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Dopamine D2

Jorge A Avila, Roseanna M Zanca, Denis Shor, Nicholas Paleologos, Amber A Alliger, Maria E Figueiredo-Pereira, Peter A Serrano
Methamphetamine (MA) is an addictive drug with neurotoxic effects on the brain producing cognitive impairment and increasing the risk for neurodegenerative disease. Research has focused largely on examining the neurochemical and behavioral deficits induced by injecting relatively high doses of MA [30 mg/kg of body weight (bw)] identifying the upper limits of MA-induced neurotoxicity. Accordingly, we have developed an appetitive mouse model of voluntary oral MA administration (VOMA) based on the consumption of a palatable sweetened oatmeal mash containing a known amount of MA...
February 2018: Heliyon
Anthony N Oliveri, Erica Ortiz, Edward D Levin
Human exposure to organophosphate flame retardants (OPFRs) is widespread, including pregnant women and young children with whom developmental neurotoxic risk is a concern. Given similarities of OPFRs to organophosphate (OP) pesticides, research into the possible neurotoxic impacts of developmental OPFR exposure has been growing. Building upon research implicating exposure to OP pesticides in dopaminergic (DA) dysfunction, we exposed developing zebrafish to the OPFR tris(1,3-dichloroisopropyl) phosphate (TDCIPP), during the first 5 days following fertilization...
March 17, 2018: Neurotoxicology and Teratology
Behnaz Bameri, Fatemeh Shaki, Nematollah Ahangar, Ramin Ataee, Mahedeh Samadi, Hamidreza Mohammadi
Tramadol (TR) is a synthetic analgesic drug with central function that can induce seizures even at therapeutic doses. The exact mechanism of TR effect on seizure generation is not clear, but inhibition of the serotonin and nitric oxide pathways and inhibitory effects on GABA receptors are the most common hypotheses about the seizure-inducing mechanism of the TR. This study aimed to evaluate the role of dopaminergic system on the seizure and oxidative damage induced by TR using agonist and antagonist drugs of this system in the Albino mice...
January 1, 2018: International Journal of Toxicology
Rebecca L Barlow, Martin Gorges, Alfie Wearn, Heiko G Niessen, Jan Kassubek, Jeffrey W Dalley, Anton Pekcec
Background: Low dopamine D2/3 receptor availability in the nucleus accumbens (NAcb) shell is associated with highly-impulsive behavior in rats, as measured by premature responses in a cued attentional task. However, it is unclear whether dopamine D2/3 receptor availability in the NAcb is equally linked to intolerance for delayed rewards, a related form of impulsivity. Methods: We investigated the relationship between D2/3 receptor availability in the NAcb and impulsivity in a delay-discounting task (DDT) where animals must choose between immediate small-magnitude rewards and delayed larger-magnitude rewards...
March 15, 2018: International Journal of Neuropsychopharmacology
Marta Sánchez-Soto, Verònica Casadó-Anguera, Hideaki Yano, Brian Joseph Bender, Ning-Sheng Cai, Estefanía Moreno, Enric I Canela, Antoni Cortés, Jens Meiler, Vicent Casadó, Sergi Ferré
The poor norepinephrine innervation and high density of Gi/o-coupled α2A - and α2C -adrenoceptors in the striatum and the dense striatal dopamine innervation have prompted the possibility that dopamine could be an effective adrenoceptor ligand. Nevertheless, the reported adrenoceptor agonistic properties of dopamine are still inconclusive. In this study, we analyzed the binding of norepinephrine, dopamine, and several compounds reported as selective dopamine D2 -like receptor ligands, such as the D3 receptor agonist 7-OH-PIPAT and the D4 receptor agonist RO-105824, to α2 -adrenoceptors in cortical and striatal tissue, which express α2A -adrenoceptors and both α2A - and α2C -adrenoceptors, respectively...
March 18, 2018: Molecular Neurobiology
Xia Zhou, Liying Ren, Zhiling Yu, Xiaoqian Huang, Yuhao Li, Chunxia Wang
Cumulative evidence has suggested that many antipsychotics cause metabolic abnormalities. Adipose tissue insulin resistance (Adipo-IR) contributes to the development and progress of metabolic abnormalities including fatty liver by inducing excessive free fatty acid release from adipose tissue. Sulpiride is an old antipsychotic still frequently used in many developing countries. However, its adverse metabolic effects remain poorly understood. Here, chronic administration of sulpiride (80 mg/kg, subcutaneously, once daily for 6 weeks) elevated fasting insulin concentration and the index of the homeostasis model assessment of insulin resistance in rats...
March 15, 2018: Toxicology and Applied Pharmacology
Jianbo Zhang, Peng Yan, Yunxiao Li, Xintong Cai, Ziyu Yang, Xinyao Miao, Bo Chen, Shengbin Li, Wei Dang, Wei Jia, Yongsheng Zhu
Ankyrin repeat and kinase domain containing 1 (ANKK1) and dopamine receptor D2 (DRD2) gene polymorphisms have long been considered to contribute to susceptibility to heroin dependence. Despite their adjacent locations, few studies have elucidated the role of the potential interaction between ANKK1 and DRD2 in heroin dependence. In the present study, we performed a systematic analysis of the association between 39 single nucleotide polymorphisms (SNPs) in these two genes and heroin dependence in 593 Chinese subjects...
