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Levodopa rat dyskinesia

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...
August 24, 2016: Oncotarget
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...
August 17, 2016: Neurobiology of Disease
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)...
2016: Biological Research
Victoria Palafox-Sánchez, Liliana Mendieta, Gabriel Ramírez-García, Ana Candalija, José Aguilera, Ilhuicamina Daniel Limón
No abstract text is available yet for this article.
June 2016: Pharmacology, Biochemistry, and Behavior
Stefania Sgroi, Christine Capper-Loup, Paolo Paganetti, Alain Kaelin-Lang
The opioidergic neuropeptides dynorphin (DYN) and enkephalin (ENK) and the D1 and D2 dopaminergic receptors (D1R, D2R) are involved in the striatal control of motor and behavioral function. In Parkinson's disease, motor disturbances such as "on-off" motor fluctuations and involuntary movements (dyskinesia) are severe complications that often arise after chronic l-dihydroxyphenylalanine (l-DOPA) treatment. Changes in the striatal expression of preproENK (PPENK), proDYN (PDYN), D1R, and D2R mRNA have been observed in parkinsonian animals treated with l-DOPA...
June 2016: Experimental Neurology
Jovana J Belić, Pär Halje, Ulrike Richter, Per Petersson, Jeanette Hellgren Kotaleski
We simultaneously recorded local field potentials (LFPs) in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats in order to study the features directly related to pathological states such as parkinsonian state and levodopa-induced dyskinesia. We analyzed the spectral characteristics of the obtained signals and observed that during dyskinesia the most prominent feature was a relative power increase in the high gamma frequency range at around 80 Hz, while for the parkinsonian state it was in the beta frequency range...
2016: Frontiers in Systems Neuroscience
Cheng-long Xie, Jing-Ya Lin, Mei-Hua Wang, Yu Zhang, Su-fang Zhang, Xi-Jin Wang, Zhen-Guo Liu
Levodopa (L-dopa) is the dominating therapy drug for exogenous dopaminergic substitution and can alleviate most of the manifestations of Parkinson's disease (PD), but long-term therapy is associated with the emergence of L-dopa-induced dyskinesia (LID). Evidence points towards an involvement of Glycogen Synthase Kinase-3β (GSK-3β) in development of LID. In the present study, we found that animals rendered dyskinetic by L-dopa treatment, administration of TDZD8 (2mg/kg) obviously prevented the severity of AIM score, as well as improvement in motor function (P < 0...
2016: Scientific Reports
Hyung Ho Yoon, Joongkee Min, Eunmi Hwang, C Justin Lee, Jun-Kyo Francis Suh, Onyou Hwang, Sang Ryong Jeon
BACKGROUND: The inhibition of neuronal activity by electrical deep brain stimulation is one of the mechanisms explaining the amelioration of levodopa-induced dyskinesia. However, electrical deep brain stimulation cannot specifically activate or inactivate selected types of neurons. OBJECTIVES: We applied optogenetics as an alternative treatment to deep brain stimulation for levodopa-induced dyskinesia, and also to confirm that the mechanism of levodopa-induced dyskinesia amelioration by subthalamic nucleus deep brain stimulation is mediated through neuronal inhibition...
2016: Stereotactic and Functional Neurosurgery
Lu Song, Zhanzhao Zhang, Rongguo Hu, Jie Cheng, Lin Li, Qinyi Fan, Na Wu, Jing Gan, Mingzhu Zhou, Zhenguo Liu
L-3,4-dihydroxyphenylalanine (L-dopa) remains the most effective therapy for Parkinson's disease (PD), but its long-term administration is associated with the development of debilitating motor complications known as L-dopa-induced dyskinesia (LID). Enhanced function of dopamine D1 receptor (D1R) and N-methyl-D-aspartate receptor (NMDAR) is believed to participate in the pathogenesis of LID. Given the existence of physical and functional interactions between D1R and NMDAR, we explored the effects of uncoupling D1R and NMDA GluN1 (GluN1) interaction on LID by using the Tat-conjugated interfering peptide (Tat-D1-t2)...
