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https://www.readbyqxmd.com/read/28340290/nucleus-accumbens-dopamine-receptors-mediate-hypothalamus-induced-antinociception-in-the-rat-formalin-test
#1
A Siahposht-Khachaki, P Pourreza, S Ezzatpanah, A Haghparast
BACKGROUND: Lateral hypothalamus (LH) involves in modulation of tonic pain. Regarding the direct and indirect neural connections between the LH and nucleus accumbens (NAc), we aimed to examine the pain modulatory role of NAc dopamine receptors in modulation of LH-induced analgesia in the formalin test. METHODS: Vehicle-control groups received saline or DMSO into the NAc and saline into the LH. Carbachol-control groups received carbachol (250 nmol/L) into the LH, 5 min after saline or DMSO injection into the NAc...
March 24, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28331332/clinical-role-of-brexpiprazole-in-depression-and-schizophrenia
#2
REVIEW
Nishant B Parikh, Diana M Robinson, Anita H Clayton
Brexpiprazole, a serotonin-dopamine activity modulator, is the second D2 partial agonist to come to market and has been approved for the treatment of schizophrenia and as an adjunctive treatment in major depressive disorder. With less intrinsic activity than aripiprazole at the D2 receptor and higher potency at 5-HT2A, 5-HT1A, and α1B receptors, the pharmacological properties of brexpiprazole suggest a more tolerable side effect profile with regard to akathisia, extrapyramidal dysfunction, and sedation. While no head-to-head data are currently available, double-blind placebo-controlled studies show favorable results, with the number needed to treat (NNT) vs placebo of 6-15 for response in acute schizophrenia treatment and 4 for maintenance...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28329817/early-life-benzo-a-pyrene-exposure-causes-neurodegenerative-syndromes-in-adult-zebrafish-danio-rerio-and-the-mechanism-involved
#3
Dongxu Gao, Chonggang Wang, Zhihui Xi, Yixi Zhou, Yuanchuan Wang, Zhenghong Zuo
There is increasing recognition of the importance of early-life environmental exposures in health disorders at later-life stages. The aim of this study was to evaluate whether early-life exposure to benzo[a]pyrene (BaP) could induce neurodegenerative syndromes at later-life stages in zebrafish. Embryos were exposed to BaP at doses of 0, 0.05, 0.5, 5, and 50 nM from early embryogenesis to 96 h post-fertilization (hpf), then transferred to clean water and maintained for 365 days. We found that BaP decreased locomotor and cognitive ability, neurotransmitter levels of dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine; and induced loss of dopaminergic neurons and resulted in neurodegeneration...
January 30, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28325790/dopamine-terminals-from-the-ventral-tegmental-area-gate-intrinsic-inhibition-in-the-prefrontal-cortex
#4
William C Buchta, Stephen V Mahler, Benjamin Harlan, Gary S Aston-Jones, Arthur C Riegel
Spike frequency adaptation (SFA or accommodation) and calcium-activated potassium channels that underlie after-hyperpolarization potentials (AHP) regulate repetitive firing of neurons. Precisely how neuromodulators such as dopamine from the ventral tegmental area (VTA) regulate SFA and AHP (together referred to as intrinsic inhibition) in the prefrontal cortex (PFC) remains unclear. Using whole cell electrophysiology, we measured intrinsic inhibition in prelimbic (PL) layer 5 pyramidal cells of male adult rats...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28324454/reward-circuitry-in-addiction
#5
REVIEW
Sarah Cooper, A J Robison, Michelle S Mazei-Robison
Understanding the brain circuitry that underlies reward is critical to improve treatment for many common health issues, including obesity, depression, and addiction. Here we focus on insights into the organization and function of reward circuitry and its synaptic and structural adaptations in response to cocaine exposure. While the importance of certain circuits, such as the mesocorticolimbic dopamine pathway, are well established in drug reward, recent studies using genetics-based tools have revealed functional changes throughout the reward circuitry that contribute to different facets of addiction, such as relapse and craving...
