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https://www.readbyqxmd.com/read/28108253/dcc-haploinsufficiency-regulates-dopamine-receptor-expression-across-postnatal-lifespan
#1
Matthew Pokinko, Alanna Grant, Florence Shahabi, Yvan Dumont, Colleen Manitt, Cecilia Flores
Adolescence is a period during which the medial prefrontal cortex (mPFC) undergoes significant remodeling. The netrin-1 receptor, DCC, controls the extent and organization of mPFC dopamine connectivity during adolescence and in turn directs mPFC functional and structural maturation. Dcc haploinsufficiency leads to increased mPFC dopamine input, which causes improved cognitive processing and resilience to behavioral effects of stimulant drugs of abuse. Here we examine the effects of Dcc haploinsufficiency on the dynamic expression of dopamine receptors in forebrain targets of C57BL6 mice...
January 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28063918/simultaneous-in-vivo-receptor-occupancy-assays-for-serotonin-1a-2a-and-dopamine-2-receptors-with-the-use-of-non-radiolabelled-tracers-proposed-method-in-screening-antipsychotics
#2
Jagadeesh Babu Thentu, Ramakrishna Nirogi, Gopinadh Bhyrapuneni, Devender Reddy Ajjala, Raghupathi Reddy Aleti, Veera Raghava Choudary Palacharla
INTRODUCTION: Conventionally, receptor occupancy assays employ radiolabelled tracer.However, recent advances with non-radiolabelled tracers brought a revolution in target engagement assays.Non-radiolabelled tracer based receptor occupancy uses LC-MS/MS based quantification.It offers simultaneous quantification of more than one tracer; thus, provides the feasibility of evaluating multiple targets in a single animal.In the present study, we demonstrated simultaneous measurement of serotonin 1A, serotonin 2A, and dopamine 2 receptor occupancy using non-radiolabelled tracers in rats...
January 4, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27984698/simultaneous-voltammetric-measurements-of-glucose-and-dopamine-demonstrate-the-coupling-of-glucose-availability-with-increased-metabolic-demand-in-the-rat-striatum
#3
Samantha K Smith, Christie A Lee, Matthew E Dausch, Brian M Horman, Heather B Patisaul, Gregory S McCarty, Leslie A Sombers
Cerebral blood flow ensures delivery of nutrients, such as glucose, to brain sites with increased metabolic demand. However, little is known about rapid glucose dynamics at discrete locations during neuronal activation in vivo. Acute exposure to many substances of abuse elicits dopamine release and neuronal activation in the striatum; however, the concomitant changes in striatal glucose remain largely unknown. Recent developments have combined fast-scan cyclic voltammetry with glucose oxidase enzyme modified carbon-fiber microelectrodes to enable the measurement of glucose dynamics with subsecond temporal resolution in the mammalian brain...
January 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27984074/alterations-in-ventral-and-dorsal-striatal-allosteric-a2ar-d2r-receptor-receptor-interactions-after-amphetamine-challenge-relevance-for-schizophrenia
#4
Julia Pintsuk, Dasiel O Borroto-Escuela, Terence K Y Lai, Fang Liu, Kjell Fuxe
Striatal dopamine D2R homodimerization is increased in the dorsal striatum after acute amphetamine challenge and in the amphetamine-induced sensitized state, a well-known animal model of schizophrenia. Therefore, it was tested if the increase in D2R homoreceptor complexes found after acute amphetamine challenge in the saline or the amphetamine sensitized state leads to changes in the antagonistic adenosine A2AR-D2R interactions in the striatum. [(3)H]-raclopride binding was performed in membrane preparations from the ventral and dorsal striatum involving competition with the D2R like agonist quinpirole...
October 29, 2016: Life Sciences
https://www.readbyqxmd.com/read/27981179/striatal-dopamine-d2-3-receptor-regulation-by-stress-inoculation-in-squirrel-monkeys
#5
Alex G Lee, Jordan M Nechvatal, Bin Shen, Christine L Buckmaster, Michael J Levy, Frederick T Chin, Alan F Schatzberg, David M Lyons
Intermittent mildly stressful situations provide opportunities to learn, practice, and improve coping in a process called stress inoculation. Stress inoculation also enhances cognitive control and response inhibition of impulsive motivated behavior. Cognitive control and motivation have been linked to striatal dopamine D2 and/or D3 receptors (DRD2/3) in rodents, monkeys, and humans. Here, we study squirrel monkeys randomized early in life to stress inoculation with or without maternal companionship and a no-stress control treatment condition...