March 14, 2018: Brain Research
Magdalena Kolasa, Joanna Solich, Agata Faron-Górecka, Dariusz Żurawek, Paulina Pabian, Sylwia Łukasiewicz, Maciej Kuśmider, Kinga Szafran-Pilch, Marta Szlachta, Marta Dziedzicka-Wasylewska
Recently, it has been shown that serotonin 5-HT1A receptor interacts with dopamine D2 receptor in vitro. However, the existence of 5-HT1A -D2 heteromers in native tissue remains unexplored. In the present study, we investigated 5-HT1A -D2 receptor heteromerization in mice treated acutely or chronically with paroxetine (10 mg/kg) or risperidone (0.05 mg/kg). Receptor heteromerization was visualized and quantified in the mouse brain by in situ proximity ligation assay (PLA). Additionally, we aimed to determine the cellular localization of 5-HT1A -D2 receptor heteromers in mouse adult primary neuronal cells by immunofluorescent staining with markers for astrocytes (GFAP) and neurons (NeuN and MAP2)...
March 12, 2018: Neuroscience
Laura J Mosher, Sean C Godar, Marc Morissette, Kenneth M McFarlin, Simona Scheggi, Carla Gambarana, Stephen C Fowler, Thérèse Di Paolo, Marco Bortolato
The enzyme steroid 5α-reductase 2 (5αR2) catalyzes the conversion of testosterone into the potent androgen 5α-dihydrotestosterone. Previous investigations showed that 5αR2 is expressed in key brain areas for emotional and socio-affective reactivity, yet the role of this enzyme in behavioral regulation remains mostly unknown. Here, we profiled the behavioral characteristics of 5αR2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates. While male 5αR2 KO mice displayed no overt alterations in motoric, sensory, information-processing and anxiety-related behaviors, they exhibited deficits in neurobehavioral correlates of dominance (including aggression against intruders, mating, and tube dominance) as well as novelty-seeking and risk-taking responses...
February 16, 2018: Psychoneuroendocrinology
Peter Kranke, Sergio D Bergese, Harold S Minkowitz, Timothy I Melson, David G Leiman, Keith A Candiotti, Ngai Liu, Leopold Eberhart, Ashraf S Habib, Jan Wallenborn, Anthony L Kovac, Pierre Diemunsch, Gabriel Fox, Tong J Gan
BACKGROUND: Postoperative nausea and vomiting causes distress for patients and can prolong care requirements. Consensus guidelines recommend use of multiple antiemetics from different mechanistic classes as prophylaxis in patients at high risk of postoperative nausea and vomiting. The prophylactic efficacy of the dopamine D2/D3 antagonist amisulpride in combination with other antiemetics was investigated. METHODS: This double-blind, randomized, placebo-controlled, international, multicenter trial was conducted in 1,147 adult surgical patients having three or four postoperative nausea and vomiting risk factors...
March 15, 2018: Anesthesiology
Adam J Stark, Christopher T Smith, Kalen J Petersen, Paula Trujillo, Nelleke C van Wouwe, Manus J Donahue, Robert M Kessler, Ariel Y Deutch, David H Zald, Daniel O Claassen
Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D2/3 receptor binding in both striatal and extrastriatal regions in PD are limited...
2018: NeuroImage: Clinical
Pablo Garrido-Gil, Antonio Dominguez-Meijide, Rosario Moratalla, Maria J Guerra, Jose L Labandeira-Garcia
Gastrointestinal dysfunction is a common problem in the elderly. Aging-related changes in interactions between local dopaminergic and renin-angiotensin systems (RAS) have been observed in the brain, renal and vascular tissues. However, it is not known if these interactions also occur in the gut, and are dysregulated with aging. We showed a mutual regulation between the colonic dopaminergic system and RAS using young and aged mice deficient for major angiotensin and dopamine receptors. Aged rats showed a marked decrease in colonic dopamine D2 receptor expression, together with an increase in angiotensin type 1 (AT1) receptor expression, a decrease in angiotensin type 2 (AT2) receptor expression (i...
February 16, 2018: Oncotarget
Eduardo F Gallo, Jozsef Meszaros, Jeremy D Sherman, Muhammad O Chohan, Eric Teboul, Claire S Choi, Holly Moore, Jonathan A Javitch, Christoph Kellendonk
Dopamine D2 receptors (D2Rs) in the nucleus accumbens (NAc) regulate motivated behavior, but the underlying neurobiological mechanisms remain unresolved. Here, we show that selective upregulation of D2Rs in the indirect pathway of the adult NAc enhances the willingness to work for food. Mechanistic studies in brain slices reveal that D2R upregulation attenuates inhibitory transmission at two main output projections of the indirect pathway, the classical long-range projections to the ventral pallidum (VP), as well as local collaterals to direct pathway medium spiny neurons...
