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https://www.readbyqxmd.com/read/28326933/attenuation-of-hyperalgesia-responses-via-the-modulation-of-5-hydroxytryptamine-signalings-in-the-rostral-ventromedial-medulla-and-spinal-cord-in-a-6-hydroxydopamine-induced-rat-model-of-parkinson-s-disease
#1
Chen-Tao Wang, Cheng-Jie Mao, Xiao-Qi Zhang, Cai-Yi Zhang, Dong-Jun Lv, Ya-Ping Yang, Kai-Lin Xia, Jun-Yi Liu, Fen Wang, Li-Fang Hu, Guang-Yin Xu, Chun-Feng Liu
Background Although pain is one of the most distressing non-motor symptoms among patients with Parkinson's disease, the underlying mechanisms of pain in Parkinson's disease remain elusive. The aim of the present study was to investigate the role of serotonin (5-hydroxytryptamine) in the rostral ventromedial medulla (RVM) and spinal cord in pain sensory abnormalities in a 6-hydroxydopamine-treated rat model of Parkinson's disease. Methods The rotarod test was used to evaluate motor function. The radiant heat test and von Frey test were conducted to evaluate thermal and mechanical pain thresholds, respectively...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28326532/common-drug-side-effects-and-drug-drug-interactions-in-elderly-adults-in-primary-care
#2
Susan E Merel, Douglas S Paauw
Prescribing medications, recognizing and managing medication side effects and drug interactions, and avoiding polypharmacy are all essential skills in the care of older adults in primary care. Important side effects of medications commonly prescribed in older adults (statins, proton pump inhibitors, trimethoprim-sulfamethoxazole and fluoroquinolone antibiotics, zolpidem, nonsteroidal antiinflammatory drugs, selective serotonin reuptake inhibitors, dipeptidyl peptidase 4 inhibitors) were reviewed. Important drug interactions with four agents or classes (statins, warfarin, factor Xa inhibitors, and calcium channel blockers) are discussed...
March 21, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28326015/serotonin-regulates-the-firing-of-principal-cells-of-the-subiculum-by-inhibiting-a-t-type-ca-2-current
#3
Anders V Petersen, Camilla S Jensen, Valérie Crépel, Mathias Falkerslev, Jean-François Perrier
The subiculum is the main output of the hippocampal formation. A high proportion of its principal neurons fire action potentials in bursts triggered by the activation of low threshold calcium currents. This firing pattern promotes synaptic release and regulates spike-timing-dependent plasticity. The subiculum receives a high density of fibers originating from the raphe nuclei, suggesting that serotonin (5-HT) modulates subicular neurons. Here we investigated if and how 5-HT modulates the firing pattern of bursting neurons...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28325682/5-httlpr-moderates-the-association-between-attention-away-from-angry-faces-and-prospective-depression-among-youth
#4
Jessica L Jenness, Jami F Young, Benjamin L Hankin
Attention bias to emotion has been studied as a risk factor associated with depression. No study has examined whether attention bias within the context of measured genetic risk leads to increased risk for clinical depressive episodes over time. The current study investigated whether genetic risk, as indexed by the serotonin-transporter-linked polymorphic region (5-HTTLPR), moderated the relationship between attention bias to emotional faces and clinical depression onset prospectively across 18-months in a community sample of youth (n = 428; mean age = 11...
February 24, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28324844/serotonin-transporter-and-receptor-ligands-with-antidepressant-activity-as-neuroprotective-and-proapoptotic-agents
#5
REVIEW
Zdzislaw Chilmonczyk, Andrzej J Bojarski, Andrzej Pilc, Ingebrigt Sylte
Serotonin exhibits multiple non-neural functions involved in essential hypertension, early embryogenesis, follicle maturation and behaviour. The growth stimulatory effects of the neurotransmitter have been described for a variety of cell types. 5-HT was found to induce migration of the human prostate cancer cell lines - PC-3 and Du145 - and several 5-HT1A antagonists and serotonin reuptake inhibitors were reported to inhibit the growth of different tumour cell lines in vitro. Recent studies suggest that neurogenesis is involved in the action of antidepressants and an involvement of antidepressants in adult hippocampal neurogenesis has been demonstrated...