June 2016: Neurobiology of Stress
https://www.readbyqxmd.com/read/27980115/role-of-dorsomedial-striatum-neuronal-ensembles-in-incubation-of-methamphetamine-craving-after-voluntary-abstinence
#6
Daniele Caprioli, Marco Venniro, Michelle Zhang, Jennifer M Bossert, Brandon L Warren, Bruce T Hope, Yavin Shaham
: We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral and dorsomedial striatum (DLS, DMS) in this incubation.We trained rats to self-administer palatable food pellets (6 days, 6-h/d) and methamphetamine (12 days, 6-h/d). We then assessed relapse to methamphetamine seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent voluntary abstinence (using a discrete choice procedure between methamphetamine and food; 20 trials/day) for 19 days...
December 15, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27914043/a-revisit-to-quantitative-pet-with-18-f-fdopa-of-high-specific-activity-using-a-high-resolution-condition-in-view-of-application-to-regenerative-therapy
#7
Go Akamatsu, Akihito Ohnishi, Kazuki Aita, Hiroyuki Nishida, Yasuhiko Ikari, Masahiro Sasaki, Nobuo Kohara, Michio Senda
OBJECTIVE: With the advent of regenerative/cell therapy for Parkinson's disease (PD), (18)F-FDOPA has drawn new attention as a biomarker of the therapeutic that cannot be evaluated with radiopharmaceuticals for dopamine transporter. Since most previous (18)F-FDOPA PET studies were carried out many years ago with a PET scanner of lower resolution and with (18)F-FDOPA of low specific activity synthesized from (18)F-F2, we used a newer PET/CT scanner with a high-resolution condition and (18)F-FDOPA synthesized from (18)F-F(-) to re-evaluate this technique on normal subjects and patients with PD, together with D2 receptor imaging with (11)C-raclopride (RAC)...
December 2, 2016: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/27894050/successful-application-of-a-neutral-organic-base-1-8-bis-tetramethylguanidino-naphthalene-tmgn-for-the-radiosynthesis-of-11-c-raclopride
#8
Jihye Lee, Il-Koo Cheong, Sang-Yoon Lee
[(11)C]Raclopride is one of the most popular PET tracers used in Parkinson's disease studies. We previously prepared [(11)C]raclopride with reasonable yields using NaOH as an inorganic base, but the reaction patterns fluctuated. In this study, we describe the successful application of a commercially available 'super basic' proton sponge, TMGN, as a base for the [(11)C]methylation step using [(11)C]CH3OTf. This novel TMGN method produced better radiochemical yields, as well as enhanced reproducibility and a reduction in side products...
December 2016: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/27893588/suite-pet-ct-neuroimaging-for-the-diagnosis-of-parkinson-s-disease-statistical-parametric-mapping-analysis
#9
Ruimin Wang, Baixuan Xu, Zhe Guo, Tong Chen, Jinming Zhang, Yingmao Chen, Haiyan Zhu
OBJECTIVES: The aim of this study was to investigate the topographical distribution of dopamine transporter (DAT), dopamine D2 receptor, and glucose metabolism in Parkinson's disease (PD) using PET/computed tomography (CT) scanning and statistical parametric mapping (SPM) analysis. PARTICIPANTS AND METHODS: Seventy-four patients (58 PD patients and 16 normal controls) underwent DAT, D2 receptor, and glucose brain PET/CT scans using C-methyl-N-2-β-carbomethoxy-3-β-(4-fluorophenyl) tropane (C-β-CFT), C-raclopride (C-RAC), and fluorine-18-fluorodeoxyglucose (F-FDG) radiotracers for the respective scans...
November 28, 2016: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/27859651/sustained-striatal-dopamine-levels-following-intestinal-levodopa-infusions-in-parkinson-s-disease-patients
#10
Marios Politis, Anna Sauerbier, Clare Loane, Nicola Pavese, Anne Martin, Benjamin Corcoran, David J Brooks, K Ray-Chaudhuri, Paola Piccini
BACKGROUND: The objective of this study was to investigate in vivo the ability of levodopa/carbidopa intestinal gel infusions to produce sustained striatal dopamine levels and to improve clinical outcomes in Parkinson's disease patients. METHODS: Six advanced Parkinson's disease patients had serial [(11) C]raclopride PET to assess levodopa/carbidopa intestinal gel infusion-induced rises in striatal dopamine as reflected by a fall in dopamine-D2/3 receptor availability...
