid and Rasagiline - A culprit for serotonin syndrome

    OpenAIRE

    Mohamed Hisham; Mundalipalayam N Sivakumar; Nandakumar, V; S Lakshmikanthcharan

    2016-01-01

    A 65-year-old female patient was admitted to the hospital for cellulitis. She had a history of diabetes mellitus and parkinsonism on levodopa/carbidopa, rasagiline, ropinirole, trihexyphenidyl, amantadine, metformin, and glipizide. We present here a case of rare incidence of serotonin syndrome associated with linezolid and rasagiline.

  20. 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.

  1. 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.

  2. 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

  3. Serotonin transporter evolution and impact of polymorphic transcriptional regulation

    DEFF Research Database (Denmark)

    Søeby, Karen; Larsen, Svend Ask; Olsen, Line;

    2005-01-01

    The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants...

  4. The serotonin 5-HT3 receptor: a novel neurodevelopmental target.

    NARCIS (Netherlands)

    Engel, M.; Smidt, M.P.; van Hooft, J.A.

    2013-01-01

    Serotonin (5-hydroxytryptamine, 5-HT), next to being an important neurotransmitter, recently gained attention as a key-regulator of pre- and postnatal development in the mammalian central nervous system (CNS). Several receptors for 5-HT are expressed in the developing brain including a ligand-gated

  5. Purification and fluorescent labeling of the human serotonin transporter

    DEFF Research Database (Denmark)

    Rasmussen, Søren G F; Gether, Ulrik

    2005-01-01

    To establish a purification procedure for the human serotonin transporter (hSERT) we expressed in Sf9 insect cells an epitope-tagged version of the transporter containing a FLAG epitope at the N-terminus and a polyhistidine tail at the C-terminus (FLAG-hSERT-12H). For purification, the transporter...

  6. 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.

  7. Chewing Over Physiology Integration

    Science.gov (United States)

    Abdulkader, Fernando; Azevedo-Martins, Anna Karenina; de Arcisio Miranda, Manoel; Brunaldi, Kellen

    2005-01-01

    An important challenge for both students and teachers of physiology is to integrate the differentareas in which physiological knowledge is didactically divided. In developing countries, such an issue is even more demanding, because budget restrictions often affect the physiology program with laboratory classes being the first on the list when it…

  8. 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.

  9. Brain serotonin system in the coordination of food intake and body weight.

    Science.gov (United States)

    Lam, Daniel D; Garfield, Alastair S; Marston, Oliver J; Shaw, Jill; Heisler, Lora K

    2010-11-01

    An inverse relationship between brain serotonin and food intake and body weight has been known for more than 30 years. Specifically, augmentation of brain serotonin inhibits food intake, while depletion of brain serotonin promotes hyperphagia and weight gain. Through the decades, serotonin receptors have been identified and their function in the serotonergic regulation of food intake clarified. Recent refined genetic studies now indicate that a primary mechanism through which serotonin influences appetite and body weight is via serotonin 2C receptor (5-HT(2C)R) and serotonin 1B receptor (5-HT(1B)R) influencing the activity of endogenous melanocortin receptor agonists and antagonists at the melanocortin 4 receptor (MC4R). However, other mechanisms are also possible and the challenge of future research is to delineate them in the complete elucidation of the complex neurocircuitry underlying the serotonergic control of appetite and body weight.

  10. Suspected serotonin syndrome in a patient being treated with methylene blue for ifosfamide encephalopathy.

    Science.gov (United States)

    McDonnell, A M; Rybak, I; Wadleigh, M; Fisher, D C

    2012-12-01

    Methylene blue has been used not only as a diagnostic agent, but also as an agent in the treatment of ifosfamide-induced encephalopathy (IIE) for several years. Recently, several cases of suspected serotonin syndrome have been reported in patients who received methylene blue in combination with serotonin active agents. Rodent models have revealed that methylene blue is a potent, reversible inhibitor of monoamine oxidase A. It is well known that serotonin active drugs, in combination with monoamine oxidase inhibitors can produce profound serotonin syndrome. To date, cases of serotonin syndrome, which resulted from concurrent methylene blue and serotonin active agents, have been published in the anesthesia literature. We report the first known case of serotonin syndrome in a patient receiving methylene blue for IIE.

  11. 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

  12. On the possible quantum role of serotonin in consciousness.

    Science.gov (United States)

    Tonello, Lucio; Cocchi, Massimo; Gabrielli, Fabio; Tuszynski, Jack A

    2015-09-01

    Cell membrane's fatty acids (FAs) have been carefully investigated in neurons and platelets in order to study a possible connection to psychopathologies. An important link between the FA distribution and membrane dynamics appears to emerge with the cytoskeleton dynamics. Microtubules (MTs) in particular have been implicated in some recent quantum consciousness models and analyses. The recently proposed quantum model of Craddock et al. (2014) states that MTs possess structural and functional characteristics that are consistent with collective quantum coherent excitations in the aromatic groups of their tryptophan residues. These excitations are consistent with a clocking mechanism on a sub-nanosecond scale. This mechanism and analogous phenomena in light-harvesting complexes in plants and bacteria, are induced by photons and have been touted as evidence of quantum processes in biology. A possible source of intra-cellular photons could be membrane lipid peroxidation processes, so the FA profile could then be linked to the bio-photon emission. The model presented here suggests new ways to understand the role serotonin plays in relation to FAs. In plants, tryptophan conversion of light to exciton energy can participate in the directional orientation of leaves toward sunlight. Since serotonin is structurally similar to tryptophan, in the human brain, neurons could use tryptophan to capture photons and also use serotonin to initiate movement toward the source of light. Hence, we postulate two possible new roles for serotonin: (1) as an antioxidant, in order to counter-balance the oxidative effect of FAs, and (2) to participate in quantum interactions with MTs, in the same way as anesthetics and psychoactive compounds have been recently shown to act. In this latter case, the FA profile could provide an indirect measure of serotonin levels.

  13. 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

  14. 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.

  15. Serotonin and GI Disorders: An Update on Clinical and Experimental Studies.

    Science.gov (United States)

    Manocha, Marcus; Khan, Waliul I

    2012-04-26

    The gastrointestinal (GI) tract is the largest producer of serotonin (5-hydroxytryptamine (5-HT)) in the body, and as such it is intimately connected with GI function and physiology. 5-HT produced by enterochromaffin (EC) cells is an important enteric mucosal signaling molecule and has been implicated in a number of GI diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. This review will focus on what is known of basic 5-HT physiology and also on the emerging evidence for its novel role in activation of immune response and inflammation in the gut. Utilizing pubmed.gov, search terms such as "5-HT," "EC cell," and "colitis," as well as pertinent reviews, were used to develop a brief overview of EC cell biology and the association between 5-HT and various GI disorders. It is the aim of this review to provide the readers with an update on EC cell biology and current understanding on the role of 5-HT in GI disorders specifically in inflammatory conditions.

  16. The Effects of Sertraline administration from adolescence to adulthood on physiological and emotional development in prenatally stressed rats of both sexes

    Directory of Open Access Journals (Sweden)

    Inês ePereira-Figueiredo

    2014-08-01

    Full Text Available Sertraline is a clinically effective Selective Serotonin Reuptake Inhibitor known to increase and stabilize serotonin levels. This neurotransmitter plays an important role in adolescent brain development in both rodents and humans, and its dysregulation has been correlated with deficits in behaviour and emotional regulation. Since prenatal stress may disturb serotoninergic homeostasis, the aim of this study was to examine the long-lasting effects of exposure to sertraline throughout adolescence on behavioural and physiological developmental parameters in prenatally stressed Wistar rats. Sertraline was administered (5mg/kg/day p.o. from the age of 1-3 months to half of the progeny, of both sexes, of gestating dams stressed by use of a restraint (PS or not stressed. Our data reveal that long-term sertraline treatment slightly reduced weight gain in both sexes, but reversed the developmental disturbed ‘catch-up’ growth found in PS females.Neither prenatal stress nor Sertraline treatment induced remarkable alterations in behaviour and had no effects on mean startle reflex values. However, a sex-dependent effects of PS was found: in males the PS paradigm slightly increased anxiety-like behaviour in the open field, while in females, it impaired startle habituation. In both cases, sertraline treatment reversed the phenomena. Additionally, the PS animals exhibited a disturbed leukocyte profile in both sexes, which was reversed by sertraline.The present findings are evidence that continuous sertraline administration from adolescence through adulthood is safe in rodents and lessens the impact of prenatal stress in rats.

  17. Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation

    Science.gov (United States)

    Layunta, Elena; Grasa, Laura; Castro, Marta; Pardo, Julián; Gomollón, Fernando; Mesonero, José E.

    2016-01-01

    TLR2 is a microbiota recognition receptor that has been described to contribute to intestinal homeostasis and to ameliorate inflammatory intestinal injury. In this context, serotonin (5-HT) has shown to be an essential intestinal physiological neuromodulator that is also involved in intestinal inflammatory diseases. Since the interaction between TLR2 activation and the intestinal serotoninergic system remains non-investigated, our main aim was to analyze the effect of TLR2 on intestinal serotonin transporter (SERT) activity and expression and the intracellular pathways involved. Caco-2/TC7 cells were used to analyze SERT and TLR2 molecular expression and SERT activity by measuring 5-HT uptake. The results showed that apical TLR2 activation inhibits SERT activity in Caco-2/TC7 cells mainly by reducing SERT protein level either in the plasma membrane, after short-term TLR2 activation or in both the plasma membrane and cell lysate, after long-term activation. cAMP/PKA pathway appears to mediate short-term inhibitory effect of TLR2 on SERT; however, p38 MAPK pathway has been shown to be involved in both short- and long-term TLR2 effect. Reciprocally, 5-HT long-term treatment yielded TLR2 down regulation in Caco-2/TC7 cells. Finally, results from in vivo showed an augmented intestinal SERT expression in mice Tlr2-/-, thus confirming our inhibitory effect of TLR2 on intestinal SERT in vitro. The present work infers that TLR2 may act in intestinal pathophysiology, not only by its inherent innate immune role, but also by regulating the intestinal serotoninergic system. PMID:28033388

  18. Electrical coupling between the human serotonin transporter and voltage-gated Ca(2+) channels.

    Science.gov (United States)

    Ruchala, Iwona; Cabra, Vanessa; Solis, Ernesto; Glennon, Richard A; De Felice, Louis J; Eltit, Jose M

    2014-07-01

    Monoamine transporters have been implicated in dopamine or serotonin release in response to abused drugs such as methamphetamine or ecstasy (MDMA). In addition, monoamine transporters show substrate-induced inward currents that may modulate excitability and Ca(2+) mobilization, which could also contribute to neurotransmitter release. How monoamine transporters modulate Ca(2+) permeability is currently unknown. We investigate the functional interaction between the human serotonin transporter (hSERT) and voltage-gated Ca(2+) channels (CaV). We introduce an excitable expression system consisting of cultured muscle cells genetically engineered to express hSERT. Both 5HT and S(+)MDMA depolarize these cells and activate the excitation-contraction (EC)-coupling mechanism. However, hSERT substrates fail to activate EC-coupling in CaV1.1-null muscle cells, thus implicating Ca(2+) channels. CaV1.3 and CaV2.2 channels are natively expressed in neurons. When these channels are co-expressed with hSERT in HEK293T cells, only cells expressing the lower-threshold L-type CaV1.3 channel show Ca(2+) transients evoked by 5HT or S(+)MDMA. In addition, the electrical coupling between hSERT and CaV1.3 takes place at physiological 5HT concentrations. The electrical coupling between monoamine neurotransmitter transporters and Ca(2+) channels such as CaV1.3 is a novel mechanism by which endogenous substrates (neurotransmitters) or exogenous substrates (like ecstasy) could modulate Ca(2+)-driven signals in excitable cells.

