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https://www.readbyqxmd.com/read/29466326/structure-of-the-d-2-dopamine-receptor-bound-to-the-atypical-antipsychotic-drug-risperidone
#1
Sheng Wang, Tao Che, Anat Levit, Brian K Shoichet, Daniel Wacker, Bryan L Roth
Dopamine is a neurotransmitter that has been implicated in processes as diverse as reward, addiction, control of coordinated movement, metabolism and hormonal secretion. Correspondingly, dysregulation of the dopaminergic system has been implicated in diseases such as schizophrenia, Parkinson's disease, depression, attention deficit hyperactivity disorder, nausea and vomiting, among others. Dopamine's actions are mediated by a family of five G-protein coupled receptors (GPCRs) (viz. D1 , D2 , D3 , D4 and D5 )1 ...
January 24, 2018: Nature
https://www.readbyqxmd.com/read/29423959/low-resilience-to-stress-is-associated-with-candidate-gene-expression-alterations-in-the-dopaminergic-signalling-pathway
#2
Esfandiar Azadmarzabadi, Arvin Haghighatfard, Alireza Mohammadi
BACKGROUND: In stressful situations, a person's ability to appropriately complete tasks with minimal anxiety is known as stress resilience. Genetic variants in neuropeptide Y, Corticotropin releasing hormone receptor 1 (CRHR1), and serotonin transporter have been previously reported to be associated with low resilience, but the relationship between low resilience and the dopaminergic signalling pathway is not well understood. Here, we aimed to describe the association between comprehensive psychological characteristics and messenger RNA levels of dopamine receptor D1 (DRD1), dopamine receptor D2 (DRD2), dopamine receptor D3 (DRD3), dopamine receptor D4 (DRD4), dopamine receptor D5 (DRD5), COMT, Dopamine Beta-Hydroxylase (DBH), Tyrosine hydroxylase (TH), monoamine oxidase A (MAOM), dopa decarboxylase (DDC), dopamine transporter (DAT), serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) genes based on peripheral blood samples from 400 subjects who react differently to major life event stressors...
February 8, 2018: Psychogeriatrics: the Official Journal of the Japanese Psychogeriatric Society
https://www.readbyqxmd.com/read/29396617/resistance-exercise-decreases-heroin-self-administration-and-alters-gene-expression-in-the-nucleus-accumbens-of-heroin-exposed-rats
#3
Mark A Smith, Gaylen E Fronk, Jean M Abel, Ryan T Lacy, Sarah E Bills, Wendy J Lynch
RATIONALE: Preclinical studies consistently report that aerobic exercise decreases drug self-administration and other forms of drug-seeking behavior; however, relatively few studies have examined other types of physical activity. OBJECTIVES: The purpose of the present study was to examine the effects of resistance exercise (i.e., strength training) on heroin self-administration and mRNA expression of genes known to mediate opioid reinforcement and addictive behavior in the nucleus accumbens (NAc) of heroin-exposed rats...
February 2, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29234042/cfdna-correlates-with-endothelial-damage-after-cardiac-surgery-with-prolonged-cardiopulmonary-bypass-and-amplifies-netosis-in-an-intracellular-tlr9-independent-manner
#4
Adnana Paunel-Görgülü, Max Wacker, Mouhamed El Aita, Shoreshfan Hassan, Georg Schlachtenberger, Antje Deppe, Yeong-Hoon Choi, Elmar Kuhn, Thorsten O Mehler, Thorsten Wahlers
Cardiopulmonary bypass (CPB) provokes inflammation culminating in organ dysfunction and increased mortality. Recently, neutrophil extracellular traps (NETs) have been found to be involved in a variety of cardiovascular diseases promoting tissue and organ injury. Here, we aimed to elaborate the proinflammatory potential of circulating cell-free (cf)DNA in patients undergoing cardiac surgery with CPB. Plasma was collected pre- and postoperatively as well as at d1, d3, d5 and d8 after surgery. At d1, we found circulating cfDNA levels to be significantly increased in patients with prolonged CPB duration (>100 min) when compared to those with shorter CPB times (CPB < 100 min)...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29228131/synaptic-potentiation-at-basal-and-apical-dendrites-of-hippocampal-pyramidal-neurons-involves-activation-of-a-distinct-set-of-extracellular-and-intracellular-molecular-cues
#5
Patrycja Brzdak, Olga Wójcicka, Monika Zareba-Koziol, Daniel Minge, Christian Henneberger, Jakub Wlodarczyk, Jerzy W Mozrzymas, Tomasz Wójtowicz
In the central nervous system, several forms of experience-dependent plasticity, learning and memory require the activity-dependent control of synaptic efficacy. Despite substantial progress in describing synaptic plasticity, mechanisms related to heterogeneity of synaptic functions at local circuits remain elusive. Here we studied the functional and molecular aspects of hippocampal circuit plasticity by analyzing excitatory synapses at basal and apical dendrites of mouse hippocampal pyramidal cells (CA1 region) in acute brain slices...
