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Levodopa rat dyskinesia

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https://www.readbyqxmd.com/read/29232769/antiparkinsonian-and-antidyskinetic-profiles-of-two-novel-potent-and-selective-nociceptin-orphanin-fq-receptor-agonists
#1
Ludovico Arcuri, Salvatore Novello, Martina Frassineti, Daniela Mercatelli, Clarissa Anna Pisanò, Ilaria Morella, Stefania Fasano, Blair V Journigan, Michael E Meyer, Willma E Polgar, Riccardo Brambilla, Nurulain T Zaveri, Michele Morari
BACKGROUND AND PURPOSE: We previously showed that Nociceptin/orphanin FQ opioid peptide (NOP) receptor agonists attenuate the expression of levodopa-induced dyskinesia in animal models of Parkinson's disease. We now investigate the efficacy of two novel, potent and chemically distinct NOP receptor agonists, AT-390 and AT-403, to improve parkinsonian disabilities and attenuate dyskinesia development and expression. EXPERIMENTAL APPROACH: Binding affinity and functional efficacy of AT-390 and AT-403 at the opioid receptors were determined in radioligand displacement assays and in GTPγS binding assay respectively, conducted in Chinese hamster ovary cells...
December 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29167476/levodopa-induced-abnormal-involuntary-movements-correlate-with-altered-permeability-of-the-blood-brain-barrier-in-the-basal-ganglia
#2
Renata P Lerner, Veronica Francardo, Koji Fujita, Zisis Bimpisidis, Vincent A Jourdain, Chris C Tang, Stephen L Dewey, Thomas Chaly, M Angela Cenci, David Eidelberg
Chronic levodopa treatment leads to the appearance of dyskinesia in the majority of Parkinson's disease patients. Neurovascular dysregulation in putaminal and pallidal regions is thought to be an underlying feature of this complication of treatment. We used microPET to study unilaterally lesioned 6-hydroxydopamine rats that developed levodopa-induced abnormal involuntary movements (AIMs) after three weeks of drug treatment. Animals were scanned with [15O]-labeled water and [18F]-fluorodeoxyglucose, to map regional cerebral blood flow and glucose metabolism, and with [11C]-isoaminobutyric acid (AIB), to assess blood-brain-barrier (BBB) permeability, following separate injections of levodopa or saline...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115484/lipoic-acid-alleviates-l%C3%A2-dopa%C3%A2-induced-dyskinesia-in-6%C3%A2-ohda-parkinsonian-rats-via-anti%C3%A2-oxidative-stress
#3
Su-Fang Zhang, Cheng-Long Xie, Jing-Ya Lin, Mei-Hua Wang, Xi-Jin Wang, Zhen-Guo Liu
Levodopa (L‑DOPA) is the gold standard for symptomatic treatment of Parkinson's disease (PD); however, long‑term therapy is associated with the emergence of L‑DOPA‑induced dyskinesia (LID). Nigral dopaminergic cell loss determines the degree of drug exposure and time required for the initial onset of LID. Accumulating evidence indicates that α‑lipoic acid (ALA) decreases this nigral dopaminergic cell loss. However, until now, the precise mechanisms of ALA have only been partially understood in LID...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29093677/levodopa-benserazide-loaded-microspheres-alleviate-l-dopa-induced-dyskinesia-through-preventing-the-over-expression-of-d1r-shp-2-erk1-2-signaling-pathway-in-a-rat-model-of-parkinson-s-disease
#4
Ying Wan, Na Wu, Lu Song, Xijin Wang, Zhenguo Liu, Weien Yuan, Jing Gan
Background: The long-term intermittent Levodopa (L-dopa) stimulation contributes to an aberrant activation of D1 receptor (D1R) mediated extracellular signal-regulated kinases1/2 (ERK1/2) in the striatal medium spiny neurons, resulting in the occurrence of L-dopa induced dyskinesia (LID). Recently, a novel signaling pathway, D1R/Shp-2/ERK1/2, was proposed to be required for the occurrence of LID. Here we designed the study in which two different methods of L-dopa delivery [continuous dopamine stimulation (CDS) vs...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29055799/altered-mglur5-binding-potential-and-glutamine-concentration-in-the-6-ohda-rat-model-of-acute-parkinson-s-disease-and-levodopa-induced-dyskinesia
#5
Melissa Crabbé, Anke Van der Perren, Akila Weerasekera, Uwe Himmelreich, Veerle Baekelandt, Koen Van Laere, Cindy Casteels
Several lines of evidence point to alterations in glutamatergic signaling in Parkinson's disease (PD) and levodopa-induced dyskinesia (LID), involving the metabotropic glutamate receptor type 5 (mGluR5). Using small-animal positron emission tomography (PET) with [(18)F]FPEB and proton magnetic resonance spectroscopy, we investigated cerebral changes in the mGluR5 and glutamate/glutamine availability in vivo in PD rats and following onset of LIDs. In parallel, behavioral tests were performed. Comparing PD to control rats, mGluR5 binding potential was decreased in a cluster comprising the bilateral caudate-putamen (CP), ipsilateral motor cortex and somatosensory cortex, and the contralateral somatosensory cortex and parietal association cortex, with the most pronounced reduction in the ipsilateral CP...
