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https://www.readbyqxmd.com/read/28075189/11-analytically-confirmed-cases-of-mexedrone-use-among-polydrug-users
#1
Liam Roberts, Loretta Ford, Neel Patel, J Allister Vale, Sally M Bradberry
INTRODUCTION: Mexedrone, 3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one, is the alpha-methoxy-derivative of mephedrone (4-methyl-N-methyl cathinone). Mexedrone inhibits the re-uptake of serotonin and dopamine in a dose-dependent manner and has affinity for serotonin and dopamine membrane transporters and receptors (5-HT2 and D2 receptors), producing sympathomimetic effects similar to amfetamines. To date there are no published clinical reports on mexedrone use that are analytically confirmed...
January 11, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28069917/dopamine-modulates-the-functional-organization-of-the-orbitofrontal-cortex
#2
Thorsten Kahnt, Philippe N Tobler
: Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons, and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain, and thereby reconfigures functional networks in the OFC...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28065748/the-effects-of-early-life-stress-on-dopamine-system-function-in-adolescent-female-rats
#3
Iwona Majcher-Maślanka, Anna Solarz, Krzysztof Wędzony, Agnieszka Chocyk
During adolescence, many neural systems, including the dopamine system, undergo essential remodeling and maturation. It is well known that early-life stress (ELS) increases the risk for many psychopathologies during adolescence and adulthood. It is hypothesized that ELS interferes with the maturation of the dopamine system. There is a sex bias in the prevalence of stress-related mental disorders. Information regarding the effects of ELS on brain functioning in females is very limited. In the current study, maternal separation (MS) procedures were carried out to study the effects of ELS on dopamine system functioning in adolescent female rats...
January 5, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28063918/simultaneous-in-vivo-receptor-occupancy-assays-for-serotonin-1a-2a-and-dopamine-2-receptors-with-the-use-of-non-radiolabelled-tracers-proposed-method-in-screening-antipsychotics
#4
Jagadeesh Babu Thentu, Ramakrishna Nirogi, Gopinadh Bhyrapuneni, Devender Reddy Ajjala, Raghupathi Reddy Aleti, Veera Raghava Choudary Palacharla
INTRODUCTION: Conventionally, receptor occupancy assays employ radiolabelled tracer.However, recent advances with non-radiolabelled tracers brought a revolution in target engagement assays.Non-radiolabelled tracer based receptor occupancy uses LC-MS/MS based quantification.It offers simultaneous quantification of more than one tracer; thus, provides the feasibility of evaluating multiple targets in a single animal.In the present study, we demonstrated simultaneous measurement of serotonin 1A, serotonin 2A, and dopamine 2 receptor occupancy using non-radiolabelled tracers in rats...
January 4, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28062254/the-effects-of-d-govadine-on-conditioned-place-preference-with-d-amphetamine-or-food-reward
#5
Maya O Nesbit, Carine Dias, Anthony G Phillips
Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB d-govadine on the acquisition, expression, extinction and reinstatement of d-amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of d-govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received d-govadine (0, 0...
January 3, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28059046/long-term-effects-of-aripiprazole-exposure-on-monoaminergic-and-glutamatergic-receptor-subtypes-comparison-with-cariprazine
#6
Yong Kee Choi, Nika Adham, Béla Kiss, István Gyertyán, Frank I Tarazi
OBJECTIVE: This study examined the chronic effects of aripiprazole and cariprazine on serotonin (5-HT1A and 5-HT2A) and glutamate (NMDA and AMPA) receptor subtypes. In addition, the effects of aripiprazole on D2 and D3 receptors were tested and compared with previously reported cariprazine data. METHODS: Rats received vehicle, aripiprazole (2, 5, or 15 mg/kg), or cariprazine (0.06, 0.2, or 0.6 mg/kg) for 28 days. Receptor levels were quantified using autoradiographic assays on brain sections from the medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), nucleus accumbens (NAc), caudate-putamen medial (CPu-M), caudate-putamen lateral (CPu-L), hippocampal CA1 (HIPP-CA1) and CA3 (HIPP-CA3) regions, and the entorhinal cortex (EC)...
