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https://www.readbyqxmd.com/read/28212944/acute-and-long-term-effects-of-adolescent-methylphenidate-on-decision-making-and-dopamine-receptor-mrna-expression-in-the-orbitofrontal-cortex
#1
Leslie R Amodeo, Eliza Jacobs-Brichford, Matthew S McMurray, Jamie D Roitman
Though commonly used as a treatment for ADHD, the psychostimulant methylphenidate (MPH) is also misused and abused in adolescence in both clinical and general populations. Although MPH acts via pathways activated by other drugs of abuse, the short- and long-term effects of MPH on reward processing in learning and decision-making are not clearly understood. We examined the effect of adolescent MPH treatment on a battery of reward-directed behaviors both in adolescence during its administration and in adulthood after its discontinuation...
February 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28209735/the-epac-phospholipase-c%C3%AE%C2%B5-pathway-regulates-endocannabinoid-signaling-and-cocaine-induced-disinhibition-of-vta-dopamine-neurons
#2
Jiaqing Tong, Xiaojie Liu, Casey Vickstrom, Yan Li, Laikang Yu, Youming Lu, Alan V Smrcka, Qing-Song Liu
Exchange protein directly activated by cAMP (Epac) is a direct effector for the ubiquitous second messenger cAMP. Epac activates the phospholipase Cε (PLCε) pathway. PLCβ has been linked to the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Here, we report that Epac facilitates endocannabinoid-mediated retrograde synaptic depression through activation of PLCε. Intracellular loading of a selective Epac agonist 8-CPT-2Me-cAMP into ventral tegmental area (VTA) dopamine neurons enabled previously ineffective stimuli to induce depolarization-induced suppression of inhibition (DSI) and long-term depression of IPSCs (I-LTD) in the VTA...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28197685/test-retest-measurements-of-dopamine-d1-type-receptors-using-simultaneous-pet-mri-imaging
#3
Simon Kaller, Michael Rullmann, Marianne Patt, Georg-Alexander Becker, Julia Luthardt, Johanna Girbardt, Philipp M Meyer, Peter Werner, Henryk Barthel, Anke Bresch, Thomas H Fritz, Swen Hesse, Osama Sabri
PURPOSE: The role of dopamine D1-type receptor (D1R)-expressing neurons in the regulation of motivated behavior and reward prediction has not yet been fully established. As a prerequisite for future research assessing D1-mediated neuronal network regulation using simultaneous PET/MRI and D1R-selective [(11)C]SCH23390, this study investigated the stability of central D1R measurements between two independent PET/MRI sessions under baseline conditions. METHODS: Thirteen healthy volunteers (7 female, age 33 ± 13 yrs) underwent 90-min emission scans, each after 90-s bolus injection of 486 ± 16 MBq [(11)C]SCH23390, on two separate days within 2-4 weeks using a PET/MRI system...
February 14, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28194935/a-potential-pet-radiotracer-for-the-5-ht2c-receptor-synthesis-and-in-vivo-evaluation-of-4-3-18-f-fluorophenethoxy-pyrimidine
#4
Juhyeon Kim, Byung Seok Moon, Byung Chul Lee, Ho-Young Lee, Hak Joong Kim, Hyunah Choo, Ae Nim Pae, Yong Seo Cho, Sun-Joon Min
The serotonin 2C receptor subtype (5-HT2C) is an excitatory 5-HT receptor widely distributed throughout the central nerve system. As the 5-HT2C receptor displays multiple actions on various neurotransmitter systems including glutamate, dopamine, epinephrine and -aminobutyric acid (GABA), abnormalities of the 5-HT2C receptor are associated with psychiatric diseases such as depression, schizophrenia, drug abuse, and anxiety. Up to date, three kinds of 5-HT2C PET radiotracers such as [11C]N-methylated arylazepine (1), [11C]WAY-163909 (2), [18F]fluorophenylcyclopropane (3) have been developed, but they may not be suitable for in vivo 5-HT2C imaging study due to their modest specific binding...
February 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28191490/dietary-triglycerides-as-signaling-molecules-that-influence-reward-and-motivation
#5
Chloé Berland, Céline Cansell, Thomas S Hnasko, Christophe Magnan, Serge Luquet
The reinforcing and motivational aspects of food are tied to the release of the dopamine in the mesolimbic system (ML). Free fatty acids from triglyceride (TG)-rich particles are released upon action of TG-lipases found at high levels in peripheral oxidative tissue (muscle, heart), but also in the ML. This suggests that local TG-hydrolysis in the ML might regulate food seeking and reward. Indeed, evidence now suggests that dietary TG directly target the ML to regulate amphetamine-induced locomotion and reward seeking behavior...