November 17, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27856625/longitudinal-micropet-imaging-of-the-zq175-mouse-model-of-huntington-s-disease-shows-in-vivo-changes-of-molecular-targets-in-the-striatum-and-the-cerebral-cortex
#11
Jenny Häggkvist, Miklós Tóth, Lenke Tari, Katarina Varnäs, Marie Svedberg, Anton Forsberg, Sangram Nag, Celia Dominguez, Ignacio Munoz-Sanjuan, Jonathan Bard, John Wityak, Andrea Varrone, Christer Halldin, Ladislav Mrzljak
RATIONALE: Since the discovery of the HTT gene in 1993, numerous animal models have been developed to study the progression of Huntington's disease, as well as to evaluate potential new therapeutics. In the present study we used small animal positron emission tomography (PET) to characterize the expression of molecular targets in the recently reported HD animal model, the zQ175 mouse model. METHODS: Male heterozygous zQ175 (Htttm1Mfc/190JChdi, CHDI-81003003) and wild type (WT, C57BL/6J) animals were imaged with the dopamine D2-receptor radioligand [(11)C]raclopride, the PDE10A radioligand [(18)F]MNI-659, the dopamine D1-receptor radioligand [(11)C]NNC 112 and the 5-HT2A radioligand [(11)C]MDL 100907 at 6 and 9 months of age...
November 10, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27853928/d1-and-d2-specific-dopamine-antagonist-modulate-the-caudate-nucleus-neuronal-responses-to-chronic-methylphenidate-exposure
#12
Sidish Venkataraman, Catherine Claussen, Nachum Dafny
The psychostimulant, methylphenidate (MPD), is the first line treatment as a pharmacotherapy to treat behavioral disorders such as attention deficit hyperactivity disorder (ADHD). MPD is commonly misused in non-ADHD (normal) youth and young adults both as a recreational drug and for cognitive enhancing effects to improve their grades. MPD is known to act on the reward circuit; including the caudate nucleus (CN). The CN is comprised of medium spiny neurons containing largely dopamine (DA) D1 and D2 receptors...
November 16, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27845187/basolateral-amygdalar-d2-receptor-activation-is-required-for-the-companions-exerted-suppressive-effect-on-the-cocaine-conditioning
#13
Wen-Yu Tzeng, Chian-Fang G Cherng, Lung Yu, Ching-Yi Wang
The presence of companions renders decreases in cocaine-stimulated dopamine release in the nucleus accumbens and cocaine-induced conditioned place preference (CPP) magnitude. Limbic systems are widely believed to underlie the modulation of accumbal dopamine release and cocaine conditioning. Thus, this study aimed to assess whether intact basolateral nucleus of amygdala (BLA), dorsal hippocampus (DH), and dorsolateral striatum (DLS) is required for the companions-exerted suppressive effect on the cocaine-induced CPP...
January 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27826109/the-significance-of-rotational-behavior-and-sensitivity-of-striatal-dopamine-receptors-in-hemiparkinsonian-rats-a-comparative-study-of-lactacystin-and-6-ohda
#14
Jolanta Konieczny, Anna Czarnecka, Tomasz Lenda, Kinga Kamińska, Lucyna Antkiewicz-Michaluk
A growing body of evidence indicates that impairment of the ubiquitin-proteasome (UPS) system in the substantia nigra (SN) plays an important role in the pathogenesis of Parkinson's disease (PD). The aim of our study was to compare two unilateral rat models, one produced by intranigral administration of the UPS inhibitor lactacystin or the other induced by 6-OHDA, in terms of their effect on the amphetamine- and apomorphine-induced rotational behavior, striatal dopamine (DA) D1 and D2 receptor sensitivity and tissue levels of DA and its metabolites...
January 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/27822602/interhemispheric-regulation-of-the-rat-medial-prefrontal-cortical-glutamate-stress-response-role-of-local-gaba-and-dopamine-sensitive-mechanisms
#15
Derek Lupinsky, Luc Moquin, Alain Gratton
RATIONALE: We previously reported that stressors increase medial prefrontal cortex (PFC) glutamate (GLU) levels as a result of activating callosal neurons located in the opposite hemisphere and that this PFC GLU stress response is regulated by GLU-, dopamine- (DA-), and GABA-sensitive mechanisms (Lupinsky et al. 2010). OBJECTIVES: Here, we examine the possibility that PFC DA regulates the stress responsivity of callosal neurons indirectly by acting at D1 and D2 receptors located on GABA interneurons...
