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Dopamine D2

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https://www.readbyqxmd.com/read/29150590/subtype-specific-effects-of-dopaminergic-d2-receptor-activation-on-synaptic-trains-in-layer-v-pyramidal-neurons-in-the-mouse-prefrontal-cortex
#1
Jonna M Leyrer-Jackson, Mark P Thomas
In humans, prefrontal cortical areas are known to support executive functions. In mice, these functions are mediated by homologous regions in the medial prefrontal cortex (mPFC). Executive processes are critically dependent on optimal levels of dopamine (DA), but the cellular mechanisms of DA modulation are incompletely understood. Stable patterns of neuronal activity may be sensitive to frequency-dependent changes in synaptic transmission. We characterized the effects of D2 receptor (D2R) activation on short-term excitatory postsynaptic potential (EPSP) dynamics evoked at varying frequencies in the two subtypes of layer V pyramidal neurons in mouse mPFC We isolated NMDA receptor and non-NMDA receptor-mediated components of EPSP trains evoked by stimulating fibers within layer V or layer I...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29141007/escitalopram-and-nht-normalized-stress-induced-anhedonia-and-molecular-neuroadaptations-in-a-mouse-model-of-depression
#2
Or Burstein, Motty Franko, Eyal Gale, Assaf Handelsman, Segev Barak, Shai Motsan, Alon Shamir, Roni Toledano, Omri Simhon, Yafit Hirshler, Gang Chen, Ravid Doron
Anhedonia is defined as a diminished ability to obtain pleasure from otherwise positive stimuli. Anxiety and mood disorders have been previously associated with dysregulation of the reward system, with anhedonia as a core element of major depressive disorder (MDD). The aim of the present study was to investigate whether stress-induced anhedonia could be prevented by treatments with escitalopram or novel herbal treatment (NHT) in an animal model of depression. Unpredictable chronic mild stress (UCMS) was administered for 4 weeks on ICR outbred mice...
2017: PloS One
https://www.readbyqxmd.com/read/29137945/the-effects-of-local-microinjection-of-selective-dopamine-d1-and-d2-receptor-agonists-and-antagonists-into-the-dorsal-raphe-nucleus-on-sleep-and-wakefulness-in-the-rat
#3
Jaime M Monti, Héctor Jantos
The effects of the dopamine (DA) D1 and D2 receptor agonists SKF38393, bromocriptine and quinpirole, respectively, on spontaneous sleep were analyzed in adult rats prepared for chronic sleep recordings. Local administration of the DAergic agonists into the dorsal raphe nucleus (DRN) during the light phase of the light-dark cycle induced a significant reduction of rapid-eye movement sleep (REMS) and the number of REM periods. Additionally, bromocriptine and quinpirole significantly increased wakefulness (W)...
November 11, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29123220/significance-of-dopamine-d1-receptor-signalling-for-steroidogenic-differentiation-of-human-induced-pluripotent-stem-cells
#4
Koji Matsuo, Masakatsu Sone, Kyoko Honda-Kohmo, Takafumi Toyohara, Takuhiro Sonoyama, Daisuke Taura, Katsutoshi Kojima, Yorihide Fukuda, Youichi Ohno, Mayumi Inoue, Akira Ohta, Kenji Osafune, Kazuwa Nakao, Nobuya Inagaki
Human induced pluripotent stem cells (hiPSCs) are expected to be both a revolutionary cell source for regenerative medicine and a powerful tool to investigate the molecular mechanisms underlying human cell development in vitro. In the present study, we tried to elucidate the steroidogenic differentiation processes using hiPSC-derived intermediate mesoderm (IM) that is known to be the origin of the human adrenal cortex and gonads. We first performed chemical screening to identify small molecules that induce steroidogenic differentiation of IM cells expressing Odd-skipped related 1 (OSR1), an early IM marker...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121220/pathway-specific-control-of-striatal-neuron-vulnerability-by-corticostriatal-cannabinoid-cb1-receptors
#5
Andrea Ruiz-Calvo, Irene B Maroto, Raquel Bajo-Grañeras, Anna Chiarlone, Ángel Gaudioso, José J Ferrero, Eva Resel, José Sánchez-Prieto, José A Rodríguez-Navarro, Giovanni Marsicano, Ismael Galve-Roperh, Luigi Bellocchio, Manuel Guzmán
The vast majority of neurons within the striatum are GABAergic medium spiny neurons (MSNs), which receive glutamatergic input from the cortex and thalamus, and form two major efferent pathways: the direct pathway, expressing dopamine D1 receptor (D1R-MSNs), and the indirect pathway, expressing dopamine D2 receptor (D2R-MSNs). While molecular mechanisms of MSN degeneration have been identified in animal models of striatal damage, the molecular factors that dictate a selective vulnerability of D1R-MSNs or D2R-MSNs remain unknown...
