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https://www.readbyqxmd.com/read/28646714/synthetic-cathinones-and-stereochemistry-s-enantiomer-of-mephedrone-reduces-anxiety-and-depressant-like-effects-in-cocaine-or-mdpv-abstinent-rats
#1
Helene L Philogene-Khalid, Callum Hicks, Allen B Reitz, Lee-Yuan Liu-Chen, Scott M Rawls
BACKGROUND AND PURPOSE: The neuropharmacological profile of the synthetic cathinone mephedrone (MEPH) is influenced by stereochemistry. Both MEPH enantiomers are monoamine transporter substrates, but R-MEPH is primarily responsible for rewarding effects of MEPH as it produces greater locomotor activation and intracranial self-stimulation than S-MEPH. S-MEPH is a 50-fold more potent 5-HT releaser than R-MEPH and does not place preference in rats. MEPH is also structurally similar to the cathinone derivative bupropion, an antidepressant and smoking cessation medication, suggesting MEPH has therapeutic and addictive properties...
June 13, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28645892/meis1-effects-on-motor-phenotypes-and-the-sensorimotor-system-in-mice
#2
Aaro V Salminen, Lillian Garrett, Barbara Schormair, Jan Rozman, Florian Giesert, Kristina M Niedermeier, Lore Becker, Birgit Rathkolb, Ildikó Rácz, Martin Klingenspor, Thomas Klopstock, Eckhard Wolf, Andreas Zimmer, Valérie Gailus-Durner, Miguel Torres, Helmut Fuchs, Martin Hrabě de Angelis, Wolfgang Wurst, Sabine M Hölter, Juliane Winkelmann
MEIS1 is a developmental transcription factor linked to restless legs syndrome (RLS) in genome-wide association studies. RLS is a movement disorder leading to severe sleep reduction and with significant impact on the quality-of-life of patients. In genome-wide association studies, MEIS1 has consistently been the gene with the highest effect size and functional studies suggest a disease-relevant downregulation. Therefore, haploinsufficiency of Meis1 could be the most potential system for modeling RLS in animals...
June 23, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28645787/striatal-hypodopamine-phenotypes-found-in-transgenic-mice-that-overexpress-glial-cell-line-derived-neurotrophic-factor
#3
Hidekazu Sotoyama, Yuriko Iwakura, Kanako Oda, Toshikuni Sasaoka, Nobuyuki Takei, Akiyoshi Kakita, Hideki Enomoto, Hiroyuki Nawa
Glial cell line-derived neurotrophic factor (GDNF) positively regulates the development and maintenance of in vitro dopaminergic neurons. However, the in vivo influences of GDNF signals on the brain dopamine system are controversial and not fully defined. To address this question, we analyzed dopaminergic phenotypes of the transgenic mice that overexpress GDNF under the control of the glial Gfap promoter in the brain. Compared with wild-type, the GDNF transgenic mice contained higher levels of GDNF protein and phosphorylated RET receptors in the brain...
June 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28645621/two-delta-opioid-receptor-subtypes-are-functional-in-single-ventral-tegmental-area-neurons-and-can-interact-with-the-mu-opioid-receptor
#4
Elyssa B Margolis, Wakako Fujita, Lakshmi A Devi, Howard L Fields
The mu and delta opioid receptors (MOR and DOR) are highly homologous members of the opioid family of GPCRs. There is evidence that MOR and DOR interact, however the extent to which these interactions occur in vivo and affect synaptic function is unknown. There are two stable DOR subtypes: DPDPE sensitive (DOR1) and deltorphin II sensitive (DOR2); both are blocked by DOR selective antagonists. Robust motivational effects are produced by local actions of both MOR and DOR ligands in the ventral tegmental area (VTA)...