  19. Functional Selectivity and Antidepressant Activity of Serotonin 1A Receptor Ligands

    Directory of Open Access Journals (Sweden)

    Zdzisław Chilmonczyk

    2015-08-01

    Full Text Available Serotonin (5-HT is a monoamine neurotransmitter that plays an important role in physiological functions. 5-HT has been implicated in sleep, feeding, sexual behavior, temperature regulation, pain, and cognition as well as in pathological states including disorders connected to mood, anxiety, psychosis and pain. 5-HT1A receptors have for a long time been considered as an interesting target for the action of antidepressant drugs. It was postulated that postsynaptic 5-HT1A agonists could form a new class of antidepressant drugs, and mixed 5-HT1A receptor ligands/serotonin transporter (SERT inhibitors seem to possess an interesting pharmacological profile. It should, however, be noted that 5-HT1A receptors can activate several different biochemical pathways and signal through both G protein-dependent and G protein-independent pathways. The variables that affect the multiplicity of 5-HT1A receptor signaling pathways would thus result from the summation of effects specific to the host cell milieu. Moreover, receptor trafficking appears different at pre- and postsynaptic sites. It should also be noted that the 5-HT1A receptor cooperates with other signal transduction systems (like the 5-HT1B or 5-HT2A/2B/2C receptors, the GABAergic and the glutaminergic systems, which also contribute to its antidepressant and/or anxiolytic activity. Thus identifying brain specific molecular targets for 5-HT1A receptor ligands may result in a better targeting, raising a hope for more effective medicines for various pathologies.

  20. Physiological effects in aromatherapy

    Directory of Open Access Journals (Sweden)

    Tapanee Hongratanaworakit

    2004-01-01

    Full Text Available The effects of aromas on humans are divided into physiological and psychological effects. The physiological effect acts directly on the physical organism, the psychological effect acts via the sense of smell or olfactory system, which in turn may cause a physiological effect. This paper reviews on the physiological effects which are used for the evaluation of the effects of aromas. Physiological parameters, i.e. heart rate blood pressure, electrodermal activity, electroencephalogram, slow potential brain waves (contingent negativevariation, and eye blink rate or pupil functions, are used as indices for the measurement of the aroma effects

  1. Doppler radar physiological sensing

    CERN Document Server

    Lubecke, Victor M; Droitcour, Amy D; Park, Byung-Kwon; Singh, Aditya

    2016-01-01

    Presents a comprehensive description of the theory and practical implementation of Doppler radar-based physiological monitoring. This book includes an overview of current physiological monitoring techniques and explains the fundamental technology used in remote non-contact monitoring methods. Basic radio wave propagation and radar principles are introduced along with the fundamentals of physiological motion and measurement. Specific design and implementation considerations for physiological monitoring radar systems are then discussed in detail. The authors address current research and commercial development of Doppler radar based physiological monitoring for healthcare and other applications.

  2. The physiological and biochemical bases of functional brain imaging

    OpenAIRE

    2007-01-01

    Functional brain imaging is based on the display of computer-derived images of changes in physiological and/or biochemical functions altered by activation or depression of local functional activities in the brain. This article reviews the physiological and biochemical mechanisms involved.

  3. Applied Cardiovascular Physiology in Dogs with Heart Failure

    Directory of Open Access Journals (Sweden)

    Iván Álvarez Ramírez

    2011-06-01

    Full Text Available Congestive heart failure is related to abnormal ventricular contraction and relaxation. Recent publications show that the alteration of systolic and diastolic function coexists in most patients with heart diseases. There are currently several ambiguities in the daily use of clinical and physiological terms regarding this topic. This paper aims to review certain physiological concepts of the cardiovascular system.

  4. Applied physiology of cycling.

    Science.gov (United States)

    Faria, I E

    1984-01-01

    Historically, the bicycle has evolved through the stages of a machine for efficient human transportation, a toy for children, a finely-tuned racing machine, and a tool for physical fitness development, maintenance and testing. Recently, major strides have been made in the aerodynamic design of the bicycle. These innovations have resulted in new land speed records for human powered machines. Performance in cycling is affected by a variety of factors, including aerobic and anaerobic capacity, muscular strength and endurance, and body composition. Bicycle races range from a 200m sprint to approximately 5000km. This vast range of competitive racing requires special attention to the principle of specificity of training. The physiological demands of cycling have been examined through the use of bicycle ergometers, rollers, cycling trainers, treadmill cycling, high speed photography, computer graphics, strain gauges, electromyography, wind tunnels, muscle biopsy, and body composition analysis. These techniques have been useful in providing definitive data for the development of a work/performance profile of the cyclist. Research evidence strongly suggests that when measuring the cyclist's aerobic or anaerobic capacity, a cycling protocol employing a high pedalling rpm should be used. The research bicycle should be modified to resemble a racing bicycle and the cyclist should wear cycling shoes. Prolonged cycling requires special nutritional considerations. Ingestion of carbohydrates, in solid form and carefully timed, influences performance. Caffeine appears to enhance lipid metabolism. Injuries, particularly knee problems which are prevalent among cyclists, may be avoided through the use of proper gearing and orthotics. Air pollution has been shown to impair physical performance. When pollution levels are high, training should be altered or curtailed. Effective training programmes simulate competitive conditions. Short and long interval training, blended with long

  5. HPLC analysis of serotonin, tryptamine, tyramine, and the hydroxycinnamic acid amides of serotonin and tyramine in food vegetables.

    Science.gov (United States)

    Ly, Dalin; Kang, Kiyoon; Choi, Jang-Yeol; Ishihara, Atsushi; Back, Kyoungwhan; Lee, Seong-Gene

    2008-06-01

    Biogenic monoamines such as serotonin, tryptamine, and tyramine function as neurotransmitters and mitogenic factors in animals and are involved in flowering, morphogenesis, and protection from and adaptation to environmental changes in plants. In plants, serotonin and tyramine are conjugated to form phenolic compounds via thioester linkages during the synthesis of hydroxycinnamic acid amides, including p-coumaroylserotonin (CS), feruloylserotonin (FS), p-coumaroyltyramine (CT), and feruloyltyramine (FT). In this study, we determined the amounts of the biogenic monoamines CS, FS, CT, and FT in commonly consumed vegetables using high-performance liquid chromatography. Serotonin, tryptamine, and tyramine were detected in all vegetables tested. The serotonin levels ranged from 1.8 to 294 microg/g of dry weight, the tryptamine levels ranged from 0.8 to 372 microg/g of dry weight, and the tyramine levels ranged from 1.4 to 286 microg/g of dry weight. The highest serotonin and tryptamine contents were found in tomato and cherry tomato (140.3-222 microg/g of dry weight), while paprika and green pepper had higher tyramine contents than the other vegetables (286 and 141.5 microg/g of dry weight, respectively). Overall, the levels of CS, FS, CT, and FT ranged from 0.03 to 13.8 microg/g of dry weight, with green onion possessing the highest levels of CS (0.69 microg/g of dry weight), FT (1.99 microg/g of dry weight), and CT (13.85 microg/g of dry weight).

  6. Cortical serotonin and norepinephrine denervation in parkinsonism: preferential loss of the beaded serotonin innervation.

    Science.gov (United States)

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

    2009-07-01

    Parkinson's Disease (PD) is marked by prominent motor symptoms that reflect striatal dopamine insufficiency. However, non-motor symptoms, including depression, are common in PD. It has been suggested that these changes reflect pathological involvement of non-dopaminergic systems. We examined regional changes in serotonin (5-HT) and norepinephrine (NE) systems in mice treated with two different 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment paradigms, at survival times of 3 or 16 weeks after the last MPTP injection. MPTP caused a decrease in striatal dopamine concentration, the magnitude of which depended on the treatment regimen and survival interval after MPTP treatment. There was significant involvement of other subcortical areas receiving a dopamine innervation, but no consistent changes in 5-HT or NE levels in subcortical sites. In contrast, we observed an enduring decrease in 5-HT and NE concentrations in both the somatosensory cortex and medial prefrontal cortex (PFC). Immunohistochemical studies also revealed a decrease in the density of PFC NE and 5-HT axons. The decrease in the cortical serotonergic innervation preferentially involved the thick beaded but not smooth fine 5-HT axons. Similar changes in the 5-HT innervation of post-mortem samples of the PFC from idiopathic PD cases were seen. Our findings point to a major loss of the 5-HT and NE innervations of the cortex in MPTP-induced parkinsonism, and suggest that loss of the beaded cortical 5-HT innervation is associated with a predisposition to the development of depression in PD.