2016: Drug Design, Development and Therapy
Annalisa Pinna, Wai Kin D Ko, Giulia Costa, Elisabetta Tronci, Camino Fidalgo, Nicola Simola, Qin Li, Mojgan Aghazadeh Tabrizi, Erwan Bezard, Manolo Carta, Micaela Morelli
BACKGROUND: The serotonin 5-HT1A/1B receptor agonist eltoprazine suppressed dyskinetic-like behavior in animal models of Parkinson's disease (PD) but simultaneously reduced levodopa (l-dopa)-induced motility. Moreover, adenosine A2A receptor antagonists, such as preladenant, significantly increased l-dopa efficacy in PD without exacerbating dyskinetic-like behavior. OBJECTIVES: We evaluated whether a combination of eltoprazine and preladenant may prevent or suppress l-dopa-induced dyskinesia, without impairing l-dopa's efficacy in relieving motor signs, in 2 PD models: unilateral 6-hydroxydopamine-lesioned rats and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys...
April 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Santiago Perez-Lloret, Olivier Rascol
Safinamide (brand name Xadago®, Zambon S.p.A) is a third-generation reversible MAO-B inhibitor, which also blocks sodium voltage-sensitive channels and modulates stimulated release of glutamate. Safinamide was recently licensed by EMA for the treatment of PD as add-on therapy to a stable dose of levodopa alone or in combination with other PD medicinal products in mid-to advanced-stage fluctuating patients. It is also under review by the US FDA. Studies in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and 6OHDA-lesioned rats suggest antiparkinsonian efficacy and antidyskinesic effects...
2016: Expert Review of Neurotherapeutics
Xingxing Jin, Kerstin Schwabe, Joachim K Krauss, Mesbah Alam
The pathophysiological mechanisms leading to dyskinesias in Parkinson's disease (PD) after long-term treatment with levodopa remain unclear. This study investigates the neuronal firing characteristics of the entopeduncular nucleus (EPN), the rat equivalent of the human globus pallidus internus and output nucleus of the basal ganglia, and its coherence with the motor cortex (MCx) field potentials in the unilateral 6-OHDA rat model of PD with and without levodopa-induced dyskinesias (LID). 6-hydroxydopamine-lesioned hemiparkinsonian (HP) rats, 6-OHDA-lesioned HP rats with LID (HP-LID) rats, and naïve controls were used for recording of single-unit activity under urethane (1...
April 2016: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
R Harun, K M Hare, M E Brough, M J Munoz, C M Grassi, G E Torres, A A Grace, A K Wagner
Parkinson's disease (PD) is a debilitating condition that is caused by a relatively specific degeneration of dopaminergic (DAergic) neurons of the substantia nigra pars compacta. Levodopa (L-DOPA) was introduced as a viable treatment option for PD over 40 years ago and still remains the most common and effective therapy for PD. Though the effects of L-DOPA to augment striatal DA production are well known, little is actually known about how L-DOPA alters the kinetics of DA neurotransmission that contribute to its beneficial and adverse effects...
November 27, 2015: Journal of Neurochemistry
Agnese Salvadè, Vincenza D'Angelo, Giuseppe Di Giovanni, Gerd Tinkhauser, Giuseppe Sancesario, Claudio Städler, Jens C Möller, Alessandro Stefani, Alain Kaelin-Lang, Salvatore Galati
Enhanced β band (βB) activity, which is suppressed by levodopa (LD) treatment, has been demonstrated within the basal ganglia (BG) of Parkinson's disease (PD) patients. However, some data suggest that Parkinsonian symptoms are not directly related to this brain frequency and therefore, its causative role remains questionable. A less explored phenomenon is the link between the γ band (γB) and PD phenomenology. Here, we monitored the development of the oscillatory activity during chronic LD depletion and LD treatment in Parkinsonian and levodopa-induced dyskinesia (LID) in rats...
January 2016: Experimental Neurology
Manuela Mellone, Jennifer Stanic, Ledia F Hernandez, Elena Iglesias, Elisa Zianni, Annalisa Longhi, Annick Prigent, Barbara Picconi, Paolo Calabresi, Etienne C Hirsch, Jose A Obeso, Monica Di Luca, Fabrizio Gardoni
Levodopa-induced dyskinesias (LIDs) are major complications in the pharmacological management of Parkinson's disease (PD). Abnormal glutamatergic transmission in the striatum is considered a key factor in the development of LIDs. This work aims at: (i) characterizing N-methyl-D-aspartate (NMDA) receptor GluN2A/GluN2B subunit ratio as a common synaptic trait in rat and primate models of LIDs as well as in dyskinetic PD patients; and (ii) validating the potential therapeutic effect of a cell-permeable peptide (CPP) interfering with GluN2A synaptic localization on the dyskinetic behavior of these experimental models of LIDs...
