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Levodopa rat dyskinesia

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...
April 6, 2017: Neuroscience Research
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
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
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...
January 26, 2017: Experimental Neurology
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
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
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
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
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
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...
March 21, 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
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