June 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28643887/personality-dopamine-and-parkinson-s-disease-insights-from-subthalamic-stimulation
#5
Eugénie Lhommée, François Boyer, Maxime Wack, Pierre Pélissier, Hélène Klinger, Emmanuelle Schmitt, Amélie Bichon, Valérie Fraix, Stéphan Chabardès, Patrick Mertens, Anna Castrioto, Andrea Kistner, Emmanuel Broussolle, Stéphane Thobois, Paul Krack
BACKGROUND: Subthalamic stimulation improves the motor and neuropsychiatric symptoms of Parkinson's disease. However, the impact of this treatment on impulse control and personality is the subject of heavy debate. The objective of this study was to investigate personality changes after subthalamic stimulation. METHODS: Using Cloninger's biosocial model, we assessed personality in 73 Parkinson's disease patients before and 12 months after subthalamic stimulation accompanied by a drastic reduction in dopaminergic medication...
June 23, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28643537/a-diffusion-weighted-imaging-study-of-basal-ganglia-in-schizophrenia
#6
Giuseppe Delvecchio, Alessandro Pigoni, Cinzia Perlini, Marco Barillari, Amelia Versace, Mirella Ruggeri, A Carlo Altamura, Marcella Bellani, Paolo Brambilla
OBJECTIVES: Several magnetic resonance imaging (MRI) studies provided evidence of selective brain abnormalities in schizophrenia, both in cortical and subcortical structures. Basal ganglia are of particular interest, given not only the high concentration of dopaminergic neurons and receptors, but also for their crucial role in cognitive functions, commonly impaired in schizophrenia. To date, very few studies explored basal ganglia using diffusion imaging, which is sensitive to microstructural organization in brain tissues...
June 23, 2017: International Journal of Psychiatry in Clinical Practice
https://www.readbyqxmd.com/read/28643183/dopaminergic-therapies-for-non-motor-symptoms-in-parkinson-s-disease
#7
REVIEW
Eva Schaeffer, Daniela Berg
Apart from the typical motor symptoms, Parkinson's disease is characterized by a wide range of different non-motor symptoms, which are highly prevalent in all stages of the disease and have an incisive influence on quality of life. Moreover, their treatment continues to be challenging. In this review, we critically summarize the evidence for the impact of dopaminergic therapies on non-motor symptoms in Parkinson's disease. We performed a PubMed search to identify relevant clinical studies that investigated the response of non-motor symptoms to dopaminergic therapy...
June 22, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28643101/cognitive-performance-correlates-with-the-degree-of-dopaminergic-degeneration-in-the-associative-part-of-the-striatum-in-non-demented-parkinson-s-patients
#8
Dorothee Kübler, Henning Schroll, Ralph Buchert, Andrea A Kühn
Parkinson's disease (PD) patients show cognitive deficits that are relevant in terms of prognosis and quality of life. Degeneration of striatal dopaminergic afferents proceeds from dorsal/caudal to anterior/ventral and is discussed to account for some of these symptoms. Treatment with dopamine (DA) has differential effects on cognitive dysfunctions, improving some and worsening others. We hypothesized that cognitive performance during the dopaminergic OFF state correlates with DAT availability in the associative striatum...
June 22, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28642851/sarcopenia-neurological-point-of-view
#9
REVIEW
Young Nam Kwon, Sung Sang Yoon
Sarcopenia is an age-related geriatric syndrome which is characterized by the gradual loss of muscle mass, muscle strength, and muscle quality. There are a lot of neurologic insults on sarcopenia at various levels from the brain to the neuromuscular junctions (NMJs) to generate a volitional task. Dopaminergic downregulation, inadequate motor programming and motor coordination impairment lead to decline of supraspinal drive. Motor unit reorganization and inflammatory changes in motor neuron decrease conduction velocity and amplitude of compound muscle action potential...