June 2016: Current Opinion in Behavioral Sciences
https://www.readbyqxmd.com/read/28188762/effects-of-the-5-ht6-receptor-antagonist-idalopirdine-on-extracellular-levels-of-monoamines-glutamate-and-acetylcholine-in-the-rat-medial-prefrontal-cortex
#6
Arne Mørk, Rasmus Vinther Russell, Inge E M de Jong, Gennady Smagin
Idalopirdine (Lu AE58054) is a high affinity and selective antagonist for the human serotonin 5-HT6 receptor (Ki 0.83nM) in phase III development for mild-to-moderate Alzheimer's disease as an adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We have studied the effects of idalopirdine on extracellular levels of monoamines, glutamate and acetylcholine in the medial prefrontal cortex (mPFC) of freely-moving rats using microdialysis. Idalopirdine (10mg/kg p.o.) increased extracellular levels of dopamine, noradrenaline and glutamate in the mPFC and showed a trend to increase serotonin levels...
February 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28187919/dopamine-d3-and-acetylcholine-nicotinic-receptor-heteromerization-in-midbrain-dopamine-neurons-relevance-for-neuroplasticity
#7
Leonardo Bontempi, Paola Savoia, Federica Bono, Chiara Fiorentini, Cristina Missale
Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer(2) (BRET(2)) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET(2) showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR...
February 7, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28187160/the-effects-of-dopamine-receptor-1-and-2-agonists-and-antagonists-on-sexual-and-aggressive-behaviors-in-male-green-anoles
#8
Alexandra N Smith, David Kabelik
The propensity to exhibit social behaviors during interactions with same-sex and opposite-sex conspecifics is modulated by various neurotransmitters, including dopamine. Dopamine is a conserved neurotransmitter among vertebrates and dopaminergic receptors are also highly conserved among taxa. Activation of D1 and D2 dopamine receptor subtypes has been shown to modulate social behaviors, especially in mammalian and avian studies. However, the specific behavioral functions of these receptors vary across taxa...
2017: PloS One
https://www.readbyqxmd.com/read/28186762/synthesis-and-pharmacological-characterization-of-novel-trans-cyclopropylmethyl-linked-bivalent-ligands-that-exhibit-selectivity-and-allosteric-pharmacology-at-the-dopamine-d3-receptor-d3r
#9
Vivek Kumar, Amy E Moritz, Thomas M Keck, Alessandro Bonifazi, Michael P Ellenberger, Christopher D Sibley, R Benjamin Free, Lei Shi, J Robert Lane, David R Sibley, Amy Hauck Newman
The development of bitopic ligands directed toward D2-like receptors has proven to be of particular interest to improve the selectivity and/or affinity of these ligands and as an approach to modulate and bias their efficacies. The structural similarities between dopamine D3 receptor (D3R)-selective molecules that display bitopic or allosteric pharmacology and those that are simply competitive antagonists are subtle and intriguing. Herein we synthesized a series of molecules in which the primary and secondary pharmacophores were derived from the D3R-selective antagonists SB269,652 (1) and SB277011A (2) whose structural similarity and pharmacological disparity provided the perfect templates for SAR investigation...
February 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28182408/design-synthesis-structure-activity-relationship-studies-and-three-dimensional-quantitative-structure-activity-relationship-3d-qsar-modeling-of-a-series-of-o-biphenyl-carbamates-as-dual-modulators-of-dopamine-d3-receptor-and-fatty-acid-amide-hydrolase
#10
Alessio De Simone, Debora Russo, Gian Filippo Ruda, Alessandra Micoli, Mariarosaria Ferraro, Rita Maria Concetta Di Martino, Giuliana Ottonello, Maria Summa, Andrea Armirotti, Tiziano Bandiera, Andrea Cavalli, Giovanni Bottegoni
We recently reported molecules designed according to the multi-target-directed ligand paradigm to exert combined activity at human fatty acid amide hydrolase (FAAH) and dopamine receptor subtype D3 (D3R). Both targets are relevant for tackling several types of addiction (most notably nicotine addiction) and other compulsive behaviors. Here, we report an SAR exploration of a series of biphenyl-N-[4-[4-(2,3-substituted-phenyl)piperazine-1-yl]alkyl]carbamates, a novel class of molecules that had shown promising activities at the FAAH - D3R target combination in preliminary studies...
