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https://www.readbyqxmd.com/read/29455579/vmat2-inhibitors-for-tardive-dyskinesia-practice-implications
#1
Alyssa M Peckham, Jessica A Nicewonder
Tardive dyskinesia is a potentially irreversible, debilitating, hyperkinetic movement disorder that can result from dopamine receptor antagonists. Prompt recognition and resolution of symptoms are instrumental in preventing disease irreversibility, though current treatment options have fallen short of robust, effective, and long-term symptom control. In April 2017, the Food and Drug Administration (FDA) approved 2 new vesicular monoamine transporter 2 (VMAT2) inhibitors, deutetrabenazine and valbenazine, for chorea related to Huntington's disease and tardive dyskinesia, respectively...
January 1, 2018: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29455417/effect-of-yulangsan-polysaccharide-on-the-reinstatement-of-morphine-induced-conditioned-place-preference-in-sprague-dawley-rats
#2
Chunxia Chen, Zhihuan Nong, Xingmei Liang, Mingyu Meng, Feifei Xuan, Qiuqiao Xie, Junhui He, Renbin Huang
We previously reported that Yulangsan polysaccharide (YLSP), which was isolated from the root of Millettia pulchra Kurz, attenuates withdrawal symptoms of morphine dependence by regulating the nitric oxide pathway and modulating monoaminergic neurotransmitters. In this study, we investigated the effects and mechanism of YLSP on the reinstatement of morphine-induced conditioned place preference (CPP) in rats. A CPP procedure was employed to assess the behavior of rats, and indicators of serum and four brain regions (nucleus accumbens, ventral tegmental area, hippocampus and prefrontal cortex) were determined to explore its underlying mechanism...
February 17, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29455292/effects-of-the-nicotinic-agonist-varenicline-nicotinic-antagonist-r-bpidi-and-dat-inhibitor-r-modafinil-on-co-use-of-ethanol-and-nicotine-in-female-p-rats
#3
Sarah E Maggio, Meredith A Saunders, Thomas A Baxter, Kimberly Nixon, Mark A Prendergast, Guangrong Zheng, Peter Crooks, Linda P Dwoskin, Rachel D Slack, Amy H Newman, Richard L Bell, Michael T Bardo
RATIONALE: Co-users of alcohol and nicotine are the largest group of polysubstance users worldwide. Commonalities in mechanisms of action for ethanol (EtOH) and nicotine proposes the possibility of developing a single pharmacotherapeutic to treat co-use. OBJECTIVES: Toward developing a preclinical model of co-use, female alcohol-preferring (P) rats were trained for voluntary EtOH drinking and i.v. nicotine self-administration in three phases: (1) EtOH alone (0 vs...
February 18, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29455021/effect-of-dopamine-receptor-d4-drd4-haplotypes-on-general-psychopathology-in-patients-with-eating-disorders
#4
Guillermo Gervasini, Luz M González, Carmen Gamero-Villarroel, Sonia Mota-Zamorano, Juan Antonio Carrillo, Isalud Flores, Angustias Garcia-Herráiz
Among the many candidate genes analyzed in eating disorder (ED) patients, those involved in dopaminergic functions may be of special relevance, as dopamine is known to play a significant role in feeding behavior, the distortion of body image, hyperactivity and reward and reinforcement processes. We aimed to determine the effect of functional polymorphisms and haplotypes in the Dopamine Receptor D4 (DRD4) gene on general psychopathological symptoms in ED patients. Two-hundred-and-seventy-three ED patients [199 with Anorexia Nervosa (AN) and 74 with Bulimia Nervosa (BN)] completed the SCL-90R inventory and were genotyped for four functional, clinically relevant DRD4 polymorphisms: three variants in the promoter region [120-bp tandem repeat (TR, long vs...
February 15, 2018: Gene
https://www.readbyqxmd.com/read/29454494/historical-perspectives-on-tardive-dyskinesia
#5
REVIEW
Stanley N Caroff, Gabor S Ungvari, David G Cunningham Owens
Tardive dyskinesia (TD) is a persistent hyperkinetic movement disorder associated with dopamine receptor blocking agents including antipsychotic medications. Although uncertainty and concern about this drug side effect has vacillated since its initial recognition 60 years ago, recent commercial interest in developing effective treatments has rekindled scientific and clinical interest after a protracted period of neglect. Although substantial research has advanced knowledge of the clinical features and epidemiology of TD, many fundamental questions raised by early investigators remain unresolved...