October 31, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29119704/pharmacokinetics-of-rp5063-following-single-doses-to-normal-healthy-volunteers-and-multiple-doses-over-10-days-to-stable-schizophrenic-patients
#6
Marc Cantillon, Robert Ings, Laxminarayan Bhat
RP5063, a multimodal dopamine (D)-serotonin (5-HT) stabilizer, possesses high affinity for D2/3/4 and 5-HT1A/2A/2B/2C/6/7 receptors and moderate affinity for the serotonin transporter. Two phase I studies characterized the pharmacokinetics of a single dose (10 and 15 mg fasting, 15 mg fed/fasting) in healthy volunteers and multiple doses (10, 20, 50, and 100 mg fed) over 10 days in patients with stable schizophrenia. RP5063 displayed a dose-dependent Cmax at 4 to 6 h, linear dose proportionality for both Cmax and AUC, and a half-life between 40 and 71 h...
November 8, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/29119668/global-improvement-with-cariprazine-in-the-treatment-of-bipolar-i-disorder-and-schizophrenia-a-pooled-post-hoc-analysis
#7
Suresh Durgam, Willie Earley, Kaifeng Lu, György Németh, István Laszlovszky, Stephen Volk, Robert E Litman
INTRODUCTION: Global rating scale measures are useful for assessing the clinical relevance of patient change. Cariprazine, a dopamine D3 and D2 receptor partial agonist, is FDA-approved for the adult treatment of acute manic/mixed episodes of bipolar I disorder and schizophrenia. Post hoc evaluations of Clinical Global Impressions-Severity (CGI-S) scores from the cariprazine pivotal trials in both indications were conducted. METHODS: Data from 3 bipolar mania and 3 schizophrenia trials were pooled by indication (bipolar disorder = 1033; schizophrenia = 1466)...
November 9, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/29119585/effects-of-dopamine-receptor-antagonist-antipsychotic-therapy-on-blood-pressure
#8
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/29116599/the-class-a-gpcr-dopamine-d2-receptor-forms-transient-dimers-stabilized-by-agonists-detection-by-single-molecule-tracking
#9
Rinshi S Kasai, Shuichi V Ito, Ryo M Awane, Takahiro K Fujiwara, Akihiro Kusumi
Whether class-A G-protein coupled receptors (GPCRs) exist and work as monomers or dimers has drawn extensive attention. A class-A GPCR dopamine D2 receptor (D2R) is involved in many physiological and pathological processes and diseases, indicating its critical role in proper functioning of neuronal circuits. In particular, D2R homodimers might play key roles in schizophrenia development and amphetamine-induced psychosis. Here, using single-molecule imaging, we directly tracked single D2R molecules in the plasma membrane at a physiological temperature of 37 °C, and unequivocally determined that D2R forms transient dimers with a lifetime of 68 ms in its resting state...
November 7, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29112770/interactive-effects-of-morphine-and-dopamine-receptor-agonists-on-spatial-recognition-memory-in-mice
#10
Yanmei Chen, Yu Fu, Yingjie Ann, Jianhong Wang, Jichuan Zhang
Both opiates and dopamine play important roles in learning and memory. Although synergistic action between these two neurotransmitters has been found, their functional roles remain unclear. Here, low dose morphine (2.5 mg/kg) and low dose dopamine receptor agonists (apomorphine: 0.05 mg/kg; SKF38393: 0.01 mg/kg; bromocriptine: 0.05 mg/kg), which have no effects on spatial recognition memory, were injected intraperitoneally into mice 30 min before a memory test in a two-trial recognition Y-maze. The Y-maze is based on the innate tendency of rodents to explore novel environments and is therefore suitable for exploring the effects of morphine on learning and memory...
