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Dopamine antagonists

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https://www.readbyqxmd.com/read/29783994/large-scale-transcriptomic-analysis-reveals-that-pridopidine-reverses-aberrant-gene-expression-and-activates-neuroprotective-pathways-in-the-yac128-hd-mouse
#1
Rebecca Kusko, Jennifer Dreymann, Jermaine Ross, Yoonjeong Cha, Renan Escalante-Chong, Marta Garcia-Miralles, Liang Juin Tan, Michael E Burczynski, Ben Zeskind, Daphna Laifenfeld, Mahmoud Pouladi, Michal Geva, Iris Grossman, Michael R Hayden
BACKGROUND: Huntington Disease (HD) is an incurable autosomal dominant neurodegenerative disorder driven by an expansion repeat giving rise to the mutant huntingtin protein (mHtt), which is known to disrupt a multitude of transcriptional pathways. Pridopidine, a small molecule in development for treatment of HD, has been shown to improve motor symptoms in HD patients. In HD animal models, pridopidine exerts neuroprotective effects and improves behavioral and motor functions. Pridopidine binds primarily to the sigma-1 receptor, (IC50 ~ 100 nM), which mediates its neuroprotective properties, such as rescue of spine density and aberrant calcium signaling in HD neuronal cultures...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29782883/a-new-outlook-on-cholinergic-interneurons-in-parkinson-s-disease-and-l-dopa-induced-dyskinesia
#2
REVIEW
Melissa M Conti, Nicole Chambers, Christopher Bishop
Traditionally, dopamine (DA) and acetylcholine (ACh) striatal systems were considered antagonistic and imbalances or aberrant signaling between these neurotransmitter systems could be detrimental to basal ganglia activity and pursuant motor function, such as in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). Herein, we discuss the involvement of cholinergic interneurons (ChIs) in striatally-mediated movement in a healthy, parkinsonian, and dyskinetic state. ChIs integrate numerous neurotransmitter signals using intrinsic glutamate, serotonin, and DA receptors and convey the appropriate transmission onto nearby muscarinic and nicotinic ACh receptors to produce movement...
May 18, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29781560/conditioned-reward-of-opioids-but-not-psychostimulants-is-impaired-in-gaba-a-receptor-%C3%AE-subunit-knockout-mice
#3
Milo S Siivonen, Elena de Miguel, Juho Aaltio, Aino K Manner, Mikko Vahermo, Jari Yli-Kauhaluoma, Anni-Maija Linden, Teemu Aitta-Aho, Esa R Korpi
Extrasynaptic δ subunit-containing γ-aminobutyric acid type A receptors (δ-GABAA Rs) are emerging as targets for a number of neuropsychopharmacological drugs, including the direct GABA-site agonist gaboxadol and neuroactive steroids. Among other regions, these δ-GABAA Rs are functionally expressed in the ventral tegmental area (VTA), the cell body region of mesocorticolimbic dopamine (DA) system important for motivated behaviors, and in the target region, the nucleus accumbens. Gaboxadol and neurosteroids induce VTA DA neuron plasticity ex vivo, by inhibiting the VTA GABA neurons, and aversive place conditioning, which are absent in the δ-GABAA R knockout mice (δ-KO)...
May 21, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29780881/nucleus-accumbens-microcircuit-underlying-d2-msn-driven-increase-in-motivation
#4
Carina Soares-Cunha, Bárbara Coimbra, Ana Verónica Domingues, Nivaldo Vasconcelos, Nuno Sousa, Ana João Rodrigues
The nucleus accumbens (NAc) plays a central role in reinforcement and motivation. Around 95% of the NAc neurons are medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). Optogenetic activation of D2-MSNs increased motivation, whereas inhibition of these neurons produced the opposite effect. Yet, it is still unclear how activation of D2-MSNs affects other local neurons/interneurons or input terminals and how this contributes for motivation enhancement...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29775777/antidepressant-potential-of-novel-flavonoids-derivatives-from-sweet-violet-viola-odorata-l-pharmacological-biochemical-and-computational-evidences-for-possible-involvement-of-serotonergic-mechanism
#5
Nasiara Karim, Imran Khan, Abeer Abdelhalim, Ajmal Khan, Sobia Ahsan Halim
Plant-derived natural constituents are of great interest in modern drug discovery due to their natural diversity. Viola odorata L has been traditionally used for the treatment of neuropsychiatric disorders. The present study was undertaken to isolate phytoconstituents including three flavonoids 5,7-Dihydroxy-3,6-dimethoxyflavone[1] 5,7,4'-trihydroxy-3',5'dimethoxyflavone [2] and 5,7,4'-trihydroxy-3'-methoxyflavone [3] from the whole plant of Viola odorata L and to investigate the antidepressant-like effects of these compounds and their possible mechanism of action using antagonists of the serotonergic, dopaminergic and adrenergic system...