February 3, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29454493/updating-the-recommendations-for-treatment-of-tardive-syndromes-a-systematic-review-of-new-evidence-and-practical-treatment-algorithm
#6
REVIEW
Roongroj Bhidayasiri, Onanong Jitkritsadakul, Joseph H Friedman, Stanley Fahn
BACKGROUND: Management of tardive syndromes (TS) is challenging, with only a few evidence-based therapeutic algorithms reported in the American Academy of Neurology (AAN) guideline in 2013. OBJECTIVE: To update the evidence-based recommendations and provide a practical treatment algorithm for management of TS by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents (DRBAs) an effective TS treatment? 2) Does switching from typical to atypical DRBAs reduce TS symptoms? 3) What is the efficacy of pharmacologic agents in treating TS? 4) Do patients with TS benefit from chemodenervation with botulinum toxin? 5) Do patients with TS benefit from surgical therapy? METHODS: Systematic reviews were conducted by searching PsycINFO, Ovid MEDLINE, PubMed, EMBASE, Web of Science and Cochrane for articles published between 2012 and 2017 to identify new evidence published after the 2013 AAN guidelines...
February 5, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29454035/high-and-low-doses-of-cocaine-intake-are-differentially-regulated-by-dopamine-d2-receptors-in-the-ventral-tegmental-area-and-the-nucleus-accumbens
#7
R Chen, S McIntosh, S E Hemby, H Sun, T Sexton, Thomas Martin, S R Childers
Dopamine D2 receptors (D2Rs) in the ventral tegmental area (VTA) and the nucleus accumbens (NAc) are associated with vulnerability to addiction; however, whether D2Rs in these two brain regions play differential roles in regulation of drug intake is unknown. Here, we compared the effect of decreased mRNA level of Drd2 in each region on cocaine self-administration in a dose-response function. Drd2 mRNA levels in rat VTA or NAc were knocked down by bilateral microinjection of lentivirus coding shRNAs against rat Drd2...
February 14, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29453947/evaluation-of-the-effects-of-rp5063-a-novel-multimodal-serotonin-receptor-modulator-as-single-agent-therapy-and-co-administrated-with-sildenafil-bosentan-and-treprostinil-in-a-monocrotaline-induced-pulmonary-arterial-hypertension-rat-model
#8
Laxminarayan Bhat, Jon Hawkinson, Marc Cantillon, Dasharatha G Reddy, Seema R Bhat, Charles-E Laurent, Annie Bouchard, Marzena Biernat, Dany Salvail
Pulmonary arterial hypertension (PAH), a condition that is defined by pulmonary vasculature constriction and remodeling, involves dysfunctional signaling of the serotonin (5-HT) receptors, 5-HT 2/2B/7 . In a rat model of monocrotaline (MCT)-induced PAH, the effectiveness of RP5063 (RP), a dopamine and 5-HT receptor modulator, was evaluated as monotherapy and as an adjunct to standard PAH treatments. After a single 60mg/kg dose of MCT, rats received vehicle (MCT+Veh; gavage twice-daily [b.i.d.]), RP (10mg/kg; gavage b...
February 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29453443/role-of-the-mesolimbic-dopamine-system-in-relief-learning
#9
Dana Mayer, Evelyn Kahl, Taygun C Uzuneser, Markus Fendt
The relief from an aversive event is rewarding. Since organisms are able to learn which environmental cues can cease an aversive event, relief learning helps to better cope with future aversive events. Literature data suggest that relief learning is affected in various psychopathological conditions, such as anxiety disorders. Here, we investigated the role of the mesolimbic dopamine system in relief learning. Using a relief learning procedure in Sprague Dawley rats, we applied a combination of behavioral experiments with anatomical tracing, c-Fos immunohistochemistry, and local chemogenetic and pharmacological interventions to broadly characterize the role of the mesolimbic dopamine system...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29451744/design-synthesis-and-biological-evaluation-of-novel-bivalent-ligands-targeting-dopamine-d2-like-receptors-and-%C3%A2%C2%B5-opioid-receptor
#10
Mingcheng Qian, Lakshmi Vasudevan, Jelle Huysentruyt, Martijn D P Risseeuw, Christophe Stove, Patrick M L Vanderheyden, Kathleen Van Craenenbroeck, Serge Van Calenbergh
Nowadays, there is mounting evidence that intermolecular receptor-receptor interactions may result in altered receptor recognition, pharmacology and signaling. Heterobivalent ligands have been proven useful molecular probes for confirming and targeting heteromeric receptors. This paper describes the design and synthesis of novel heterobivalent ligands for dopamine D2-like receptors (D2-likeR) and the µ opioid receptor (µOR) and their evaluation using radioactive ligand binding and functional assays.