January 22, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28323941/the-diverse-metabolic-roles-of-peripheral-serotonin
#6
Alyce M Martin, Richard L Young, Lex Leong, Geraint B Rogers, Nick J Spencer, Claire F Jessup, Damien J Keating
Serotonin (5-hydroxytryptamine, 5-HT) is a multi-functional bioamine with important signaling roles in a range of physiological pathways. Almost all the 5-HT in our body is synthesized in specialized enteroendocrine cells within the gastrointestinal (GI) mucosa called enterochromaffin (EC) cells. These cells provide all our circulating 5-HT. While we have long appreciated the important roles of 5-HT within the gut including the modulation of GI motility, there is recently emerging evidence of the physiological and clinical significance of gut-derived 5-HT outside of the gut...
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323624/conventional-or-natural-pharmacotherapy-and-the-prevalence-of-anxiety-and-depression-during-menopause
#7
Dorota Kopciuch, Anna Paczkowska, Tomasz Zaprutko, Michał Michalak, Elżbieta Nowakowska
Context • Psychoneurological symptoms are present in nearly all women in the perimenopausal period. Key elements of care in the period may include hormone replacement therapy (HRT). Alternatively, phytoestrogens, antidepressant pharmacotherapy, or a combination of hormonal and antidepressant therapies may be recommended. Objective • The study intended to verify whether women who are menopausal believe that a reduction in their symptoms of anxiety and depression depends on the type of pharmacotherapy used...
March 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28323425/structure-based-design-of-highly-selective-and-potent-g-protein-coupled-receptor-kinase-2-inhibitors-based-on-paroxetine
#8
Helen V Waldschmidt, Kristoff T Homan, Marilyn C Cato, Osvaldo Cruz-Rodríguez, Alessandro Cannavo, Michael W Wilson, Jianliang Song, Joseph Y Cheung, Walter J Koch, John J G Tesmer, Scott D Larsen
In heart failure, the β-adrenergic receptors (βARs) become desensitized and uncoupled from heterotrimeric G proteins. This process is initiated by G protein-coupled receptor kinases (GRKs), some of which are upregulated in the failing heart making them desirable therapeutic targets. The selective serotonin reuptake inhibitor, paroxetine, was previously identified as a GRK2 inhibitor. Utilizing a structure based drug design approach we modified paroxetine to generate a small compound library. Included in this series is a highly potent and selective GRK2 inhibitor, 14as, with an IC50 of 30 nM against GRK2 and greater than 230-fold selectivity over other GRKs and kinases...
March 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28323288/citalopram-amplifies-the-influence-of-living-conditions-on-mood-in-depressed-patients-enrolled-in-the-star-d-study
#9
F Chiarotti, A Viglione, A Giuliani, I Branchi
Selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressant drugs, have a variable and incomplete efficacy. In order to better understand SSRI action, we explored the hypothesis that SSRIs do not affect mood per se but amplify the influence of the living conditions on mood. To this aim, we exploited the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) data set, selected a subpopulation of 591 patients with an overlapping clinical history and analyzed treatment outcome according to dosage -20 or 40 mg per day of citalopram...
March 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28323287/experimental-medication-treatment-approaches-for-depression
#10
REVIEW
D F Ionescu, G I Papakostas
Depression is one of the most common psychiatric conditions. Symptoms can lead to significant disability, which result in impairments in overall quality of life. Though there are many approved antidepressant treatments for depression-including selective serotonin reuptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors-about a third of patients do not respond to these medications. Therefore, it is imperative for drug discovery to continue towards the development of novel and rapidly acting compounds, especially for patients with treatment-resistant depression...