May 15, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29775630/the-basolateral-amygdala-dopaminergic-system-contributes-to-the-improving-effect-of-nicotine-on-stress-induced-memory-impairment-in-rats
#6
Elnaz Keshavarzian, Zahra Ghasemzadeh, Ameneh Rezayof
Stress seems to be an important risk factor in the beginning and continuing stages of cigarette tobacco smoking in humans. Considering that both of nicotine administration and stress exposure affect cognitive functions including memory formation, the aim of the present study was 1) to evaluate the effect of subcutaneous (s.c.) administration of nicotine on memory formation under stress and 2) to assess the possible role of the basolateral amygdala (BLA) dopamine D1 and D2 receptors in the effect of nicotine on stress-induced memory retrieval impairment...
May 15, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29772497/the-role-of-the-vasopressin-system-and-dopamine-d1-receptors-in-the-effects-of-social-housing-condition-on-morphine-reward
#7
M L Shawn Bates, Rebeca S Hofford, Michael A Emery, Paul J Wellman, Shoshana Eitan
BACKGROUND: The association with opioid-abusing individuals or even the perception of opioid abuse by peers are risk factors for the initiation and escalation of abuse. Similarly, we demonstrated that morphine-treated animals housed with only morphine-treated animals (referred to as morphine only) acquire morphine conditioned place-preference (CPP) more readily than morphine-treated animals housed with drug-naïve animals (referred to as morphine cage-mates). However, the molecular mechanisms underlying these effects are still elusive...
April 22, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29769465/effects-of-oral-calcium-dosage-and-timing-on-ethanol-induced-sensitization-of-locomotion-in-dba-2-mice
#8
Chikako Shimizu, Yutaka Mitani, Youichi Tsuchiya, Toshitaka Nabeshima
Ethanol (EtOH) dosage, frequency, and paired associative learning affect the risk of alcoholism. Recently, Spanagel et al. reported that acamprosate calcium (Acam Ca) prescribed for alcoholism exerts an anti-relapse effect via Ca. Ca is contained in foods, sometimes consumed with alcohol. Therefore, we investigated the association among oral Ca ingestion, EtOH-induced locomotor sensitization, and plasma Ca levels on how to consume Ca for moderate drinking. We used DBA/2 CrSlc mice, and CaCl2 as water-soluble Ca salts...
May 16, 2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29767374/the-effect-of-ca1-dopaminergic-system-on-amnesia-induced-by-harmane-in-mice
#9
Mohammad Nasehi, Simin Hasanvand, Fatemeh Khakpai, Mohammad-Reza Zarrindast
In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmane-induced amnesia were examined in mice. We used a single-trial step-down inhibitory avoidance task for the assessment of memory acquisition in adult male mice. Our data indicated that pre-training intra-peritoneal (i.p.) administration of harmane (12 mg/kg) impaired memory acquisition. Moreover, intra-CA1 administration of dopamine D1 receptor agonist, SKF38393 (0.25 µg/mouse), dopamine D1 receptor antagonist, SCH23390 (0...