December 8, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29214400/vasomodulatory-effects-of-the-angiotensin-ii-type-1-receptor-antagonist-losartan-on-experimentally-induced-cerebral-vasospasm-after-subarachnoid-haemorrhage
#6
Stefan Wanderer, Jan Mrosek, Gessler Florian, Seifert Volker, Juergen Konczalla
BACKGROUND: Cerebral vasospasm following subarachnoid haemorrhage (SAH) remains one of the major factors contributing to poor overall patient outcome. Prostaglandin F2-alpha (PGF2a) induces vasoconstriction. After SAH, PGF2a leads to cerebral inflammation and enhanced vasoconstriction, resulting in cerebral vasospasm. Losartan is already known to have beneficial effects in stroke models and also on several cerebral inflammatory processes. Therefore, the aim of the study was to analyse the effect of losartan on PGF2a-enhanced vasoconstriction after SAH...
December 6, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/29178941/s100a8-a9-and-srage-kinetic-after-polytrauma-an-explorative-observational-study
#7
Philippe Joly, John C Marshall, Philippe A Tessier, Chantal Massé, Nathalie Page, Anne Julie Frenette, François Khazoom, Soazig Le Guillan, Yves Berthiaume, Emmanuel Charbonney
BACKGROUND: Following tissue injury after trauma, the activation of innate immune pathways results in systemic inflammation, organ failure and an increased risk of infections. The objective of this study was to characterize the kinetics of the S100A8/S100A9 complex, a new-recognized alarmin, as well as its soluble receptor sRAGE, over time after trauma as potential early biomarkers of the risk of organ damage. METHODS: We collected comprehensive data from consenting patients admitted to an ICU following severe trauma...
November 25, 2017: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
https://www.readbyqxmd.com/read/29167404/a-critical-role-for-dopamine-d5-receptors-in-pain-chronicity-in-male-mice
#8
Salim Megat, Stephanie Shiers, Jamie K Moy, Paulino Barragan-Iglesias, Grishma Pradhan, Rebecca P Seal, Gregory Dussor, Theodore J Price
Dopaminergic modulation of spinal cord plasticity has long been recognized but circuits affected by this system and the precise receptor subtypes involved in this modulation have not been defined. Dopaminergic modulation from the A11 nucleus of the hypothalamus contributes to plasticity in a model of chronic pain called hyperalgesic priming. Here we tested the hypothesis that the key receptor subtype mediating this effect is the D5 receptor (D5R). We find that a spinally-directed lesion of dopaminergic neurons reverses hyperalgesic priming in both sexes and that a D1/D5 antagonist transiently inhibits neuropathic pain...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29164312/efficacy-and-safety-of-rotigotine-in-elderly-patients-with-parkinson-s-disease-in-comparison-with-the-non-elderly-a-post-hoc-analysis-of-randomized-double-blind-placebo-controlled-trials
#9
Masahiro Nomoto, Hirotaka Iwaki, Hiroyuki Kondo, Masaya Sakurai
Rotigotine-a non-ergot dopamine agonist-has two advantages; it can stimulate all dopamine receptors (D1-D5) like innate dopamine, and its transdermal administration provides continuous dopaminergic stimulation. The age of the patient impacts the effect and adverse events of anti-parkinsonian treatment. We conducted a post hoc analysis on three randomized, double-blind, placebo-controlled trials performed in Japan to clarify the difference of anti-parkinsonian treatment in elderly and non-elderly patients. Data from two combination therapy trials (with levodopa) in advanced stage Parkinson's disease patients and one monotherapy trial in early stage patients were pooled and grouped by age (non-elderly aged < 70, elderly aged 70 +)...