January 6, 2017: CNS Spectrums
https://www.readbyqxmd.com/read/28057528/role-of-d2-dopamine-receptors-of-the-ventral-pallidum-in-inhibitory-avoidance-learning
#7
László Lénárd, Tamás Ollmann, Kristóf László, Anita Kovács, Rita Gálosi, Veronika Kállai, Tóth Attila, Erika Kertes, Olga Zagoracz, Zoltán Karádi, László Péczely
In our present experiments, the role of D2 dopamine (DA) receptors of the ventral pallidum (VP) was investigated in one trial step-through inhibitory avoidance paradigm. Animals were shocked 3 times in the conditioning trial, with 0.5mA current for 1s. Subsequently bilateral microinjection of the D2 DA receptor agonist quinpirole was administered into the VP in three doses (0.1μg, 1.0μg or 5.0μg in 0.4μl saline). We also applied the D2 DA receptor antagonist sulpiride (0.4μg in 0.4μl saline) alone or 15min prior to the agonist treatment to elucidate whether the agonist effect was specific for the D2 DA receptors...
January 3, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28057524/involvement-of-presynaptic-5-ht1a-receptors-in-the-low-propensity-of-brexpiprazole-to-induce-extrapyramidal-side-effects-in-rats
#8
Cedric Mombereau, Jørn Arnt, Arne Mørk
Previous studies have shown that partial and full 5-HT1A receptor agonists reduce antipsychotic-induced catalepsy. Consequently, some antipsychotics combining balanced efficacy between dopamine (DA) D2 antagonism or partial agonism and 5-HT1A receptor agonism have a low propensity to induce extrapyramidal side effects (EPS), as reflected by low cataleptogenic activity in rodents. In the present experiments, we attempted to explore the importance of pre- and postsynaptic 5-HT1A agonistic properties of brexpiprazole and aripiprazole in the context of neurological side-effect liabilities...
January 3, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28052701/potential-for-targeting-dopamine-darpp-32-signaling-in-neuropsychiatric-and-neurodegenerative-disorders
#9
Akinori Nishi, Takahide Shuto
Alterations in dopamine neurotransmission has been implicated in pathophysiology of neuropsychiatric and neurodegenerative disorders, and DARPP-32 plays a pivotal role in dopamine neurotransmission. DARPP-32 likely influences dopamine-mediated behaviors in animal models of neuropsychiatric and neurodegenerative disorders and therapeutic effects of pharmacological treatment. Areas covered: We will review animal studies on the biochemical and behavioral roles of DARPP-32 in drug addiction, schizophrenia and Parkinson's disease...
January 13, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28051998/prex1-integrates-g-protein-coupled-receptor-and-phosphoinositide-3-kinase-signaling-to-promote-glioblastoma-invasion
#10
Alexander Gont, Manijeh Daneshmand, John Woulfe, Sylvie J Lavictoire, Ian A J Lorimer
A defining feature of the brain cancer glioblastoma is its highly invasive nature. When glioblastoma cells are isolated from patients using serum free conditions, they accurately recapitulate this invasive behaviour in animal models. The Rac subclass of Rho GTPases has been shown to promote invasive behaviour in glioblastoma cells isolated in this manner. However the guanine nucleotide exchange factors responsible for activating Rac in this context have not been characterized previously. PREX1 is a Rac guanine nucleotide exchange factor that is synergistically activated by binding of G protein αγ subunits and the phosphoinositide 3-kinase pathway second messenger phosphatidylinositol 3,4,5 trisphosphate...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28041956/basal-ganglia-dysfunction-contributes-to-physical-inactivity-in-obesity
#11
Danielle M Friend, Kavya Devarakonda, Timothy J O'Neal, Miguel Skirzewski, Ioannis Papazoglou, Alanna R Kaplan, Jeih-San Liow, Juen Guo, Sushil G Rane, Marcelo Rubinstein, Veronica A Alvarez, Kevin D Hall, Alexxai V Kravitz
Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, whereas restoring Gi signaling in these neurons increased activity in obese mice...