May 2017: Journal of Bone Metabolism
https://www.readbyqxmd.com/read/28642732/autonomic-function-impairment-and-brain-perfusion-deficit-in-parkinson-s-disease
#10
Wei-Che Lin, Pei-Chin Chen, Chih-Cheng Huang, Nai-Wen Tsai, Hsiu-Ling Chen, Hung-Chen Wang, Kun-Hsien Chou, Meng-Hsiang Chen, Yi-Wen Chen, Cheng-Hsien Lu
INTRODUCTION: Autonomic disorders have been recognized as important Parkinson's disease (PD) components. Some vulnerable structures are related to the central autonomic network and have also been linked to autonomic function alterations. The aims of the study are to evaluate the severity of the autonomic dysfunction and the cortical hypoperfusion using arterial spin labeling (ASL) MRI. And then, possible relationships of significant between-group differences in perfusion pattern to clinical variables and autonomic functions were examined to determine the pharmaceutical effects of dopaminergic treatment on cerebral blood flow (CBF) in patients with PD...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28642697/targeting-microglial-activation-states-as-a-therapeutic-avenue-in-parkinson-s-disease
#11
REVIEW
Sudhakar R Subramaniam, Howard J Federoff
Parkinson's disease (PD) is a chronic and progressive disorder characterized neuropathologically by loss of dopamine neurons in the substantia nigra, intracellular proteinaceous inclusions, reduction of dopaminergic terminals in the striatum, and increased neuroinflammatory cells. The consequent reduction of dopamine in the basal ganglia results in the classical parkinsonian motor phenotype. A growing body of evidence suggest that neuroinflammation mediated by microglia, the resident macrophage-like immune cells in the brain, play a contributory role in PD pathogenesis...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28641491/nicotine-and-cigarette-smoke-modulate-nrf2-bdnf-dopaminergic-signal-and-neurobehavioral-disorders-in-adult-rat-cerebral-cortex
#12
Nibedita Naha, D N Gandhi, A K Gautam, J Ravi Prakash
BACKGROUND: Nicotine and cigarette smoking (CS) are associated with addiction behavior, drug-seeking, and abuse. However, the mechanisms that mediate this association especially, the role of brain-derived neurotrophic factor (BDNF), dopamine (DA), and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in the cerebral cortex, are not fully known. Therefore, we hypothesized that overexpression of BDNF and DA, and suppression of Nrf2 contribute to several pathological and behavioral alterations in adult cerebral cortex...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28641131/children-s-brain-activation-during-risky-decision-making-a-contributor-to-substance-problems
#13
Thomas J Crowley, Manish S Dalwani, Joseph T Sakai, Kristen M Raymond, Shannon K McWilliams, Marie T Banich, Susan K Mikulich-Gilbertson
OBJECTIVE: Among young children excessive externalizing behaviors often predict adolescent conduct and substance use disorders. Adolescents with those disorders show aberrant brain function when choosing between risky or cautious options. We therefore asked whether similarly aberrant brain function during risky decision-making accompanies excessive externalizing behaviors among children, hypothesizing an association between externalizing severity and regional intensity of brain activation during risky decision-making...
June 4, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28640434/catechol-o-methyltransferase-genotype-and-gait-speed-changes-over-10-years-in-older-adults
#14
Andrea L Metti, Caterina Rosano, Robert Boudreau, Robyn Massa, Kristine Yaffe, Suzanne Satterfield, Tamara Harris, Andrea L Rosso
OBJECTIVES: To determine the association between catechol-O-methyltransferase (COMT) genotype and 6-m walk time and to determine whether these associations are quadratic in nature, similar to previously reported U-shaped associations between dopamine and gait and cognition. DESIGN: Prospective cohort study. SETTING: Health, Aging and Body Composition Study. PARTICIPANTS: Black (n = 850) and white (n = 1,352) men and women with a mean age of 73...
