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D4 receptor

Laurence D Picton, Keith T Sillar
Dopamine plays important roles in the development and modulation of motor control circuits. Here we show that dopamine exerts potent effects on the central pattern generator circuit controlling locomotory swimming in post-embryonic Xenopus tadpoles. Dopamine (0.5-100 μM) reduced fictive swim bout occurrence and caused both spontaneous and evoked episodes to become shorter, slower and weaker. The D2-like receptor agonist quinpirole mimicked this repertoire of inhibitory effects on swimming, whilst the D4 receptor antagonist, L745,870, had the opposite effects...
October 20, 2016: Scientific Reports
Andresa H Betti, Camila B Antonio, Thais E T Pompeu, Thaise S Martins, Vivian Herzfeldt, Eveline D Stolz, Carlos A M Fraga, Eliezer Barreiro, François Noël, Stela M K Rates
Aiming to identify new antipsychotic lead-compounds, our group has been working on the design and synthesis of new N-phenylpiperazine derivatives. Here, we characterized LASSBio-1422 as a pharmacological prototype of this chemical series. Adult male Wistar rats and CF1 mice were used for in-vitro and in-vivo assays, respectively. LASSBio-1422 [1 and 5 mg/kg, postoperatively (p.o.)] inhibited apomorphine-induced climbing as well as ketamine-induced hyperlocomotion (1 and 5 mg/kg, p.o.), animal models predictive of efficacy on positive symptoms...
October 13, 2016: Behavioural Pharmacology
Patrick Vancura, Tanja Wolloscheck, Kenkichi Baba, Gianluca Tosini, P Michael Iuvone, Rainer Spessert
The energy metabolism of the retina might comply with daily changes in energy demand and is impaired in diabetic retinopathy-one of the most common causes of blindness in Europe and the USA. The aim of this study was to investigate putative adaptation of energy metabolism in healthy and diabetic retina. Hence expression analysis of metabolic pathway genes was performed using quantitative polymerase chain reaction, semi-quantitative western blot and immunohistochemistry. Transcriptional profiling of key enzymes of energy metabolism identified transcripts of mitochondrial fatty acid β-oxidation enzymes, i...
2016: PloS One
Erika J Olson, Bernhard C Lechtenberg, Chunxia Zhao, Elena Rubio de la Torre, Ilaria Lamberto, Stefan J Riedl, Philip E Dawson, Elena B Pasquale
EphA4 is a receptor tyrosine kinase with a critical role in repulsive axon guidance and synaptic function. However, aberrant EphA4 activity can inhibit neural repair after injury and exacerbate neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's. We previously identified the cyclic peptide APY-d2 (APYCVYRβASWSC-nh2, containing a disulfide bond) as a potent and selective EphA4 antagonist. However, APY-d2 lacks sufficient plasma stability to be useful for EphA4 inhibition in vivo through peripheral administration...
September 8, 2016: ACS Medicinal Chemistry Letters
Xiaowei Zhang, Kyeong-Man Kim
The amino acid sequences and signaling pathways of D2-like dopamine receptors (D2R, D3R, and D4R) are highly conserved. D4R has been suggested to be associated with novelty seeking, and binds with high affinity to an atypical antipsychotic drug with fewer motor function-related side effects than typical neuroleptics. A study comparing D2R and D3R reported that palmitoylation is important for the proper functioning of D3R. Although D4R is a member of the D2-like receptor family, its palmitoylation status and the functional significance of any such posttranslational modification are unknown...
October 14, 2016: Biochemical and Biophysical Research Communications
Mona Hadad, Seyed Mohammad Abedi, Seyed Jalal Hosseinimehr
The aim of this study was to evaluate the 99mTc-HYNIC-D4 peptide as a new radiotracer for tumor targeting in non small cell lung tumor that overexpresses epidermal growth factor receptor (EGFR). D4 small peptide (Leu-Ala-Arg-Leu-Leu-Thr) was selected as a candidate for specific targeting on EGFR. It was conjugated with HYNIC on N-terminus and labeled with 99mTc using tricine as a co-ligand. Radiochemical purity was determined to be 98% by instant thin layer chromatograph and reverse-phase high-pressure liquid chromatography...
September 7, 2016: Anti-cancer Agents in Medicinal Chemistry
Irene Sebastianutto, Natallia Maslava, Corey R Hopkins, M Angela Cenci
Rodent models of l-DOPA-induced dyskinesia (LID) are essential to investigate pathophysiological mechanisms and treatment options. Ratings of abnormal involuntary movements (AIMs) are used to capture both qualitative and quantitative features of dyskinetic behaviors. Thus far, validated rating scales for the mouse have anchored the definition of severity to the time during which AIMs are present. Here we have asked whether the severity of axial, limb, and orolingual AIMs can be objectively assessed with scores based on movement amplitude...