November 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29112197/association-of-genetic-ancestry-with-striatal-dopamine-d2-d3-receptor-availability
#11
C E Wiers, P C Towb, C A Hodgkinson, P-H Shen, C Freeman, G Miller, E Lindgren, E Shokri-Kojori, Ş B Demiral, S W Kim, D Tomasi, H Sun, G-J Wang, D Goldman, N D Volkow
Despite ethnic differences in allele frequencies of variants in dopaminergic genes associated with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship between genetic ancestry and striatal D2R. Here, we show that ancestry-informative markers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the New York metropolitan area using Positron Emission Tomography (PET) with [(11)C]raclopride (P<0.0001), while correcting for age, sex, BMI, education, smoking status, and estimated socioeconomic status (ZIP codes)...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29112191/identifying-specific-prefrontal-neurons-that-contribute-to-autism-associated-abnormalities-in-physiology-and-social-behavior
#12
A C Brumback, I T Ellwood, C Kjaerby, J Iafrati, S Robinson, A T Lee, T Patel, S Nagaraj, F Davatolhagh, V S Sohal
Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29110353/amotivation-is-associated-with-smaller-ventral-striatum-volumes-in-older-patients-with-schizophrenia
#13
Fernando Caravaggio, Gagan Fervaha, Yusuke Iwata, Eric Plitman, Jun Ku Chung, Shinichiro Nakajima, Wanna Mar, Philip Gerretsen, Julia Kim, M Mallar Chakravarty, Benoit Mulsant, Bruce Pollock, David Mamo, Gary Remington, Ariel Graff-Guerrero
OBJECTIVE: Motivational deficits are prevalent in patients with schizophrenia, persist despite antipsychotic treatment, and predict long-term outcomes. Evidence suggests that patients with greater amotivation have smaller ventral striatum (VS) volumes. We wished to replicate this finding in a sample of older, chronically medicated patients with schizophrenia. Using structural imaging and positron emission tomography, we examined whether amotivation uniquely predicted VS volumes beyond the effects of striatal dopamine D2/3 receptor (D2/3 R) blockade by antipsychotics...
November 7, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/29107519/direct-dopaminergic-projections-from-the-snc-modulate-visuomotor-transformation-in-the-lamprey-tectum
#14
Juan Pérez-Fernández, Andreas A Kardamakis, Daichi G Suzuki, Brita Robertson, Sten Grillner
Dopamine neurons in the SNc play a pivotal role in modulating motor behavior via striatum. Here, we show that the same dopamine neuron that targets striatum also sends a direct branch to the optic tectum (superior colliculus). Whenever SNc neurons are activated, both targets will therefore be affected. Visual stimuli (looming or bars) activate the dopamine neurons coding saliency and also elicit distinct motor responses mediated via tectum (eye, orienting or evasive), which are modulated by the dopamine input...
November 15, 2017: Neuron
https://www.readbyqxmd.com/read/29107444/dopamine-d2l-receptor-interacting-proteins-regulate-dopaminergic-signaling
#15
REVIEW
Norifumi Shioda
Dopamine receptor family proteins include seven transmembrane and trimeric GTP-binding protein-coupled receptors (GPCRs). Among them, the dopamine D2 receptor (D2R) is most extensively studied. All clinically used antipsychotic drugs serve as D2R antagonists in the mesolimbic dopamine system, and their ability to block D2R signaling is positively correlated with antipsychotic efficiency. Human genetic studies also show a significant association of DRD2 polymorphisms with disorders including schizophrenia and Parkinson's disease...