March 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28323282/an-autism-associated-serotonin-transporter-variant-disrupts-multisensory-processing
#11
J K Siemann, C L Muller, C G Forsberg, R D Blakely, J Veenstra-VanderWeele, M T Wallace
Altered sensory processing is observed in many children with autism spectrum disorder (ASD), with growing evidence that these impairments extend to the integration of information across the different senses (that is, multisensory function). The serotonin system has an important role in sensory development and function, and alterations of serotonergic signaling have been suggested to have a role in ASD. A gain-of-function coding variant in the serotonin transporter (SERT) associates with sensory aversion in humans, and when expressed in mice produces traits associated with ASD, including disruptions in social and communicative function and repetitive behaviors...
March 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28322832/dapoxetine-induces-neuroprotective-effects-against-glutamate-induced-neuronal-cell-death-by-inhibiting-calcium-signaling-and-mitochondrial-depolarization-in-cultured-rat-hippocampal-neurons
#12
Imju Jeong, Ji Seon Yang, Yi Jae Hong, Hee Jung Kim, Sang June Hahn, Shin Hee Yoon
Selective serotonin reuptake inhibitors (SSRIs) have an inhibitory effect on various ion channels including Ca(2+) channels. We used fluorescent dye-based digital imaging, whole-cell patch clamping and cytotoxicity assays to examine whether dapoxetine, a novel rapid-acting SSRI, affect glutamate-induced calcium signaling, mitochondrial depolarization and neuronal cell death in cultured rat hippocampal neurons. Pretreatment with dapoxetine for 10min inhibited glutamate-induced intracellular free Ca(2+) concentration ([Ca(2+)]i) increases in a concentration-dependent manner (Half maximal inhibitory concentration= 4...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28322750/supradural-inflammatory-soup-in-awake-and-freely-moving-rats-induces-facial-allodynia-that-is-blocked-by-putative-immune-modulators
#13
Julie Wieseler, Amanda Ellis, Andrew McFadden, Kendra Stone, Kimberley Brown, Sara Cady, Leandro F Bastos, David Sprunger, Niloofar Rezvani, Kirk Johnson, Kenner C Rice, Steven F Maier, Linda R Watkins
Facial allodynia is a migraine symptom that is generally considered to represent a pivotal point in migraine progression. Treatment before development of facial allodynia tends to be more successful than treatment afterwards. As such, understanding the underlying mechanisms of facial allodynia may lead to a better understanding of the mechanisms underlying migraine. Migraine facial allodynia is modeled by applying inflammatory soup (histamine, bradykinin, serotonin, prostaglandin E2) over the dura. Whether glial and/or immune activation contributes to such pain is unknown...
March 16, 2017: Brain Research
https://www.readbyqxmd.com/read/28322281/identification-of-a-novel-fast-acting-gabaergic-antidepressant
#14
K M J McMurray, M J Ramaker, A M Barkley-Levenson, P S Sidhu, P K Elkin, M K Reddy, M L Guthrie, J M Cook, V H Rawal, L A Arnold, S C Dulawa, A A Palmer
Current pharmacotherapies for depression exhibit slow onset, side effects and limited efficacy. Therefore, identification of novel fast-onset antidepressants is desirable. GLO1 is a ubiquitous cellular enzyme responsible for the detoxification of the glycolytic byproduct methylglyoxal (MG). We have previously shown that MG is a competitive partial agonist at GABA-A receptors. We examined the effects of genetic and pharmacological inhibition of GLO1 in two antidepressant assay models: the tail suspension test (TST) and the forced swim test (FST)...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28322276/identifying-fast-onset-antidepressants-using-rodent-models
#15
M J Ramaker, S C Dulawa