March 14, 2018: Nature Communications
Mariusz Papp, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Ewa Litwa, Monika Niemczyk, Katarzyna Tota-Glowczyk, Agata Faron-Gorecka, Maciej Kusmider, Joanna Solich, Marta Szlachta, Paul Willner
We have previously reported the effects of intracranial injections of dopamine D1, D2 and D3 ligands in animals subjected to the Novel Object Recognition (NOR) test following exposure to chronic mild stress (CMS) and chronic treatment with risperidone (RSP). Here, we present some molecular biological data from the same animals. It was predicted that brain-derived neurotrophic factor (BDNF) signalling in the prefrontal cortex (PFC) would reflect behavioural performance, implying an increase following acute administration of a D2 agonist or a D3 antagonist, blockade of this effect by CMS and its restoration by chronic RSP...
March 13, 2018: Behavioural Pharmacology
Ramin Ekhteiari Salmas, Philip Seeman, Matthias Stein, Serdar Durdagi
The active (D2HighR) and inactive (D2LowR) states of dimeric dopamine D2 receptor (D2R) models were investigated to clarify the binding mechanisms of the dopamine agonist bromocriptine, using Molecular Dynamics (MD) simulation. The aim of this comprehensive study was to investigate the critical effects of bromocriptine binding on each distinct receptor conformation. The different binding modes of the bromocriptine ligand in the active and inactive states have a significant effect on the conformational changes of the receptor...
March 14, 2018: Journal of Chemical Information and Modeling
Eugenia Tomasella, Lucila Bechelli, Mora Belén Ogando, Camilo Mininni, Mariano N Di Guilmi, Fernanda De Fino, Silvano Zanutto, Ana Belén Elgoyhen, Antonia Marin-Burgin, Diego M Gelman
Excessive dopamine neurotransmission underlies psychotic episodes as observed in patients with some types of bipolar disorder and schizophrenia. The dopaminergic hypothesis was postulated after the finding that antipsychotics were effective to halt increased dopamine tone. However, there is little evidence for dysfunction within the dopaminergic system itself. Alternatively, it has been proposed that excessive afferent activity onto ventral tegmental area dopaminergic neurons, particularly from the ventral hippocampus, increase dopamine neurotransmission, leading to psychosis...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jérôme Linden, Alexander S James, Colin McDaniel, J David Jentsch
Neuroimaging studies in animal models and human subjects have each revealed that relatively low striatal dopamine D2-like receptor binding potential is associated with poor impulse control and with vulnerability for addiction-related behaviors. These studies cannot, however, disambiguate the roles for various pools of D2 receptors found in the striatum (e.g., those expressed on medium spiny striato-pallidal neurons vs on dopamine-releasing nerve terminals) in these behavioral outcomes. To clarify the role of the latter pool, namely, D2 autoreceptors, we studied mice carrying a conditional DRD2 gene, with or without Cre-recombinase expressed under the transcriptional control of the dopamine transporter gene locus (autoDrd2-KO, n = 19 and controls, n = 21)...
January 2018: ENeuro
Hector R Mendez-Gomez, Jasbir Singh, Craig Meyers, Weijun Chen, Oleg S Gorbatyuk, Nicholas Muzyczka
Phospholipase D2 (PLD2), an enzyme involved in vesicle trafficking and membrane signaling, interacts with α-synuclein, a protein known to contribute in the development of Parkinson disease. We previously reported that PLD2 overexpression in rat substantia nigra pars compacta (SNc) causes a rapid neurodegeneration of dopamine neurons, and that α-synuclein suppresses PLD2-induced nigral degeneration (Gorbatyuk et al., 2010). Here, we report that PLD2 toxicity is due to its lipase activity. Overexpression of a catalytically inactive mutant (K758R) of PLD2 prevents the loss of dopaminergic neurons in the SNc and does not show signs of toxicity after 10 weeks of overexpression...
March 8, 2018: Neuroscience
P A Caro Aponte, C A Otálora, J C Guzmán, L F Turner, J P Alcázar, E L Mayorga
Parkinson's disease (PD) is characterised by motor alterations, which are commonly treated with L-DOPA. However, long-term L-DOPA use may cause dyskinesia. Although the pathogenic mechanism of L-DOPA-induced dyskinesia is unclear, the condition has been associated with alterations in dopamine receptors, among which D2 receptors (D2R) have received little attention. This study aims to: (i)develop and standardise an experimental model of L-DOPA-induced dyskinesia in rats with hemiparkinsonism; and (ii)evaluate the correlation between D2R expression and presence of abnormal involuntary movements (AIM)...
March 7, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Stefano Cinque, Francesca Zoratto, Anna Poleggi, Damiana Leo, Luca Cerniglia, Silvia Cimino, Renata Tambelli, Enrico Alleva, Raul R Gainetdinov, Giovanni Laviola, Walter Adriani
Alterations in dopamine neurotransmission are generally associated with diseases such as attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Such diseases typically feature poor decision making and lack of control on executive functions and have been studied through the years using many animal models. Dopamine transporter (DAT) knockout (KO) and heterozygous (HET) mice, in particular, have been widely used to study ADHD. Recently, a strain of DAT KO rats has been developed (1)...
2018: Frontiers in Psychiatry
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