June 22, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28638325/dopamine-noradrenaline-and-differences-in-sexual-behavior-between-roman-high-and-low-avoidance-male-rats-a-microdialysis-study-in-the-medial-prefrontal-cortex
#15
Fabrizio Sanna, Jessica Bratzu, Maria A Piludu, Maria G Corda, Maria R Melis, Osvaldo Giorgi, Antonio Argiolas
Roman High- (RHA) and Low-Avoidance (RLA) outbred rats, which differ for a respectively rapid vs. poor acquisition of the active avoidance response in the shuttle-box, display differences in sexual activity when put in the presence of a sexually receptive female rat. Indeed RHA rats show higher levels of sexual motivation and copulatory performance than RLA rats, which persist also after repeated sexual activity. These differences have been correlated to a higher tone of the mesolimbic dopaminergic system of RHA rats vs...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28637978/mechanisms-underlying-%C3%AE-and-%C3%AE-opioid-receptor-agonist-induced-increases-in-extracellular-dopamine-level-in-the-nucleus-accumbens-of-freely-moving-rats
#16
Tadashi Saigusa, Yuri Aono, John L Waddington
The nucleus accumbens is a terminal area of the mesolimbic dopaminergic system that arises in the ventral tegmental area. Opioids are thought to enhance dopaminergic activity in the nucleus accumbens by activating δ- and μ-opioid receptors in the ventral tegmental area. However, δ- and μ-opioid receptor agonists increase extracellular levels of accumbal dopamine when infused directly into the nucleus accumbens of rats. Therefore, the roles of δ- and μ-opioid receptors in regulation of accumbal dopaminergic neural activity have been analyzed by using δ- and μ-opioid receptor ligands...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28637871/phosphorylation-at-serine-31-targets-tyrosine-hydroxylase-to-vesicles-for-transport-along-microtubules
#17
Ana Jorge-Finnigan, Rune Kleppe, Kunwar Jung-Kc, Ming Ying, Michael Marie, Ivan Rios-Mondragon, Michael F Salvatore, Jaakko Saraste, Aurora Martinez
Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine into L-Dopa, which is the rate-limiting step in the synthesis of catecholamines, particularly dopamine in dopaminergergic neurons. Low dopamine levels and death of the dopaminergic neurons are hallmarks of Parkinson's disease (PD), where α-synuclein is also a key player. TH is highly regulated, notably by phosphorylation of several Ser/Thr residues in the N-terminal tail. However, the functional role of TH phosphorylation at the Ser31 site (THpSer31) remains unclear...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#18
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28635134/locomotor-sensitization-is-expressed-by-ghrelin-and-d1-dopamine-receptor-agonist-in-the-nucleus-accumbens-core-in-amphetamine-pre-exposed-rat
#19
Ju Kyong Jang, Wha Young Kim, Bo Ram Cho, Jung Won Lee, Jeong-Hoon Kim
Ghrelin modulates mesolimbic dopaminergic pathways in the brain in addition to its role in feeding. We investigated what roles ghrelin in the nucleus accumbens (NAcc) core may play in mediating locomotor activating effects of amphetamine (AMPH). First, when rats were administered with AMPH (1 mg/kg, i.p.) following a bilateral microinjection of ghrelin (0.1 or 0.5 μg/side) into the NAcc core, their locomotor activity was significantly enhanced, while these effects were blocked by co-microinjection of ghrelin receptor antagonist (0...
June 21, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28634108/disturbances-of-novel-object-exploration-and-recognition-in-a-chronic-ketamine-mouse-model-of-schizophrenia
#20
Maria Jelena Hauser, Dirk Isbrandt, Jochen Roeper
Schizophrenia is a chronic and devastating disease with an overall lifetime risk of 1%. While positive symptoms of schizophrenia such as hallucinations and delusions are reduced by antipsychotic medication based on the inhibition of type 2 dopaminergic receptors (D2R), negative symptoms (e.g. reduced motivation) and cognitive symptoms (e.g. impaired working memory) of schizophrenia are not effectively treated by current medication. This dichotomy might arise in part because of our limited understanding of the pathophysiology of negative and cognitive symptoms in schizophrenia...
June 17, 2017: Behavioural Brain Research
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