March 21, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28323555/influence-of-dopamine-related-genes-on-neurobehavioral-recovery-after-traumatic-brain-injury-during-early-childhood
#6
Amery Treble-Barna, Shari L Wade, Lisa J Martin, Valentina Pilipenko, Keith Owen Yeates, H Gerry Taylor, Brad G Kurowski
The present study examined the association of dopamine-related genes with short- and long-term neurobehavioral recovery, as well as neurobehavioral recovery trajectories over time, in children who had sustained early childhood traumatic brain injuries (TBI) relative to children who had sustained orthopedic injuries (OI). Participants were recruited from a prospective, longitudinal study evaluating outcomes of children who sustained a TBI (n = 68) or OI (n = 72) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at the immediate post-acute period (0-3 months after injury); 6, 12, and 18 months after injury; and an average of 3...
March 21, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28319749/antidepressant-activity-of-zinc-further-evidence-for-the-involvement-of-the-serotonergic-system
#7
Bernadeta Szewczyk, Katarzyna Kotarska, Agata Siwek, Łukasz Olech, Katarzyna Kuter
BACKGROUND: The present study sought to further evaluate the role of the serotonergic system especially the postsynaptic 5-HT1A receptors (5-HT1AR) in the mechanism of antidepressant action of zinc. METHODS: Messenger RNA (mRNA), protein level, and 5-HT1AR density as well as the rate of monoamine (dopamine, DA, and serotonin) metabolism in the prefrontal cortex (PFC) and hippocampus (Hp) of rats subjected to acute and chronic (21days) zinc (5mg Zn/kg) treatment were measured...
January 19, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28319392/scaffold-repurposing-of-nucleosides-adenosine-receptor-agonists-enhanced-activity-at-the-human-dopamine-and-norepinephrine-sodium-symporters
#8
Dilip K Tosh, Aaron Janowsky, Amy J Eshleman, Eugene Warnick, Zhan-Guo Gao, Zhoumou Chen, Elizabeth Gizewski, John A Auchampach, Daniela Salvemini, Kenneth A Jacobson
We have repurposed (N)-methanocarba adenosine derivatives (A3 adenosine receptor (AR) agonists) to enhance radioligand binding allosterically at the human dopamine (DA) transporter (DAT) and inhibit DA uptake. We extended the structure-activity relationship of this series with small N(6)-alkyl substitution, 5'-esters, deaza modifications of adenine, and ribose restored in place of methanocarba. C2-(5-Halothien-2-yl)-ethynyl 5'-methyl 9 (MRS7292) and 5'-ethyl 10 (MRS7232) esters enhanced binding at DAT (EC50 ∼ 35 nM) and at the norepinephrine transporter (NET)...
March 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28316587/characterization-of-the-antinociceptive-mechanisms-of-khat-extract-catha-edulis-in-mice
#9
Elham A Afify, Huda M Alkreathy, Ahmed S Ali, Hassan A Alfaifi, Lateef M Khan
This study investigated the antinociceptive mechanisms of khat extract (100, 200, and 400 mg/kg, i.p.) in four pain models: two thermic (hot plate, tail-flick) and two chemical (acetic acid, formalin) models. Male mice were pretreated intraperitoneally (i.p.) with the opioid receptor blocker naloxone (5 mg/kg), the cholinergic antagonist atropine (2 mg/kg), the selective α1 blocker prazosin (1 mg/kg), the dopamine D2 antagonist haloperidol (1.5 mg/kg), or the GABAA receptor antagonist, bicuculline (1 mg/kg) 15 minutes prior to i...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28306571/cns-syndromes-associated-with-antibodies-against-metabotropic-receptors
#10
Eric Lancaster
PURPOSE OF REVIEW: Autoantibodies to Central nervous system (CNS) metabotropic receptors are associated with a growing family of autoimmune brain diseases, including encephalitis, basal ganglia encephalitis, Ophelia syndrome, and cerebellitis. The purpose of this review is to summarize the state of knowledge regarding the target receptors, the neurological autoimmune disorders, and the pathogenic mechanisms. RECENT FINDINGS: Antibodies to the γ-aminobutyric acid B receptor are associate with limbic encephalitis and severe seizures, often with small cell lung cancers...