  7. Ontogeny of serotonin and serotonin2A receptors in rat auditory cortex.

    Science.gov (United States)

    Basura, Gregory J; Abbas, Atheir I; O'Donohue, Heather; Lauder, Jean M; Roth, Bryan L; Walker, Paul D; Manis, Paul B

    2008-10-01

    Maturation of the mammalian cerebral cortex is, in part, dependent upon multiple coordinated afferent neurotransmitter systems and receptor-mediated cellular linkages during early postnatal development. Given that serotonin (5-HT) is one such system, the present study was designed to specifically evaluate 5-HT tissue content as well as 5-HT(2A) receptor protein levels within the developing auditory cortex (AC). Using high performance liquid chromatography (HPLC), 5-HT and the metabolite, 5-hydroxyindoleacetic acid (5-HIAA), was measured in isolated AC, which demonstrated a developmental dynamic, reaching young adult levels early during the second week of postnatal development. Radioligand binding of 5-HT(2A) receptors with the 5-HT(2A/2C) receptor agonist, (125)I-DOI ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl; in the presence of SB206553, a selective 5-HT(2C) receptor antagonist, also demonstrated a developmental trend, whereby receptor protein levels reached young adult levels at the end of the first postnatal week (P8), significantly increased at P10 and at P17, and decreased back to levels not significantly different from P8 thereafter. Immunocytochemical labeling of 5-HT(2A) receptors and confocal microscopy revealed that 5-HT(2A) receptors are largely localized on layer II/III pyramidal cell bodies and apical dendrites within AC. When considered together, the results of the present study suggest that 5-HT, likely through 5-HT(2A) receptors, may play an important role in early postnatal AC development.

  8. 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

  9. Alterações fisiológicas da pele percebidas por gestantes assistidas em serviços públicos de saúde Alteraciones fisiológicas de la piel percibidas por gestantes asistidas en servicios públicos de salud Skin physiological alterations perceived by pregnant women attended at public health services

    Directory of Open Access Journals (Sweden)

    Maristela Belletti Mutt Urasaki

    2010-01-01

    , 345 physiological alterations were recorded. The alterations most frequently cited were: skin spots, vascular changes and grooves. The majority of them reported discomfort due to those changes. CONCLUSION: The knowledge about the alterations allows the health professional to not undervalue these problems and to not invest in unnecessary interventions.

  10. Is Serum Serotonin Involved in the Bone Loss of Young Females with Anorexia Nervosa?

    Science.gov (United States)

    Maïmoun, L; Guillaume, S; Lefebvre, P; Philibert, P; Bertet, H; Picot, M-C; Courtet, P; Mariano-Goulart, D; Renard, E; Sultan, C

    2016-03-01

    Recent experimental data suggest that circulating serotonin interacts with bone metabolism, although this is less clear in humans. This study investigated whether serum serotonin interferes with bone metabolism in young women with anorexia nervosa (AN), a clinical model of energy deprivation. Serum serotonin, markers of bone turnover [osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), type I-C telopeptide breakdown products (CTX)], leptin, soluble leptin receptor (sOB-R), and insulin-like growth factor-1 (IGF-1) and its binding protein (IGFBP-3) were assessed. Whole body, spine, hip, and radius areal bone mineral density BMD (aBMD) were assessed by dual-energy X-ray absorptiometry in 21 patients with AN and 19 age-matched controls. Serum serotonin, leptin, IGF-1, IGFBP-3, OC, PINP, and aBMD at all sites, radius excepted, were significantly reduced in AN whereas CTX and sOB-R were increased compared with controls. Serum serotonin levels were positively correlated with weight, body mass index, whole body fat mass, leptin, and IGF-1, and negatively with CTX for the entire population. Low serum serotonin levels are observed in patients with AN. Although no direct link between low serum serotonin levels and bone mass was identified in these patients, the negative relationship between serotonin and markers of bone resorption found in all population nevertheless suggests the implication of serotonin in bone metabolism. Impact of low serum serotonin on bone in AN warrants further studies.

  11. Biological clocks in the duodenum and the diurnal regulation of duodenal and plasma serotonin.

    Directory of Open Access Journals (Sweden)

    Elizabeth Ebert-Zavos

    Full Text Available Serotonin in blood plasma is primarily synthesized in the duodenum, as brain derived serotonin does not cross the blood-brain barrier. Because serotonin in the brain and retina is synthesized under the control of a circadian clock, we sought to determine if a circadian clock in the duodenum regulates serotonin synthesis and release in blood. We examined gene expression in the duodenum of chickens at different times of the day and found that the duodenum rhythmically expresses molecular circadian clock genes and genes controlling serotonin biosynthesis, specifically tryptophan hydroxylase, in a light dark cycle (LD. Analysis of the duodenum and blood plasma showed that the amount of serotonin in the duodenum varies across the day and that serotonin profiles in blood plasma are also rhythmic in LD, but were not rhythmic in constant darkness. Because serotonin in the gut affects duodenal nutrient absorption and gut motility, the control of serotonin production in the duodenum by LD cycles could provide an additional mechanism by which the external environment controls nutrient uptake and digestive function. The diurnal regulation of plasma serotonin may also serve as an additional biochemical signal in the blood encoding time and could be used by target tissues to indicate the status of nutrient absorption.

  12. Selection, characterisation and mapping of complex electrochemical processes at individual single-walled carbon nanotubes: the case of serotonin oxidation.

    Science.gov (United States)

    Güell, Aleix G; Meadows, Katherine E; Dudin, Petr V; Ebejer, Neil; Byers, Joshua C; Macpherson, Julie V; Unwin, Patrick R

    2014-01-01

    The electrochemical (EC) oxidation of the neurotransmitter, serotonin, at individual single-walled carbon nanotubes (SWNTs) is investigated at high resolution using a novel platform that combines flow-aligned SWNTs with atomic force microscopy, Raman microscopy, electronic conductance measurements, individual SWNT electrochemistry and high-resolution scanning electrochemical cell microscopy (SECCM). SECCM has been used to visualise the EC activity along side-wall sections of metallic SWNTs to assess the extent to which side-walls promote the electrochemistry of this complex multi-step process. Uniform and high EC activity is observed that is consistent with significant reaction at the side-wall, rather than electrochemistry being driven by defects alone. By scanning forward and reverse (trace and retrace) over the same region of a SWNT, it is also possible to assess any blocking of EC activity by serotonin oxidation reaction products. At a physiologically relevant concentration (5 μM), there is no detectable blocking of SWNTs, which can be attributed, at least in part, to the high diffusion rate to an individual, isolated SWNT in the SECCM format. At higher serotonin concentration (2 mM), oligomer formation from oxidation products is much more significant and major blocking of the EC process is observed from line profiles recorded as the SECCM meniscus moves over an SWNT. The SECCM line profile morphology is shown to be highly diagnostic of whether blocking occurs during EC processes. The studies herein add to a growing body of evidence that various EC processes at SWNTs, from simple outer sphere redox reactions to complex multi-step processes, occur readily at pristine SWNTs. The platform described is of general applicability to various types of nanostructures and nanowires.

  13. Helional induces Ca2+ decrease and serotonin secretion of QGP-1 cells via a PKG-mediated pathway.

    Science.gov (United States)

    Kalbe, Benjamin; Schlimm, Marian; Mohrhardt, Julia; Scholz, Paul; Jansen, Fabian; Hatt, Hanns; Osterloh, Sabrina

    2016-10-01

    The secretion, motility and transport by intestinal tissues are regulated among others by specialized neuroendocrine cells, the so-called enterochromaffin (EC) cells. These cells detect different luminal stimuli, such as mechanical stimuli, fatty acids, glucose and distinct chemosensory substances. The EC cells react to the changes in their environment through the release of transmitter molecules, most importantly serotonin, to mediate the corresponding physiological response. However, little is known about the molecular targets of the chemical stimuli delivered from consumed food, spices and cosmetics within EC cells. In this study, we evaluated the expression of the olfactory receptor (OR) 2J3 in the human pancreatic EC cell line QGP-1 at the mRNA and protein levels. Using ratiofluorometric Ca(2+) imaging experiments, we demonstrated that the OR2J3-specific agonist helional induces a transient dose-dependent decrease in the intracellular Ca(2+) levels. This Ca(2+) decrease is mediated by protein kinase G (PKG) on the basis that the specific pharmacological inhibition of PKG with Rp-8-pCPT-cGMPS abolished the helional-induced Ca(2+) response. Furthermore, stimulation of QGP-1 cells with helional caused a dose-dependent release of serotonin that was comparable with the release induced by the application of a direct PKG activator (8-bromo-cGMP). Taken together, our results demonstrate that luminal odorants can be detected by specific ORs in QGP-1 cells and thus cause the directed release of serotonin and a PKG-dependent decrease in intracellular Ca(2.)

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

    Science.gov (United States)

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

    2012-02-01

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

  15. Reversibility of ecstasy-induced reduction in serotonin transporter availability in polydrug ecstasy users

    Energy Technology Data Exchange (ETDEWEB)

    Buchert, Ralph; Wilke, Florian; Nebeling, Bruno; Clausen, Malte [University Medical Center Hamburg-Eppendorf, Department of Nuclear Medicine, Hamburg (Germany); Thomasius, Rainer; Petersen, Kay; Obrocki, Jost; Wartberg, Lutz; Zapletalova, Pavlina [University Medical Center Hamburg-Eppendorf, Departments of Psychiatry and Psychotherapy, Hamburg (Germany)

    2006-02-01

    Animal data suggest that the synthetic drug ecstasy may damage brain serotonin neurons. Previously we reported protracted reductions in the availability of the serotonin transporter (SERT), an index of integrity of the axon terminals of brain serotonergic neurons, in SERT-rich brain regions in current human ecstasy users. Comparison of current ecstasy users and former ecstasy users yielded some evidence that this reduction might be reversible. However, participant selection effects could not be ruled out. Therefore, follow-up examinations were performed in these subjects to test the following a priori hypothesis in a prospective longitudinal design that eliminates participant selection effects to a large extent: availability of the SERT increases towards normal levels when ecstasy use is stopped, and remains unchanged or is further decreased if use is continued. Two follow-up positron emission tomography measurements using the SERT ligand [{sup 11}C](+)McN5652 were completed by 15 current and nine former ecstasy users. All subjects used illicit drugs other than ecstasy, too. The time interval between repeated measurements was about 1 year. The time course of the availability of the SERT was analysed in the following SERT-rich regions: mesencephalon, putamen, caudate and thalamus. Current ecstasy users showed a consistent increase in the availability of the SERT in the mesencephalon during the study (Friedman test: p=0.010), which most likely was caused by a decrease in the intensity of ecstasy consumption (Spearman correlation coefficient -0.725, p=0.002). Former ecstasy users showed a consistent increase in SERT availability in the thalamus (Friedman test: p=0.006). Ecstasy-induced protracted alterations in the availability of the SERT might be reversible. (orig.)