September 2, 2016: Neurobiology of Disease
E M Leerkes, J Su, S Calkins, V C Henrich, A Smolen
We examined the extent to which the arginine vasopressin receptor 1a (AVPR1a) and dopamine receptor D4 (DRD4) were related to sensitive maternal behavior directly or indirectly via maternal social cognition. Participants were 207 (105 European-American and 102 African-American) mothers and their children (52% females). Sensitive maternal behavior was rated and aggregated across a series of tasks when infants were 6 months, 1 year and 2 years old. At 6 months, mothers were interviewed about their empathy, attributions about infant behavior and beliefs about crying to assess their parenting-related social cognition...
September 1, 2016: Genes, Brain, and Behavior
Junhan Cho, Steven M Kogan, Gene H Brody
The present study addressed the ways in which parent and child dopamine D4 receptor (DRD4) genotypes jointly moderate the transactional relations between parenting practices and child self-regulation. African American children (N = 309) and their parents provided longitudinal data spanning child ages 11 to 15 years and a saliva sample from which variation at DRD4 was genotyped. Based on the differential susceptibility perspective, this study examined moderation effects of DRD4 status on (a) the extent to which parenting practices affect child self-regulation and (b) the extent to which child self-regulation, as an environmental influence on the parent, affects parenting behavior...
October 2016: Journal of Family Psychology: JFP
Ulf Simonsen, Simon Comerma-Steffensen, Karl-Erik Andersson
The currently recommended first-line treatments of erectile dysfunction, phosphodiesterase type 5 inhibitors (PDE5i), e.g. sildenafil, are efficacious in many patients with erectile dysfunction of vascular origin, but this therapy is insufficient in approximately 30-40% of men with erectile dysfunction where there is also a neuronal affection. There is a demand of novel approaches to treat the condition. We review the possibility of modulating the dopaminergic pathways to improve erectile function. Dopamine D1 (D1 , D5 )-and D2 (D2 -D4 )-like receptors in the paraventricular area, the medial preoptic area, the spinal cord, and in the erectile tissue are involved in erection, and several agonists developed for treatment of Parkinson's disease are associated with increased libido...
August 19, 2016: Basic & Clinical Pharmacology & Toxicology
Marthe S Thagaard, Stephen V Faraone, Edmund J Sonuga-Barke, Søren D Østergaard
OBJECTIVE: ADHD is a prevalent and highly heritable mental disorder associated with significant impairment, morbidity and increased rates of mortality. This combination of high prevalence and high morbidity/mortality seen in ADHD and other mental disorders presents a challenge to natural selection-based models of human evolution. Several hypotheses have been proposed in an attempt to resolve this apparent paradox. The aim of this study was to review the evidence for these hypotheses. METHODS: We conducted a systematic review of the literature on empirical investigations of natural selection-based evolutionary accounts for ADHD in adherence with the PRISMA guideline...
October 2016: Acta Neuropsychiatrica
Adam J Prus, Laura E Wise, Alan L Pehrson, Scott D Philibin, Benny Bang-Andersen, Jørn Arnt, Joseph H Porter
The atypical antipsychotic drug clozapine remains one of most effective treatments for schizophrenia, given a lack of extrapyramidal side effects, improvements in negative symptoms, cognitive impairment, and in symptoms in treatment-resistant schizophrenia. The adverse effects of clozapine, including agranulocytosis, make finding a safe clozapine-like a drug a goal for drug developers. The drug discrimination paradigm is a model of interoceptive stimulus that has been used in an effort to screen experimental drugs for clozapine-like atypical antipsychotic effects...
October 1, 2016: Brain Research
Suyun Li, Qiang Wang, Lulu Pan, Huijie Li, Xiaorong Yang, Fan Jiang, Nan Zhang, Mingkui Han, Chongqi Jia
BACKGROUND AND OBJECTIVES: Smoking and smoking cessation are both psychological and physiological traits. We aimed to investigate the interaction between dopamine pathway gene scores and nicotine dependence on smoking cessation in a rural Chinese male population. METHODS: Participants were recruited from 17 villages in Shandong, China. DNA was extracted from blood sample of 819 participants. 25 single nucleotide polymorphisms (SNPs) in 8 dopamine (DA) pathway genes were genotyped...
September 2016: American Journal on Addictions
Florine C Martin, Ching-Seng Ang, David K Gardner, Marilyn B Renfree, Geoff Shaw
The marsupial tammar wallaby has the longest period of embryonic diapause of any mammal, up to 11 months, during which there is no cell division or blastocyst growth. Since the blastocyst in diapause is surrounded by acellular coats, the signals that maintain or terminate diapause involve factors that reside in uterine secretions. The nature of such factors remains to be resolved. In this study, uterine flushings (UFs) were used to assess changes in uterine secretions of tammars using liquid chromatography-mass spectrometry (LC-MS/MS) during diapause (day 0 and 3) and reactivation days (d) 4, 5, 6, 8, 9, 11 and 24 after removal of pouch young (RPY), which initiates embryonic development...