February 16, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29451703/mechanisms-of-imidazoline-i-2-receptor-agonist-induced-antinociception-in-rats-involvement-of-monoaminergic-neurotransmission
#11
Justin N Siemian, Kaixuan Wang, Yanan Zhang, Jun-Xu Li
BACKGROUND AND PURPOSE: Although studies have established the antinociceptive efficacies of imidazoline I2 receptor (I2 R) agonists, its exact post-receptor mechanism remains unknown. This study tested the hypothesis that monoaminergic transmission is critical for I2 R agonist-induced antinociception. EXPERIMENTAL APPROACH: The von Frey filament test was used to examine the antinociceptive effects of the I2 R agonists 2-BFI and CR4056 on chronic constriction injury (CCI)-induced neuropathic pain or complete Freund's adjuvant (CFA)-induced inflammatory pain in rats...
February 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29450650/access-to-the-cns-biomarker-strategies-for-dopaminergic-treatments
#12
REVIEW
Willem Johan van den Brink, Semra Palic, Isabelle Köhler, Elizabeth Cunera Maria de Lange
Despite substantial research carried out over the last decades, it remains difficult to understand the wide range of pharmacological effects of dopaminergic agents. The dopaminergic system is involved in several neurological disorders, such as Parkinson's disease and schizophrenia. This complex system features multiple pathways implicated in emotion and cognition, psychomotor functions and endocrine control through activation of G protein-coupled dopamine receptors. This review focuses on the system-wide effects of dopaminergic agents on the multiple biochemical and endocrine pathways, in particular the biomarkers (i...
February 15, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29449373/tyrosine-hydroxylase-down-regulation-after-loss-of-abelson-helper-integration-site-1-ahi1-promotes-depression-via-the-circadian-clock-pathway-in-mice
#13
Dongkai Guo, Shun Zhang, Hongyang Sun, Xingyun Xu, Zongbing Hao, Chenchen Mu, Xingshun Xu, Guanghui Wang, Haigang Ren
Abelson helper integration site 1 (AHI1) is associated with several neuropsychiatric and brain developmental disorders such as schizophrenia, depression, autism, and Joubert syndrome. Ahi1 deficiency in mice leads to behaviors typical of depression. However, the mechanisms by which AHI1 regulates behavior remain to be elucidated. Here, we found that down-regulation of expression of the rate-limiting enzyme in dopamine biosynthesis, tyrosine hydroxylase (TH), in the midbrains of Ahi1 -knockout (KO) mice is responsible for Ahi1 -deficiency-mediated depressive symptoms...
February 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29449008/tardive-dyskinesia-out-of-the-shadows
#14
REVIEW
Robert A Hauser, Daniel Truong
The approvals of the first two medications, valbenazine and deutetrabenazine, to treat tardive dyskinesia have ushered in a new era in neuropsychiatric care. Tardive syndromes are defined as delayed onset, persistent movement disorders or sensory phenomena that occur in association with exposure to dopamine receptor blocking agents (DRBAs). Their underlying pathophysiology remains to be fully elucidated, but clinicians can conceptualize tardive syndromes as persistent dopamine supersensitivity states. Tardive syndromes can potentially cause distress, disfigurement, embarrassment, and dysfunction, and are often permanent...