  16. Adult spinal V2a interneurons show increased excitability and serotonin-dependent bistability.

    Science.gov (United States)

    Husch, Andreas; Dietz, Shelby B; Hong, Diana N; Harris-Warrick, Ronald M

    2015-02-15

    In mice, most studies of the organization of the spinal central pattern generator (CPG) for locomotion, and its component neuron classes, have been performed on neonatal [postnatal day (P)2-P4] animals. While the neonatal spinal cord can generate a basic locomotor pattern, it is often argued that the CPG network is in an immature form whose detailed properties mature with postnatal development. Here, we compare intrinsic properties and serotonergic modulation of the V2a class of excitatory spinal interneurons in behaviorally mature (older than P43) mice to those in neonatal mice. Using perforated patch recordings from genetically tagged V2a interneurons, we revealed an age-dependent increase in excitability. The input resistance increased, the rheobase values decreased, and the relation between injected current and firing frequency (F/I plot) showed higher excitability in the adult neurons, with almost all neurons firing tonically during a current step. The adult action potential (AP) properties became narrower and taller, and the AP threshold hyperpolarized. While in neonates the AP afterhyperpolarization was monophasic, most adult V2a interneurons showed a biphasic afterhyperpolarization. Serotonin increased excitability and depolarized most neonatal and adult V2a interneurons. However, in ∼30% of adult V2a interneurons, serotonin additionally elicited spontaneous intrinsic membrane potential bistability, resulting in alternations between hyperpolarized and depolarized states with a dramatically decreased membrane input resistance and facilitation of evoked plateau potentials. This was never seen in younger animals. Our findings indicate a significant postnatal development of the properties of locomotor-related V2a interneurons, which could alter their interpretation of synaptic inputs in the locomotor CPG.

  17. Anorectic activities of serotonin uptake inhibitors: correlation with their potencies at inhibiting serotonin uptake in vivo and /sup 3/H-mazindol binding in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Angel, I.; Taranger, M.A.; Claustre, Y.; Scatton, B.; Langer, S.Z.

    1988-01-01

    The mechanism of anorectic action of several serotonin uptake inhibitors was investigated by comparing their anorectic potencies with several biochemical and pharmacological properties and in reference to the novel compound SL 81.0385. The anorectic effect of the potent serotonin uptake inhibitor SL 81.0385 was potentiated by pretreatment with 5-hydroxytryptophan and blocked by the serotonin receptor antagonist metergoline. A good correlation was obtained between the ED/sub 50/ values of anorectic action and the ED/sub 50/ values of serotonin uptake inhibition in vivo (but not in vitro) for several specific serotonin uptake inhibitors. Most of the drugs tested displaced (/sup 3/H)-mazindol from its binding to the anorectic recognition site in the hypothalamus, except the pro-drug zimelidine which was inactive. Excluding zimelidine, a good correlation was obtained between the affinities of these drugs for (/sup 3/H)-mazindol binding and their anorectic action indicating that their anorectic activity may be associated with an effect mediated through this site. Taken together these results suggest that the anorectic action of serotonin uptake inhibitors is directly associated to their ability to inhibit serotonin uptake and thus increasing the synaptic levels of serotonin. The interactions of these drugs with the anorectic recognition site labelled with (/sup 3/H)-mazindol is discussed in connection with the serotonergic regulation of carbohydrate intake.

  18. Effect of the selective serotonin reuptake inhibitor paroxetine on platelet function is modified by a SLC6A4 serotonin transporter polymorphism

    NARCIS (Netherlands)

    Abdelmalik, N.; Ruhé, H.G.; Barwari, K.; Van Den Dool, E.-J.; Meijers, J.C.M.; Middeldorp, S.; Büller, H.R.; Schene, A.H.; Kamphuisen, P.W.

    2008-01-01

    Background: Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased bleeding tendency. Objectives: To prospectively quantify the dose-response effects of paroxetine and the influence of the serotonin transporter gene (SLC6A4) promoter polymorphism (5-HTTLPR) on platele

  19. Serotonin control of sleep-wake behavior.

    Science.gov (United States)

    Monti, Jaime M

    2011-08-01

    Based on electrophysiological, neurochemical, genetic and neuropharmacological approaches, it is currently accepted that serotonin (5-HT) functions predominantly to promote wakefulness (W) and to inhibit REM (rapid eye movement) sleep (REMS). Yet, under certain circumstances the neurotransmitter contributes to the increase in sleep propensity. Most of the serotonergic innervation of the cerebral cortex, amygdala, basal forebrain (BFB), thalamus, preoptic and hypothalamic areas, raphe nuclei, locus coeruleus and pontine reticular formation comes from the dorsal raphe nucleus (DRN). The 5-HT receptors can be classified into at least seven classes, designated 5-HT(1-7). The 5-HT(1A) and 5-HT(1B) receptor subtypes are linked to the inhibition of adenylate cyclase, and their activation evokes a membrane hyperpolarization. The actions of the 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptor subtypes are mediated by the activation of phospholipase C, with a resulting depolarization of the host cell. The 5-HT(3) receptor directly activates a 5-HT-gated cation channel which leads to the depolarization of monoaminergic, aminoacidergic and cholinergic cells. The primary signal transduction pathway of 5-HT(6) and 5-HT(7) receptors is the stimulation of adenylate cyclase which results in the depolarization of the follower neurons. Mutant mice that do not express 5-HT(1A) or 5-HT(1B) receptor exhibit greater amounts of REMS than their wild-type counterparts, which could be related to the absence of a postsynaptic inhibitory effect on REM-on neurons of the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT). 5-HT(2A) and 5-HT(2C) receptor knock-out mice show a significant increase of W and a reduction of slow wave sleep (SWS) which has been ascribed to the increase of catecholaminergic neurotransmission involving mainly the noradrenergic and dopaminergic systems. Sleep variables have been characterized, in addition, in 5-HT(7) receptor knock-out mice; the mutants spend less time

  20. DEVELOPMENTAL CHANGES IN SEROTONIN SIGNALING: IMPLICATIONS FOR EARLY BRAIN FUNCTION, BEHAVIOR AND ADAPTATION

    Science.gov (United States)

    BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.

    2017-01-01

    The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950

  1. Hydrogen peroxide stimulates the active transport of serotonin into human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Bosin, T.R. (Indiana Univ., Bloomington (United States))

    1991-03-11

    The effect of hydrogen peroxide on the active transport of serotonin (5-HT) by human platelets was investigated. Platelets were exposed to either a single dose of H{sub 2}O{sub 2} or to H{sub 2}O{sub 2} generated by the glucose/glucose oxidase or xanthine/xanthine oxidase enzyme systems. H{sub 2}{sub 2} produced a rapid, dose-dependent and time-dependent increase in 5-HT transport which was maximal after a 2 min incubation and decreased with continued incubation. Catalase completely prevented H{sub 2}O{sub 2}-induced stimulation and fluoxetine totally blocked 5-HT uptake into stimulated platelets. The glucose/glucose oxidase and the xanthine/xanthine oxidase generating systems produced a similar response to that of H{sub 2}O{sub 2}. In the xanthine/xanthine oxidase system, superoxide dismutase failed to alter the stimulation, while catalase effectively prevented the response. The kinetics of 5-HT transport indicated that H{sub 2}O{sub 2} treatment did not alter the K{sub m} of 5-HT transport but significantly increased the maximal rate of 5-HT transport. These data demonstrated that exposure of human platelets to H{sub 2}O{sub 2} resulted in a stimulation of the active transport of 5-HT and suggested that H{sub 2}O{sub 2} may function to regulate this process.

  2. Unifying concept of serotonin transporter-associated currents.

    Science.gov (United States)

    Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H; Sandtner, Walter

    2012-01-02

    Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents.

  3. 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.

  4. 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.

  5. The Physiology of Fear and Sound

    DEFF Research Database (Denmark)

    Garner, Tom Alexander; Grimshaw, Mark

    2013-01-01

    The potential value of a looping biometric feedback system as a key component of adaptive computer video games is significant. Psychophysiological measures are essential to the development of an automated emotion recognition program, capable of interpreting physiological data into models of affect...... and systematically altering the game environment in response. This article presents empirical data the analysis of which advocates electrodermal activity and electromyography as suitable physiological measures to work effectively within a computer video game-based biometric feedback loop, within which sound...

  6. Synthesis of serotonin transporter imaging agent [125I]ADAM

    Institute of Scientific and Technical Information of China (English)

    LU Chun-Xiong; WU Chun-Ying; JIANG Quan-Fu; CHEN Zheng-Ping; ZHANG Tong-Xing; LI Xiao-Ming; WANG Song-Pei

    2005-01-01

    The synthesis of serotonin transporter imaging agent [125I] -2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine([125I] ADAM) was reported. The chemical structure of the labeling precursor 5- (tributylstannyl) -2-((2-((dimethylamino)methyl)phenyl)thio)phenylamine and all its intermediates were verified by IR,1HNMR and MS. The .radioiodinated compound was prepared using iododestannylation reaction by hydrogen peroxide. Final radiochemical purity was above 95% determined by TLC.

  7. Serotonin as a Biomarker: Stress Resilience among Battlefield Airmen Trainees

    Science.gov (United States)

    2016-05-21

    depression or anxiety, or if depression or anxiety cause serotonin levels to drop [11]. None of the correlations for the sub-scales of subjective...subjectively measure affect and mood on six scales: (1) tension-anxiety, (2) depression -dejection, (3) anger- hostility, (4) vigor-activity, (5) fatigue... depression -dejection, (3) anger-hostility, (4) vigor-activity, (5) fatigue-inertia, (6) confusion-bewilderment, and (7) friendliness (not counted as a

  8. 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.

  9. Crystal Structure of an LSD-Bound Human Serotonin Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wacker, Daniel; Wang, Sheng; McCorvy, John D.; Betz, Robin M.; Venkatakrishnan, A.J.; Levit, Anat; Lansu, Katherine; Schools, Zachary L.; Che, Tao; Nichols, David E.; Shoichet, Brian K.; Dror, Ron O.; Roth, Bryan L. (UNCSM); (UNC); (Stanford); (Stanford-MED); (UCSF)

    2017-01-01

    The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD’s key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT2BR and 5-HT2AR—a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD’s slow binding kinetics may be due to a “lid” formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD’s binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD’s actions at human serotonin receptors.

  10. 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.