May 16, 2018: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/29740319/pharmacological-blockade-of-adenosine-a-2a-but-not-a-1-receptors-enhances-goal-directed-valuation-in-satiety-based-instrumental-behavior
#10
Yan Li, Xinran Pan, Yan He, Yang Ruan, Linshan Huang, Yuling Zhou, Zhidong Hou, Chaoxiang He, Zhe Wang, Xiong Zhang, Jiang-Fan Chen
The balance and smooth shift between flexible, goal-directed behaviors and repetitive, habitual actions are critical to optimal performance of behavioral tasks. The striatum plays an essential role in control of goal-directed versus habitual behaviors through a rich interplay of the numerous neurotransmitters and neuromodulators to modify the input, processing and output functions of the striatum. The adenosine receptors (namely A2A R and A1 R), with their high expression pattern in the striatum and abilities to interact and integrate dopamine, glutamate and cannabinoid signals in the striatum, may represent novel therapeutic targets for modulating instrumental behavior...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29735678/dopamine-receptors-mediate-strategy-abandoning-via-modulation-of-a-specific-prelimbic-cortex-nucleus-accumbens-pathway-in-mice
#11
Qiaoling Cui, Qian Li, Hongyan Geng, Lei Chen, Nancy Y Ip, Ya Ke, Wing-Ho Yung
The ability to abandon old strategies and adopt new ones is essential for survival in a constantly changing environment. While previous studies suggest the importance of the prefrontal cortex and some subcortical areas in the generation of strategy-switching flexibility, the fine neural circuitry and receptor mechanisms involved are not fully understood. In this study, we showed that optogenetic excitation and inhibition of the prelimbic cortex-nucleus accumbens (NAc) pathway in the mouse respectively enhances and suppresses strategy-switching ability in a cross-modal spatial-egocentric task...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29734953/cortical-structures-and-their-clinical-correlates-in-antipsychotic-na%C3%A3-ve-schizophrenia-patients-before-and-after-6-weeks-of-dopamine-d2-3-receptor-antagonist-treatment
#12
Kasper Jessen, Egill Rostrup, Rene C W Mandl, Mette Ø Nielsen, Nikolaj Bak, Birgitte Fagerlund, Birte Y Glenthøj, Bjørn H Ebdrup
BACKGROUND: Schizophrenia has been associated with changes in both cortical thickness and surface area, but antipsychotic exposure, illness progression and substance use may confound observations. In antipsychotic-naïve schizophrenia patients, we investigated cortical thickness and surface area as well as mean curvature before and after monotherapy with amisulpride, a relatively selective dopamine D2/3 receptor antagonist. METHODS: Fifty-six patients and 59 matched healthy controls (HCs) underwent T1-weighted 3T magnetic resonance imaging...
May 8, 2018: Psychological Medicine
https://www.readbyqxmd.com/read/29732159/ultrasound-imaging-improves-hormone-therapy-strategies-for-induction-of-ovulation-and-in-vitro-fertilization-in-the-endangered-dusky-gopher-frog-lithobates-sevosa
#13
Katherine M Graham, Cecilia J Langhorne, Carrie K Vance, Scott T Willard, Andrew J Kouba
Establishing captive breeding populations of amphibians is an important conservation strategy to safeguard against ongoing declines of wild populations and provide broodstock for reintroduction programs. The endangered dusky gopher frog (DGF) has never naturally reproduced in captivity and requires breeding intervention to sustain the population. Methods for inducing ovulation in female DGFs using hormone therapies have not been evaluated. To address this need, we tested four exogenous hormone treatments to induce ovulation in DGFs ( n = 11/treatment), including: treatment (A) gonadotropin-releasing hormone agonist (GnRHa); (B) GnRHa with dopamine antagonist metoclopramide hydrochloride; (C) GnRHa and human chorionic gonadotropin (hCG) and (D) GnRHa with hCG following two low hCG priming doses...
2018: Conservation Physiology
https://www.readbyqxmd.com/read/29729893/memantine-ameliorates-depressive-like-behaviors-by-regulating-hippocampal-cell-proliferation-and-neuroprotection-in-olfactory-bulbectomized-mice
#14
Kohei Takahashi, Osamu Nakagawasai, Wataru Nemoto, Shogo Kadota, Jinichi Isono, Takayo Odaira, Wakana Sakuma, Yuichiro Arai, Takeshi Tadano, Koichi Tan-No
Our previous study suggested that the non-competitive N-methyl-d-aspartate receptor antagonist memantine (MEM) inhibits dopamine (DA) reuptake and turnover by inhibiting brain monoamine oxidase. Clinical studies have reported that MEM may improve depressive symptoms; however, specific mechanisms underlying this effect are unclear. We performed emotional behavior, tail suspension, and forced swimming tests to examine whether MEM has antidepressant effects in olfactory bulbectomized (OBX) mice, an animal model of depression...
May 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29729086/the-novel-atypical-antipsychotic-cariprazine-demonstrates-dopamine-d-2-receptor-dependent-partial-agonist-actions-on-rat-mesencephalic-dopamine-neuronal-activity
#15
Sarah Delcourte, Charles R Ashby, Renaud Rovera, Béla Kiss, Nika Adham, Bence Farkas, Nasser Haddjeri
AIM: Cariprazine, a dopamine D3 -preferring D3 /D2 receptor partial agonist, is FDA approved for the treatment of schizophrenia and acute manic or mixed episodes of bipolar disorder. This study used in vivo electrophysiological techniques in anesthetized rats to determine cariprazine's effect on dopaminergic cell activity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). METHODS: Extracellular recordings of individual dopaminergic neurons were performed after oral or intravenous administration of cariprazine, the D3 receptor antagonist SB 277011A, the D2 receptor antagonist L741,626, and/or the D3 receptor agonist PD 128,907...