November 21, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/29163081/activation-of-d1-5-dopamine-receptors-in-the-dorsal-medial-prefrontal-cortex-promotes-incubated-like-aversive-responses
#10
Fernando Castillo Díaz, Cecilia P Kramar, Micaela A Hernandez, Jorge H Medina
It is well established that neurons of the mammalian medial prefrontal cortex (mPFC) modulate different behavioral outputs, including several memory types. This behavioral modulation is, at least in part, under the control of the D1-like Dopamine (DA) receptor (D1/5R) which comprises D1 and D5-specific subtypes (D1R and D5R, respectively). Here, combining a set of behavioral assays with pharmacology, we determined whether the activation of D1/5R in the mPFC during almost neutral or weak negative-valence experiences induces aversive behaviors...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29123927/locus-coeruleus-and-dopamine-dependent-memory-consolidation
#11
REVIEW
Miwako Yamasaki, Tomonori Takeuchi
Most everyday memories including many episodic-like memories that we may form automatically in the hippocampus (HPC) are forgotten, while some of them are retained for a long time by a memory stabilization process, called initial memory consolidation. Specifically, the retention of everyday memory is enhanced, in humans and animals, when something novel happens shortly before or after the time of encoding. Converging evidence has indicated that dopamine (DA) signaling via D1/D5 receptors in HPC is required for persistence of synaptic plasticity and memory, thereby playing an important role in the novelty-associated memory enhancement...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29119585/effects-of-dopamine-receptor-antagonist-antipsychotic-therapy-on-blood-pressure
#12
REVIEW
N H Gonsai, V H Amin, C G Mendpara, R Speth, G M Hale
WHAT IS KNOWN AND OBJECTIVE: Hypertension, a major risk factor for adverse cardiovascular events, such as stroke and myocardial infarction, affects 80 million American adults. The aetiology of hypertension is multifaceted and difficult to identify. Dopamine receptors, especially those in the kidneys, play a role in blood pressure regulation, and alterations in their function can cause hypertension. The objective of this review was to investigate the association between the use of dopamine antagonists with hypertension focusing especially on second-generation antipsychotics, like clozapine that is D4 receptor antagonist...
November 8, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29106549/the-in-vitro-actions-of-loxapine-on-dopaminergic-and-serotonergic-receptors-time-to-consider-atypical-classification-of-this-antipsychotic-drug
#13
Florian Ferreri, Dominique Drapier, Emmanuelle Baloche, Mehemed Ouzid, Luc Zimmer, Pierre-Michel Llorca
Background: The denomination of typical antipsychotic for loxapine has poor relation to current knowledge of the molecule's relevant modes of action. Method: Competition binding experiments were performed on expressed human recombinant receptors in CHO cells and HEK-293 cells for D1 to D5, 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro autoradiographies using [ 11C]-Raclopride [18F]-Altanserin [18F]-MPPF [11C]-SB207145 and [18F]-2FNQ1P were measured in brain tissue of a male primate followed by addition of increasing doses of loxapine succinate...
November 2, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29056909/the-dopamine-d5-receptor-is-involved-in-working-memory
#14
Gregory V Carr, Federica Maltese, David R Sibley, Daniel R Weinberger, Francesco Papaleo
Pharmacological studies indicate that dopamine D1-like receptors (D1 and D5) are critically involved in cognitive function. However, the lack of pharmacological ligands selective for either the D1 or D5 receptors has made it difficult to determine the unique contributions of the D1-like family members. To circumvent these pharmacological limitations, we used D5 receptor homozygous (-/-) and heterozygous (+/-) knockout mice, to identify the specific role of this receptor in higher order cognitive functions. We identified a novel role for D5 receptors in the regulation of spatial working memory and temporal order memory function...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28975698/dopamine-d4-receptor-activation-restores-ca1-ltp-in-hippocampal-slices-from-aged-mice
#15
Fangli Guo, Jianhua Zhao, Dandan Zhao, Jiangang Wang, Xiaofang Wang, Zhiwei Feng, Martin Vreugdenhil, Chengbiao Lu
Normal aging is characterized with a decline in hippocampal memory functions that is associated with changes in long-term potentiation (LTP) of the CA3-to-CA1 synapse. Age-related deficit of the dopaminergic system may contribute to impairment of CA1 LTP. Here we assessed how the modulation of CA1 LTP by dopamine is affected by aging and how it is dependent on the Ca(2+) source. In slices from adult mice, the initial slope of the field potential showed strong LTP, but in slices from aged mice LTP was impaired...
