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5-HT, serotonin

Mikael Tiger, Katarina Varnäs, Yoshiro Okubo, Johan Lundberg
Major depressive disorder (MDD) is the leading cause of disability worldwide. The serotonin hypothesis may be the model of MDD pathophysiology with the most support. The majority of antidepressants enhance synaptic serotonin levels quickly, while it usually takes weeks to discern MDD treatment effect. It has been hypothesized that the time lag between serotonin increase and reduction of MDD symptoms is due to downregulation of inhibitory receptors such as the serotonin 1B receptor (5-HT1BR). The research on 5-HT1BR has previously been hampered by a lack of selective ligands for the receptor...
March 15, 2018: Psychopharmacology
Magdalena Kolasa, Joanna Solich, Agata Faron-Górecka, Dariusz Żurawek, Paulina Pabian, Sylwia Łukasiewicz, Maciej Kuśmider, Kinga Szafran-Pilch, Marta Szlachta, Marta Dziedzicka-Wasylewska
Recently, it has been shown that serotonin 5-HT1A receptor interacts with dopamine D2 receptor in vitro. However, the existence of 5-HT1A -D2 heteromers in native tissue remains unexplored. In the present study, we investigated 5-HT1A -D2 receptor heteromerization in mice treated acutely or chronically with paroxetine (10 mg/kg) or risperidone (0.05 mg/kg). Receptor heteromerization was visualized and quantified in the mouse brain by in situ proximity ligation assay (PLA). Additionally, we aimed to determine the cellular localization of 5-HT1A -D2 receptor heteromers in mouse adult primary neuronal cells by immunofluorescent staining with markers for astrocytes (GFAP) and neurons (NeuN and MAP2)...
March 12, 2018: Neuroscience
Alexander V Kulikov, Raul R Gainetdinov, Evgeni Ponimaskin, Allan V Kalueff, Vladimir S Naumenko, Nina K Popova
Selective serotonin reuptake inhibitors (SSRIs) are the most effective and most used antidepressant drugs. Acting by inhibiting serotonin (5-HT) transporter, SSRIs display a typical 3-4-week delay in their therapeutic effects, with nearly 40% of depressed patients remaining treatment-resistant. Recent evidence suggests complex interplay between 5-HT receptors and key proteins of 5-HT metabolism in molecular mechanisms of such delay and resistance to SSRIs. Area covered: This paper concentrates on the interplay between 5-HT receptors in the delay of therapeutic effect of SSRIs, and the interaction between tryptophan hydroxylase 2 and 5-HT transporter in the SSRI resistance...
March 15, 2018: Expert Opinion on Therapeutic Targets
Houari Boukersi, Nemcha Lebaili, Nathalie Samson, Sylvie Granon
The objective of this work was to investigate the implication of serotonin (5-HT) produced in the dorsal and medial raphé nuclei (DRN and MRN) in water homeostasis in desert animal Gerbillus tarabuli. For that, we measured the density of 5-HT immunolabeled neurons in hydrated and dehydrated animals (over 1 and six months). In this work, 5-HT positive neurons showed some change in shape and colour intensity in dehydrated gerbils comparing with hydrated gerbils. Furthermore a differential increase of 5-HT neurons density was observed in DRN subregions and in MRN following 1 and 6 months of dehydration...
March 9, 2018: Journal of Chemical Neuroanatomy
Patrick D Ganzer, Carl R Beringer, Jed S Shumsky, Chiemela Nwaobasi, Karen A Moxon
Severe spinal cord injury (SCI) damages descending motor and serotonin (5-HT) fiber projections leading to paralysis and serotonin depletion. 5-HT receptors (5-HTRs) subsequently upregulate following 5-HT fiber degeneration, and dendritic density decreases indicative of atrophy. 5-HT pharmacotherapy or exercise can improve locomotor behavior after SCI. One might expect that 5-HT pharmacotherapy acts on upregulated spinal 5-HTRs to enhance function, and that exercise alone can influence dendritic atrophy. In the current study, we assessed locomotor recovery and spinal proteins influenced by SCI and therapy...
March 8, 2018: Experimental Neurology
Eran Lottem, Dhruba Banerjee, Pietro Vertechi, Dario Sarra, Matthijs Oude Lohuis, Zachary F Mainen
The neuromodulator serotonin (5-HT) has been implicated in a variety of functions that involve patience or impulse control. Many of these effects are consistent with a long-standing theory that 5-HT promotes behavioral inhibition, a motivational bias favoring passive over active behaviors. To further test this idea, we studied the impact of 5-HT in a probabilistic foraging task, in which mice must learn the statistics of the environment and infer when to leave a depleted foraging site for the next. Critically, mice were required to actively nose-poke in order to exploit a given site...