February 5, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29445764/quantified-coexpression-analysis-of-central-amygdala-subpopulations
#15
Kenneth M McCullough, Filomene G Morrison, Jakob Hartmann, William A Carlezon, Kerry J Ressler
Molecular identification and characterization of fear controlling circuitries is a promising path towards developing targeted treatments of fear-related disorders. Three-color in situ hybridization analysis was used to determine whether somatostatin (SOM, Sst ), neurotensin (NTS, Nts ), corticotropin-releasing factor (CRF, Crf ), tachykinin 2 (TAC2, Tac2 ), protein kinase c-δ (PKC-δ, Prkcd ), and dopamine receptor 2 (DRD2, Drd2 ) mRNA colocalize in male mouse amygdala neurons. Expression and colocalization was examined across capsular (CeC), lateral (CeL), and medial (CeM) compartments of the central amygdala...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29445200/impaired-%C3%AE-arrestin-recruitment-and-reduced-desensitization-by-non-catechol-agonists-of-the-d1-dopamine-receptor
#16
David L Gray, John A Allen, Scot Mente, Rebecca E O'Connor, George J DeMarco, Ivan Efremov, Patrick Tierney, Dmitri Volfson, Jennifer Davoren, Edward Guilmette, Michelle Salafia, Rouba Kozak, Michael D Ehlers
Selective activation of dopamine D1 receptors (D1Rs) has been pursued for 40 years as a therapeutic strategy for neurologic and psychiatric diseases due to the fundamental role of D1Rs in motor function, reward processing, and cognition. All known D1R-selective agonists are catechols, which are rapidly metabolized and desensitize the D1R after prolonged exposure, reducing agonist response. As such, drug-like selective D1R agonists have remained elusive. Here we report a novel series of selective, potent non-catechol D1R agonists with promising in vivo pharmacokinetic properties...
February 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29444518/effects-of-environmental-enrichment-on-nicotine-sensitization-in-rats-neonatally-treated-with-quinpirole-analyses-of-glial-cell-line-derived-neurotrophic-factor-and-implications-towards-schizophrenia
#17
Russell W Brown, Marjorie A Schlitt, Alex S Owens, Caitlynn C DePreter, Elizabeth D Cummins, Seth L Kirby, W Drew Gill, Katherine C Burgess
The current study analyzed the effects of environmental enrichment versus isolation housing on the behavioral sensitization to nicotine in the neonatal quinpirole (NQ; dopamine D2-like agonist) model of dopamine D2 receptor supersensitivity, a rodent model of schizophrenia. NQ treatment in rats increases dopamine D2 receptor sensitivity throughout the animal's lifetime, consistent with schizophrenia. Animals were administered NQ (1 mg/kg) or saline (NS) from postnatal day (P)1 to P21, weaned, and immediately placed into enriched housing or isolated in wire cages throughout the experiment...
February 14, 2018: Developmental Neuroscience
https://www.readbyqxmd.com/read/29441778/nickel-catalyzed-phosphine-free-direct-n-alkylation-of-amides-with-alcohols
#18
Jagadish Das, Debasis Banerjee
Herein, we developed an operational simple, practical and selective Ni-catalyzed synthesis of secondary amides. Application of renewable alcohols, earth-abundant and non-precious nickel catalyst enable the transformations, releasing water as by product. The catalytic system is tolerant to variety of functional groups including nitrile, allylic ether and alkene and could be extended to the synthesis of bis-amide, antiemetic drug Tigan and dopamine D2 receptor antagonist Itopride. Preliminary mechanistic studies, revealed the participation of benzylic C-H bond in the rate-determining step...
February 14, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29440997/layer-and-cell-type-specific-modulation-of-excitatory-neuronal-activity-in-the-neocortex
#19
REVIEW
Gabriele Radnikow, Dirk Feldmeyer
From an anatomical point of view the neocortex is subdivided into up to six layers depending on the cortical area. This subdivision has been described already by Meynert and Brodmann in the late 19/early 20. century and is mainly based on cytoarchitectonic features such as the size and location of the pyramidal cell bodies. Hence, cortical lamination is originally an anatomical concept based on the distribution of excitatory neuron. However, it has become apparent in recent years that apart from the layer-specific differences in morphological features, many functional properties of neurons are also dependent on cortical layer or cell type...
2018: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29439093/dysregulated-genes-and-their-functional-pathways-in-luteinized-granulosa-cells-from-pcos-patients-after-cabergoline-treatment
#20
Hortensia Ferrero, Patricia Diaz-Gimeno, Patricia Sebastian-Leon, Amparo Faus, Raul Gómez, Antonio Pellicer
Polycystic ovarian syndrome (PCOS) is a common reproductive disorder frequently associated with a substantial risk factor for ovarian hyperstimulation syndrome (OHSS). Dopamine receptor 2 (D2) agonists, like Cabergoline (Cb2), have been used to reduce the OHSS risk. However, lutein granulosa cells (LGCs) from PCOS patients treated with Cb2 still show a deregulated dopaminergic tone (decreased D2 expression and low dopamine production) and increased vascularization compared to non-PCOS LGCs. Therefore, to understand the PCOS ovarian physiology, it is important to explore the mechanisms that underlie syndrome based on the therapeutic effects of Cb2...
February 9, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
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