October 14, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29106979/development-of-a-population-pharmacokinetic-model-to-predict-brain-distribution-and-dopamine-d2-receptor-occupancy-of-raclopride-in-non-anesthetized-rat
#16
Yin Cheong Wong, Trayana Ilkova, Rob C van Wijk, Robin Hartman, Elizabeth C M de Lange
BACKGROUND: Raclopride is a selective antagonist of the dopamine D2 receptor. It is one of the most frequently used in vivo D2 tracers (at low doses) for assessing drug-induced receptor occupancy (RO) in animals and humans. It is also commonly used as a pharmacological blocker (at high doses) to occupy the available D2 receptors and antagonize the action of dopamine or drugs on D2 in preclinical studies. The aims of this study were to comprehensively evaluate its pharmacokinetic (PK) profiles in different brain compartments and to establish a PK-RO model that could predict the brain distribution and RO of raclopride in the freely moving rat using a LC-MS based approach...
November 4, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29100664/tyrosine-hydroxylase-in-the-ventral-tegmental-area-of-rams-with-high-or-low-libido-a-role-for-dopamine
#17
A C Kramer, A J Mirto, K J Austin, C E Roselli, B M Alexander
Dopamine synthesis in the ventral tegmental area (VTA) is necessary for the reinforcement of sexual behavior. The objective of this study determined if sexual stimuli initiates reward, and whether reward is attenuated in sexually inactive rams. Sexually active rams were exposed to urine from estrous (n=4) or ovariectomized (n=3) ewes with inactive rams (n=3) exposed to urine from estrous ewes. Following exposure, rams were exsanguinated and brains perfused. Alternating sections of the VTA were stained for Fos related antigens (FRA), tyrosine hydroxylase, and dopamine beta-hydroxylase activity...
October 31, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/29100412/the-therapeutic-effect-of-bromocriptine-in-combination-with-spironolactone-in-patients-with-primary-aldosteronism-a-hypothesis-generating-pilot-study
#18
Vin-Cent Wu, Che-Hsiung Wu, Ya-Wen Yang, Kuo-How Huang, Chia-Hui Chang, Shao-Yu Yang, Yen-Hung Lin, Kwan-Dun Wu
Background: Dopamine D2-like receptors are attenuated in aldosterone producing adenoma, lead to overproduction of aldosterone in affected patients, and thus reported to serve as a potential treatment target for primary aldosteronism. The D2 dopamine receptor agonist bromocriptine has been used clinically for reducing tumor mass of pituitary adenomas of lactotroph origin. The aim of the present study was to assess the efficacy of adding bromocriptine to spironolactone in the biochemical control of primary aldosteronism...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29097596/ck2-oppositely-modulates-l-dopa-induced-dyskinesia-via-striatal-projection-neurons-expressing-d1-or-d2-receptors
#19
Marisol Cortés, Lauren Malave, Julia Castello, Marc Flajolet, M Angela Cenci, Eitan Friedman, Heike Rebholz
We have previously shown that casein kinase 2 (CK2) negatively regulates dopamine D1- and adenosine A2a receptor signaling in the striatum. Ablation of CK2 in D1-receptor-positive striatal neurons caused enhanced locomotion and exploration at baseline, whereas CK2 ablation in D2 receptor-positive neurons caused increased locomotion after treatment with A2a antagonist, caffeine. Since both, D1 and A2a receptors, play major roles in the cellular responses to L-DOPA in the striatum, these findings prompted us to examine the impact of CK2 ablation on the effects of L-DOPA treatment in the unilateral 6-OHDA lesioned mouse model of Parkinson's disease...
November 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29093348/the-role-of-dopaminergic-signaling-in-the-medial-prefrontal-cortex-for-the-expression-of-cocaine-induced-conditioned-place-preference-in-rats
#20
Fumiya Shinohara, Hironori Kamii, Masabumi Minami, Katsuyuki Kaneda
The expression phase of cocaine-induced conditioned place preference (CPP) represents a cocaine-seeking behavior triggered by contextual cues associated with the rewarding effects of cocaine. However, the exact mechanisms underlying the cocaine CPP expression remain unclear. Here, we investigated the role of dopaminergic (DAergic) transmission in the medial prefrontal cortex (mPFC) for the expression of cocaine CPP. An intra-ventral tegmental area (VTA) injection of a cocktail of γ-aminobutyric acid (GABA)B and GABAA receptor agonists (baclofen and muscimol, respectively) immediately before the posttest inhibited the expression of cocaine CPP...
2017: Biological & Pharmaceutical Bulletin
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