September 21, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28893517/differential-effects-of-levodopa-and-apomorphine-on-neuronal-population-oscillations-in-the-cortico-basal-ganglia-loop-circuit-in-vivo-in-experimental-parkinsonism
#6
Johanna Kühn, Jens K Haumesser, Maximilian H Beck, Jennifer Altschüler, Andrea A Kühn, Vadim V Nikulin, Christoph van Riesen
The current pharmacotherapy of Parkinson's disease (PD) is primarily based on two classes of drugs: dopamine precursors, namely levodopa, and dopamine receptor agonists, such as apomorphine. Although both types of agents exert their beneficial clinical effects on motor and non-motor symptoms in PD via dopamine receptors, clinical efficiency and side effects differ substantially between levodopa and apomorphine. Levodopa can provide a greater symptomatic relief than dopamine receptor agonists. However, because long-term levodopa use is associated with early debilitating motor fluctuations, dopamine receptor agonists are often recommended in younger patients...
December 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28843453/receptor-heteromer-mediated-regulation-of-endocannabinoid-signaling-in-activated-microglia-role-of-cb1-and-cb2-receptors-and-relevance-for-alzheimer-s-disease-and-levodopa-induced-dyskinesia
#7
Gemma Navarro, Dasiel Borroto-Escuela, Edgar Angelats, Íñigo Etayo, Irene Reyes-Resina, Marta Pulido-Salgado, Ana I Rodríguez-Pérez, Enric I Canela, Josep Saura, José Luis Lanciego, José Luis Labandeira-García, Carlos A Saura, Kjell Fuxe, Rafael Franco
Endocannabinoids are important regulators of neurotransmission and, acting on activated microglia, they are postulated as neuroprotective agents. Endocannabinoid action is mediated by CB1 and CB2 receptors, which may form heteromeric complexes (CB1-CB2Hets) with unknown function in microglia. We aimed at establishing the expression and signaling properties of cannabinoid receptors in resting and LPS/IFN-γ-activated microglia. In activated microglia mRNA transcripts increased (2 fold for CB1 and circa 20 fold for CB2), whereas receptor levels were similar for CB1 and markedly upregulated for CB2; CB1-CB2Hets were also upregulated...
January 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28583881/altered-adenosine-2a-and-dopamine-d2-receptor-availability-in-the-6-hydroxydopamine-treated-rats-with-and-without-levodopa-induced-dyskinesia
#8
X Zhou, J Doorduin, P H Elsinga, R A J O Dierckx, E F J de Vries, C Casteels
Several lines of evidence imply alterations in adenosine signaling in Parkinson's disease (PD). Here, we investigated cerebral changes in adenosine 2A receptor (A2AR) availability in 6-hydroxydopamine (6-OHDA)-lesioned rats with and without levodopa-induced dyskinesia (LID) using positron-emission tomography (PET) with [(11)C]preladenant. In parallel dopamine type 2 receptor (D2R) imaging with [(11)C]raclopride PET and behavioral tests for motor and cognitive function were performed. METHODS: Parametric A2AR and D2R binding potential (BPND) images were reconstructed using reference tissue models with midbrain and cerebellum as reference tissue, respectively...
June 2, 2017: NeuroImage
https://www.readbyqxmd.com/read/28577977/zonisamide-ameliorates-levodopa-induced-dyskinesia-and-reduces-expression-of-striatal-genes-in-parkinson-model-rats
#9
Mitsuaki Oki, Satoshi Kaneko, Satoshi Morise, Norihiro Takenouchi, Takanori Hashizume, Ayako Tsuge, Masataka Nakamura, Reika Wate, Hirofumi Kusaka
To investigate the difference in results according to the mode of levodopa administration and the effect of zonisamide (ZNS), we analyzed the mRNA expression of dopaminergic and non-dopaminergic receptors in the striatum of Parkinson model rats in relation to the development of levodopa-induced dyskinesia (LID). Unilateral Parkinson model rats were subdivided into 4 groups and treated as follows: no medication (group N), continuous levodopa infusion (group C), intermittent levodopa injection (group I), and intermittent levodopa and ZNS injection (group Z)...