March 8, 2018: Nature Communications
Angela D'Ascola, Giuseppe Bruschetta, Gabriella Zanghì, Salvatore Campo, Pietro Medica, Stefania Campana, Guido Ferlazzo, Bernhard F Gibbs, Alida Maria Ferlazzo
Serotonin (5-HT) is a neurohormone transported from plasma into platelets and leukocytes by a specific transporter (SERT). While it is known that the brain 5-HT system is modulated by physical exercise, the peripheral serotoninergic response to exercise is not yet fully elucidated. In particular, this study aimed to evaluate changes in plasma 5-HT levels and equine leukocyte SERT expression in response to treadmill exercise in untrained horses. Analyses were carried out pre- and post-treadmill exercise. 5-HT plasma levels were analysed by HPLC...
February 27, 2018: Research in Veterinary Science
Lianwei Mu, Dong Dong Xia, Teresa Michalkiewicz, Matthew Hodges, Gary Mouradian, Girija G Konduri, Margaret T T Wong-Riley
We have identified a critical period of respiratory development in rats at postnatal days P12-13, when inhibitory influence dominates and when the response to hypoxia is at its weakest. This critical period has significant implications for Sudden Infant Death Syndrome (SIDS), the cause of which remains elusive. One of the known risk factors for SIDS is prematurity. A common intervention used in premature infants is hyperoxic therapy, which, if prolonged, can alter the ventilatory response to hypoxia and induce sustained inhibition of lung alveolar growth and pulmonary remodeling...
March 2018: Physiological Reports
Tadashi Takada, Naoki Yoneda, Tetsushi Hirano, Shogo Yanai, Anzu Yamamoto, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Yoshiaki Tabuchi, Nobuhiko Hoshi
It has been suggested that an increase in the use of pesticides affects neurodevelopment, but there has been no animal experiment showing a causal relation between neonicotinoid pesticides (NNs) and depression. We examined whether dinotefuran (DIN), the most widely used NN in Japan, induces depression. Male mice were administered DIN between 3 and 8 weeks of age, referring to the no-observed-effect level (NOEL). The mice were then subjected to a tail suspension test (TST) and a forced swimming test (FST). After these tests, their brains were dissected for immunohistochemical analyses of serotonin (5-HT)...
March 8, 2018: Journal of Veterinary Medical Science
Julien Volle, Tatiana Bregman, Brian Scott, Mustansir Diwan, Roger Raymond, Paul J Fletcher, José N Nobrega, Clement Hamani
Both selective serotonin reuptake inhibitors (SSRIs) and ventromedial prefrontal cortex (vmPFC) deep brain stimulation (DBS) modulate serotonergic activity. We compared the acute (1 day) and long-term (12 days) effects of vmPFC stimulation and fluoxetine on serotonin (5-HT) release and receptor expression in rats. Samples to measure serotonin levels were collected from the hippocampus using microdialysis. Serotonin transporter (SERT), 5-HT1A and 5-HT1B mRNA were measured using in situ hybridization. [3 H]8-OH-DPAT and [125 I]cyanopindolol autoradiography were used to measure 5-HT1A and 5-HT1B binding...
March 2, 2018: Neuropharmacology
Michele M Moraes, Patrícia C R Rabelo, Valéria A Pinto, Washington Pires, Samuel P Wanner, Raphael E Szawka, Danusa D Soares
Listening to melodic music is regarded as a non-pharmacological intervention that ameliorates various disease symptoms, likely by changing the activity of brain monoaminergic systems. Here, we investigated the effects of exposure to melodic music on the concentrations of dopamine (DA), serotonin (5-HT) and their respective metabolites in the caudate-putamen (CPu) and nucleus accumbens (NAcc), areas linked to reward and motor control. Male adult Wistar rats were randomly assigned to a control group or a group exposed to music...
February 27, 2018: Neuroscience Letters
V P Nikitin, S V Solntseva, S A Kozyrev, P V Nikitin, A V Shevelkin
Elucidation of amnesia mechanisms is one of the central problems in neuroscience with immense practical application. Previously, we found that conditioned food presentation combined with injection of a neurotransmitter receptor antagonist or protein synthesis inhibitor led to amnesia induction. In the present study, we investigated the time course and features of two amnesias: induced by impairment of memory reconsolidation using an NMDA glutamate receptor antagonist (MK-801) and a serotonin receptor antagonist (methiothepin, MET) on snails trained with food aversion conditioning...
February 27, 2018: Behavioural Brain Research
Marta Szlachta, Maciej Kuśmider, Paulina Pabian, Joanna Solich, Magdalena Kolasa, Dariusz Żurawek, Marta Dziedzicka-Wasylewska, Agata Faron-Górecka
G-protein-coupled receptor (GPCR) heterodimers are new targets for the treatment of schizophrenia. Dopamine D2 receptors and serotonin 5-HT1A and 5-HT2A receptors play an important role in neurotransmission and have been implicated in many human psychiatric disorders, including schizophrenia. Therefore, in this study, we investigated whether antipsychotic drugs (clozapine (CLZ) and haloperidol (HAL)) affected the formation of heterodimers of D2 -5-HT1A receptors as well as 5-HT1A -5-HT2A receptors. Proximity ligation assay (PLA) was used to accurately visualize, for the first time, GPCR heterodimers both at in vitro and ex vivo levels...