  11. Role of serotonin transporter inhibition in the regulation of tryptophan hydroxylase in brainstem raphe nuclei: time course and regional specificity.

    Science.gov (United States)

    MacGillivray, L; Lagrou, L M; Reynolds, K B; Rosebush, P I; Mazurek, M F

    2010-12-01

    Drugs that selectively inhibit the serotonin transporter (SERT) are widely prescribed for treatment of depression and a range of anxiety disorders. We studied the time course of changes in tryptophan hydroxylase (TPH) in four raphe nuclei after initiation of two different SERT inhibitors, citalopram and fluoxetine. In the first experiment, groups of Sprague-Dawley rats received daily meals of rice pudding either alone (n=9) or mixed with citalopram 5 mg/kg/day (n=27). Rats were sacrificed after 24 h, 7 days or 28 days of treatment. Sections of dorsal raphe nucleus (DRN), median raphe nucleus (MRN), raphe magnus nucleus (RMN) and caudal linear nucleus (CLN) were processed for TPH immunohistochemistry. Citalopram induced a significant reduction in DRN TPH-positive cell counts at 24 h (41%), 7 days (38%) and 28 days (52%). Similar reductions in TPH-positive cell counts were also observed at each timepoint in the MRN and in the RMN. In the MRN, citalopram resulted in significant reductions at 24 h (26%), 7 days (16%) and 28 days (23%). In the RMN, citalopram induced significant reductions of TPH-positive cell counts at 24 h (45%), 7 days (34%) and 28 days (43%). By contrast, no significant differences between control and treatment groups were observed in the CLN at any of the time points that we studied. To investigate whether these changes would occur with other SERT inhibitors, we conducted a second experiment, this time with a 28-day course of fluoxetine. As was observed with citalopram, fluoxetine induced significant reductions of TPH cell counts in the DRN (39%), MRN (38%) and RMN (41%), with no significant differences in the CLN. These results indicate that SERT inhibition can alter the regulation of TPH, the rate limiting enzyme for serotonin biosynthesis. This persistent and regionally specific downregulation of serotonin biosynthesis may account for some of the clinical withdrawal symptoms associated with drugs that inhibit SERT.

  12. Neurobiology of Anorexia Nervosa: Serotonin Dysfunctions Link Self-Starvation with Body Image Disturbances through an Impaired Body Memory

    Science.gov (United States)

    Riva, Giuseppe

    2016-01-01

    The etiology of anorexia nervosa (AN) is still unclear, despite that it is a critical and potentially mortal illness. A recent neurobiological model considers AN as the outcome of dysfunctions in the neuronal processes related to appetite and emotionality (Kaye et al., 2009, 2013). However, this model still is not able to answer a critical question: What is behind body image disturbances (BIDs) in AN? The article starts its analysis from reviewing some of the studies exploring the effects of the serotonin systems in memory (episodic, working, and spatial) and its dysfunctions. The review suggests that serotonin disturbances may: (a) facilitate the encoding of third person (allocentric) episodic memories; (b) facilitate the consolidation of emotional episodic memories (e.g., teasing), if preceded by repeated stress; (c) reduce voluntary inhibition of mnestic contents; (d) impair allocentric spatial memory. If we discuss these results within the interpretative frame suggested by the “Allocentric Lock Hypothesis” (Riva, 2012, 2014), we can hypothesize that altered serotoninergic activity in AN patients: (i) improves their ability to store and consolidate negative autobiographical memories, including those of their body, in allocentric perspective; (ii) impairs their ability to trigger voluntary inhibition of the previously stored negative memory of the body; (iii) impairs their capacity to retrieve/update allocentric information. Taken together, these points suggest a possible link between serotonin dysfunctions, memory impairments and BIDs: the impossibility of updating a disturbed body memory using real time experiential data—I'm locked to a wrong body stored in long term memory—pushes AN patients to control body weight and shape even when underweight. PMID:27932968

  13. The differential effects of chronic imipramine or citalopram administration on physiological and behavioral outcomes in naïve mice.

    Science.gov (United States)

    Strekalova, Tatyana; Anthony, Daniel C; Dolgov, Oleg; Anokhin, Konstantin; Kubatiev, Aslan; Steinbusch, Harry M W; Schroeter, Careen

    2013-05-15

    Tricyclics and selective serotonin reuptake inhibitors (SSRIs) are probably the most widely employed reference antidepressants in animal studies on depression. Using imipramine and citalopram, we sought to assess which drug would be more appropriate as pharmacological reference in paradigms of depression in C57BL6N mice by measuring their effect on liquid consumption, home cage activity, body weight and long-term memory in naïve animals treated with each compound at generally used dose of 15 mg/kg/day. Continuous logging of home cage movement, weekly monitoring of vertical activity in a novel cage, and body weight was recorded during four-week treatment period and for four weeks after discontinuation of the antidepressant; sucrose preference was evaluated at weekly intervals during drug administration. A novel object recognition memory test was performed in mice treated the antidepressants for two weeks. Compared to control, imipramine-treated mice displayed increased sucrose and water intake, as well as enhanced home-cage and novelty exploration activities, and reduced body weight. Imipramine also impaired learning in the object recognition task, but citalopram diminished object exploration sufficiently to invalidate the test. Citalopram-treated animals demonstrated no changes in a sucrose test and had elevated body mass. Thus basic physiological and behavioral outcomes in naïve mice were significantly altered by the chronic administration of imipramine and, to a lesser extent, citalopram. As altered variables are crucial for the evaluation of antidepressant-like effects in mice, our data suggest that, at commonly used doses, both drugs must be applied in mouse models of depression with caution.

  14. Identification and developmental expression of the enzymes responsible for dopamine, histamine, octopamine and serotonin biosynthesis in the copepod crustacean Calanus finmarchicus.

    Science.gov (United States)

    Christie, Andrew E; Fontanilla, Tiana M; Roncalli, Vittoria; Cieslak, Matthew C; Lenz, Petra H

    2014-01-01

    Neurochemicals are likely to play key roles in physiological/behavioral control in the copepod crustacean Calanus finmarchicus, the biomass dominant zooplankton for much of the North Atlantic Ocean. Previously, a de novo assembled transcriptome consisting of 206,041 unique sequences was used to characterize the peptidergic signaling systems of Calanus. Here, this assembly was mined for transcripts encoding enzymes involved in amine biosynthesis. Using known Drosophila melanogaster proteins as templates, transcripts encoding putative Calanus homologs of tryptophan-phenylalanine hydroxylase (dopamine, octopamine and serotonin biosynthesis), tyrosine hydroxylase (dopamine biosynthesis), DOPA decarboxylase (dopamine and serotonin biosynthesis), histidine decarboxylase (histamine biosynthesis), tyrosine decarboxylase (octopamine biosynthesis), tyramine β-hydroxylase (octopamine biosynthesis) and tryptophan hydroxylase (serotonin biosynthesis) were identified. Reverse BLAST and domain analyses show that the proteins deduced from these transcripts possess sequence homology to and the structural hallmarks of their respective enzyme families. Developmental profiling revealed a remarkably consistent pattern of expression for all transcripts, with the highest levels of expression typically seen in the early nauplius and early copepodite. These expression patterns suggest roles for amines during development, particularly in the metamorphic transitions from embryo to nauplius and from nauplius to copepodite. Taken collectively, the data presented here lay a strong foundation for future gene-based studies of aminergic signaling in this and other copepod species, in particular assessment of the roles they may play in developmental control.

  15. Regulating prefrontal cortex activation: an emerging role for the 5-HT₂A serotonin receptor in the modulation of emotion-based actions?

    Science.gov (United States)

    Aznar, Susana; Klein, Anders B

    2013-12-01

    The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings of a regulatory effect of the PFC on the emotional control of our actions.

  16. [CROSS-TALK BETWEEN 5-HT1A AND 5-HT7 RECEPTORS: ROLE IN THE AUTOREGULATION OF THE BRAIN SEROTONIN SYSTEM AND IN MECHANISM OF ANTIDEPRESSANTS ACTION].

    Science.gov (United States)

    Popova, N K; Ponimaskin, E G; Naumenko, V S

    2015-11-01

    Recent studies considerably extended our knowledge of the mechanisms and physiological role of the interaction between different receptors in the brain. Current review summarizes data on the formation of receptor complexes and the role of such complexes in the autoregulation of the brain serotonin system, behavioral abnormalities and mechanism of antidepressants action. Particular attention is paid to 5-HT1A and 5-HT7 receptor heterodimers. The results described in the present review indicate that: i) dimerization and formation of mobile receptor complexes is a common feature for the members of G-protein coupled receptor superfamily; ii) 5-HT7 receptor appears to be a modulator for 5-HT1A receptor - the key autoregulator of the brain serotonin system; iii) 5-HT1A/5-HT7 receptor complexes formation is one of the mechanisms for inactivation and desensitization of the 5-HTIA receptors in the brain; iv) differences in the 5-HT7 receptor and 5-HTIA/5-HT7 heterodimers density define different sensitivity of pre- and postsynaptic 5-HTlA receptors to chronic treatment with selective serotonin reuptake inhibitors.

  17. Modulation of neuronal serotonin uptake by a putative endogenous ligand of imipramine recognition sites.

    OpenAIRE

    Barbaccia, M. L.; Gandolfi, O; Chuang, D M; Costa, E

    1983-01-01

    Imipramine inhibits the serotonin uptake by binding with high affinity to regulatory sites of this uptake located on axons that release serotonin. The number of imipramine recognition sites located on crude synaptic membrane preparations is reduced by two daily injections of imipramine or desmethylimipramine for 3 weeks. When the binding sites for [3H]imipramine are down-regulated the Vmax of the neuronal uptake of serotonin is increased. Moreover, in minces prepared from the brain hippocampu...

  18. Sleep patterns of the monkey and brain serotonin concentration: effect of p-chlorophenylalanine.

    Science.gov (United States)

    Weitzman, E D; Rapport, M M; McGregor, P; Jacoby, J

    1968-06-21

    The amount of time that monkeys (Macaca mulatta) slept was reduced after they were given p-chlorophenylalanine, a selective depletor of serotonin in animal tissues. The time spent in the rapid eye movement stage of sleep was unchanged, but the time in other sleep stages decreased. Seven regions of the brain had a 31 to 46 percent decrease in serotonin content; the concentration of cerebellar serotonin increased by 44 percent.