December 2017: Aging Cell
https://www.readbyqxmd.com/read/28955227/stress-induced-reduction-of-dorsal-striatal-d2-dopamine-receptors-prevents-retention-of-a-newly-acquired-adaptive-coping-strategy
#16
Paolo Campus, Sonia Canterini, Cristina Orsini, Maria Teresa Fiorenza, Stefano Puglisi-Allegra, Simona Cabib
The inability to learn an adaptive coping strategy in a novel stressful condition leads to dysfunctional stress coping, a marker of mental disturbances. This study tested the involvement of dorsal striatal dopamine receptors in the dysfunctional coping with the Forced Swim test fostered by a previous experience of reduced food availability. Adult male mice were submitted to a temporary (12 days) reduction of food availability [food-restricted (FR)] or continuously free-fed (FF). Different groups of FF and FR mice were used to evaluate: (1) dorsal striatal mRNA levels of the two isoforms of the dopamine D2 receptor (D2S, D2L)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28950781/blockade-of-dopamine-d1-family-receptors-attenuates-the-mania-like-hyperactive-risk-preferring-and-high-motivation-behavioral-profile-of-mice-with-low-dopamine-transporter-levels
#17
Morgane Milienne-Petiot, Lucianne Groenink, Arpi Minassian, Jared W Young
BACKGROUND: Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D1-family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice...
October 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28940477/camp-levels-in-lymphocytes-and-cd4-regulatory-t-cell-functions-are-affected-by-dopamine-receptor-gene-polymorphisms
#18
Marco Cosentino, Natasa Kustrimovic, Marco Ferrari, Emanuela Rasini, Franca Marino
The neurotransmitter dopamine (DA) has prominent effects in the immune system and between the immune cells, CD4+ regulatory T lymphocytes (Treg), a specialized T cell subsets crucial for the control of immune homeostasis, are especially sensitive to DA. Dopaminergic receptors (DR) are grouped into two families according to their pharmacological profile and main second messenger coupling: the D1 -like (D1 and D5 ) which activate adenylate cyclase and the D2 -like (D2 , D3 and D4 ) which inhibit adenylate cyclase and exist in several variants, which have been associated to clinical conditions such as schizophrenia, bipolar disorder, substance abuse and addiction...
September 20, 2017: Immunology
https://www.readbyqxmd.com/read/28922504/selective-remodeling-of-glutamatergic-transmission-to-striatal-cholinergic-interneurons-after-dopamine-depletion
#19
Jose de Jesus Aceves Buendia, Lior Tiroshi, Wei-Hua Chiu, Joshua A Goldberg
The widely held view that the pathophysiology of Parkinson's disease arises from an under-activation of the direct pathway striatal spiny neurons (dSPNs) has gained support from a recently described weakening of the glutamatergic projection from the parafascicular nucleus (PfN) to dSPNs in experimental parkinsonism. However, the impact of the remodeling of the thalamostriatal projection cannot be fully appreciated without considering its impact on cholinergic interneurons (ChIs) that themselves preferentially activate indirect pathway spiny neurons (iSPNs)...
September 18, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28894586/a-pilot-study-on-the-impact-of-dopamine-serotonin-and-brain-derived-neurotrophic-factor-genotype-on-long-term-functional-outcomes-after-subarachnoid-hemorrhage
#20
Ansley Stanfill, Claire Simpson, Paula Sherwood, Samuel Poloyac, Elizabeth Crago, Hyungsuk Kim, Yvette Conley
OBJECTIVES: Many that survive an aneurysmal subarachnoid hemorrhage experience lasting physical disability, which might be improved by medications with effects on the dopaminergic, serotonergic, and brain-derived neurotrophic factor neurotransmitter systems. But it is not clear which patients are most likely to benefit from these therapies. The purpose of this pilot study was to explore the relationship of genetic polymorphisms in these pathways with 12-month functional outcomes after aneurysmal subarachnoid hemorrhage...
2017: SAGE Open Medicine
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