2018: Frontiers in Molecular Neuroscience
Yu Kyong Kim, Kwang-Hee Shin, Jeffrey Alderman, Kyung-Sang Yu, In-Jin Jang, SeungHwan Lee
Background: Migraine is one of the most common headache disorders that greatly affect the quality of life. Selective serotonin (5-HT) receptor agonists such as triptamine-based drugs called triptans are used for treatment of migraine. Purpose: This study aimed to evaluate the pharmacokinetic (PK) and tolerability profiles of eletriptan hydrobromide (eletriptan HBr), a selective 5-hydroxytryptamine (also known as serotonin) 1B/1D receptor agonist, in Koreans and compare the results to those observed in non-Koreans in a previously published study...
2018: Drug Design, Development and Therapy
Farwa Sajadi, Carmela Curcuruto, Afra Al Dhaheri, Jean-Paul V Paluzzi
The mosquito, Aedes aegypti , is a vector responsible for transmitting various pathogens to humans, and their prominence as chief vectors of human disease is largely due to their anthropophilic blood feeding behaviour. Larval stage mosquitoes must deal with the potential dilution of their haemolymph in fresh water, whereas the haematophagus A. aegypti female faces the challenge of excess ion and water intake after a blood meal. The excretory system, comprised of the Malpighian tubules (MTs) and hindgut, is strictly controlled by neuroendocrine factors, responsible for the control of diuresis across all developmental stages...
March 1, 2018: Journal of Experimental Biology
Molly H B Amador, M Danielle McDonald
The serotonin transporter (SERT) functions in the uptake of the neurotransmitter serotonin (5-HT) from the extracellular milieu and is the molecular target of the selective serotonin reuptake inhibitors (SSRIs), a common group of antidepressants. The current study comprehensively assesses the sequence, tissue distribution, transport kinetics, and physiological function of a teleost SERT. The 2,022-bp toadfish SERT sequence encodes a protein of 673 amino acids, which shows 83% similarity to zebrafish SERT and groups with SERT of other teleosts in phylogenetic analysis...
February 27, 2018: Journal of Experimental Biology
Qiang Lu, Suguru Komenoi, Takako Usuki, Daisuke Takahashi, Fumio Sakane
We previously reported that brain-specific diacylglycerol kinase (DGK) δ-knockout (KO) mice showed obsessive-compulsive disorder (OCD)-like behaviors, which were alleviated by a serotonin (5-HT) transporter (SERT) inhibitor. However, the molecular mechanisms causing the OCD-like abnormal behaviors remain unclear. In the present study, we found that DGKδ deficiency increased SERT protein levels in the mouse cerebral cortex. Moreover, DGKδ interacted and co-localized with SERT. Furthermore, DGKδ-KO decreased tryptophan hydroxylase-2 expression and increased monoamine oxidase-A expression...
February 24, 2018: Biochemical and Biophysical Research Communications
Katsunori Nonogaki, Takao Kaji
A recent report suggested that brain-derived serotonin (5-HT) is critical for maintaining weight loss induced by glucagon-like peptide-1 (GLP-1) receptor activation in rats and that 5-HT2A receptors mediate the feeding suppression and weight loss induced by GLP-1 receptor activation. Here, we show that changes in daily food intake and body weight induced by intraperitoneal administration of liraglutide, a GLP-1 receptor agonist, over 4 days did not differ between mice treated with the tryptophan hydroxylase (Tph) inhibitor p-chlorophenylalanine (PCPA) for 3 days and mice without PCPA treatment...
2018: Journal of Diabetes Research
Françoise Dellu-Hagedorn, Marion Rivalan, Aurélie Fitoussi, Philippe De Deurwaerdère
Several impulse control disorders such as ADHD, mania, personality disorders or substance abuse share common behavioural traits, like impulsiveness, risk-taking or inflexible behaviour. These disorders are treated with drugs targeting dopamine (DA) and/or serotonin (5-HT). However, the patient's monoamine imbalance that these neurotransmitters compensate is unclear. This study aims to investigate the patterns of DA and 5-HT metabolisms at rest within selected brain regions related to inter-individual variability in six main components of impulsivity/compulsivity (anticipatory hyperactivity, premature responses, delay discounting, risk-taking, perseveration, flexibility)...
April 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Francis Delicata, Cristiano Bombardi, Massimo Pierucci, Roberto Di Maio, Philippe De Deurwaerdère, Giuseppe Di Giovanni
AIMS: Serotonergic (5-HT) modulation of the lateral habenula (LHb) activity is central in normal and pathologic conditions such as mood disorders. Among the multiple 5-HT receptors (5-HTRs) involved, the 5-HT2C R seems to play a pivotal role. Yet, the role of 5-HT2A Rs in the control of the LHb neuronal activity is completely unknown. METHODS: Single-cell extracellular recording of the LHb neurons was used in rats to study the effect of the general activation and blockade of the 5-HT2C R and 5-HT2A R with Ro 60-0175 and SB242084, TCB-2 and MDL11939, respectively...
February 25, 2018: CNS Neuroscience & Therapeutics
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