2015: Frontiers in Cellular Neuroscience
Giovanna Paolone, Alberto Brugnoli, Ludovico Arcuri, Daniela Mercatelli, Michele Morari
BACKGROUND: Preclinical and clinical evidence that the serotonergic system plays a major role in levodopa-induced dyskinesias has been provided. Selective serotonin (5-hydroxytryptamine; 5-HT) 5-HT1A or 5-HT1B receptor agonists, and, very recently, the mixed 5-HT1A /5-HT1B receptor agonist, eltoprazine, proved effective in inhibiting L-dopa-induced dyskinesias in experimental animals and parkinsonian patients. Here, we investigate the mechanisms underlying this effect. METHODS: Microdialysis was employed in 6-hydroxydopamine-hemilesioned rats chronically treated with L-dopa alone or in combination with eltoprazine...
November 2015: Movement Disorders: Official Journal of the Movement Disorder Society
Carol A Lazzara, Rebeccah R Riley, Anand Rane, Julie K Andersen, Yong-Hwan Kim
Lithium has recently been suggested to have neuroprotective effects in several models of neurodegenerative disease including Parkinson׳s disease (PD). Levodopa (l-Dopa) replacement therapy remains the most common and effective treatment for PD, although it induces the complication of l-Dopa induced dyskinesia after years of use. Here we examined the potential use of lithium in combination with l-Dopa/Carbidopa for both reducing MPTP-induced abnormal involuntary movements (AIMs) as well as protecting against cell death in MPTP-lesioned mice...
October 5, 2015: Brain Research
C Marin, M Bonastre, G Mengod, R Cortés, M C Rodríguez-Oroz
The mechanisms underlying lateralization and progression of motor symptoms from unilateral to bilateral in Parkinson's disease (PD) remain to be elucidated. In addition, the molecular mechanisms involved in levodopa-induced dyskinesias (LIDs) depending on lateralization and disease progression from unilaterally to bilateral have not been described yet. We investigated motor symptoms, LIDs and associated striatal molecular markers expression after unilateral left or right, and after a sequential bilateral 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions in rats...
October 2015: Neuropharmacology
Hongjuan Shi, Xinxin Yang, Hui Zhao, Shenyang Zhang, Jie Zu, Wei Zhang, Xia Shen, Guiyun Cui, Fang Hua, Chuanzhu Yan
BACKGROUND: Levodopa (l-dopa) remains the best drug in the treatment of Parkinson's disease (PD). Unfortunately, long-term l-dopa caused motor complications, one of which is l-dopa-induced dyskinesia (LID). The precise mechanisms of LID are not fully understood. We have previously reported that ranitidine could reduce LID by inhibiting the activity of protein kinase A pathway in a rat model of PD. It is demonstrated that neurotransmitters such as γ-aminobutyric-acid (GABA) and glutamate (Glu) are also involved in the expression of LID...
2015: Neuropsychiatric Disease and Treatment
Xinxin Yang, Hui Zhao, Hongjuan Shi, Xiaoying Wang, Shenyang Zhang, Zunsheng Zhang, Jie Zu, Wei Zhang, Xia Shen, Guiyun Cui, Fang Hua
Levodopa (L-dopa) remains the most effective drug in the treatment of Parkinson's disease (PD). However, L-dopa-induced dyskinesia (LID) has hindered its use for PD patients. The mechanisms of LID are not fully understood. Substance P (SP) receptor antagonist has been shown to reduce parkinsonism in animal models of PD, and ameliorate LID in PD rats. But the concrete mechanism is not fully understood. To address this issue, we produced a rat model of PD using 6-hydroxydompamine (6-OHDA) injections, and valid PD rats were intranigrally administrated with different doses of SP receptor antagonist LY303870 (5 nmol/day, 10 nmol/day and 20 nmol/day) following L-dopa (6 mg/kg/day, i...
September 2015: Experimental Neurology
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