March 16, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28304244/intravitreally-administered-dopamine-d2-like-and-d4-but-not-d1-like-receptor-agonists-reduce-form-deprivation-myopia-in-tree-shrews
#11
Alexander H Ward, John T Siegwart, Michael R Frost, Thomas T Norton
We examined the effect of intravitreal injections of D1-like and D2-like dopamine receptor agonists and antagonists and D4 receptor drugs on form-deprivation myopia (FDM) in tree shrews, mammals closely related to primates. In eleven groups (n = 7 per group), we measured the amount of FDM produced by monocular form deprivation (FD) over an 11-day treatment period. The untreated fellow eye served as a control. Animals also received daily 5 µL intravitreal injections in the FD eye. The reference group received 0...
January 2017: Visual Neuroscience
https://www.readbyqxmd.com/read/28300398/novel-bivalent-ligands-based-on-the-sumanirole-pharmacophore-reveal-dopamine-d2-receptor-d2r-biased-agonism
#12
Alessandro Bonifazi, Hideaki Yano, Michael P Ellenberger, Ludovic Muller, Vivek Kumar, Mu-Fa Zou, Ning Sheng Cai, Adrian M Guerrero, Amina S Woods, Lei Shi, Amy Hauck Newman
The development of bivalent ligands has attracted interest as a way to potentially improve the selectivity and/or affinity for a specific receptor subtype. The ability to bind two distinct receptor binding sites simultaneously can allow the selective activation of specific G-protein dependent or β-arrestin-mediated cascade pathways. Herein, we developed an extended SAR study using sumanirole (1) as the primary pharmacophore. We found that substitutions in the N-1- and/or N-5-positions, physiochemical properties of those substituents, and secondary aromatic pharmacophores can enhance agonist efficacy for the cAMP inhibition mediated by Gi/o-proteins, while reducing or suppressing potency and efficacy toward β-arrestin recruitment...
March 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28297025/association-of-stimulant-use-with-dopaminergic-alterations-in-users-of-cocaine-amphetamine-or-methamphetamine-a-systematic-review-and-meta-analysis
#13
Abhishekh H Ashok, Yuya Mizuno, Nora D Volkow, Oliver D Howes
Importance: Stimulant use disorder is common, affecting between 0.3% and 1.1% of the population, and costs more than $85 billion per year globally. There are no licensed treatments to date. Several lines of evidence implicate the dopamine system in the pathogenesis of substance use disorder. Therefore, understanding the nature of dopamine dysfunction seen in stimulant users has the potential to aid the development of new therapeutics. Objective: To comprehensively review the in vivo imaging evidence for dopaminergic alterations in stimulant (cocaine, amphetamine, or methamphetamine) abuse or dependence...
March 15, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28294132/5-ht2c-agonists-modulate-schizophrenia-like-behaviors-in-mice
#14
Vladimir M Pogorelov, Ramona M Rodriguiz, Jianjun Cheng, Mei Huang, Claire M Schmerberg, Herbert Y Meltzer, Bryan L Roth, Alan P Kozikowski, William C Wetsel
All FDA-approved antipsychotic drugs (APDs) target primarily dopamine D2 or serotonin (5-HT2A) receptors, or both; however, these medications are not universally effective, they may produce undesirable side-effects, and provide only partial amelioration of negative and cognitive symptoms. The heterogeneity of pharmacological responses in schizophrenic patients suggests additional drug-targets may be effective in improving aspects of this syndrome. Recent evidence suggests that 5-HT2C receptors may be a promising target for schizophrenia since their activation reduces mesolimbic nigrostriatal dopamine release (which conveys antipsychotic action), they are expressed almost exclusively in CNS, and have weight-loss promoting capabilities...