December 20, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28032295/antagonism-of-muscarinic-acetylcholine-receptors-alters-synaptic-erk-phosphorylation-in-the-rat-forebrain
#12
Li-Min Mao, Henry H Wang, John Q Wang
Acetylcholine (ACh) is a key transmitter in the mesocorticolimbic circuit. By interacting with muscarinic ACh receptors (mAChR) enriched in the circuit, ACh actively regulates various neuronal and synaptic activities. The extracellular signal-regulated kinase (ERK) is one of members of the mitogen-activated protein kinase family and is subject to the regulation by dopamine receptors, although the regulation of ERKs by limbic mAChRs is poorly understood. In this study, we investigated the role of mAChRs in the regulation of ERK phosphorylation (activation) in the mesocorticolimbic system of adult rat brains in vivo...
December 28, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/28032125/effects-of-dopamine-d1-and-d2-receptor-agonists-on-environmental-enrichment-attenuated-sucrose-cue-reactivity-in-rats
#13
Edwin Glueck, Darren Ginder, Jeff Hyde, Katherine North, Jeffrey W Grimm
RATIONALE: Acute or chronic environmental enrichment (EE) reduces sucrose cue reactivity in rats. This effect may be mediated by dopamine receptors. OBJECTIVES: We examined whether dopamine D1 or D2 receptor agonism could reverse the EE effect. We also examined whether any reversal effects would vary with the incubation of sucrose craving. METHODS: Following 10 days (2 h/day) of sucrose self-administration, rats experienced either 1 or 30 days of forced abstinence and either overnight (acute) or 29 day (chronic) EE...
December 28, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/28031402/presynaptic-gain-control-by-endogenous-cotransmission-of-dopamine-and-gaba-in-the-olfactory-bulb
#14
Christopher E Vaaga, Jordan T Yorgason, John T Williams, Gary L Westbrook
In the olfactory bulb, lateral inhibition mediated by local juxtaglomerular interneurons has been proposed as a gain control mechanism, important for de-correlating odorant responses. Among juxtaglomerular interneurons, short axon cells are unique as dual-transmitter neurons that release dopamine and GABA. To examine their intraglomerular function, we expressed channelrhodopsin under control of the DAT-cre promoter, and activated olfactory afferents within individual glomeruli. Optical stimulation of labeled cells triggered endogenous dopamine release as measured by cyclic voltammetry, and GABA release as measured by whole-cell GABAA receptor currents...
December 28, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28025713/cyclic-adp-ribose-as-an-endogenous-inhibitor-of-the-mtor-pathway-downstream-of-dopamine-receptors-in-the-mouse-striatum
#15
Haruhiro Higashida, Shin-Ya Kamimura, Takeshi Inoue, Osamu Hori, Mohammad Saharul Islam, Olga Lopatina, Chiharu Tsuji
The role of cyclic ADP-ribose (cADPR) as a second messenger and modulator of the mTOR pathway downstream of dopamine (DA) receptors and/or CD38 was re-examined in the mouse. ADP-ribosyl activity was low in the membranes of neonates, but DA stimulated it via both D1- and D2-like receptors. ADP-ribosyl cyclase activity increased significantly during development in association with increased expression of CD38. The cADPR binding proteins, FKBP12 and FKBP12.6, were expressed in the adult mouse striatum. The ratio of phosphorylated to non-phosphorylated S6 kinase (S6K) in whole mouse striatum homogenates decreased after incubation of adult mouse striatum with extracellular cADPR for 5 min...