November 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Huihui Ji, Yunliang Wang, Danjie Jiang, Guili Liu, Xuting Xu, Dongjun Dai, Xiaohui Zhou, Wei Cui, Jinfeng Li, Zhongming Chen, Ying Li, Dongsheng Zhou, Qin Zha, Renjie Zhuo, Liting Jiang, Yu Liu, Lili Shen, Beibei Zhang, Lei Xu, Haochang Hu, Yuzheng Zhang, Honglei Yin, Shiwei Duan, Qinwen Wang
Aberrant promoter methylation of multiple genes is associated with various diseases, including Alzheimer's disease (AD). The goal of the present study was to determine whether dopamine receptor D4 (DRD4) promoter methylation is associated with AD. In the current study, the methylation levels of the DRD4 promoter were measured in 46 AD patients and 61 controls using bisulfite pyrosequencing technology. The results of the present study demonstrated that DRD4 promoter methylation was significantly higher in AD patients than in controls...
September 2016: Molecular Medicine Reports
Luye Qin, Wenhua Liu, Kaijie Ma, Jing Wei, Ping Zhong, Kei Cho, Zhen Yan
The human dopamine D4 receptor (hD4R) variants with long tandem repeats in the third intracellular loop have been strongly associated with attention deficit hyperactivity disorder (ADHD) and risk taking behaviors. To understand the potential molecular mechanism underlying the connection, we have investigated the synaptic function of human D4R polymorphism by virally expressing the ADHD-linked 7-repeat allele, hD4.7, or its normal counterpart, hD4.4, in the prefrontal cortex (PFC) of D4R knockout mice. We found that hD4R bound to the SH3 domain of PSD-95 in a state-dependent manner...
November 2016: Neurobiology of Disease
Cathryn Gordon Green, Vanessa Babineau, Alexia Jolicoeur-Martineau, Andrée-Anne Bouvette-Turcot, Klaus Minde, Roberto Sassi, Martin St-André, Normand Carrey, Leslie Atkinson, James L Kennedy, Meir Steiner, John Lydon, Helene Gaudreau, Jacob A Burack, Robert Levitan, Michael J Meaney, Ashley Wazana
Prenatal maternal depression and a multilocus genetic profile of two susceptibility genes implicated in the stress response were examined in an interaction model predicting negative emotionality in the first 3 years. In 179 mother-infant dyads from the Maternal Adversity, Vulnerability, and Neurodevelopment cohort, prenatal depression (Center for Epidemiologic Studies Depressions Scale) was assessed at 24 to 36 weeks. The multilocus genetic profile score consisted of the number of susceptibility alleles from the serotonin transporter linked polymorphic region gene (5-HTTLPR): no long-rs25531(A) (LA: short/short, short/long-rs25531(G) [LG], or LG/LG] vs...
July 18, 2016: Development and Psychopathology
P J Cocker, M Y Lin, M M Barrus, B Le Foll, C A Winstanley
RATIONALE: Rats, like humans, are susceptible to the reinforcing effects of reward-related stimuli presented within a compound stimulus array, putatively analogous to the so-called near-miss effect. We have previously demonstrated using a rodent slot machine task (rSMT) that the reward expectancy these stimuli elicit is critically mediated by the dopamine D4 receptor. D4 receptors are principally located in prefrontal regions activated during slot machine play in humans, such as the insular cortex...
September 2016: Psychopharmacology
Beth M Stadtmueller, Zhongyu Yang, Kathryn E Huey-Tubman, Helena Roberts-Mataric, Wayne L Hubbell, Pamela J Bjorkman
The polymeric Ig receptor (pIgR) transports polymeric Abs across epithelia to the mucosa, where proteolytic cleavage releases the ectodomain (secretory component [SC]) as an integral component of secretory Abs, or as an unliganded protein that can mediate interactions with bacteria. SC is conserved among vertebrates, but domain organization is variable: mammalian SC has five domains (D1-D5), whereas avian, amphibian, and reptilian SC lack the D2 domain, and fish SC lacks domains D2-D4. In this study, we used double electron-electron resonance spectroscopy and surface plasmon resonance binding studies to characterize the structure, dynamics, and ligand binding properties of avian SC, avian SC domain variants, and a human SC (hSC) variant lacking the D2 domain...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Jodi L Lukkes, Nadja Freund, Britta S Thompson, Shirisha Meda, Susan L Andersen
Clinical and preclinical studies on attention deficit hyperactivity disorder (ADHD) show that juvenile males that are exposed to methylphenidate (MPH) show reduced risk for substance use later in life. In contrast, little is known about whether females have the same enduring treatment response to stimulants and how gonadal hormones influence their behavior later in life. Females received either a sham or 6-hydroxydopamine (6-OHDA) microinjection in the prefrontal cortex (PFC) at postnatal day (P)10. Subjects were then treated with Vehicle or MPH (2mg/kg, p...
September 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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