March 15, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28291301/-acute-dystonia-due-to-aripiprazole-use-in-two-children-with-autism-spectrum-disorder-in-the-first-five-years-of-life
#15
Mustafa Küçükköse, Bürge Kabukçu Başay
Autism spectrum disorders (ASD) are neuropsychiatric disorders characterized by impairment in social interactions, in verbal and non-verbal communication, and restricted and stereotyped patterns of interest and behavior within the first 3 years of life. Pharmacologic interventions may be needed for the treatment of temper tantrums, aggression, hyperactivity, and stereotypes in children with ASD. The approval of aripiprazole by the United States Food and Drug Administration (USFDA) for the treatment of temper tantrums in children and adolescents with ASD has gained increased interest for the use in these patients...
2017: Türk Psikiyatri Dergisi, Turkish Journal of Psychiatry
https://www.readbyqxmd.com/read/28283756/dopamine-t-cells-and-multiple-sclerosis-ms
#16
REVIEW
Mia Levite, Franca Marino, Marco Cosentino
Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others...
March 10, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28280881/tryptophan-depletion-affects-compulsive-behaviour-in-rats-strain-dependent-effects-and-associated-neuromechanisms
#17
A Merchán, S V Navarro, A B Klein, S Aznar, L Campa, C Suñol, M Moreno, P Flores
RATIONALE: Compulsive behaviour, present in different psychiatric disorders, such as obsessive-compulsive disorder, schizophrenia and drug abuse, is associated with altered levels of monoamines, particularly serotonin (5-hydroxytryptamine) and its receptor system. OBJECTIVES: The present study investigated whether 5-HT manipulation, through a tryptophan (TRP) depletion by diet in Wistar and Lister Hooded rats, modulates compulsive drinking in schedule-induced polydipsia (SIP) and locomotor activity in the open-field test...
March 9, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28280410/lamotrigine-an-antiepileptic-drug-inhibits-5-ht3-receptor-currents-in-ncb-20-neuroblastoma-cells
#18
Ki Jung Kim, Seung Hyun Jeun, Ki-Wug Sung
Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine (5-HT)3 receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine (1~300 µM) resulted in a concentration-dependent reduction in peak amplitude of currents induced by 3 µM of 5-HT for an IC50 value of 28.2±3.6 µM with a Hill coefficient of 1.2±0.1. These peak amplitude decreases were accompanied by the rise slope reduction...
March 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28270751/understanding-the-role-of-gpcr-heteroreceptor-complexes-in-modulating-the-brain-networks-in-health-and-disease
#19
REVIEW
Dasiel O Borroto-Escuela, Jens Carlsson, Patricia Ambrogini, Manuel Narváez, Karolina Wydra, Alexander O Tarakanov, Xiang Li, Carmelo Millón, Luca Ferraro, Riccardo Cuppini, Sergio Tanganelli, Fang Liu, Malgorzata Filip, Zaida Diaz-Cabiale, Kjell Fuxe
The introduction of allosteric receptor-receptor interactions in G protein-coupled receptor (GPCR) heteroreceptor complexes of the central nervous system (CNS) gave a new dimension to brain integration and neuropsychopharmacology. The molecular basis of learning and memory was proposed to be based on the reorganization of the homo- and heteroreceptor complexes in the postjunctional membrane of synapses. Long-term memory may be created by the transformation of parts of the heteroreceptor complexes into unique transcription factors which can lead to the formation of specific adapter proteins...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28262947/exposure-of-mice-to-mdpv-during-adolescence-increases-the-psychostimulant-rewarding-and-reinforcing-effects-of-cocaine-in-adulthood
#20
R López-Arnau, M A Luján, L Duart-Castells, D Pubill, J Camarasa, O Valverde, E Escubedo
BACKGROUND AND PURPOSE: 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with powerful psychostimulant effects. It selectively inhibits dopamine transporter (DAT) being 10-50-fold more potent as DAT blocker than cocaine, pointing to a high abuse liability. The main objective of the present study was to assess the consequences of an early (adolescence) MDPV exposure on the psychostimulant, rewarding and reinforcing effects induced by cocaine in adult mice. EXPERIMENTAL APPROACH: 21 days after MDPV pretreatment (1...
March 6, 2017: British Journal of Pharmacology
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