February 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28181484/bim-23a760-influences-key-functional-endpoints-in-pituitary-adenomas-and-normal-pituitaries-molecular-mechanisms-underlying-the-differential-response-in-adenomas
#11
Alejandro Ibáñez-Costa, Laura M López-Sánchez, Manuel D Gahete, Esther Rivero-Cortés, Mari C Vázquez-Borrego, María A Gálvez, Andrés de la Riva, Eva Venegas-Moreno, Luis Jiménez-Reina, Alberto Moreno-Carazo, Francisco J Tinahones, Silvia Maraver-Selfa, Miguel A Japón, Juan A García-Arnés, Alfonso Soto-Moreno, Susan M Webb, Rhonda D Kineman, Michael D Culler, Justo P Castaño, Raúl M Luque
Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca(2+) signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3-5)...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181134/the-effect-and-mechanism-of-dopamine-d1-receptors-on-the-proliferation-of-osteosarcoma-cells
#12
Jun Gao, Chao Zhang, Feng Gao, Hongzhu Li
The physiological and pathological roles of dopamine D1 receptors (DR1) in the regulation of functions in tissues and organs have been recognized. However, whether DR1 are expressed in the osteosarcoma cells and inhibit the proliferation of these cells is unknown. In the present study, we found that DR1 were expressed in the osteosarcoma cells (OS732 cells). SKF-38393 (DR1 agonist) and the overexpression of DR1 decreased the proliferation of OS732 cells; SCH-23390 (DR1 antagonist) and the knockdown of DR1 increased the proliferation of OS732 cells, and both SCH-23390 and the knockdown of DR1 abolished the effect of SKF-38393 on the proliferation of OS732 cells...
February 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28181071/neurotrophic-effect-of-asiatic-acid-a-triterpene-of-centella-asiatica-against-chronic-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-hydrochloride-probenecid-mouse-model-of-parkinson-s-disease-the-role-of-mapk-pi3k-akt-gsk3%C3%AE-and-mtor-signalling-pathways
#13
Jagatheesan Nataraj, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa
Regulation of various signalling (Ras-MAPK, PI3K and AKT) pathways by augmented activity of neurotrophic factors (NTFs) could prevent or halt the progress of dopaminergic loss in Parkinson's disease (PD). Various in vitro and in vivo experimental studies indicated anti-parkinsonic potential of asiatic acid (AA), a pentacyclic triterpene obtained from Centella asiatica. So the present study is designed to determine the neurotrophic effect of AA against 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine hydrochloride/probenecid (MPTP/p) neurotoxicity in mice model of PD...
February 8, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28180960/dissociable-effects-of-the-d-and-l-enantiomers-of-govadine-on-the-disruption-of-prepulse-inhibition-by-mk-801-and-apomorphine-in-male-long-evans-rats
#14
Brittney R Lins, Wendie N Marks, Anthony G Phillips, John G Howland
RATIONALE: The search for novel antipsychotic drugs to treat schizophrenia is driven by the poor treatment efficacy, serious side effects, and poor patient compliance of current medications. Recently, a class of compounds known as tetrahydroprotoberberines, which includes the compound d,l-govadine, have shown promise in preclinical rodent tests relevant to schizophrenia. To date, the effect of govadine on prepulse inhibition (PPI), a test for sensorimotor gating commonly used to assess the effects of putative treatments for schizophrenia, has not been determined...
February 8, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28177213/characterization-of-optically-and-electrically-evoked-dopamine-release-in-striatal-slices-from-digenic-knock-in-mice-with-dat-driven-expression-of-channelrhodopsin
#15
Brian O'Neill, Jyoti C Patel, Margaret E Rice
Fast-scan cyclic voltammetry (FCV) is an established method to monitor increases in extracellular dopamine (DA) concentration ([DA]o) in the striatum, which is densely innervated by DA axons. Ex vivo brain slice preparations provide an opportunity to identify endogenous modulators of DA release. For these experiments, local electrical stimulation is often used to elicit release of DA, as well as other transmitters, in the striatal microcircuitry; changes in evoked increases in [DA]o after application of a pharmacological agent (e...