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

    Science.gov (United States)

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

    2016-06-01

    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 of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists. Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50mM) and rebaudioside A (12.5mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release. Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155μM) further enhanced casein and safflower oil induced-serotonin release. Exposure of ileal tissue segments to serotonin (30μM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100μM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10μM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process.

  20. Physiological changes in pregnancy

    OpenAIRE

    SOMA-PILLAY, Priya; Catherine, Nelson-Piercy; Tolppanen, Heli; Mebazaa, Alexandre

    2016-01-01

    Abstract Physiological changes occur in pregnancy to nurture the developing foetus and prepare the mother for labour and delivery. Some of these changes influence normal biochemical values while others may mimic symptoms of medical disease. It is important to differentiate between normal physiological changes and disease pathology. This review highlights the important changes that take place during normal pregnancy.

  1. Physiology of sport.

    Science.gov (United States)

    Maughan, Ron

    2007-07-01

    The elite athlete represents the extreme of the human gene pool, where genetic endowment is developed by an intensive training programme. Sport encompasses many different activities, calling for different physical and mental attributes. Understanding the physiology of exercise provides insights into normal physiological function.

  2. Advances in physiological computing

    CERN Document Server

    Fairclough, Stephen H

    2014-01-01

    This edited collection will provide an overview of the field of physiological computing, i.e. the use of physiological signals as input for computer control. It will cover a breadth of current research, from brain-computer interfaces to telemedicine.

  3. Phun Week: Understanding Physiology

    Science.gov (United States)

    Limson, Mel; Matyas, Marsha Lakes

    2009-01-01

    Topics such as sports, exercise, health, and nutrition can make the science of physiology relevant and engaging for students. In addition, many lessons on these topics, such as those on the cardiovascular, respiratory, and digestive systems, align with national and state life science education standards. Physiology Understanding Week (PhUn…

  4. Role of serotonin in the pathogenesis of chronic constipation%五羟色胺与慢性便秘

    Institute of Scientific and Technical Information of China (English)

    张卫平; 江滨

    2011-01-01

    五羟色胺(5-hydroxytryptamine,5-HT)是肠神经系统中一重要的单胺类神经递质.95%来源于消化系统,其中90%位于肠黏膜的嗜铬细胞(enterochromaffin cells,EC),10%位于肠道神经元.5-HT在引发胃肠蠕动和分泌反射,以及调节内脏感觉中起关键作用.有关5-HT在功能性胃肠疾病中的作用研究较多,主要集中在对肠易激综合征(irritable bowel syndrome,IBS)的研究,而在便秘中的研究相对较少.慢性便秘(chronic constipation,CC)是消化系统常见病,老年患者尤其多见.5-HT在便秘中扮演的角色已被重视,在便秘的生理、病理及治疗中的作用正在不断得到解析,现将近年来5-HT和便秘的研究作一简要综述.%Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter of profound importance in the enteric nervous system. About 95% of the serotonin in the body is found in the GI tract; 90% is in enterochromaffin cells (EC cells) and the remaining 10% in enteric neurons. It plays a key role in the initiation of peristaltic and secretory reflexes and in the modulation of visceral sensations. There are many reports of serotonin in functional bowel disorders, and most of them mainly focus on irritable bowel syndrome (IBS), but serotonin in constipation is rarely reported. Chronic constipation (CC) is a commonly encountered disease, especially in elderly patients. The role of 5-HT plays in CC has been emphasized, and its effects in physiology, pathology and treatment of CC are continuously being resolved. This article is a review of the progress in understanding the role of 5-HT in the pathogenesis and treatment of chronic constipation.

  5. Exocytosis of serotonin from the neuronal soma is sustained by a serotonin and calcium-dependent feedback loop

    Directory of Open Access Journals (Sweden)

    Carolina eLeon-Pinzon

    2014-06-01

    Full Text Available The soma of many neurons releases large amounts of transmitter molecules through an exocytosis process that continues for hundreds of seconds after the end of the triggering stimulus. Transmitters released in this way modulate the activity of neurons, glia and blood vessels over vast volumes of the nervous system. Here we studied how somatic exocytosis is maintained for such long periods in the absence of electrical stimulation and transmembrane Ca2+ entry. Somatic exocytosis of serotonin from dense core vesicles could be triggered by a train of 10 action potentials at 20 Hz in Retzius neurons of the leech. However, the same number of action potentials produced at 1 Hz failed to evoke any exocytosis. The 20-Hz train evoked exocytosis through a sequence of intracellular Ca2+ transients, with each transient having a different origin, timing and intracellular distribution. Upon electrical stimulation, transmembrane Ca2+ entry through L-type channels activated Ca2+-induced Ca2+ release. A resulting fast Ca2+ transient evoked an early exocytosis of serotonin from sparse vesicles resting close to the plasma membrane. This Ca2+ transient also triggered the transport of distant clusters of vesicles towards the plasma membrane. Upon exocytosis, the released serotonin activated autoreceptors coupled to phospholipase C, which in turn produced an intracellular Ca2+ increase in the submembrane shell. This localized Ca2+ increase evoked new exocytosis as the vesicles in the clusters arrived gradually at the plasma membrane. In this way, the extracellular serotonin elevated the intracellular Ca2+ and this Ca2+ evoked more exocytosis. The resulting positive feedback loop maintained exocytosis for the following hundreds of seconds until the last vesicles in the clusters fused. Since somatic exocytosis displays similar kinetics in neurons releasing different types of transmitters, the data presented here contributes to understand the cellular basis of paracrine

  6. Radioenzymatic microassay for picogram quantities of serotonin or acetylserotonin in biological fluids and tissues

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, M.N.; Benedict, C.R.

    1987-06-01

    This paper describes several modifications of the original radioenzymatic assay for serotonin which increase the sensitivity of the assay 20-fold as well as enhance its reliability. Using this method serotonin concentrations can be directly measured in biological examples without precleaning the sample. When compared to currently available methods this assay is specific and sensitive to approximately 1 pg of serotonin and can be used to measure serotonin levels in individual brain nuclei or microliter quantities of biological fluids. This assay can be easily adapted for the direct measurement of N-acetylserotonin. A large number of samples can be assayed in a single working day.

  7. Serotonin syndrome caused by minimum doses of SSRIS in a patient with spinal cord injury

    OpenAIRE

    Satoh, Koichiro; Takano, Shizuko; Onogi, Takashi; Ohtsuki, Koji; Kobayashi, Toshio

    2006-01-01

    There have been only a few reports of serotonin syndrome developing after mono-therapy with a selective serotonin reuptake inhibitor (SSRI). We report a case of serotonin syndrome caused by long-term therapy with fluvoxamine prior to treatment with paroxetine. An 18-year-old man with spinal cord injury (SCI) at thoracic level 2-3 presented with onset of serotonin syndrome after taking fluvoxamine (50 mg per day) for 8 weeks prior to treatment with paroxetine (10 mg per day) for 6 days. He had...

  8. 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.

  9. The effect of antenatal depression and selective serotonin reuptake inhibitor treatment on nerve growth factor signaling in human placenta.

    Directory of Open Access Journals (Sweden)

    Helena Kaihola

    Full Text Available Depressive symptoms during pregnancy are common and may have impact on the developing child. Selective serotonin reuptake inhibitors (SSRIs are the most prescribed antidepressant treatment, but unfortunately, these treatments can also negatively affect the behavioral development and health of a child during pregnancy. In addition, serotonin (5-HT exerts neurotrophic actions with thus far not fully known effects in the offspring. The neurotrophic growth factor (NGF is involved in neuronal cell survival and differentiation, and altered placenta levels have been found to increase the risk for pregnancy complications, similar to those found in women treated with SSRIs. We therefore investigated whether the NGF signaling pathway was altered in the placenta from women treated with SSRIs (n = 12 and compared them with placenta from depressed (n = 12 and healthy mothers (n = 12. Results from immunohistochemical stainings revealed that placental NGF protein levels of SSRI-treated women were increased in both trophoblasts and endothelial cells compared with depressed and control women. In addition, downstream of the NGF receptor TrkA, increased levels of the signaling proteins ROCK2 and phosphorylated Raf-1 were found in stromal cells and a tendency towards increased levels of ROCK2 in trophoblasts and endothelial cells in SSRI-treated women when compared to healthy controls. SSRI-treated women also displayed increased levels of phosphorylated ROCK2 in all placental cell types studied in comparison with depressed and control women. Interestingly, in placental endothelial cells from depressed women, NGF levels were significantly lower compared to control women, but ROCK2 levels were increased compared with control and SSRI-treated women. Taken together, these results show that the NGF signaling and downstream pathways in the placenta are affected by SSRI treatment and/or antenatal depression. This might lead to an altered placental function, although the

  10. Psychobiology of Altered States of Consciousness

    Science.gov (United States)

    Vaitl, Dieter; Birbaumer, Niels; Gruzelier, John; Jamieson, Graham A.; Kotchoubey, Boris; Kubler, Andrea; Lehmann, Dietrich; Miltner, Wolfgang H. R.; Ott, Ulrich; Sammer, Gebhard; Strauch, Inge; Strehl, Ute; Wackermann, Jiri; Weiss, Thomas

    2005-01-01

    The article reviews the current knowledge regarding altered states of consciousness (ASC) (a) occurring spontaneously, (b) evoked by physical and physiological stimulation, (c) induced by psychological means, and (d) caused by diseases. The emphasis is laid on psychological and neurobiological approaches. The phenomenological analysis of the…

  11. Physiologic and pharmacokinetic changes in pregnancy

    OpenAIRE

    2014-01-01

    Physiologic changes in pregnancy induce profound alterations to the pharmacokinetic properties of many medications. These changes affect distribution, absorption, metabolism, and excretion of drugs, and thus may impact their pharmacodynamic properties during pregnancy. Pregnant women undergo several adaptations in many organ systems. Some adaptations are secondary to hormonal changes in pregnancy, while others occur to support the gravid woman and her developing fetus. Some of the changes in ...

  12. In vivo regulation of the serotonin-2 receptor in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Stockmeier, C.A.; Kellar, K.J.