May 4, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29723641/contributions-of-dopaminergic-and-non-dopaminergic-neurons-to-vta-stimulation-induced-neurovascular-responses-in-brain-reward-circuits
#16
Marta Brocka, Cornelia Helbing, Daniel Vincenz, Thomas Scherf, Dirk Montag, Jürgen Goldschmidt, Frank Angenstein, Michael Lippert
Mapping the activity of the human mesolimbic dopamine system by BOLD-fMRI is a tempting approach to non-invasively study the action of the brain reward system during different experimental conditions. However, the contribution of dopamine release to the BOLD signal is disputed. To assign the actual contribution of dopaminergic and non-dopaminergic VTA neurons to the formation of BOLD responses in target regions of the mesolimbic system, we used two optogenetic approaches in rats. We either activated VTA dopaminergic neurons selectively, or dopaminergic and mainly glutamatergic projecting neurons together...
April 30, 2018: NeuroImage
https://www.readbyqxmd.com/read/29720711/in-vitro-and-in-vivo-characterization-of-pcc0104005-a-novel-modulator-of-serotonin-dopamine-activity-as-an-atypical-antipsychotic-drug
#17
Yanan Xu, Xiaoyin Zhu, Hongbo Wang, Shanyue Sun, Xin Yue, Jingwei Tian
PCC0104005 is a novel drug candidate for treating schizophrenia that displays high affinity for serotonin, dopamine, and noradrenaline receptors, including partial agonism at dopamine D2 , D3 , D4 , serotonin 5-HT1A , and 5-HT2A receptors and antagonism at 5-HT2B , 5-HT6 , and 5-HT7 receptors. PCC0104005 blocks MK-801-induced hyperactivity in rats, consistent with the reduction in dopamine D2 receptor stimulation and increased dopamine release in the medial prefrontal cortex. PCC0104005 inhibits 5-HTP-induced head twitches in rats, due to its moderate affinity for human 5-HT2A receptors (Ki = 5...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29717334/the-role-of-striatal-dopamine-d-2-3-receptors-in-cognitive-performance-in-drug-free-patients-with-schizophrenia
#18
Tanja Veselinović, Ingo Vernaleken, Hildegard Janouschek, Paul Cumming, Michael Paulzen, Felix M Mottaghy, Gerhard Gründer
OBJECTIVE: A considerable body of research links cognitive function to dopaminergic transmission in the prefrontal cortex, but less is known about cognition in relation to striatal dopamine D2/3 receptors in unmedicated patients with psychosis. METHODS: We investigated this association by obtaining PET recordings with the high-affinity D2/3 antagonist ligand [18 F] fallypride in 15 medication-free patients with schizophrenia and 11 healthy controls. On the day of PET scanning, we undertook comprehensive neuropsychological testing and assessment of psychopathology using the Positive and Negative Syndrome Scale (PANSS)...
May 1, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29705546/chronic-restraint-stress-during-withdrawal-increases-vulnerability-to-drug-priming-induced-cocaine-seeking-via-a-dopamine-d1-like-receptor-mediated-mechanism
#19
Kevin T Ball, Eric Stone, Olivia Best, Tyler Collins, Hunter Edson, Erin Hagan, Salvatore Nardini, Phelan Neuciler, Michael Smolinsky, Lindsay Tosh, Kristin Woodlen
BACKGROUND: A major obstacle in the treatment of individuals with cocaine addiction is their high propensity for relapse. Although the clinical scenario of acute stress-induced relapse has been well studied in animal models, few pre-clinical studies have investigated the role of chronic stress in relapse or the interaction between chronic stress and other relapse triggers. METHODS: We tested the effect of chronic restraint stress on cocaine seeking in rats using both extinction- and abstinence-based animal relapse models...
April 22, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29705534/increasing-kynurenine-brain-levels-reduces-ethanol-consumption-in-mice-by-inhibiting-dopamine-release-in-nucleus-accumbens
#20
Pablo Giménez-Gómez, Mercedes Pérez-Hernández, María Dolores Gutiérrez-López, Rebeca Vidal, Cristina Abuin-Martínez, Esther O'Shea, María Isabel Colado
Recent research suggests that ethanol (EtOH) consumption behaviour can be regulated by modifying the kynurenine (KYN) pathway, although the mechanisms involved have not yet been well elucidated. To further explore the implication of the kynurenine pathway in EtOH consumption we inhibited kynurenine 3-monooxygenase (KMO) activity with Ro 61-8048 (100 mg/kg, i.p.), which shifts the KYN metabolic pathway towards kynurenic acid (KYNA) production. KMO inhibition decreases voluntary binge EtOH consumption and EtOH preference in mice subjected to "drinking in the dark" (DID) and "two-bottle choice" paradigms, respectively...
April 18, 2018: Neuropharmacology
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