Depression is a leading cause of disability worldwide and a major contributor to the burden of suicide. A major limitation of classical antidepressants is that 2-4 weeks of continuous treatment is required to elicit therapeutic effects, prolonging the period of depression, disability and suicide risk. Therefore, the development of fast-onset antidepressants is crucial. Preclinical identification of fast-onset antidepressants requires animal models that can accurately predict the delay to therapeutic onset. Although several well-validated assay models exist that predict antidepressant potential, few thoroughly tested animal models exist that can detect therapeutic onset...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28322272/neuroanatomic-epigenetic-and-genetic-differences-in-monozygotic-twins-discordant-for-attention-deficit-hyperactivity-disorder
#16
Y-C Chen, G Sudre, W Sharp, F Donovan, S C Chandrasekharappa, N Hansen, L Elnitski, P Shaw
The study of monozygotic twins discordant for attention deficit hyperactivity disorder can elucidate mechanisms that contribute to the disorder, which affects ~7% of children. First, using in vivo neuroanatomic imaging on 14 pairs of monozygotic twins (mean age 9.7, s.d. 1.9 years), we found that discordance for the disorder is mirrored by differing dimensions of deep brain structures (the striatum and cerebellum), but not the cerebral cortex. Next, using whole-blood DNA from the same twins, we found a significant enrichment of epigenetic differences in genes expressed in these 'discordant' brain structures...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28322235/impact-of-tryptophan-depletion-on-executive-system-function-during-menopause-is-moderated-by-childhood-adversity
#17
Sheila Shanmugan, James Loughead, Wen Cao, Mary D Sammel, Theodore D Satterthwaite, Kosha Ruparel, Ruben C Gur, C Neill Epperson
Many healthy women with no history of cognitive dysfunction experience subjective executive difficulties during menopause. Preclinical literature suggests latent effects of early life adversity on serotonin function may play a role in this phenomenon. However, evidence in human participants regarding the mechanisms by which loss of estradiol contributes to this vulnerability is lacking. Here we examined the impact of tryptophan depletion (TD) and adverse childhood experiences (ACE) on brain activation during a working memory task in menopausal women...
March 21, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28322190/activity-patterns-of-serotonin-neurons-underlying-cognitive-flexibility
#18
Sara Matias, Eran Lottem, Guillaume P Dugué, Zachary F Mainen
Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics. We found that these neurons are activated by both positive and negative prediction errors, and thus report signals similar to those proposed to promote learning in conditions of uncertainty...
March 21, 2017: ELife
https://www.readbyqxmd.com/read/28322166/glutamate-modulating-drugs-as-a-potential-therapeutic-strategy-in-obsessive-compulsive-disorder
#19
Zoya Marinova, De-Maw Chuang, Naomi Fineberg
OBJECTIVE: Obsessive-compulsive disorder (OCD) is a mental disease commonly associated with severe distress and impairment of social functioning. Serotonin reuptake inhibitors and/or cognitive behavioural therapy are the therapy of choice, however up to 40% of patients do not respond to treatment. Glutamatergic signalling has also been implicated in OCD. The aim of the current study was to review the clinical evidence for therapeutic utility of glutamate-modulating drugs as an augmentation or monotherapy in OCD patients...
March 20, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28322152/serotonin-receptor-binding-characteristics-of-geissoschizine-methyl-ether-an-indole-alkaloid-in-uncaria-hook
#20
Yasushi Ikarashi, Kyoji Sekiguchi, Kazushige Mizoguchi
Geissoschizine methyl ether (GM) is one of the indole alkaloids in Uncaria hook, and an active ingredient of yokukansan (YKS) that improves behavioral and psychological symptoms of dementia (BPSD) in patients with several types of dementia. The pharmacological action of GM has been related to various serotonin (5-HT) receptor subtypes. Here we describe previous findings and our own data to review the binding characteristics of GM to the 5-HT receptor subtypes. Competitive receptor-binding assays showed that GM bound the following 5-HT receptor subtypes: 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT4, 5-HT5A, 5-HT6, and 5-HT7...
March 20, 2017: Current Medicinal Chemistry
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