November 7, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27790823/the-new-designer-drug-buphedrone-produces-rewarding-properties-via-dopamine-d1-receptor-activation
#16
Ji-Hwan Oh, Ji-Young Hwang, Sa-Ik Hong, Shi-Xun Ma, Jee-Yeon Seo, Seok-Yong Lee, Hyoung-Chun Kim, Choon-Gon Jang
Substituted cathinones are synthetic analogs of the active components of natural products and are widely abused worldwide. However, the rewarding properties of these agents have not yet been evaluated. In this study, we investigated the abuse potential of buphedrone [2-(methylamino)-1-phenylbutan-1-one, α-methylamino-butyrophenone] and its effects on the mesolimbic dopaminergic system in mice using conditioned place preference (CPP) analysis, a self-administration test, a locomotor activity test, a behavioral sensitization test and Western blot analysis...
October 27, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27766370/measurement-of-psychological-state-changes-at-low-dopamine-transporter-occupancy-following-a-clinical-dose-of-mazindol
#17
Y Kimura, J Maeda, M Yamada, K Takahata, K Yokokawa, Y Ikoma, C Seki, H Ito, M Higuchi, T Suhara
RATIONALE: The beneficial effects of psychostimulant drugs in the treatment of psychiatric disorders occur because they increase the extracellular dopamine concentration by inhibiting re-uptake of extracellular dopamine at dopamine transporters. However, the psychological effects at low dopamine transporter occupancy have not been well demonstrated. OBJECTIVES: The purpose of the study was to evaluate the psychological effects, dopamine transporter occupancy, and dopamine release induced by a single oral administration of a clinical dose of mazindol...
October 20, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27751503/the-role-of-dopamine-in-positive-and-negative-prediction-error-utilization-during-incidental-learning-insights-from-positron-emission-tomography-parkinson-s-disease-and-huntington-s-disease
#18
David Mathar, Leonora Wilkinson, Anna K Holl, Jane Neumann, Lorenz Deserno, Arno Villringer, Marjan Jahanshahi, Annette Horstmann
Incidental learning of appropriate stimulus-response associations is crucial for optimal functioning within our complex environment. Positive and negative prediction errors (PEs) serve as neural teaching signals within distinct ('direct'/'indirect') dopaminergic pathways to update associations and optimize subsequent behavior. Using a computational reinforcement learning model, we assessed learning from positive and negative PEs on a probabilistic task (Weather Prediction Task - WPT) in three populations that allow different inferences on the role of dopamine (DA) signals: (1) Healthy volunteers that repeatedly underwent [(11)C]raclopride Positron Emission Tomography (PET), allowing for assessment of striatal DA release during learning, (2) Parkinson's disease (PD) patients tested both on and off L-DOPA medication, (3) early Huntington's disease (HD) patients, a disease that is associated with hyper-activation of the 'direct' pathway...
September 19, 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/27745822/cognition-and-dopamine-d2-receptor-availability-in-the-striatum-in-older-patients-with-schizophrenia
#19
Tarek K Rajji, Benoit H Mulsant, Shinichiro Nakajima, Fernando Caravaggio, Takefumi Suzuki, Hiroyuki Uchida, Philip Gerretsen, Wanna Mar, Bruce G Pollock, David C Mamo, Ariel Graff-Guerrero
OBJECTIVES: To assess the impact of reducing the dose of antipsychotics on cognition and dopaminergic D2 receptor availability in the whole striatum, and identify their relationship in patients with schizophrenia aged 50 years or older. DESIGN: Open-label prospective PET [(11)C]-raclopride study. SETTING: A tertiary care center outpatient setting. PARTICIPANTS: Thirty-seven clinically stable participants with schizophrenia or schizoaffective disorder, aged 50 years or greater, and having been treated with olanzapine or risperidone monotherapy at the same dose for at least 6 months...
January 2017: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/27733628/modafinil-activates-phasic-dopamine-signaling-in-dorsal-and-ventral-striata
#20
Martin J Bobak, Matthew W Weber, Melissa A Doellman, Douglas R Schuweiler, Jeana M Athens, Steven A Juliano, Paul A Garris
Modafinil (MOD) exhibits therapeutic efficacy for treating sleep and psychiatric disorders; however, its mechanism is not completely understood. Compared with other psychostimulants inhibiting dopamine (DA) uptake, MOD weakly interacts with the dopamine transporter (DAT) and modestly elevates striatal dialysate DA, suggesting additional targets besides DAT. However, the ability of MOD to induce wakefulness is abolished with DAT knockout, conversely suggesting that DAT is necessary for MOD action. Another psychostimulant target, but one not established for MOD, is activation of phasic DA signaling...
December 2016: Journal of Pharmacology and Experimental Therapeutics
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