May 31, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28450828/spine-enlargement-of-pyramidal-tract-type-neurons-in-the-motor-cortex-of-a-rat-model-of-levodopa-induced-dyskinesia
#10
Tatsuya Ueno, Haruo Nishijima, Shinya Ueno, Masahiko Tomiyama
Growing evidence suggests that abnormal synaptic plasticity of cortical neurons underlies levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). Spine morphology reflects synaptic plasticity resulting from glutamatergic transmission. We previously reported that enlargement of the dendritic spines of intratelencephalic-type (IT) neurons in the primary motor cortex (M1) is linked to the development of LID. However, the relevance of another M1 neuron type, pyramidal-tract (PT) neurons, to LID remains unknown...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28445715/altered-somatosensory-cortex-neuronal-activity-in-a-rat-model-of-parkinson-s-disease-and-levodopa-induced-dyskinesias
#11
Mesbah Alam, Regina Rumpel, Xingxing Jin, Christof von Wrangel, Sarah K Tschirner, Joachim K Krauss, Claudia Grothe, Andreas Ratzka, Kerstin Schwabe
Several findings support the concept that sensorimotor integration is disturbed in Parkinson's disease (PD) and in levodopa-induced dyskinesias. In this study, we explored the neuronal firing activity of excitatory pyramidal cells and inhibitory interneurons in the forelimb region of the primary somatosensory cortex (S1FL-Ctx), along with its interaction with oscillatory activity of the primary motor cortex (MCtx) in 6-hydroxydopamine lesioned hemiparkinsonian (HP) and levodopa-primed dyskinetic (HP-LID) rats as compared to controls under urethane (1...
August 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28392304/morphological-dendritic-spine-changes-of-medium-spiny-neurons-in-the-nucleus-accumbens-in-6-hydroxydopamine-lesioned-rats-treated-with-levodopa
#12
Yukihisa Funamizu, Haruo Nishijima, Tatsuya Ueno, Shinya Ueno, Hiroki Mizukami, Soroku Yagihashi, Masahiko Tomiyama
The mechanisms of dopamine dysregulation syndrome (DDS) in Parkinson's disease (PD) remain unclear, although it is known that the nucleus accumbens (NAc) plays a role in its development. Based on the hypothesis that DDS and levodopa-induced dyskinesia (LID) share a pathophysiological basis, we investigated dendritic spine morphology of medium spiny neurons (MSNs) in the NAc of a rat model of LID, because spine enlargement in MSNs of the caudate/putamen has been proposed to be a morphological hallmark of LID...
August 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28363801/continuous-cerebroventricular-administration-of-dopamine-a-new-treatment-for-severe-dyskinesia-in-parkinson-s-disease
#13
C Laloux, F Gouel, C Lachaud, K Timmerman, B Do Van, A Jonneaux, M Petrault, G Garcon, N Rouaix, C Moreau, R Bordet, J A Duce, J C Devedjian, D Devos
In Parkinson's disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia...
March 29, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28256089/striatal-activation-by-optogenetics-induces-dyskinesias-in-the-6-hydroxydopamine-rat-model-of-parkinson-disease
#14
Ledia F Hernández, Ivan Castela, Irene Ruiz-DeDiego, Jose A Obeso, Rosario Moratalla
BACKGROUND: Long-term levodopa (l-dopa) treatment is associated with the development of l-dopa-induced dyskinesias in the majority of patients with Parkinson disease (PD). The etiopathogonesis and mechanisms underlying l-dopa-induced dyskinesias are not well understood. METHODS: We used striatal optogenetic stimulation to induce dyskinesias in a hemiparkinsonian model of PD in rats. Striatal dopamine depletion was induced unilaterally by 6-hydroxydopamine injection into the medial forebrain bundle...
April 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28131725/the-5-alpha-reductase-inhibitor-finasteride-reduces-dyskinesia-in-a-rat-model-of-parkinson-s-disease
#15
Roberto Frau, Paola Savoia, Silvia Fanni, Chiara Fiorentini, Camino Fidalgo, Elisabetta Tronci, Roberto Stancampiano, Mario Meloni, Antonino Cannas, Francesco Marrosu, Marco Bortolato, Paola Devoto, Cristina Missale, Manolo Carta
Levodopa-induced dyskinesia (LID) is a disabling motor complication occurring in Parkinson's disease patients (PD) after long-term l-DOPA treatment. Although its etiology remains unclear, there is accumulating evidence that LID relies on an excessive dopamine receptor transmission, particularly at the downstream signaling of D1 receptors. We previously reported that the pharmacological blockade of 5-alpha reductase (5AR), the rate limiting enzyme in neurosteroids synthesis, rescued a number of behavioral aberrations induced by D1 receptor-selective and non-selective agonists, without inducing extrapyramidal symptoms...