February 8, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28176268/no-genetic-association-between-attention-deficit-hyperactivity-disorder-adhd-and-parkinson-s-disease-in-nine-adhd-candidate-snps
#16
Julia M Geissler, Marcel Romanos, Manfred Gerlach, Daniela Berg, Claudia Schulte
Attention-deficit/hyperactivity disorder (ADHD) and Parkinson's disease (PD) involve pathological changes in brain structures such as the basal ganglia, which are essential for the control of motor and cognitive behavior and impulsivity. The cause of ADHD and PD remains unknown, but there is increasing evidence that both seem to result from a complicated interplay of genetic and environmental factors affecting numerous cellular processes and brain regions. To explore the possibility of common genetic pathways within the respective pathophysiologies, nine ADHD candidate single nucleotide polymorphisms (SNPs) in seven genes were tested for association with PD in 5333 cases and 12,019 healthy controls: one variant, respectively, in the genes coding for synaptosomal-associated protein 25 k (SNAP25), the dopamine (DA) transporter (SLC6A3; DAT1), DA receptor D4 (DRD4), serotonin receptor 1B (HTR1B), tryptophan hydroxylase 2 (TPH2), the norepinephrine transporter SLC6A2 and three SNPs in cadherin 13 (CDH13)...
February 7, 2017: Attention Deficit and Hyperactivity Disorders
https://www.readbyqxmd.com/read/28167674/ventrolateral-striatal-medium-spiny-neurons-positively-regulate-food-incentive-goal-directed-behavior-independently-of-d1-and-d2-selectivity
#17
Akiyo Natsubori, Iku Tsustui-Kimura, Hiroshi Nishida, Youcef Bouchekioua, Hiroshi Sekiya, Motokazu Uchigashima, Masahiko Watanabe, Alban de Kerchove d'Exaerde, Masaru Mimura, Norio Takata, Kenji F Tanaka
: The ventral striatum is involved in motivated behavior. Akin to the dorsal striatum, the ventral striatum contains two parallel pathways: the striatomesencephalic pathway consisting of dopamine receptor type 1-expressing medium spiny neurons (D1-MSNs) and the striatopallidal pathway consisting of D2-MSNs. These two genetically identified pathways are thought to encode opposing functions in motivated behavior. It has also been reported that D1/D2 genetic selectivity is not attributed to the anatomical discrimination of two pathways...
February 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28163672/targeting-neuroblastoma-cell-surface-proteins-recommendations-for-homology-modeling-of-hnet-alk-and-trkb
#18
Yazan Haddad, Zbyněk Heger, Vojtech Adam
Targeted therapy is a promising approach for treatment of neuroblastoma as evident from the large number of targeting agents employed in clinical practice today. In the absence of known crystal structures, researchers rely on homology modeling to construct template-based theoretical structures for drug design and testing. Here, we discuss three candidate cell surface proteins that are suitable for homology modeling: human norepinephrine transporter (hNET), anaplastic lymphoma kinase (ALK), and neurotrophic tyrosine kinase receptor 2 (NTRK2 or TrkB)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28162057/pramipexole-reduces-inflammation-in-the-experimental-animal-models-of-inflammation
#19
Heibatollah Sadeghi, Mohammad Parishani, Mehdi Akbartabar Touri, Mehdi Ghavamzadeh, Mehrzad Jafari Barmak, Vahid Zarezade, Hamdollah Delaviz, Hossein Sadeghi
Pramipexole is a dopamine (DA) agonist (D2 subfamily receptors) that widely use in the treatment of Parkinson's diseases. Some epidemiological and genetic studies propose a role of inflammation in the pathophysiology of Parkinson's disease. To our knowledge, there is no study regarding the anti-inflammatory activity of pramipexol. Therefore, the aim of the study was to investigate anti-inflammatory effect of pramipexol. Anti-inflammatory effects of pramipexole were studied in three well-characterized animal models of inflammation, including carrageenan- or formalin-induced paw inflammation in rats, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice...
February 6, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28161458/effect-of-mptp-on-mrna-expression-of-pgc-1%C3%AE-in-mouse-brain
#20
Rita Torok, Andras Salamon, Evelin Sumegi, Denes Zadori, Gabor Veres, Mate Fort Molnar, Laszlo Vecsei, Peter Klivenyi
The peroxisome proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC-1α) is a key regulator of mitochondrial biogenesis, respiration and adaptive thermogenesis. Besides the full-length protein (FL-PGC-1α), several other functionally active PGC-1α isoforms were identified as a result of alternative splicing (e.g., N-truncated PGC-1α; NT-PGC-1α) or alternative promoter usage (e.g., central nervous system-specific PGC-1α isoforms; CNS-PGC-1α). Achieving neuroprotection via CNS-targeted pharmacological stimulation is limited due to poor penetration of the blood brain barrier (BBB) by the proposed pharmaceutical agents, so preconditioning emerged as another option...
February 1, 2017: Brain Research
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