    1986-01-13

    Serotonin-2 (5-HT-2) receptors in brain were measured using (/sup 3/H)ketanserin. The authors examined the effects of amitriptyline, an anti-depressant drug, of electroconvulsive shock (ECS) and of drug-induced alterations in presynaptic 5-HT function on (/sup 3/H)ketanserin binding to 5-HT-2 receptors in rat brain. The importance of intact 5-HT axons to the up-regulation of 5-HT-2 receptors by ECS was also investigated, and an attempt was made to relate the ECS-induced increase in this receptor to changes in 5-HT presynaptic mechanisms. Twelve days of ECS increased the number of 5-HT-2 receptors in frontal cortex. Neither the IC/sub 50/ nor the Hill coefficient of 5-HT in competing for (/sup 3/H)ketanserin binding sites was altered by ECS. Repeated injections of amitriptyline reduced the number of 5-HT-2 receptors in frontal cortex. Reserpine, administered daily for 12 days, caused a significant increase in 5-HT-2 receptors, but neither daily injections of p-chlorophenylalanine (PCPA) nor lesions of 5-HT axons with 5,7-dihydroxytryptamine (5,7-DHT) affected 5-HT-2 receptors. However, regulation of 5-HT-2 receptors by ECS was dependent on intact 5-HT axons since ECS could not increase the number of 5-HT-2 receptors in rats previously lesioned with 5,7-DHT. Repeated ECS, however, does not appear to affect either the high-affinity uptake of (/sup 3/H)5-HT or (/sup 3/H)imipramine binding, two presynaptic markers of 5-HT neuronal function. 5-HT-2 receptors appear to be under complex control. ECS or drug treatments such as reserpine or amitriptyline, which affect several monoamine neurotransmission systems including 5-HT, can alter 5-HT-2 receptors. 28 references, 1 figure, 7 tables.

  13. Fetal cardiovascular physiology.

    Science.gov (United States)

    Rychik, J

    2004-01-01

    The cardiovascular system of the fetus is physiologically different than the adult, mature system. Unique characteristics of the myocardium and specific channels of blood flow differentitate the physiology of the fetus from the newborn. Conditions of increased preload and afterload in the fetus, such as sacrococcygeal teratoma and twin-twin transfusion syndrome, result in unique and complex pathophysiological states. Echocardiography has improved our understanding of human fetal cadiovasvular physiology in the normal and diseased states, and has expanded our capability to more effectively treat these disease processes.

  14. The role of serotonin in nonnormative risky choice: the effects of tryptophan supplements on the "reflection effect" in healthy adult volunteers.

    Science.gov (United States)

    Murphy, Susannah E; Longhitano, Carlo; Ayres, Rachael E; Cowen, Philip J; Harmer, Catherine J; Rogers, Robert D

    2009-09-01

    Risky decision-making involves weighing good and bad outcomes against their probabilities in order to determine the relative values of candidate actions. Although human decision-making sometimes conforms to rational models of how this weighting is achieved, irrational (or nonnormative) patterns of risky choice, including shifts between risk-averse and risk-seeking choices involving equivalent-value gambles (the "reflection effect"), are frequently observed. In the present experiment, we investigated the role of serotonin in decision-making under conditions of uncertainty. Fifteen healthy adult volunteers received a treatment of 3 g per day of the serotonin precursor, tryptophan, in the form of dietary supplements over a 14-day period, whereas 15 age- and IQ-matched control volunteers received a matched placebo substance. At test, all participants completed a risky decision-making task involving a series of choices between two simultaneously presented gambles, differing in the magnitude of their possible gains, the magnitude of their possible losses, and the probabilities with which these outcomes were delivered. Tryptophan supplements were associated with alterations in the weighting of gains and small losses perhaps reflecting reduced loss-aversion, and a marked and significant diminution of the reflection effect. We conclude that serotonin activity plays a significant role in nonnormative risky decision-making under conditions of uncertainty.

  15. 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.

  16. Decreased serotonin2C receptor responses in male patients with schizophrenia.

    Science.gov (United States)

    Lee, Myung Ae; Jayathilake, Karuna; Sim, Min Young; Meltzer, Herbert Y

    2015-03-30

    Serotonin (5-HT)2C receptors in brain affect psychosis, reward, substance abuse, anxiety, other behaviors, appetite, body temperature, and other physiological measures. They also have been implicated in antipsychotic drug efficacy and side effects. We previously reported that the hyperthermia following administration of MK-212, a predominantly 5-HT(2C) receptor agonist, was diminished in a small sample of patients with schizophrenia (SCH), suggesting decreased 5-HT(2C) receptor responsiveness. We have now studied the responses to oral MK-212 and placebo in a larger sample of unmedicated male SCH (n = 69) and normal controls (CON) (n = 33), and assessed the influence of comorbid substance abuse (SA) on oral body temperature, behavioral responses, etc. The placebo-adjusted oral body temperature response to MK-212 was significantly lower in SCH compared to CON and not significantly different between the SCH with or without SA. Some behavioral responses to MK-212, e.g. self-rated feelings of increased anxiety, depression and decreased calmness, or good overall feeling, were significantly lower in the SCH patients compared to CON. These results add to the evidence for diminished 5-HT(2C) receptor responsiveness in SCH patients compared to CON and are consistent with reported association of HTR(2C) polymorphisms, leading to decreased expression or function of the HTR(2C) in patients with SCH.

  17. The serotonin receptor 7 and the structural plasticity of brain circuits

    Directory of Open Access Journals (Sweden)

    Floriana eVolpicelli

    2014-09-01

    Full Text Available Serotonin (5-hydroxytryptamine, 5-HT modulates numerous physiological processes in the nervous system. Together with its function as neurotrasmitter, 5-HT regulates neurite outgrowth, dendritic spine shape and density, growth cone motility and synapse formation during development. In the mammalian brain 5-HT innervation is virtually ubiquitous and the diversity and specificity of its signaling and function arise from at least 20 different receptors, grouped in 7 classes. Here we will focus on the role 5-HT7 receptor (5-HT7R in the correct establishment of neuronal cytoarchitecture during development, as also suggested by its involvement in several neurodevelopmental disorders. The emerging picture shows that this receptor is a key player contributing not only to shape brain networks during development but also to remodel neuronal wiring in the mature brain, thus controlling cognitive and emotional responses. The activation of 5-HT7R might be one of the mechanisms underlying the ability of the CNS to respond to different stimuli by modulation of its circuit configuration.

  18. Production and Peripheral Roles of 5-HTP, a Precursor of Serotonin

    Directory of Open Access Journals (Sweden)

    Kazuhiro Nakamura

    2009-01-01

    Full Text Available Serotonin (5-hydroxytryptamine [5-HT] has been implicated in a variety of physiological and pathological functions. Multiple steps of enzyme reactions enable biosynthesis of 5-HT. The first and rate-limiting step of the reaction is the synthesis of 5-hydroxy-L-tryptophan (5-HTP from L-tryptophan. This step is dictated by an enzyme, tryptophan hydroxylase (TPH. TPH requires 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4 as a co-substrate of TPH. 5-HTP has been simply regarded as a precursor of 5-HT and it is believed that the biological significance of 5-HTP is essentially ascribed to the production of 5-HT. However, recent works shed light on the specific functions of 5-HTP in the periphery. In this review article, we focus on the specific roles of exogenous 5-HTP as well as the endogenous 5-HTP in the gut epithelial cells. Since systemic treatment with 5-HTP is applied to patients with lower 5-HT levels, the studies on the specific role of 5-HTP might create an opportunity to explore the effects of exogenously-applied 5-HTP in the gut in man.

  19. Melatonin Supports CYP2D-Mediated Serotonin Synthesis in the Brain.

    Science.gov (United States)

    Haduch, Anna; Bromek, Ewa; Wójcikowski, Jacek; Gołembiowska, Krystyna; Daniel, Władysława A

    2016-03-01

    Melatonin is used in the therapy of sleep and mood disorders and as a neuroprotective agent. The aim of our study was to demonstrate that melatonin supported (via its deacetylation to 5-methoxytryptamine) CYP2D-mediated synthesis of serotonin from 5-methoxytryptamine. We measured serotonin tissue content in some brain regions (the cortex, hippocampus, nucleus accumbens, striatum, thalamus, hypothalamus, brain stem, medulla oblongata, and cerebellum) (model A), as well as its extracellular concentration in the striatum using an in vivo microdialysis (model B) after melatonin injection (100 mg/kg i.p.) to male Wistar rats. Melatonin increased the tissue concentration of serotonin in the brain structures studied of naïve, sham-operated, or serotonergic neurotoxin (5,7-dihydroxytryptamine)-lesioned rats (model A). Intracerebroventricular quinine (a CYP2D inhibitor) prevented the melatonin-induced increase in serotonin concentration. In the presence of pargyline (a monoaminoxidase inhibitor), the effect of melatonin was not visible in the majority of the brain structures studied but could be seen in all of them in 5,7-dihydroxytryptamine-lesioned animals when serotonin storage and synthesis via a classic tryptophan pathway was diminished. Melatonin alone did not significantly increase extracellular serotonin concentration in the striatum of naïve rats but raised its content in pargyline-pretreated animals (model B). The CYP2D inhibitor propafenone given intrastructurally prevented the melatonin-induced increase in striatal serotonin in those animals. The obtained results indicate that melatonin supports CYP2D-catalyzed serotonin synthesis from 5-methoxytryptamine in the brain in vivo, which closes the serotonin-melatonin-serotonin biochemical cycle. The metabolism of exogenous melatonin to the neurotransmitter serotonin may be regarded as a newly recognized additional component of its pharmacological action.

  20. 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.

  1. Physiologic and Pharmacokinetic Changes in Pregnancy

    Directory of Open Access Journals (Sweden)

    Maged eCostantine

    2014-04-01

    Full Text Available Physiologic changes in pregnancy induce profound alterations to the pharmacokinetic properties of many medications. These changes affect distribution, absorption, metabolism, and excretion of drugs, and thus may impact their pharmacodynamic properties during pregnancy. Pregnant women undergo several adaptations in many organ systems. Some adaptations are secondary to hormonal changes in pregnancy, while others occur to support the gravid woman and her developing fetus. Some of the changes in maternal physiology during pregnancy include, for example, increased maternal fat and total body water, decreased plasma protein concentrations, especially albumin, increased maternal blood volume, cardiac output and blood flow to the kidneys and uteroplacental unit, and decreased blood pressure. The maternal blood volume expansion occurs at a larger proportion than the increase in red blood cell mass, which results in physiologic anemia and hemodilution. Other physiologic changes include increased tidal volume, partially compensated respiratory alkalosis, delayed gastric emptying and gastrointestinal motility, and altered activity of hepatic drug metabolizing enzymes. Understating these changes and their profound impact on the pharmacokinetic properties of drugs in pregnancy is essential to optimize maternal and fetal health.