May 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27904494/anti-apoptotic-effect-of-shudipingchan-granule-in-the-substantia-nigra-of-rat-models-of-parkinson-s-disease
#16
Qing Ye, Xiao-Lei Yuan, Jing He, Jie Zhou, Can-Xing Yuan, Xu-Ming Yang
Levodopa is the gold-standard treatment for Parkinson's disease. However, although it alleviates the clinical symptoms, it cannot delay the progressive apoptosis of dopaminergic neurons or prevent motor complications in the long term. In the present study, we investigated the effect of Shudipingchan granule on neuronal apoptosis in a rat model of Parkinson's disease, established by injecting 6-hydroxydopamine into the substantia nigra pars compacta and ventral tegmental area. We then administered levodopa (20 mg/kg intraperitoneally, twice daily) with or without Shudipingchan granule (7...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27882828/morinda-citrifolia-mitigates-rotenone-induced-striatal-neuronal-loss-in-male-sprague-dawley-rats-by-preventing-mitochondrial-pathway-of-intrinsic-apoptosis
#17
S Narasimhan Kishore Kumar, Jayakumar Deepthy, Uthamaraman Saraswathi, Mohan Thangarajeswari, Sathyamoorthy Yogesh Kanna, Pannerselvam Ezhil, Periandavan Kalaiselvi
OBJECTIVES: Parkinson disease (PD) is a neurodegenerative disorder affecting mainly the motor system, as a result of death of dopaminergic neurons in the substantia nigra pars compacta. The present scenario of research in PD is directed to identify novel molecules that can be administered individually or co-administered with L-Dopa to prevent the L-Dopa-Induced Dyskinesia (LID) like states that arise during chronic L-Dopa administration. Hence, in this study, we investigated whether Morinda citrifolia has therapeutic effects in rotenone-induced Parkinson's disease (PD) with special reference to mitochondrial dysfunction mediated intrinsic apoptosis...
November 24, 2016: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/27613848/repetitive-transcranial-magnetic-stimulation-rtms-improves-behavioral-and-biochemical-deficits-in-levodopa-induced-dyskinetic-rats-model
#18
Maowen Ba, Min Kong, Lina Guan, Maoli Yi, Hongli Zhang
Fluctuations of dopamine levels and upregulations of NR2B tyrosine phosphorylation in the striatum have been connected with levodopa (L-dopa)-induced dyskinesia (LID) in Parkinson's disease (PD). Repetitive transcranial magnetic stimulation (rTMS) is one of the noninvasive and potential method treating dyskinesia. Yet, the effect of rTMS on the above key pathological events remains unclear. In this study, we gave L-dopa treatment intraperitoneally for 22 days to 6-hydroxydopamine-lesioned PD rats to prepare LID rats model, and subsequently applied rTMS daily for 3 weeks to LID rats model...
September 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27544483/dissociation-of-metabolic-and-hemodynamic-levodopa-responses-in-the-6-hydroxydopamine-rat-model
#19
Renata P Lerner, Zisis Bimpisidis, Stergiani Agorastos, Sandra Scherrer, Stephen L Dewey, M Angela Cenci, David Eidelberg
Dissociation of vasomotor and metabolic responses to levodopa has been observed in human subjects with Parkinson's disease (PD) studied with PET and in autoradiograms from 6-hydroxydopamine (6-OHDA) rat. In both species, acute levodopa administration was associated with increases in basal ganglia cerebral blood flow (CBF) with concurrent reductions in cerebral metabolic rate (CMR) for glucose in the same brain regions. In this study, we used a novel dual-tracer microPET technique to measure CBF and CMR levodopa responses in the same animal...
December 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27378167/effects-and-molecular-mechanism-of-chitosan-coated-levodopa-nanoliposomes-on-behavior-of-dyskinesia-rats
#20
Xuebing Cao, Dongzhi Hou, Lei Wang, Sai Li, Shengang Sun, Qineng Ping, Yan Xu
BACKGROUND: Chitosan, the N-deacetylated derivative of chitin, is a cationic polyelectrolyte due to the presence of amino groups, one of the few occurring in nature. The use of chitosan in protein and drug delivery systems is being actively researched and reported in the literature. RESULTS: In this study, we used chitosan-coated levodopa liposomes to investigate the behavioral character and the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2), dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) and FosB/ΔFosB in striatum of rat model of levodopa-induced dyskinesia (LID)...
July 4, 2016: Biological Research
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