December 26, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28017790/the-cb1-receptor-is-required-for-the-establishment-of-the-hyperlocomotor-phenotype-in-developmentally-induced-hypothyroidism-in-mice
#16
Elena Giné, Victor Echeverry-Alzate, Jose Antonio Lopez-Moreno, Fernando Rodriguez de Fonseca, Ana Perez-Castillo, Angel Santos
Alterations in motor functions are well-characterized features observed in humans and experimental animals with thyroid hormone dysfunctions during development. We have previously suggested the implication of the endocannabinoid system in the hyperlocomotor phenotype observed in developmentally induced hypothyroidism in rats. In this work we have further analyzed the implication of endocannabinoids in the effect of hypothyroidism on locomotor activity. To this end, we evaluated the locomotor activity in adult mice lacking the cannabinoid receptor type 1 (CB1R(-/-)) and in their wild type littermates (CB1R(+/+)), whose hypothyroidism was induced in day 12 of gestation and maintained during the experimental period...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28012732/gabaergic-control-of-neostriatal-dopamine-d2-receptor-binding-and-behaviors-in-the-rat
#17
Susanne Nikolaus, Markus Beu, Maria Angelica de Souza Silva, Joseph P Huston, Christina Antke, Hans-Wilhelm Müller, Hubertus Hautzel
PURPOSE: The present study assessed the influence of the GABAA receptor agonist muscimol and the GABAA receptor antagonist bicuculline on neostriatal dopamine D2 receptor binding in relation to motor and exploratory behaviors in the rat. METHODS: D2 receptor binding was measured in baseline and after challenge with either 1mg/kg muscimol or 1mg/kg bicuculline. In additional rats, D2 receptor binding was measured after injection of saline. After treatment with muscimol, bicuculline and saline, motor and exploratory behaviors were assessed for 30min in an open field prior to administration of [(123)I]S-3-iodo-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide ([(123)I]IBZM)...
December 21, 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28011253/a-single-scan-protocol-for-absolute-d2-3-receptor-quantification-with-123-i-ibzm-spect
#18
Stergios Tsartsalis, Benjamin B Tournier, Karl Aoun, Selim Habiby, Diego Pandolfo, Andrea Dimiziani, Nathalie Ginovart, Philippe Millet
PURPOSE: Molecular imaging of the D2/3 receptor is widely used in neuropsychiatric research. Non-displaceable binding potential (BPND) is a very popular quantitative index, defined as the product of the receptor concentration (Bavail) and the radiotracer affinity for the receptor (1/appKd). As the appKd is influenced by parameters such as the endogenous neurotransmitter dynamics, it often constitutes a confounding factor in research studies. A simplified method for absolute quantification of both these parameters would be of great interest in this context...
December 21, 2016: NeuroImage
https://www.readbyqxmd.com/read/28009769/movement-disorders-induced-by-the-atypical-antipsychotic-aripiprazole
#19
Karim Selfani, Valérie L Soland, Sylvain Chouinard, Philippe Huot
OBJECTIVES: Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine D2 receptors. Because of its partial agonist activity, it was believed that aripiprazole would be less susceptible than typical antipsychotics to induce extrapyramidal side effects. However, a few case-reports and case-series detailing aripiprazole-induced movement disorders have been published, suggesting that aripiprazole-induced movement disorders may arise. Here, we seek to report further cases of aripiprazole-induced movement disorders to raise the awareness of clinicians on this adverse effect...
January 2017: Neurologist
https://www.readbyqxmd.com/read/28009293/calcium-release-from-stores-inhibits-girk
#20
Paul F Kramer, John T Williams
Synaptic transmission is mediated by ionotropic and metabotropic receptors that together regulate the rate and pattern of action potential firing. Metabotropic receptors can activate ion channels and modulate other receptors and channels. The present paper examines the interaction between group 1 mGluR-mediated calcium release from stores and GABAB/D2-mediated GIRK currents in rat dopamine neurons of the Substantia Nigra. Transient activation of mGluRs decreased the GIRK current evoked by GABAB and D2 receptors, although less efficaciously for D2...
December 20, 2016: Cell Reports
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