  2. Physiologic and pharmacokinetic changes in pregnancy.

    Science.gov (United States)

    Costantine, Maged M

    2014-01-01

    Physiologic changes in pregnancy induce profound alterations to the pharmacokinetic properties of many medications. These changes affect distribution, absorption, metabolism, and excretion of drugs, and thus may impact their pharmacodynamic properties during pregnancy. Pregnant women undergo several adaptations in many organ systems. Some adaptations are secondary to hormonal changes in pregnancy, while others occur to support the gravid woman and her developing fetus. Some of the changes in maternal physiology during pregnancy include, for example, increased maternal fat and total body water, decreased plasma protein concentrations, especially albumin, increased maternal blood volume, cardiac output, and blood flow to the kidneys and uteroplacental unit, and decreased blood pressure. The maternal blood volume expansion occurs at a larger proportion than the increase in red blood cell mass, which results in physiologic anemia and hemodilution. Other physiologic changes include increased tidal volume, partially compensated respiratory alkalosis, delayed gastric emptying and gastrointestinal motility, and altered activity of hepatic drug metabolizing enzymes. Understating these changes and their profound impact on the pharmacokinetic properties of drugs in pregnancy is essential to optimize maternal and fetal health.

  3. Schizophrenia-like disruptions of sensory gating by serotonin receptor stimulation in rats: effect of MDMA, DOI and 8-OH-DPAT.

    Science.gov (United States)

    Thwaites, Shane J; Gogos, Andrea; Van den Buuse, Maarten

    2013-11-01

    Schizophrenia pathophysiology is associated with alterations in several neurotransmitter systems, particularly dopamine, glutamate and serotonin (5-HT). Schizophrenia patients also have disruptions in sensory gating, a brain information filtering mechanism in response to repeated sensory stimuli. Dopamine and glutamate have been implicated in sensory gating; however, little is known about the contribution of serotonin. We therefore investigated the effects of several psychoactive compounds that alter serotonergic neuronal activity on event-related potentials (ERP) to paired auditory pulses. Male Sprague-Dawley rats were implanted with cortical surface electrodes to measure ERPs to 150 presentations of two 85 dB bursts of white noise, 500 ms apart (S1 and S2). Saline-treated animals suppressed the response to S2 to less than 50% of S1. In contrast, treatment with the serotonin releaser, MDMA (ecstasy; 2.0mg/kg), the 5-HT2A/2C receptor agonist, DOI (0.5mg/kg), or the 5-HT1A/7 receptor agonist, 8-OH-DPAT (0.5mg/kg), caused an increase in S2/S1 ratios. Analysis of waveform components suggested that the S2/S1 ratio disruption by MDMA was due to subtle effects on the ERPs to S1 and S2; DOI caused the disruption primarily by reducing the ERP to S1; 8-OH-DPAT-induced disruptions were due to an increase in the ERP to S2. These results show that 5-HT receptor stimulation alters S2/S1 ERP ratios in rats. These results may help to elucidate the sensory gating deficits observed in schizophrenia patients.

  4. Reproduction, physiology and biochemistry

    Science.gov (United States)

    This chapter summarizes fundamental knowledge and recent discoveries about the reproduction, physiology and biochemistry of plant-parasitic nematodes. Various types of reproduction are reviewed, including sexual reproduction and mitotic and meiotic parthenogenesis. Although much is known about the p...

  5. 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

  6. 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

  7. Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats Role of serotonin synthesis

    NARCIS (Netherlands)

    Bosker, Fokko J.; Tanke, Marit A. C.; Jongsma, Minke E.; Cremers, Thomas I. F. H.; Jagtman, Evelien; Pietersen, Charmaine Y.; van der Hart, Marieke G. C.; Gladkevich, Anatoliy V.; Kema, Ido P.; Westerink, Ben H. C.; Korf, Jakob; den Boer, Johan A.

    2010-01-01

    We have investigated effects of continuous SSRI administration and abrupt discontinuation on biochemical and behavioral indices of rat brain serotonin function and attempted to identify underlying mechanisms Biochemistry of serotonin was assessed with brain tissue assays and microdialysis behavior w

  8. 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.

  9. 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...

  10. 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

    Postmortem investigations and the receptor affinity profile of atypical antipsychotics have implicated the participation of serotonin(2A) receptors in the pathophysiology of schizophrenia. Most postmortem studies point toward lower cortical serotonin(2A) binding in schizophrenic patients. However...

  11. Amphetamine Action at the Cocaine- and Antidepressant-Sensitive Serotonin Transporter Is Modulated by αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Montgomery, Therese R; Hofmaier, Tina

    2015-01-01

    Serotonergic neurotransmission is terminated by reuptake of extracellular serotonin (5-HT) by the high-affinity serotonin transporter (SERT). Selective 5-HT reuptake inhibitors (SSRIs) such as fluoxetine or escitalopram inhibit SERT and are currently the principal treatment for depression...

  12. Transporters in human platelets: physiologic function and impact for pharmacotherapy.

    Science.gov (United States)

    Jedlitschky, Gabriele; Greinacher, Andreas; Kroemer, Heyo K

    2012-04-12

    Platelets store signaling molecules (eg, serotonin and ADP) within their granules. Transporters mediate accumulation of these molecules in platelet granules and, on platelet activation, their translocation across the plasma membrane. The balance between transporter-mediated uptake and elimination of signaling molecules and drugs in platelets determines their intracellular concentrations and effects. Several members of the 2 major transporter families, ATP-binding cassette (ABC) transporters and solute carriers (SLCs), have been identified in platelets. An example of an ABC transporter is MRP4 (ABCC4), which facilitates ADP accumulation in dense granules. MRP4 is a versatile transporter, and various additional functions have been proposed, notably lipid mediator release and a role in aspirin resistance. Several other ABC proteins have been detected in platelets with functions in glutathione and lipid homeostasis. The serotonin transporter (SERT, SLC6A4) in the platelet plasma membrane represents a well-characterized example of the SLC family. Moreover, recent experiments indicate expression of OATP2B1 (SLCO2B1), a high affinity transporter for certain statins, in platelets. Changes in transporter localization and expression can affect platelet function and drug sensitivity. This review summarizes available data on the physiologic and pharmacologic role of transporters in platelets.

  13. 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.

  14. Effect of daytime-restricted feeding in the daily variations of liver metabolism and blood transport of serotonin in rat

    OpenAIRE

    Valdés-Fuentes, Marlen; Vera-Rivera, Gabriela; De Ita-Pérez, Dalia; Méndez, Isabel; Miranda, María Isabel; Díaz-Muñoz, Mauricio

    2015-01-01

    The biogenic amine serotonin is a signaling molecule in the gastrointestinal tract, platelets, and nervous tissue. In nervous system, serotonin and its metabolites are under the control of the circadian timing system, but it is not known if daily variations of serotonin exist in the liver. To explore this possibility, we tested if the rhythmic pattern of serotonin metabolism was regulated by daytime restricted feeding (DRF) which is a protocol associated to the expression of the food entraine...

  15. 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....

  16. 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.

  17. Reduced serotonin synthesis and regional cerebral blood flow after anxiolytic treatment of social anxiety disorder.

    Science.gov (United States)

    Frick, Andreas; Åhs, Fredrik; Appel, Lieuwe; Jonasson, My; Wahlstedt, Kurt; Bani, Massimo; Merlo Pich, Emilio; Bettica, Paolo; Långström, Bengt; Lubberink, Mark; Fredrikson, Mats; Furmark, Tomas

    2016-11-01

    Social anxiety disorder (SAD) is associated with increased fear-related neural activity in the amygdala and we recently found enhanced serotonin synthesis rate in the same region. Anxiolytic agents like selective serotonin re-uptake inhibitors (SSRIs) and neurokinin-1 receptor (NK1R) antagonists reduce amygdala activity and may attenuate serotonin formation according to animal studies. Here, we examined the effects of SSRI pharmacotherapy, NK1R antagonism, and placebo on serotonin synthesis rate in relation to neural activity, measured as regional cerebral blood flow (rCBF), and symptom improvement in SAD. Eighteen SAD patients were randomized to receive daily double-blind treatment for six weeks either with the SSRI citalopram (n=6; 40mg), the NK1R antagonist GR205171 (n=6; 5mg; 4 weeks following 2 weeks of placebo), or placebo (n=6). Serotonin synthesis rate at rest and rCBF during stressful public speaking were assessed, before and after treatment, using positron emission tomography with the tracers [(11)C]5-hydroxytryptophan and [(15)O]water respectively. The Liebowitz Social Anxiety Scale (LSAS-SR) indexed symptom severity. All groups exhibited attenuated amygdala serotonin synthesis rate after treatment, which was associated with reduced amygdala rCBF during public speaking and accompanied by symptom improvement. These results are consistent with the notion that serotonin in the amygdala exerts an anxiogenic influence and, conversely, that anxiolysis is achieved through decreased serotonin formation in the amygdala.

  18. Fast-scan cyclic voltammetry analysis of dynamic serotonin reponses to acute escitalopram.

    Science.gov (United States)

    Wood, Kevin M; Hashemi, Parastoo

    2013-05-15

    The treatment of depression with selective serotonin reuptake inhibitors, SSRIs, is important to study on a neurochemical level because of the therapeutic variability experienced by many depressed patients. We employed the rapid temporal capabilities of fast scan cyclic voltammetry at carbon fiber microelectrodes to study the effects of a popular SSRI, escitalopram (ESCIT), marketed as Lexapro, on serotonin in mice. We report novel, dynamic serotonin behavior after acute ESCIT doses, characterized by a rapid increase in stimulated serotonin release and a gradual rise in serotonin clearance over 120 min. Dynamic changes after acute SSRI doses may be clinically relevant to the pathology of increased depression or suicidality after onset of antidepressant treatment. Due to the short-term variability of serotonin responses after acute ESCIT, we outline difficulties in creating dose response curves and we suggest effective means to visualize dynamic serotonin changes after SSRIs. Correlating chemical serotonin patterns to clinical findings will allow a finer understanding of SSRI mechanisms, ultimately providing a platform for reducing therapeutic variability.

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

    NARCIS (Netherlands)

    Ripken, D.; Wielen, N. van der; Wortelboer, H.M.; Meijerink, J.; Witkamp, R.F.; Hendriks, H.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 fo

  20. 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. 862.1390 Section 862.1390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Test Systems § 862.1390 5-Hydroxyindole acetic acid/serotonin test system. (a) Identification. A...